Medical abortion

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A medical abortion, also known as medication abortion, occurs when drugs (medication) are used to bring about an abortion. Medical abortions are an alternative to surgical abortions such as vacuum aspiration or dilation and curettage. Medical abortions are more common than surgical abortions in most places, including Europe, India, China, and the United States.

200 mg mifepristone and 800 μg misoprostol, the typical regimen for early medical abortion

Quotes[edit]

  • Data show that an outpatient regimen of 200-mg mifepristone followed by a single dose of misoprostol is safe and effective for medical abortion for up to 70 days from last menstrual period (LMP). Yet, many clinics only provide services up to 63 days LMP, and some practice guidelines do not recommend the higher gestational age limit. We review the studies published to date that include women 64 to 70 days LMP and conclude that outpatient medical abortion is safe and effective in this interval and that there are no clinically meaningful differences between outcomes at 57 to 63 days LMP and 64 to 70 days LMP. Updating clinical protocols and revising the Food and Drug administration label for Mifeprex® to change the indication for termination of pregnancies through 70 days LMP will give women more choices and expand access to safe abortion services.
  • One known complication of induced abortion is upper genital tract infection, which is relatively uncommon in the current era of safe, legal abortion. Currently, rates of upper genital tract infection in the setting of legal induced abortion in the United States are generally less than 1%. Randomized controlled trials support the use of prophylactic antibiotics for surgical abortion in the first trimester. For medical abortion, treatment-dose antibiotics may lower the risk of serious infection. However, the number-needed-to-treat is high. Consequently, the balance of risk and benefits warrants further investigation. Perioperative oral doxycycline given up to 12 h before a surgical abortion appears to effectively reduce infectious risk. Antibiotics that are continued after the procedure for extended durations meet the definition for a treatment regimen rather than a prophylactic regimen. Prophylactic efficacy of antibiotics begun after abortion has not been demonstrated in controlled trials. Thus, the current evidence supports pre-procedure but not post-procedure antibiotics for the purpose of prophylaxis. No controlled studies have examined the efficacy of antibiotic prophylaxis for induced surgical abortion beyond 15 weeks of gestation. The risk of infection is not altered when an intrauterine device is inserted immediately post-procedure. The presence of Chlamydia trachomatis, Neisseria gonorrhoeae or acute cervicitis carries a significant risk of upper genital tract infection; this risk is significantly reduced with antibiotic prophylaxis. Women with bacterial vaginosis (BV) also have an elevated risk of post-procedural infection as compared with women without BV; however, additional prophylactic antibiotics for women with known BV has not been shown to reduce their risk further than with use of typical pre-procedure antibiotic prophylaxis. Accordingly, evidence to support pre-procedure screening for BV is lacking. Neither povidone-iodine nor chlorhexidine have been shown to alter the risk of infection when used as cervicovaginal preparation. However, chlorhexidine appears to be more effective than povidone iodine at reducing bacteria within the vagina. The Society of Family Planning recommends the routine use of antibiotic prophylaxis, preferably with doxycycline, before surgical abortion. Use of treatment doses of antibiotics with medical abortion may decrease the rare risk of serious infection but universal requirement for such treatment has not been established.
  • The Royal Australian College of General Practitioners president, Dr Nicole Higgins, said the move would improve access to the service for those living in rural and remote communities.
    "The [[w:Therapeutic Goods Administration TGA’s changes will enable greater access to medical abortion for women throughout Australia and will reduce unnecessary red tape for the GPs who provide these essential services," she said.
    Higgins said GPs were better placed to provide holistic support and counselling on medical abortions and were often the only health services available in regional areas. "These services are vital, and they must be affordable and accessible for everyone who needs them," she said.
    The assistant health minister, Ged Kearney, welcomed the effort to remove prescription red tape.
    "Our government has no higher priority than strengthening primary care and welcome the changes that allow these trusted and highly skilled providers to provide care within their scope of practice," she said.
  • The PBAC recommended listing of mifepristone and misoprostol for termination of an intra-uterine pregnancy of up to 49 days gestation on the basis of similar effectiveness and lower cost compared with surgical termination of pregnancy.
  • The Supreme Court decision to strike down Roe v. Wade on Friday was met with immediate protests and celebrations alike around the United States. But online, social media users mobilized just as quickly to share critical resources for those whose constitutional right to get an abortion had suddenly been taken away.
    Social media platforms flooded with infographics, articles, memes and videos aimed at mitigating the chaos left in the wake of the ruling — boosting resources for those seeking abortion services. Links to donate to abortion funds trended on Twitter. On TikTok, feeds flooded with explainers on what the decision means state-by-state. People offering transportation and housing for those traveling for an abortion took to Reddit and Facebook. Instagram filled with guidance on how to obtain abortion pills and emergency contraceptives online.
  • A two-slide infographic posted by Mayday Medicines on Instagram sharing resources on how to get an abortion by mail received over 75 thousand likes within one day. A tweet with similar information garnered over 3.5 million impressions, according to screenshots of engagement metrics provided by the group.
    "The information that we shared was clear, vetted and our support of resources are easily citable," said 27-year-old Sydney Levin-Epstein, a founding board member of Mayday Medicines. "What our generation is calling for is clear action with accessible information and equitable distribution of resources."
  • A study comparing medical abortion using mifepristone±misoprostol with early surgical abortion in China, Cuba, and India found medical abortion to be safe, efficacious and acceptable under a range of conditions. Fully established services for routine surgical abortion are not required prior to introducing medical abortion, although vacuum aspiration is a necessary back-up to both first and

second trimester medical procedures for the small number of cases of incomplete abortion. It has been persuasively argued that medical abortion can be largely self-administered as long as the woman considers the method acceptable, is early enough in pregnancy (up to 9 weeks LMP), can adhere to the protocol, is able to manage minor adverse reactions and seek help for more serious ones, can notice and cope with the expulsion of the embryo, and can recognize a complete abortion, return for a follow-up visit or use a home pregnancy test.

  • Medical abortion is a safe, effective, and acceptable option for patients seeking an early nonsurgical abortion. In 2014, medical abortion accounted for nearly one third (31%) of all abortions performed in the United States. State-level attempts to restrict reproductive and sexual health have recently included bills that require physicians to inform women that a medical abortion is reversible. In this commentary, we will review the history, current evidence-based regimen, and regulation of medical abortion. We will then examine current proposed and existing abortion reversal legislation. The objective of this commentary is to ensure physicians are armed with rigorous evidence to inform patients, communities, and policy makers about the safety of medical abortion. Furthermore, given the current paucity of evidence for medical abortion reversal, physicians and policy makers can dispel bad science and misinformation and advocate against medical abortion reversal legislation.
  • Labor induction abortion is effective throughout the second trimester. Patterns of use and gestational age limits vary by locality. Earlier gestations (typically 12 to 20 weeks) have shorter abortion times than later gestational ages, but differences in complication rates within the second trimester according to gestational age have not been demonstrated. The combination of mifepristone and misoprostol is the most effective and fastest regimen. Typically, mifepristone 200 mg is followed by use of misoprostol 24-48 h later. Ninety-five percent of abortions are complete within 24 h of misoprostol administration. Compared with misoprostol alone, the combined regimen results in a clinically significant reduction of 40% to 50% in time to abortion and can be used at all gestational ages. However, mifepristone is not widely available. Accordingly, prostaglandin analogues without mifepristone (most commonly misoprostol or gemeprost) or high-dose oxytocin are used. Misoprostol is more widely used because it is inexpensive and stable at room temperature. Misoprostol alone is best used vaginally or sublingually, and doses of 400 mcg are generally superior to 200 mcg or less. Dosing every 3 h is superior to less frequent dosing, although intervals of up to 12 h are effective when using higher doses (600 or 800 mcg) of misoprostol. Abortion rates at 24 h are approximately 80%-85%. Although gemeprost has similar outcomes as compared to misoprostol, it has higher cost, requires refrigeration, and can only be used vaginally. High-dose oxytocin can be used in circumstances when prostaglandins are not available or are contraindicated. Osmotic dilators do not shorten induction times when inserted at the same time as misoprostol; however, their use prior to induction using misoprostol has not been studied. Preprocedure-induced fetal demise has not been studied systematically for possible effects on time to abortion. While isolated case reports and retrospective reviews document uterine rupture during second-trimester induction with misoprostol, the magnitude of the risk is not known. The relationship of individual uterotonic agents to uterine rupture is not clear. Based on existing evidence, the Society of Family Planning recommends that, when labor induction abortion is performed in the second trimester, combined use of mifepristone and misoprostol is the ideal regimen to effect abortion quickly and completely. The Society of Family Planning further recommends that alternative regimens, primarily misoprostol alone, should only be used when mifepristone is not available.
  • Objectives
    Compare proportion lost to follow-up, successful abortion, and staff effort in women who choose office or telephone-based follow-up evaluation for medical abortion at a teaching institution.
    Study design
    We performed a chart review of all medical abortions provided in the first three years of service provision. Women receiving mifepristone and misoprostol could choose office follow-up with an ultrasound evaluation one to two weeks after mifepristone or telephone follow-up with a scheduled telephone interview at one week post abortion and a second telephone call at four weeks to review the results of a home urine pregnancy test.
    Results
    Of the 176 medical abortion patients, 105 (59.7%) chose office follow-up and 71 (40.3%) chose telephone follow-up. Office evaluation patients had higher rates of completing all required follow-up compared to telephone follow-up patients (94.3% vs 84.5%, respectively, p=.04), but proportion lost to follow-up was similar in both groups (4.8% vs 5.6%, respectively, p=1.0). Medical abortion efficacy was 94.0% and 92.5% in women who chose office and telephone follow-up, respectively. We detected two (1.2%) ongoing pregnancies, both in the office group. Staff rescheduled 15.0% of appointments in the office group. For the telephone follow-up cohort, staff made more than one phone call to 43.9% and 69.4% of women at one week and four weeks, respectively.
    Conclusions
    Proportion lost to follow-up is low in women who have the option of office or telephone follow-up after medical abortion. Women who choose telephone-based evaluation compared to office follow-up may require more staff effort for rescheduling of contact, but overall outcomes are similar.
    Implications Although women who choose telephone evaluation may require more rescheduling of contact as compared to office follow-up, having alternative follow-up options may decrease the proportion of women who are lost to follow-up.
  • Kacsmaryk’s ruling also threatens to create problems for the approval of future drugs or to open the way to legal challenges for existing drugs. And it is another sign of a prominent conservative figure substituting his own lack of scientific expertise for that of doctors and the rigor of clinical trials. Since its approval in the US in 2000, there have been 5 deaths associated with mifepristone for every 1 million people who used it, according to the FDA. The risk of death from the use of penicillin is four times greater.
    Kacsmaryk, however, argued that the FDA had “entirely failed to consider the psychological effects of the drug or an evaluation of its long term-term medical consequences.” American Medical Association President Jack Resneck, Jr. criticized the judge’s “disregard for well-established scientific facts in favor of speculative allegations and ideological assertions will cause harm to our patients and undermines the health of the nation.” He added: “By rejecting medical facts, the court has intruded into the exam room and has intervened in decisions that belong to patients and physicians.”
  • METHODS:
    We planned to enroll 40 patients in a double-blind, placebo-controlled, randomized trial. We enrolled patients at 44–63 days of gestation with ultrasound-confirmed gestational cardiac activity who were planning surgical abortion. Participants ingested mifepristone 200 mg and initiated oral progesterone 400 mg or placebo 24 hours later twice daily for 3 days, then once daily until their planned surgical abortion 14–16 days after enrollment. Follow-up visits were scheduled 3±1, 7±1, and 15±1 days after mifepristone intake with ultrasonography and blood testing for human chorionic gonadotropin and progesterone. Participants exited from the study when they had their surgical abortion or earlier for gestational cardiac activity absence, gestational sac expulsion, or medically indicated suction aspiration. We assessed the primary outcome of continued gestational cardiac activity at approximately 2 weeks (15±1 day), side effects after drug ingestion, and safety outcomes including hemorrhage and emergent treatment.
    RESULTS:
    We enrolled participants from February to July 2019 and stopped enrollment after 12 patients for safety concerns. Mean gestational age was 52.5 days. Two (one per group) voluntarily discontinued 3 days after mifepristone ingestion for subjective symptoms (nausea and vomiting, bleeding). Among the remaining 10 patients (five per group), gestational cardiac activity continued for 2 weeks in four in the progesterone group and two in the placebo group. One patient in the placebo group had no gestational cardiac activity 3 days after mifepristone use. Severe hemorrhage requiring ambulance transport to hospital occurred in three patients; one received progesterone (complete expulsion, no aspiration) and two received placebo (aspiration for both, one required transfusion). We halted enrollment after the third hemorrhage. No other significant side effects were reported.
    CONCLUSION:
    We could not estimate the efficacy of progesterone for mifepristone antagonization due to safety concerns when mifepristone is administered without subsequent prostaglandin analogue treatment. Patients in early pregnancy who use only mifepristone may be at high risk of significant hemorrhage.
  • Justice Alito, who wrote so passionately about returning abortion to the states to be decided by their elected representatives, would have allowed an order to take effect that made abortion less accessible only in states where abortion remained legal.
  • Pharmacological abortions first became possible in the 1980s, when French researchers (Baulieu and Rosenblum, 1990) succeeded in developing RU486, a molecule very similar to progesterone (which is necessary for an early pregnancy to proceed) that blocks the action of the ovarian hormone. RU486, when given alone within the first seven weeks of pregnancy, caauses an abortion in 80 percent of cases (Baulieu, 1985). This antiprogesterone drug, which has been given the name mifepristone, is currently used in combination with a prostaglandin, which softens and dilates the cervix and stimulates uterine contractions. When a prostaglandin is administered forty-eight hours after mifepristone, effectiveness is raised to 96 percent (Peyron et al., 1993; Ulmann and Silvestre, 1994; Hollander, 1995).
    Since the 1960s, prostaglandins have also been used alone, administred intravaginally or intracervically, to induce abortion (Karim and Filshie, 1970a; Karim and Filshie, 1970b; Krim, 1971); however, unpleasant side effects, high cost, and instability at normal temperature (requiring refrigeration) have limited their use. In the late 1980s, a new synthetic prostaglandin for the treatment or prevention of gastric peptic ulers was registred. The new synthetic prostaglandin, misoprostol, is stable at room temperature and therefore easier to store and dispense. Many clinical studies have shown misprostol to be at least as effective as other prostaglandings for abortion induction, and it has become part of the most commonly used mifepristone-plus-prostaglandin regimen (Wong et al., 1998; Schaff et al, 2000; WHO, 2000; Schaff, Fielding, and Westhoff, 2001) <br In addition, misprostol alone, administred in dosages of 800 mcg by the vaginal route, has proven to be close to 90 percent effective in inducing abortions (Carbonell et al., 1999; Bugalho et al., 2000). Its advantage over mifepristione is that it is effective at any gestational ag and requires lower doses as pregnancy advances at full term, only a 45-mcg dose is required to induce labor (ACOF, 2000). Misprostol when used alone has a lowe effectiveness than when it is used in combination with mifepristone, but it is also associated with fewer side effects, such as nausea and vomiting (Jain, Meckstroth, and Mishell, 1999; Kain et al, 2002).
    The mifepristione-plus misprostol regimen is effective up to nine weeks of pregnancy. Vacuum aspiration canbe used to terminate pregnancies up to twelve weeks. D & C can be used up to fourteen weeks of pregnancy. For second-trimester abortion, misoprostol is the preferred method.
  • From January 2001 to March 2006, Planned Parenthood Federation of America (Planned Parenthood) health centers throughout the U.S. provided medical abortion principally by a regimen of 200 mg oral mifepristone followed 24–48 h later by 800 mcg of misoprostol administered vaginally, at home, by the woman herself. An in-depth retrospective chart audit was conducted in 2003 of 11,290 clients in which the overall success rate of medical abortion with mifepristone and vaginal misoprostol through 63 days since the start of the last menstrual period was 98.5%. Over the years, data consistently informed us that medical abortion with mifepristone and vaginal misoprostol had a rate of ongoing pregnancy of about 0.5% and that an additional 1% of patients had uterine evacuation for various reasons including problematic bleeding, persistent gestational sac, clinician judgment or patient request. Although its national guidelines permitted delivery of medical abortion through 63 days of gestation, by the time PPFA suspended the vaginal route, some clinics in the system had adopted more restrictive gestational age criteria.
    Healthcare organizations providing medical abortion have been interested in alternatives to vaginal administration of misoprostol for several reasons. One is a frequently reported patient dislike of vaginal self-manipulation, particularly in women from cultures where tampon and diaphragm use have low prevalence. In countries in which abortion is severely legally restricted, should patients need hospital care, having remnants of misoprostol tablets in the vagina could put the patient and the provider in legal jeopardy. In addition, there was conjecture, but no evidence, that the vaginal route of misoprostol contributed to the incidence of rare but serious infection among women having medical abortion. One alternative to the vaginal route has been the oral administration of misoprostol, the regimen on which U.S. Food and Drug Administration (FDA) approval was based. A more recent regimen is buccal administration of misoprostol. An open-label randomized U.S. trial through 56 days from last menses (n=429) compared self-administered buccal with vaginal misoprostol 800 mcg taken 1 or 2 days after 200 mg of mifepristone. The success rates were not significantly different for the two different routes of administration: 95.0% in the buccal group and 93.0% in the vaginal group (Χ2=.043, p=0.51.
  • Information about the extent to which misoprostol was used in countries where abortion access was restricted was largely anecdotal, misoprostol-sales data collected by the pharmaceutical industry were not available for all countries, and misoprostol regulations within countries did not necessarily correlate with actual availability and sales in the formal and informal markets.
  • The duration of bleeding after a medical abortion using mifepristone varies among studies. Three studies, including 2 from France, found an average duration of bleeding of 9 days (16, 17, 28), with a range of 1 to 32 days (16, 17). However, the remainder of studies, including those from the United States, report a mean duration of bleeding of 14 to 17 days (22, 23, 29), with a range of 1 to 69 days (18, 23, 30). Davis and colleagues (31) followed women by using bleeding diaries to document bleeding patterns after administration of mifepristone and vaginal misoprostol. They reported bleeding for a mean of 14 days and spotting for a mean of 10 days. Overall, women had bleeding or spotting for an average of 24 days, longer than what is typically reported in efficacy studies. Twenty percent of women had bleeding or spotting that lasted more than 35 days.
  • Although gynecologists provide most surgical abortions, a broader variety of physicians may be able to provide medical abortions. These include family physicians, internists, and pediatricians. If the physician providing medical abortion does not have the skills or equipment for suction curettage, referral to other physicians can meet this occasional need.
  • Medication abortion has come to play a pivotal role in abortion care. Even while the overall number of abortions declined, the number of medication abortions and the proportion of all abortions that were medication abortions increased.
  • Global advocacy efforts must focus on changing laws and formulating national policies that respect reproductive freedom and a woman’s right to choose as a matter of basic human rights. In rural areas where access to services is scarce and few obstetricians are available, training community health workers in manual vacuum aspiration and early medical abortion is critical. Even in the case of India, where abortion services are generally legal, the lack of trained personnel remains a critical public health challenge.
  • Mifepristone may be the least marketed pharmaceutical product in the U.S. There aren’t any ads for it on TV. Most doctors can’t prescribe it. Pharmacists don’t know much about it, since it doesn’t sit on the shelves at CVS or Walgreens. It would be reasonable to assume this is all because mifepristone is exceptionally dangerous. But it sends fewer people to the ER than Tylenol or Viagra.
  • Most women undergoing first-trimester abortion are healthy. However, abortion providers also encounter women with a wide variety of medical conditions, some of which are serious and complex. When such a condition exists, consultation with the woman's physician or a specialist can facilitate decision making regarding hospital referral and additional preparations that may be required. Medical conditions may determine the approach to abortion. Surgical abortion is preferred when mifepristone or methotrexate is contraindicated. Medication abortion may be preferred when lithotomy position is not possible or in patients with extreme obesity. Limited data suggest that women treated with anticoagulation therapy bleed more than other women during surgical abortion, although this additional bleeding may be clinically unimportant. The decision to temporarily discontinue anticoagulation therapy will depend on the agent used and the underlying risk of thrombosis. According to the American Heart Association, additional antibiotics are not recommended to prevent endocarditis in women with cardiac lesions during surgical abortion. We review specific recommendations for women with common medical conditions. In some women, highly effective postabortion contraception is essential to prevent pregnancy-related morbidity. The U.S. Medical Eligibility Criteria for Contraceptive Use, 2010, provides guidance for method selection for women with medical problems.
  • Background: Advances in prenatal diagnosis make it possible to detect many fetal pathologies for which a termination of pregnancy (TOP) is possible in France. In pregnancies which go beyond 3 months, the use of prostaglandins combined with mifepristone has simplified this procedure. Since mifepristone must be taken 48 h before using prostaglandins, we have used only misoprostol intravaginally.
    Methods: Our report deals with a continuous series of terminated pregnancies in the second and third trimesters. The time period in question is January 1, 1996 through July 31, 2001. When this treatment was used within the first 30 weeks of gestation, four tablets (800 microg) of misoprostol were administered intravaginally. When there were no contractions, two additional tablets (400 microg) of misoprostol were given orally every 3 h, not exceeding 3 times. Beyond 30 weeks of amenorrhoea, because of the risk of uterine rupture, the initial dose was lower: 1/4 tablet (50 microg) of misoprostol intravaginally was increased to 100 microg (1/2 tablet) every 3 h until expulsion.
    Results: In the second and third trimesters, 55 pregnancies were terminated medically; only 1 case was not successful. In the other 54 cases, the average time interval between administering misoprostol intravaginally and expulsion was 12.7 +/- 8 h. Side effects included nausea or vomiting for 12 patients (22%) and hyperthermia for 11 patients (20%). Thirty-three patients (60%) had no side effects at all. In 10 cases (18%), the fetus and the placenta were removed in one movement. In 11 cases (20%), the placenta had to be removed by artificial means. In 7 cases (13%), a curettage with a curette foam was done. In the long run perspective, only 1 patient needed a curettage to remove placental residue.
    Conclusion: Treatment by misoprostol without mifepristone during the second and third trimesters makes it possible to terminate a pregnancy easily and quickly without significant complications.
  • Recent findings: Across studies published in the recent past, it is apparent that women prefer shorter procedures and procedure times. Several randomized controlled trials have confirmed adding mifepristone to the second trimester medication abortion regimen results in shorter abortion intervals from first misoprostol administration to complete fetal expulsion. A study of simultaneous administration of mifepristone and misoprostol yielded shorter mean 'total' abortion times, presenting several logistical advantages. Recent studies on the continuous dosing of misoprostol have produced critical evidence to support continued dosing until expulsion. These studies had a more practical design compared with previous protocols that capped the number of misoprostol doses.
    Summary: Second trimester surgical abortion is well tolerated and increasingly expeditious. Further research is needed to refine second trimester medical abortion methods, specific to the mifepristone, misoprostol dosing interval. A 12-hour mifepristone to misoprostol interval may be the optimal interval balancing patient preferences and logistical considerations. Pragmatic dosing, including continuous dosing of misoprostol, could yield results that better inform clinical guidelines and reduce burden on patient, provider, and health facility.
  • Leah Litman, a law professor at the University of Michigan, said she found Justice Alito’s critique curious. If there was questionable conduct, she said, it was in the Texas litigation, as the lead plaintiff, a coalition of anti-abortion groups known as the Alliance for Hippocratic Medicine, had taken steps to ensure that the case would appear before a friendly judge.
    “It was remarkable that Alito accused the federal government of bad faith in this matter for choosing not to appeal the initial order in the Washington case,” Professor Litman said, “when the plaintiffs in the Texas case incorporated in Amarillo so they could select Judge Kacsmaryk as the one to hear their request for a nationwide medication abortion ban.”
    Justice Alito added that Danco, the pill’s manufacturer, would have had nothing to fear had the Supreme Court curtailed the F.D.A.’s approval of the drug while the case moved forward because, he said, the Biden administration would most likely have ignored the court’s ruling.
    “The government,” Justice Alito wrote, “has not dispelled legitimate doubts that it would even obey an unfavorable order in these cases, much less that it would choose to take enforcement actions to which it has strong objections.”
  • Adam Liptak, “In Abortion Pill Ruling, the Supreme Court Trades Ambition for Prudence”, New York Times, (April 22, 2023)
  • Background: A systematic review was conducted to compare with other methods, using the best available evidence, the benefits and risks associated with the administration of misoprostol to terminate pregnancy with fetal demise in the second and third trimesters (defined as gestational age of more than 14 weeks).
    Study design: We assessed all published randomized controlled trials identified from the Cochrane Pregnancy and Childbirth Group Trials Register, MEDLINE, POPLINE, LILACS and CINHAL from 1987 to 2008 comparing misoprostol alone (vaginal, oral or sublingual administration) with placebo or no treatment or any other method of uterine evacuation (including cervical ripening with other prostaglandins administered vaginally or extra-amniotically, oxytocin, as well as mechanical methods of evacuation including extra-amniotic Foley catheter or laminaria placement) in women with diagnosis of intrauterine fetal death in the second and third trimester of pregnancy. We also evaluated the use of misoprostol alone with misoprostol plus other adjuncts such as intravenous oxytocin. Meta-analyses were performed using relative risks (RRs) as the measure of effect size for binary outcomes and weighted mean differences for continuous outcome measures. For all data, 95% confidence intervals (CIs) were also computed.
    Results: Fourteen studies comparing different interventions were included. The induction regimens varied considerably in the number of applications of medication, dosages and time intervals between doses. The main outcome was uterine evacuation at 48 h. In all studies evaluated, both vaginal and oral misoprostol showed 100% success rate in achieving uterine evacuation at 48 h. We also evaluated the success at achieving uterine evacuation at 24 h. Although the differences were not statistically significant and heterogeneity was observed, vaginal misoprostol was as effective as oral administration, achieving uterine evacuation within 48 h (RR=0.96, 95% CI=0.85 to 1.09). Oral administration was associated with more side effects than vaginal administration. The mean time intervals from induction to delivery were not significantly different between the vaginal and oral treatment groups [-1.97 (95% CI=-3.22 to 0.72)], so that the clinical benefit of oral administration and avoidance of repeated vaginal administration is probably marginal. Vaginal misoprostol alone was less effective in achieving uterine evacuation at 24 h compared with vaginal misoprostol plus oxytocin. However, there was no statistically significant difference (RR=1.00, 95% CI=0.89 to 1.12) in uterine evacuation at 48 h for vaginal misoprostol either with or without oxytocin administration.
    Conclusions: Overall, the body of evidence regarding induction of labor and delivery for second and third trimester of pregnancy is limited and the studies vary in methodology and selected outcome measures, making direct comparisons difficult. Vaginal misoprostol was less effective than oral misoprostol for effecting delivery within 24 h, but not within 48 h.
  • Medical abortions accounted for 90% of abortions before 9 weeks' gestation in Norway in 2016.
    • Løkeland M, Mjaatvedt AG, Akerkar R, Pedersen Y, Bøyum B, Hornæs MT, Ebbing M (March 8, 2017). "Rapport om svangerskapsavbrot for 2016" [Report on pregnancy terminations for 2016] (PDF) (in Norwegian). Oslo: Divisjon for epidemiologi (Division of Epidemiology), Nasjonalt Folkehelseinstitutt (Norwegian Institute of Public Health), Norway. ISSN 1891-6392. Archived from the original (PDF) on April 15, 2017. Retrieved April 25, 2017.
  • Results: Preliminary analysis (n=226) revealed that women utilized multiple strategies to manage pain during medical abortion, and 19% reported marijuana use. All of those women (43/43) found it to be at least somewhat effective at relieving pain and cramps. About half used marijuana after ingesting mifepristone, and half used it within 24 h after administering the misoprostol. The majority (75%) smoked the marijuana, and almost all would use it again if they were to have another abortion.
    Conclusions: Initial findings suggest that a sizable proportion of women in states with progressive marijuana policies use marijuana during first-trimester medical abortion and find it helpful in managing pain. Further research is needed to investigate the clinical effectiveness of marijuana in relieving pain in this population.
  • Objectives: To assess the effectiveness of a prostaglandin E1 analog, misoprostol, using different regimens compared with dinoprostone in termination of pregnancies in second and early third trimester complicated by either congenital fetal anomalies or intrauterine fetal demise.
    Methods: A retrospective review of 59 pregnancies between 15 and 30 weeks was performed which were terminated due to congenital fetal anomalies or intrauterine fetal demise. In group 1 (n=29) 400 microg oral and 600 microg vaginal misoprostol, in group 2 (n=12) 600 microg vaginal misoprostol and in group 3 (n=18) 0.5 mg dinoprostone gel were given for the termination of the pregnancies. All these groups were evaluated for demographic characteristics and delivery findings. Statistical analysis were performed by one-way ANOVA, Kruskal-Wallis and chi(2)-test.
    Results: No significant statistical difference was observed in terms of age, gravidity, parity, previous abortion, gestational week, frequency of prostaglandin usage, and birth weights among the three groups. The time intervals between the first administration and delivery were 20.3 h for oral vaginal misoprostol, 17.3 h for vaginal misoprostol and 22.5 h for the dinoprostone group (P=0.594). Evacuation rates after single doses were similar in all groups (83%, 73% and 72%, respectively). Uterine tachysystole was the only major side effect encountered in the oral-vaginal misoprostol group.
    Conclusions: All three regimens yielded similar results for termination of pregnancies in second and third trimester. The major advantage of misoprostol was the cost.
  • Lagging well behind rates in Europe, medication abortions have become increasingly common in the United States. That has marked a turning point for the procedure 16 years after the option became legal in the country, according to a Reuters review of data published Monday.
    As a testy political issue that evokes heated debate between Democrats and Republicans in the U.S., American public health policy toward abortions has still managed to be restricted in certain states. However, medication abortions still managed to jump to 43 percent of the total pregnancy terminations in 2014 up from 35 percent in 2010, Planned Parenthood and state health department data shows.
  • The demand for medication abortions In Texas, Ohio and North Dakota — the states impacted the most by the changing rates — tripled in the past several months, bringing the share to around 30 percent of the total. In states like Michigan and Iowa, where there are relatively few abortion restrictions, the share of abortions administered through medication came out to 55 and 64 percent, respectively.
    The overall rate of abortions in the United States has declined recently to one of the lowest in four decades.
  • Reason for posting: Mifepristone is used with misoprostol to terminate early pregnancies and has been taken by more than 460 000 women. The US Food and Drug Administration (FDA) recently advised of 4 women in the United States who died of sepsis after taking the drugs for medical abortion. Two of the women had Clostridium sordellii-related sepsis (www.fda.gov/cder/drug/advisory/mifeprex.htm). A Canadian woman died in 2001 of C. sordellii-related septic shock after taking the drugs in a clinical trial.1
    The drugs: Mifepristone is a progesterone receptor antagonist and abortifacient, but was originally investigated for its antiglucocorticoid effects as a potential treatment for Cushing's syndrome. Widely used in Europe and the United States, it is not licensed for use in Canada. According to the FDA-approved protocol, 600 mg of mifepristone is taken orally within 49 days after the start of a woman's last menstrual period. Two days later 400 μg of the prostaglandin misoprostol is taken orally to soften the cervix and induce uterine contractions if the pregnancy has not already ended. Ten days later the woman is followed up clinically, often with ultrasonography, to confirm termination of her pregnancy. Complete medical abortion occurs in about 92% of women taking the regimen, but 5%–8% require a surgical procedure because of incomplete abortion, excessive bleeding or continuing pregnancy. Common adverse effects of the regimen include abdominal cramping and vaginal bleeding, headache, nausea and vomiting, and diarrhea. Rare but fatal cases of ruptured ectopic pregnancy have occurred. Mifepristone is metabolized in the liver by CYP3A4.
    The 4 FDA-reported deaths occurred between 2003 and 2005 in California and involved women who had taken the misoprostol (800 μg) intravaginally. The infective agent was not identified in 2 of the cases. The patients with C. sordellii infection apparently had similar presentations (Box 1).
    C. sordellii is a gram-positive anaerobe found ubiquitously in soil and as part of the human intestinal flora. Ten percent of women's vaginas are colonized. Infections are rare but have been reported in patients of all ages with both intact and compromised immune systems. Death is common, and the infections often occur after transcutaneous, perineal or gastrointestinal procedures.2 The organism produces an endotoxin and can produce 2 potent exotoxins. C. sordellii sepsis in mifepristone users may occur through effects on cortisol or cytokine responses.3
    What to do: Women should be warned of this rare but potentially fatal adverse effect. They should seek immediate attention if they have fever, severe abdominal pain, very heavy bleeding, syncope or general malaise.
  • NAF strongly opposes the criminalization of actions taken by women to voluntarily end their pregnancies.
    All patients have the right to access abortion care from a qualified health care provider. As a membership organization, NAF supports abortion providers so that they are able to provide the highest-quality care to their patients. NAF works to remove barriers to abortion care. We are committed to disseminating evidence-based standards and guidelines related to abortion care throughout pregnancy.
    NAF believes that all people should be able to consult with and obtain care from a clinician at any point during the process of terminating their pregnancy. NAF recognizes, however, that there are situations in which pregnant people will not be able to access the care they need within the current health cares ystem. NAF further recognizes that there are pregnant people who might choose to obtain care outside of the health care system. In these instances, pregnant people (and those who support them) must have access to accurate information about abortion and high-quality follow-up care.
  • Medical abortions accounted for 94% of abortions before 9 weeks' gestation in Sweden in 2016.
  • Medical literature and newspapers in the late 1700s and early 1800s regularly referred to herbs and medications as abortion-inducing methods, since surgical procedures were rare. Reproductive care including abortion was unregulated in those days; it was provided by skilled midwives, nurses, and other unlicensed women’s health care providers. Midwives were trusted, legitimate medical professionals who provided essential reproductive health care.
  • On May 2, 2022, a draft Supreme Court of the United States (SCOTUS) majority opinion was leaked, foreshadowing the decision to overturn the 1973 Roe V Wade decision and allow states to further restrict or ban abortions. Concerns about lost access to legal abortions2 may lead to the public educating themselves about how to obtain abortion services. We evaluated whether internet searches for abortion medications increased following the leak.
  • Background: The dose of mifepristone approved by most government agencies for medical abortion is 600 mg. Our aim was to summarize extant data on the effectiveness and safety of regimens using the widely recommended lower mifepristone dose, 200 mg, followed by misoprostol in early pregnancy and to explore potential correlates of abortion failure.
    Study design: To identify eligible reports, we searched Medline, reviewed reference lists of published reports, and contacted experts to identify all prospective trials of any design of medical abortion using 200 mg mifepristone followed by misoprostol in women with viable pregnancies up to 63 days' gestation. Two authors independently extracted data from each study. We used logistic regression models to explore associations between 15 characteristics of the trial groups and, separately, the rates of medical abortion failure and of ongoing pregnancy.
    Results: We identified 87 trials that collectively included 120 groups of women treated with a regimen of interest. Of the 47,283 treated subjects in these groups, abortion outcome data were reported for 45,528 (96%). Treatment failure occurred in 2,192 (4.8%) of these evaluable subjects. Ongoing pregnancy was reported in 1.1% (499/45,150) of the evaluable subjects in the 117 trial groups reporting this outcome. The risk of medical abortion failure was higher among trial groups in which at least 25% of subjects had gestational age >8 weeks, the specified interval between mifepristone and misoprostol was less than 24 h, the total misoprostol dose was 400 mcg (rather than higher), or the misoprostol was administered by the oral route (rather than by vaginal, buccal, or sublingual routes). Across all trials, 119 evaluable subjects (0.3%) were hospitalized, and 45 (0.1%) received blood transfusions.
    Conclusions: Early medical abortion with mifepristone 200 mg followed by misoprostol is highly effective and safe.
  • Objectives
    To evaluate the safety, feasibility, and acceptability of a direct-to-patient telemedicine service that enabled people to obtain medical abortion without visiting an abortion provider in person.
    Study design
    We offered the service in five states. Each participant had a videoconference with a study clinician and had pre-treatment laboratory tests and ultrasound at facilities of her choice. If the participant was eligible for medical abortion, the clinician sent a package containing mifepristone, misoprostol, and instructions to her by mail. After taking the medications, the participant obtained follow-up tests and had a follow-up consultation with the clinician by telephone or videoconference to evaluate abortion completeness. The analysis was descriptive.
    Results
    Over 32 months, we conducted 433 study screenings and shipped 248 packages. The median interval between screening and mailing was 7 days (91st percentile 17 days), and no participant took the mifepristone at ≫71 days of gestation. We ascertained abortion outcomes of 190/248 package recipients (77%): 177/190 (93%) had complete abortion without a procedure. Of the 217/248 package recipients who provided meaningful follow-up data (88%), one was hospitalized for postoperative seizure and another for excessive bleeding, and 27 had other unscheduled clinical encounters, 12 of which resulted in no treatment. A total of 159/248 participants who received packages (64%) completed satisfaction questionnaires at study exit; all were satisfied with the service.
    Conclusions
    This direct-to-patient telemedicine abortion service was safe, effective, efficient, and satisfactory. The model has the potential to increase abortion access by enhancing the reach of providers and by offering people a new option for obtaining care conveniently and privately.
    Implications
    Provision of medical abortion by direct-to-patient telemedicine and mail has the potential to increase abortion access by increasing the reach of providers and by offering people the option of obtaining abortion care without an in-person visit to an abortion provider.
  • Introduction: The safety and acceptability of medical abortion using mifepristone and misoprostol at home at ≤9+0 weeks' gestation is well established. However, the upper gestational limit at which the procedure remains safe and acceptable at home is not known. To inform a national guideline on abortion care we conducted a systematic review to determine what gestational limit for expulsion at home offers the best balance of benefits and harms for women who are having medical abortion.

    Material and methods: We searched Embase, MEDLINE, Cochrane Library, Cinahl Plus and Web-of-Science on 2 January 2020 for prospective and retrospective cohort studies with ≥50 women per gestational age group, published in English from 1995 onwards, that included women undergoing medical abortion and compared home expulsion of pregnancies of ≤9+0 weeks' gestational age with pregnancies of 9+1 -10+0 weeks or >10+1 weeks' gestational age, or compared the latter two gestational age groups. We assessed risk-of-bias using the Newcastle-Ottowa scale. All outcomes were meta-analyzed as risk ratios (RR) using the Mantel-Haenszel method. The certainty of the evidence was assessed using GRADE.
    Results: Six studies (n = 3381) were included. The "need for emergency care/admission to hospital" (RR = 0.79, 95% confidence interval [CI] 0.45-1.4), "hemorrhage requiring transfusion/≥500 mL blood loss" (RR = 0.62, 95% CI 0.11-3.55), patient satisfaction (RR = 0.99, 95% CI 0.95-1.03), pain (RR = 0.91, 95% CI 0.82-1.02), and "complete abortion without the need for surgical intervention" (RR = 1.03, 95% CI 1-1.05) did not differ statistically significantly between the ≤9+0 and >9+0 weeks' gestation groups. The rates of vomiting (RR = 0.8, 95% CI 0.69-0.93) and diarrhea (RR = 0.85, 95% CI 0.73-0.99) were statistically significantly lower in the ≤9+0 weeks group but these differences were not considered clinically important. We found no studies comparing pregnancies of 9+1 -10+0 weeks' gestation with pregnancies of >10+0 weeks' gestation. The certainty of this evidence was predominantly low and mainly compromised by low event rates and loss to follow up.
    Conclusions: Women who are having a medical abortion and will be taking mifepristone up to and including 10+0 weeks' gestation should be offered the option of expulsion at home after they have taken the misoprostol. Further research needs to determine whether the gestational limit for home expulsion can be extended beyond 10+0 weeks.
  • Medical abortion with mifepristone and misoprostol is a two-step process where some women will change their minds about going through the abortion process after taking mifepristone. Of these, some pregnancies will continue. A woman with a twin pregnancy who changed her mind is presented. Twin pregnancies may need higher dosages of mifepristone than single pregnancies due to the presence of two corpora lutea and increased amount of trophoblast tissue. There is little, if any, documentation regarding congenital abnormalities after taking mifepristone. Therefore, there is little evidence to support persuasion of the patient to continue the abortion process with the prostaglandin analouge.
  • Randall K. O'Bannon of the National Right-to-Life Committee argued that increased efforts to promote abortions, especially medical abortions using the drug known as RU-486, probably playing a greater role.
    "The abortion industry has been busy promoting its products," O'Bannon said. "It's trying to change what the image of abortion is - like it's as safe and simple as taking a pill. That's certainly a major factor."
    The survey, which was conducted in 2009 and 2010, found use of RU-486, also known as mifepristone, continued to increase, jumping 24 percent, from 161,000 to 199,000, to account for 17 percent of all abortions. Although that increase was enough to account for the stall, Jones said research suggests that the availability of RU-486 has not yet increased the overall number of women having abortions.
  • Pregnant people can face many barriers to accessing abortion at clinics, including distance, scheduling difficulties and long wait times for appointments, the need to take time off from work and/or arrange for childcare, and harassment from clinic protesters.
    In an effort to combat some of these barriers, Gynuity Health Projects, a non-profit reproductive health research organization, launched a project in 2016 called TelAbortion to provide medical abortion using telemedicine. Medical abortion is the use of pills (called mifepristone and misoprostol) to end a pregnancy. The Food and Drug Administration (FDA) approved mifepristone in 2000, and since then over 3.5 million people in the U.S. have had a medical abortion.
    The TelAbortion project is a way for people to access medical abortion without going to an abortion clinic. An abortion provider conducts a video evaluation, reviews test results obtained at facilities in the patient’s community (if tests are needed), and sends the abortion pills by mail. The project is a research study conducted under a protocol filed with the U.S. Food and Drug Administration and approved by ethical review boards. The project is running in 13 states and DC: CO, GA, HI, IA, IL, MD, ME, MN, MT, NM, NY, OR, and WA.
    As of May 2020, the project has enrolled more than 1000 patients. 95% of participants completed their abortion without surgery, and satisfaction has been high among both patients and providers.
  • In early pregnancy, medical abortion avoids surgery but is associated with more pain and bleeding and a slightly higher risk of incomplete abortion. Data show that neither type of abortion increases the risk of long-term mental health problems or breast cancer or adversely affects fertility.
  • Objective: This study aims to evaluate the impact of the implementation a mifepristone-misoprostol protocol (MIFE/MISO) on the induction-to-expulsion interval in the context of second- and third-trimester pregnancy termination or intrauterine fetal death (IUFD) compared with misoprostol alone (MISO), and to share the experience of a Canadian tertiary hospital concerning the feasibility and safety of such a protocol.
    Methods: This is a single-centre retrospective pre-post cohort study carried out at the Centre Hospitalier Universitaire (CHU) Sainte-Justine between 2017 and 2019. Women in the MIFE/MISO group were instructed to take mifepristone 24-48 hours before induction. Induction in the MIFE/MISO group was performed with misoprostol dosages adjusted to gestational age and the presence of previous uterine scars, while, in the MISO group, all patients received 400 μg of misoprostol vaginally every 4 hours.
    Results: Ninety-four patients were included in the MIFE/MISO group and 103 patients, in the MISO group. Median time to expulsion was significantly lower in the MIFE/MISO group than the MISO group (13.5 and 19.5 h respectively; P < 0.001). The total dose of misoprostol administered was significantly lower in the MIFE/MISO group than the MISO group, and adverse effects were reported in 60% and 82% of patient records, respectively (P < 0.001). Complication rates were similar between the 2 groups.
    Conclusion: The MIFE/MISO protocol is highly effective for second- and third-trimester induction for pregnancy termination or IUFD, without increasing complication rates and with fewer reported adverse effects. Its implementation is safe and feasible in a tertiary medical centre.
  • Tennessee Governor Bill Lee signed a bill Thursday criminalizing abortion-inducing drugs that are provided via mail.
    The measure, known as HB2416, establishes criminal penalties for offenders, but would not apply to the patient who was provided the abortion drugs.
    The legislation sets strict parameters around abortion-inducing drugs. The drugs “may be provided only by a qualified physician,” the bill says, stipulating also that a “manufacturer, supplier, pharmacy, physician, qualified physician, or other person may not provide an abortion-inducing drug via courier, delivery, or mail service.”
    The bill also lays out other limitations including: the patient must be examined in-person, the doctor must “inform the patient that the patient may see the remains of the unborn child in the process of completing the abortion,” the physician must schedule a follow-up appointment within two weeks, and none of the abortion-inducing drugs can be provided on elementary, secondary, or post-secondary school facilities.
    “An individual who intentionally, knowingly, or recklessly violates this bill commits a Class E felony and, upon conviction, will be fined an amount not to exceed $50,000, be imprisoned for a term not to exceed 20 years, or both,” the bill sets forth, noting a criminal penalty will not be leveled against the patient.
  • Main results: Fourty RCTs were included, addressing various agents for pregnancy termination and methods of administration. When used alone, misoprostol was an effective inductive agent, though it appeared to be more effective in combination with mifepristone. However, the evidence from RCTs is limited. Misoprostol was preferably administered vaginally, although among multiparous women sublingual administration appeared equally effective. A range of doses of vaginally administered misoprostol has been used. No randomised trials comparing doses of misoprostol were identified; however low doses of misoprostol appear to be associated with fewer side-effects while moderate doses appear to be more efficient in completing abortion. Four RCTs showed that the induction to abortion interval with 3-hourly vaginal administration of prostaglandins is shorter than 6-hourly administration without an increase in side-effects. Many studies reported the need for surgical evacuation. Indications for surgical evacuation include retained products of the placenta and heavy vaginal bleeding. Fewer women required surgical evacuation when misoprostol was administrated vaginally compared with women receiving intra-amniotical PGF(2a) . Mild, self-limiting diarrhoea was more common among women who received misoprostol compared to other agents.
    Authors' conclusions: Medical abortion in the second trimester using the combination of mifepristone and misoprostol appeared to have the highest efficacy and shortest abortion time interval. Where mifepristone is not available, misoprostol alone is a reasonable alternative. The optimal route for administering misoprostol is vaginally, preferably using tablets at 3-hourly intervals. Apart from pain, the side-effects of vaginal misoprostol are usually mild and self limiting. Conclusions from this review are limited by the gestational age ranges and variable medical regimens, including dosing, administrative routes and intervals of medication, of the included trials.
    • Wildschut, H; Both, MI; Medema, S; Thomee, E; Wildhagen, MF; Kapp, N (19 January 2011). "Medical methods for mid-trimester termination of pregnancy". The Cochrane Database of Systematic Reviews (1): CD005216. doi:10.1002/14651858.CD005216.pub2. PMID 21249669.
  • Background: Medical abortion became an alternative method of pregnancy termination following the development of prostaglandins and antiprogesterone in the 1970s and 1980s. Recently, synthesis inhibitors of oestrogen (such as letrozole) have also been used to enhance efficacy. The most widely researched drugs are prostaglandins (such as misoprostol, which has a strong uterotonic effect), mifepristone, mifepristone with prostaglandins, and letrozole with prostaglandins. More evidence is needed to identify the best dosage, regimen, and route of administration to optimise patient outcomes.
  • Objectives: To compare the effectiveness and side effects of different medical methods for first trimester abortion.
    Search methods: We searched CENTRAL, MEDLINE, Embase, Global Health, and LILACs on 28 February 2021. We also searched Clinicaltrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform, and reference lists of retrieved papers.
    Selection criteria: We considered randomised controlled trials (RCTs) that compared different medical methods for abortion before the 12th week of gestation. The primary outcome is failure to achieve complete abortion. Secondary outcomes are mortality, surgical evacuation, ongoing pregnancy at follow-up, time until passing of conceptus, blood transfusion, side effects and women's dissatisfaction with the method.
    Data collection and analysis: Two review authors independently selected and evaluated studies for inclusion, and assessed the risk of bias. We processed data using Review Manager 5 software. We assessed the certainty of the evidence using the GRADE approach.
    Main results: We included 99 studies in the review (58 from the original review and 41 new studies). 1. Combined regimen mifepristone/prostaglandin Mifepristone dose: high-dose (600 mg) compared to low-dose (200 mg) mifepristone probably has similar effectiveness in achieving complete abortion (RR 1.07, 95% CI 0.87 to 1.33; I2 = 0%; 4 RCTs, 3494 women; moderate-certainty evidence). Prostaglandin dose: 800 µg misoprostol probably reduces abortion failure compared to 400 µg (RR 0.63, 95% CI 0.51 to 0.78; I2= 0%; 3 RCTs, 4424 women; moderate-certainty evidence). Prostaglandin timing: misoprostol administered on day one probably achieves more success on complete abortion than on day three (RR 1.94, 95% CI 1.05 to 3.58; 1489 women; 1 RCT; moderate-certainty evidence). Administration strategy: there may be no difference in failure of complete abortion with self-administration at home compared with hospital administration (RR 1.63, 95% CI 0.68 to 3.94; I2 = 84%; 2263 women; 4 RCTs; low-certainty evidence), but failure may be higher when administered by nurses in hospital compared to by doctors in hospital (RR 2.69, 95% CI 1.39 to 5.22; I2 = 66%; 3 RCTs, 3056 women; low-certainty evidence). Administration route: oral misoprostol probably leads to more failures than the vaginal route (RR 2.38, 95% CI 1.46 to 3.87; I2 = 39%; 3 RCTs, 1704 women; moderate-certainty evidence) and may be associated with more frequent side effects such as nausea (RR 1.14, 95% CI 1.03 to 1.26; I2 = 0%; 2 RCTs, 1380 women; low-certainty evidence) and diarrhoea (RR 1.80 95% CI 1.49 to 2.17; I2 = 0%; 2 RCTs, 1379 women). Compared with the vaginal route, complete abortion failure is probably lower with sublingual (RR 0.68, 95% CI 0.22 to 2.11; I2 = 59%; 2 RCTs, 3229 women; moderate-certainty evidence) and may be lower with buccal administration (RR 0.71, 95% CI 0.34 to 1.46; I2 = 0%; 2 RCTs, 479 women; low-certainty evidence), but sublingual or buccal routes may lead to more side effects. Women may experience more vomiting with sublingual compared to buccal administration (RR 1.33, 95% CI 1.01 to 1.77; low-certainty evidence). 2. Mifepristone alone versus combined regimen The efficacy of mifepristone alone in achieving complete abortion compared to combined mifepristone/prostaglandin up to 12 weeks is unclear (RR of failure 3.25, 95% CI 0.81 to 13.09; I2 = 83%; 3 RCTs, 273 women; very low-certainty evidence). 3. Prostaglandin alone versus combined regimen Nineteen studies compared prostaglandin alone to a combined regimen (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate). Compared to any of the combination regimens, misoprostol alone may increase the risk for failure to achieve complete abortion (RR of failure 2.39, 95% CI 1.89 to 3.02; I2 = 64%; 18 RCTs, 3471 women; low-certainty evidence), and with more diarrhoea. 4. Prostaglandin alone (route of administration) Oral misoprostol alone may lead to more failures in complete abortion than the vaginal route (RR 3.68, 95% CI 1.56 to 8.71, 2 RCTs, 216 women; low-certainty evidence). Failure to achieve complete abortion may be slightly reduced with sublingual compared with vaginal (RR 0.69, 95% CI 0.37 to 1.28; I2 = 87%; 5 RCTs, 2705 women; low-certainty evidence) and oral administration (RR 0.58, 95% CI 0.11 to 2.99; I2 = 66%; 2 RCTs, 173 women). Failure to achieve complete abortion may be similar or slightly higher with sublingual administration compared to buccal administration (RR 1.11, 95% CI 0.71 to 1.74; 1 study, 401 women).
    Authors' conclusions: Safe and effective medical abortion methods are available. Combined regimens (prostaglandin combined with mifepristone, letrozole, estradiol valerate, tamoxifen, or methotrexate) may be more effective than single agents (prostaglandin alone or mifepristone alone). In the combined regimen, the dose of mifepristone can probably be lowered to 200 mg without significantly decreasing effectiveness. Vaginal misoprostol is probably more effective than oral administration, and may have fewer side effects than sublingual or buccal. Some results are limited by the small numbers of participants on which they are based. Almost all studies were conducted in settings with good access to emergency services, which may limit the generalisability of these results.

"Change cuts infections linked to abortion pill" (July 9, 2009)[edit]

Allday Erin (July 9, 2009). "Change cuts infections linked to abortion pill". San Francisco Chronicle. p. A1.

  • A simple change in the technique used to deliver the abortion pill reduced the number of serious infections attributed to the drug by more than half, and dropped infection rates to nearly zero when antibiotics were introduced, according to a study released today.
    The results were a welcome relief to abortion providers, who fought for years to get federal approval of the pill in the United States and had faced renewed criticism of the drug after dozens of severe infections were reported and seven women died.
  • The controversial pill was approved for use in the United States in 2000 after years of debate. Over the next six years, seven women - four of them in California - died from serious infections after taking the pill, including an 18-year-old Livermore woman whose father urged federal regulators to ban the drug.
    In March 2006, Planned Parenthood - the pill's main supplier - announced it was changing the way it delivered the drug. Since then, there have been no reported deaths from the pill and the number of serious infections fell from about 1 per 1,000 to 0.06 per 1,000.
    "When medical abortion was first developed, there was an assumption that risk of infection would be nil," Fjerstad said. "We learned over time that actually that's not true, serious infection can occur. You just have to test your assumptions."
  • When the U.S. Food and Drug Administration approved the drug, the agency recommended that women swallow the second pill, which is how the drug typically is taken in Europe. But Planned Parenthood, and many other clinics in the United States, had women insert misoprostol vaginally, based on studies that showed that technique was more effective, causing contractions to start faster and last longer.
  • There were almost no serious infections in Europe, where the drug is much more popular and has been used for far longer than in the United States. So when U.S. doctors began noticing cases of serious infection, seven of which were fatal, in patients undergoing medical abortions, they considered that the method of delivery was at least partially to blame.
  • Since March 2006, Planned Parenthood has had women take the second drug by placing it in their mouth, between their cheek and gums, and letting it dissolve. Some researchers say that method retains the effectiveness of the drug, and according to the latest study, it significantly cuts the rate of infection.
    "Just changing the route of the misoprostol, which costs nothing, had an effect. And it's certainly no less convenient for women," said Dr. Paul Blumenthal, a professor of obstetrics and gynecology at Stanford University School of Medicine and director of Stanford's Center for Contraceptive Health and Research.
    He and other doctors said there's not yet a good explanation for why vaginal insertion seemed to be related to a higher incidence of infection.
  • Planned Parenthood also changed policies in July 2007, requiring that all women undergoing medical abortions be given antibiotics.
    The study looked at nearly 250,000 medical abortions performed between January 2005 and June 2008. In the first 15 months, before the policy change, there were 69 serious infections, which the study defined as infections requiring treatment with intravenous antibiotics. In the final 12 months, after the change in drug delivery and the addition of preventive antibiotic treatment, five serious infections were recorded.

"Drug Company Leaders Condemn Ruling Invalidating F.D.A.’s Approval of Abortion Pill” (4/10/2023)[edit]

Pam Belluck, Christina Jewett, “Drug Company Leaders Condemn Ruling Invalidating F.D.A.’s Approval of Abortion Pill”, New York Times, (4/10/2023)

  • The pharmaceutical industry plunged into a legal showdown over the abortion pill mifepristone on Monday, issuing a scorching condemnation of a ruling by a federal judge that invalidated the Food and Drug Administration’s approval of the drug and calling for the decision to be reversed.
    The statement was signed by more than 400 leaders of some of the drug and biotech industry’s most prominent investment firms and companies, none of which make mifepristone, the first pill in the two-drug medication abortion regimen. It shows that the reach of this case stretches far beyond abortion. Unlike Roe v. Wade and other past landmark abortion lawsuits, this one could challenge the foundation of the regulatory system for all medicines in the United States.
    “If courts can overturn drug approvals without regard for science or evidence, or for the complexity required to fully vet the safety and efficacy of new drugs, any medicine is at risk for the same outcome as mifepristone,” said the statement.
  • “If allowed to take effect, the court’s order would thwart F.D.A.’s scientific judgment and severely harm women, particularly those for whom mifepristone is a medical or practical necessity,” said the Justice Department motion, which noted that mifepristone was also used in treating miscarriages.
    It added: “This harm would be felt throughout the country, given that mifepristone has lawful uses in every state. The order would undermine health care systems and the reliance interests of businesses and medical providers.”
  • A lawyer for the plaintiffs, Erin Hawley, said in a statement on Monday, “Chemical abortion drugs don’t provide a therapeutic benefit — they can cause serious and life-threatening complications to the mother, in addition to ending a baby’s life.”
    She added that “the F.D.A. put women in harm’s way, and the agency should be held accountable for its reckless actions.”

"Abortion by Telemedicine: A Growing Option as Access to Clinics Wanes" (April 28, 2020)[edit]

Pam Belluck, "Abortion by Telemedicine: A Growing Option as Access to Clinics Wanes". The New York Times. (Published April 28, 2020; Updated June 29, 2020)

  • Abortion through telemedicine is a quietly growing phenomenon, driven in part by restrictions from conservative states and the Trump administration that have limited access and increased the distance many women must travel to abortion clinics.
    Now, the coronavirus pandemic is catapulting demand for telemedicine abortion to a new level, with much of the nation under strict stay-at-home advisories and as several states, including Arkansas, Oklahoma and Texas, have sought to suspend access to surgical abortions during the crisis.
    The telemedicine program that Ms. Dale participated in has been allowed to operate as a research study for several years under a special arrangement with the Food and Drug Administration. It allows women seeking abortions to have video consultations with certified doctors and then receive abortion pills by mail to take on their own.
  • As of April 22, TelAbortion had mailed a total of 841 packages containing abortion pills and confirmed 611 completed abortions, Dr. Raymond said. Another 216 participants were either still in the follow-up process or have not been in contact to confirm their results. The program’s growth is significant enough that Republican senators recently introduced a bill to ban telemedicine abortion.
  • Abortion through medication, first approved by the F.D.A. in 2000, is increasingly becoming women’s preferred method. Recent research estimated that about 60 percent of abortion patients early enough in pregnancy to be eligible — 10 weeks pregnant or less — chose medication abortion over suction or surgery.
    But the F.D.A. requires that the first drug in the two-medication regimen, mifepristone, be dispensed in clinics or hospitals by specially certified doctors or other medical providers.
    The F.D.A. rules, however, do not specify that providers must see patients in person, so some clinics have begun allowing women to come in for video consultations with certified doctors based elsewhere.
  • Based on state laws governing telemedicine and abortion, Dr. Raymond estimated TelAbortion might be legal in slightly over half of the states, including some conservative ones. It now serves Colorado, Georgia, Hawaii, Illinois, Iowa, Maine, Maryland, Minnesota, Montana, New Mexico, New York, Oregon and Washington.
    The doctors (and nurses or midwives in some states) who do TelAbortion’s video consultations must be licensed in states where medication is mailed, but do not have to practice there. Likewise, patients do not have to live in the states that TelAbortion serves; they just have to be in one of them during the videoconference and provide an address there — that of a friend, relative, even a motel or post office — to which pills can be shipped.
  • During such consultations, doctors explain that most women do not experience discomfort from mifepristone, which blocks a hormone necessary for pregnancy to develop. Cramping and bleeding, resembling a heavy period, occur after the expulsion of fetal tissue caused by the second drug, misoprostol, which is taken up to 48 hours later. After several hours, bleeding dwindles but might continue for two weeks. In rare cases, women can develop fevers, infections or extensive bleeding requiring medical attention.
    Lee received a package marked only with her name and address; it contained the pills, tea bags, peppermints, maxipads, prescription ibuprofen and nausea medication.
  • TelAbortion reports that of the 611 completed abortions documented through April 22, most were accomplished with only the pills and without complications. In 26 cases, aspiration was performed to finish the termination.
    Dr. Raymond said 46 women went to emergency rooms or urgent care centers with issues that appear just as likely to have occurred if the women had followed the common practice of visiting abortion clinics for consultations, taking the first medication there and the second at home. Two women went before receiving the pills and two before taking them, either because of morning sickness or because they thought they were miscarrying. Fifteen ended up needing no medical treatment. Some were given medicine for pain or nausea.
    Three were hospitalized, all successfully treated: two women had excessive bleeding, and another had a seizure after an aspiration, Dr. Raymond said.
    Eleven women decided not to have abortions and did not take the pills they were sent. Another woman continued her pregnancy after the medication failed, as did another after vomiting the mifepristone. Sixteen women have undergone two telabortions, Dr. Raymond said.
  • TelAbortion typically charges $200 to $375 for consultations and pills. Women must also pay for an ultrasound and lab tests, obtained from any provider. During the coronavirus pandemic, TelAbortion may waive its requirement for an ultrasound to gauge the gestational age of the pregnancy if women are unable to visit a doctor to obtain one, Dr. Raymond said.
    In some states, some or all of the costs are covered by private insurance or Medicaid. For women facing financial hardship, like Ms. Kirby in Denver, the program taps abortion grant networks.

“Drug Company Leaders Condemn Ruling Invalidating F.D.A.’s Approval of Abortion Pill” (4/10/2023)[edit]

Pam Belluck, Christina Jewett, “Drug Company Leaders Condemn Ruling Invalidating F.D.A.’s Approval of Abortion Pill”, New York Times, (4/10/2023)

  • The pharmaceutical industry plunged into a legal showdown over the abortion pill mifepristone on Monday, issuing a scorching condemnation of a ruling by a federal judge that invalidated the Food and Drug Administration’s approval of the drug and calling for the decision to be reversed.
    The statement was signed by more than 400 leaders of some of the drug and biotech industry’s most prominent investment firms and companies, none of which make mifepristone, the first pill in the two-drug medication abortion regimen. It shows that the reach of this case stretches far beyond abortion. Unlike Roe v. Wade and other past landmark abortion lawsuits, this one could challenge the foundation of the regulatory system for all medicines in the United States.
    “If courts can overturn drug approvals without regard for science or evidence, or for the complexity required to fully vet the safety and efficacy of new drugs, any medicine is at risk for the same outcome as mifepristone,” said the statement.
  • “If allowed to take effect, the court’s order would thwart F.D.A.’s scientific judgment and severely harm women, particularly those for whom mifepristone is a medical or practical necessity,” said the Justice Department motion, which noted that mifepristone was also used in treating miscarriages.
    It added: “This harm would be felt throughout the country, given that mifepristone has lawful uses in every state. The order would undermine health care systems and the reliance interests of businesses and medical providers.”
  • A lawyer for the plaintiffs, Erin Hawley, said in a statement on Monday, “Chemical abortion drugs don’t provide a therapeutic benefit — they can cause serious and life-threatening complications to the mother, in addition to ending a baby’s life.”
    She added that “the F.D.A. put women in harm’s way, and the agency should be held accountable for its reckless actions.”

“New York Passes Bill to Shield Abortion Providers Sending Pills Into States With Bans” (June 20, 2023)[edit]

Pam Belluck and Emily Bazelon, “New York Passes Bill to Shield Abortion Providers Sending Pills Into States With Bans”, New York Times, (June 20, 2023)

  • Since the Supreme Court ended the nationwide right to an abortion last year, legislation known as telemedicine abortion shield laws have been enacted in Massachusetts, Colorado, Vermont and Washington. But New York’s legislation is expected to have a notable impact. Several providers in New York say they plan to send abortion pills to patients in all restrictive states, and a few providers are speaking publicly, which those in other states with shield laws have so far not done.
  • “I’m going to mail pills as soon as the governor signs the bill,” said Dr. Linda Prine, a New York physician and co-founder of the Miscarriage and Abortion Hotline, which answers patients’ questions about medication abortion. “This is the first time we’re able to do something to fight back,” she added.
    Dr. Prine said she and at least three other doctors would mail pills to patients in all states with restrictions or bans. A telemedicine service in New York, Juniper Midwifery, also said it hoped to use the shield law to mail pills to patients in states with abortion bans.
    “It’s definitely something that we would want to explore and make it happen,” Jillian Barovick, a midwife and co-founder of Juniper, said.
  • Since the overturning of Roe v. Wade, tens of thousands of patients in states with bans or severe restrictions have taken abortion pills. Many have traveled to states where abortion is legal to obtain pills at clinics or at addresses in those states where pills were sent by mail. But many patients cannot afford the cost and time of traveling.
    “The telemedicine option and protecting providers who are providing telemedicine abortion services is going to help tremendously the people here in Mississippi and other restricted states,” said Michelle Colón, the executive director of SHERo Mississippi, an organization focused on supporting reproductive rights for people of color. “This will expand access, which we so desperately need.”
    Other patients receive pills in the mail from overseas, either prescribed by doctors abroad, through a European telemedicine service, or ordered directly from online pharmacies in India or other countries. By the time the pills arrive, often two to three weeks later, patients may be past the 12-week threshold of pregnancy that the World Health Organization endorses for using medication abortion. Mailing pills from within the United States, as doctors operating under shield laws are doing, cuts delivery time to a few days.
  • “Texas could prosecute them for murder,” said Jonathan Mitchell, a former Texas solicitor general and the architect of a 2021 Texas law that banned abortion after six weeks into pregnancy and deputized private citizens to enforce it by suing for cash judgments of $10,000 per abortion.
    “Under Texas law, killing a fetus through an illegal abortion is no different from killing a baby, except that the mother cannot be prosecuted (or sued) for death of a fetus,” Mr. Mitchell wrote in an email.
    Because of the substantial risks, only about 10 health care providers in states with shield laws are known to have begun sending pills to patients in states that restrict abortion. These providers have proceeded cautiously.
  • Lawyers on each side of the issue say that state shield laws undermine basic premises of interstate cooperation. Rather than recognizing one state’s arrest warrant or court order, another state effectively throws a wrench into the enforcement of that state’s laws.
    And a law that shields telehealth abortions disrupts the usual model for telemedicine law and policy, which “presumes that you’re providing care in the place where the patient is,” Professor Rebouché said.
  • “It’s very clear that in other states, citizens can still sue doctors who engage in the unlawful practice of medicine,” said Denise Harle, senior counsel for the Alliance Defending Freedom, a conservative Christian legal organization that represents the anti-abortion plaintiffsseeking to remove mifepristone from the market in their lawsuit against the F.D.A. “They can sue to protect against bad acts by people who are committing crimes.”

"Analysis of Medication Abortion Risk and the FDA report - "Mifepristone U.S. Post-Marketing Adverse Events Summary through 12/31/2018" (April 1, 2019)[edit]

"Analysis of Medication Abortion Risk and the FDA report - "Mifepristone U.S. Post-Marketing Adverse Events Summary through 12/31/2018"" (PDF). Bixby Center for Global Reproductive Health. (April 1, 2019).

  • As of December 2018, the FDA reports that 24 women, out of approximately 3.7 million, have died after taking mifepristone for medication abortion. However, as the FDA notes, “The adverse events cannot with certainty be causally attributed to mifepristone because of concurrent use of other drugs, other medical or surgical treatments, coexisting medical conditions, and information gaps about patient health status and clinical management of the patient.”
    • p.1
  • [T]he overall mortality rate associated with medication abortion is 0.65 deaths per 100,000 medication abortions (24 deaths/3.7 million medication abortion cases). This mortality rate is similar to that reported for abortion overall (0.7 deaths per 100,000 procedures). If only the cases that appear to be related to the abortion are included, the mortality rate is 0.35 deaths per 100,000 medication abortions (13 deaths/3.7 million medication abortion cases).
    • p.1
  • The FDA also published the number of cases of hospitalization and other complications (some already counted in the hospitalization cases) reported to them among women using medication abortion. However, unlike for deaths, there is no active surveillance program, so this report should not be considered as conclusive. We do know that serious complications are rare with medication abortion. The most rigorous study of medication abortion safety included data from 11,319 Medi-Cal patients in California. In this study, only 35 (0.31%) had a major complication, defined as hospitalization, blood transfusion, or surgery.
    • pp.1-2
  • The FDA conducted a rigorous review of research from the United States and other countries to assess the safety profile before it approved mifepristone in 2000. The safety of medication abortion has been highlighted repeatedly since then:
    In 2016, the FDA approved an updated label for mifepristone that allowed for using medication abortion later in pregnancy (up to 10 weeks from last menstrual period) and simplified the drug regimen. It also removed the requirement that all serious adverse events be reported to the agency and now only requires that deaths be reported.
    In 2018, the US Government Accountability Office published a report that evaluated the process that FDA used when it updated the mifepristone label. The report concluded that the agency used its standard review process to incorporate the best available evidence into the updated label.
    In 2018, the National Academies of Sciences, Engineering, and Medicine released a report that highlighted the safety and effectiveness of medication abortion.
    In April 2019, the FDA approved a generic form of mifepristone for medication abortion, which gave the agency another opportunity to review the safety of the treatment.
    • p.2
  • The mortality rate for women known to have had a live-born infant is 8.8 per 100,000 live births, which is about 14 times higher than the mortality rate associated with medication abortion. Other medications that are commonly prescribed or administered in outpatient settings also have risks, including a small risk of death. Penicillin causes a fatal anaphylactic reaction at a rate of 2 deaths per 100,000 patients administered the drug. Phosphodiesterase type-5 inhibitors, which are used for erectile dysfunction and include Viagra, have a fatality rate of 4 deaths per 100,000 users. These risks are several times higher than the risk of death with medication abortion.
    • p.2
  • Medication abortion with mifepristone and misoprostol is very safe and effective. The safety profile is similar to that of vacuum aspiration abortion, and medication abortion is safer than continuing a pregnancy to term or using other common medications.
    • p.2

"State regulations are shutting down doctors prescribing abortion pills" (April 15, 2022)[edit]

Rachel Bluth (April 15, 2022). "State regulations are shutting down doctors prescribing abortion pills". Salon.

  • Fleming is among a wave of doctors, nurse practitioners, and other health care providers who are getting licensed in multiple states so they can use telemedicine and mail-order pharmacies to help more women get medication abortions.
    But they're increasingly being stymied by state regulations. Many states already restrict doctors' ability to consult with patients online or by phone and/or dispense abortion pills through mail-order pharmacies. A crop of new legislation could shut them out, pushed by lawmakers who oppose abortion and argue the medication is too risky to be prescribed without a thorough, in-person examination.
    So far this year, 22 states have introduced a combined 104 proposals attempting to restrict medication abortions, such as by prohibiting the mailing of abortion pills and/or requiring them to be dispensed in person, according to the Guttmacher Institute, an organization that researches and advocates for abortion rights. Four of those proposals have already been enacted by South Dakota.
  • In Georgia, lawmakers are considering a measure that would require the pills to be dispensed in person and would prohibit anyone from sending them through the mail. The bill, which has passed one of two chambers of the Georgia legislature, also requires pregnant patients to appear in person for tests to check for rare complications and gather other information, a common strategy anti-abortion lawmakers have used to make medication abortion more difficult to obtain.
    "We wouldn't have a telemedicine visit and teach a woman how to perform a surgical abortion," said Bruce Thompson (R-White), the Georgia state senator who introduced the measure. "Why would we do that with pills when, frankly, we have plenty of physicians or medical clinics around the state?"
    If it passes, Georgia will join the 19 other states that prohibit telemedicine for medication abortions.
  • Dr. Lester Ruppersberger, a retired OB-GYN and president of the Catholic Medical Association in 2016, opposes telemedicine abortion, saying patients should make the decision face-to-face with a doctor.
    Women need testing beforehand, he said, as well as access to surgeons or OB-GYNs in case of complications afterward.
    "If somebody really wants an abortion, whether it's surgical or it's medical, and the closest facility where you can safely get access to that particular procedure is three hours away, then you'll get in your car, perfectly healthy, and drive three hours to take advantage of the medical system," said Ruppersberger, who is the medical director of two crisis pregnancy centers in Pennsylvania that provide pregnancy care while discouraging abortion.
  • Now, Fleming primarily uses telemedicine to try to bring abortions to more people, despite the crackdowns. Many of her patients are from states with permissive abortion rules but live in rural or other areas where abortions are hard to find.
    "Ultimately this kind of work does broaden access to folks who have no other options," Fleming said. "But it's not actually solving the root issue and the restrictions that shouldn't exist in the first place."
  • "We're reaching a point where the states with favorable regulatory situations are already served," said Elisa Wells, the co-founder and co-director of Plan C, which helps patients get medication abortions.
  • Aid Access relies on nine U.S.-based clinicians to provide medication abortions in the states that allow it via telemedicine. To serve patients in the remaining states, the group works through a doctor and pharmacy based outside the U.S.; neither is subject to U.S. regulations. Gomperts practices in Austria and prescribes abortion medication through an Indian pharmacy.
    Joanne Spetz, director of the Philip R. Lee Institute for Health Policy Studies at the University of California-San Francisco, said doctors interested in providing medication abortions across state lines can only do so much as more states shut down the practice.
    "These efforts to credential and train and educate more clinicians certainly can help to reduce the pressure on the system," Spetz said. But "unless somebody wants to try to flout those state laws, it doesn't necessarily help."

“The long and winding history of the war on abortion drugs” (04/26/2023)[edit]

Lara Bullens, “The long and winding history of the war on abortion drugs”, France24.com, (04/26/2023)

  • Along with the stethoscope and camembert cheese, mifepristone may be one of France’s greatest inventions. It’s one of two drugs taken for medical abortions, along with misoprostol, and has been making headlines in the US, where a Texas judge issued a ruling to ban it nationwide. FRANCE 24 takes a look at the history of these two drugs.
  • Where it is legal, a medical abortion means taking a combination of two pills. Mifepristone is taken first. It’s a synthetic steroid that blocks progesterone, the hormone necessary for a pregnancy to develop. Then between 24 and 48 hours later, misoprostol, a prostaglandin that induces contractions, is taken to clear the uterus. “But ‘medical abortion’ gets used as a blanket term to cover two different methods,” explained Dr. Sydney Calkin, senior lecturer at Queen Mary University in London and author of “Abortion Pills Go Global”. In many places where mifepristone is not available, misoprostol is used on its own.
  • Misoprostol was developed in 1973 by US pharmaceutical company Searle. Under the name Cytotec, the pill was originally marketed as a treatment for gastrointestinal problems and ulcers. Up until the late 1980s, it had not been associated with abortions. But when misoprostol hit the Brazilian market in August 1986 and was approved for over-the-counter sale in pharmacies, everything changed.
    Brazilian activists at the time read the “do not use if pregnant” warning on Cytotec bottles and decided to take a chance. Which worked. Off-label use of misoprostol was effective in causing an abortion. In a country where access to abortion had been illegal since 1890, with exceptions in case of rape or danger to a mother’s life added in 1940, misoprostol provided a way out. “That realisation then spread informally across Latin America through informal activist networks that would share information and practices about how to safely use it,” said Calkin.
    What began as an operation led by activists under the radar started making headlines. Researchers eventually caught on to the workaround and in 1991, after a German physician published an article warning of its “misuse” in Brazil, the drug was no longer available in the country without a prescription. Mifepristone, the other abortion pill, had also recently been approved for sale in France and China, and the recommended combination of taking both quickly came into use.
    As misoprostol became more and more entangled with abortion, laws around the drug toughened. In 1998, Brazilian health authority Anvisa put misoprostol (and opiates) on a list of controlled drugs, meaning anyone caught importing or buying the pill could face up to 15 years in prison. Its use in Brazil is now restricted to registered hospitals for narrowly prescribed uses.
    “Misoprostol’s patent holder has always been very resistant to its association with abortion,” explained Calkin, “so it has resisted licensing the drug for any kind of reproductive uses".
  • “Mifepristone has always been understood as an abortion drug, first and foremost,” Dr. Calkin explained. Its inventor, endocrinologist and biochemist Étienne-Émile Baulieu, said so himself. In a recent interview with the New York Times, the 96-year-old described being haunted by memories of his medical residency, which he completed before France passed its abortion bill in 1975. He recalled how women were admitted to the hospital he worked in after terminating pregnancies with sticks, and how surgeons would instruct their employees not to administer anaesthesia “to teach them a lesson”. So he began brainstorming the idea for an “unpregnancy pill” and convinced pharmaceutical company Roussel-Uclaf, for which he was consulting at the time, to let him develop a progesterone blocker.
    Baulieu first synthesised mifepristone in 1980 under the name “RU-468”, “RU” referring to Roussel-Uclaf and “468” to the sequencing number of the molecule. But the rollout of the pill, from its first medical trials to its market approval, was a hard-fought battle. “There was a trans-national effort by anti-abortion activists from France and the US … to stop its market introduction,” said Dr. Claudia Roesch, a research fellow at the German Historical Institute Washington who studied the backlash around mifepristone. Anti-abortion protesters blocked the entrances of French embassies in the US, as well as company headquarters in the US, France and Germany.
    “Protesters would even compare medical abortion to the Holocaust,” Roesch said. Roussel-Uclaf’s main stakeholder was German company Hoechst AG, which had been part of IG Farben during World War II, the company that produced the cyanide gas used by Nazis in concentration camps. “They sent gruesome images to their headquarters in Germany and the US,” she said.
    Mifepristone was eventually approved for use by French health authorities in September 1988. But opposition was so intense that less than a month later, Roussel-Uclaf said it would pull the pill from the market. Luckily the French government held a stake in the company, so the then French health minister Claude Évin pressured the company to resume selling it. "From the moment government approval for the drug was granted, RU 486 became the moral property of women, not just the property of the drug company,” he said in a televised address.
    China approved mifepristone the same year that France did, in 1988, “for very different reasons", said Dr. Sydney Calkin. It was approved in the UK in 1991, Sweden in 1992 and in the US in 2000. Countries with access to abortion like Australia and Canada only approved the drug much later, in 2012 and 2014 respectively. “The kind of controversy around abortion politics in those countries means there was a lot of delay,” Calkin explained.
    Even after it was approved, Baulieu’s revolutionary pill was, and continues to be, a hot topic. The Vatican went as far as denouncing RU-468 in the 1990s as “the pill of Cain: the monster that cynically kills its brothers", according to a Boston Globe article from 1997. And as recently as March 2022, Republican lawmaker Danny Bentley falsely claimed the pill was developed in WWII under the name Zyklon B, the name of the gas used to kill Jewish people during the Holocaust. This is a sign of how long-lasting and effective the anti-abortion tactics used in the 80s were.
  • In Latin American countries, the misoprostol-only regimen is still widely used. “It’s much easier to get than mifepristone,” Calkin explained.
    “It’s a lifeline for many people. But the risks vary from country to country. In El Salvador for example, abortion can land you anywhere from two to 50 years in prison. Women who have miscarried have ended up incarcerated because authorities suspect they performed an abortion. In Uruguay, on the other hand, if someone has taken misoprostol and suffers complications as a result, they won’t face penalties. “Doctors will help you manage the consequences of your abortion,” Calkin said.
    Thanks to generic versions of both pills that are mass-manufactured in India and China, and the fact that they are also readily available in Mexico, activist networks like Aid Access and Women on Waves have ways of providing people living in restricted areas with medical abortions. The Covid-19 pandemic has also paved the way for telemedicine to become more common, meaning pills can be sent by mail.
  • As for France, 76% of all abortions are medical, whether carried out in clinics or at home. And while Macron promised to enshrine abortion rights into the constitution “in the coming months” on International Women’s Day, he may find that it will be more challenging than he thought.

"FDA relaxes restrictions on abortion pill" (December 16, 2021)[edit]

Sarah McCammon, Audie Cornish, Fabiola Carrion; "FDA relaxes restrictions on abortion pill". NPR.org. All Things Considered, December 16, 2021. Retrieved May 19, 2022.

  • CORNISH: Tell us more about the FDA decision. What exactly does it do?
    MCCAMMON: Well, the FDA is loosening one of the rules for prescribing an abortion pill called mifepristone, which advocates have said is a major barrier to access for patients. Mifepristone is subject to a series of additional regulations on top of normal prescription drugs. These are for drugs deemed particularly dangerous, and they include special requirements for doctors who prescribe the pills. Until recently, patients had to pick up the pills in person at a hospital or clinic. Now, that rule was suspended because of COVID, and now the Biden administration is permanently doing away with that rule while leaving some of the other regulations in place. And this all comes in response to a lawsuit from the ACLU on behalf of reproductive rights and medical groups who say the rules are outdated and medically unnecessary.
    CORNISH: So what will access to the drug look like now?
    MCCAMMON: Well, it means doctors can continue prescribing the drug and sending it through the mail. Currently, since the rules have been somewhat relaxed during the pandemic, patients in many states, depending on their state laws, can get a prescription using telemedicine. So doctors screen the patients with a series of questions, and then they can prescribe the abortion pill and have them mailed. Fabiola Carrion with the National Health Law Program says many patients prefer this, taking the pills at home, to going into a clinic for a surgical procedure.
    FABIOLA CARRION: It's less intrusive. They can have their abortions at home. So it provides - especially now that potentially half of the states could lose access to abortion, it could be one of the additional tools that people can use to access their abortion.
    MCCAMMON: So she's saying this option could be especially important for patients in states with increasing restrictions, especially if Roe v. Wade is overturned.
    CORNISH: What's been the response so far?
    MCCAMMON: Well, it's an action that both reproductive rights groups and many medical groups, like the American Medical Association, have been calling for for years now. They point to decades of data. Mifepristone was approved by the FDA in 2000, and they say that demonstrates that it's very safe and effective. So abortion rights groups are pleased, although they would have liked the FDA to go further and do away with all of these extra layers of rules. Opponents of abortion rights, meanwhile, are concerned. They're taking note of the fact that about 40% of abortions today are medication abortions. Here's Kristan Hawkins with Students for Life of America on a press call earlier today.
    (SOUNDBITE OF ARCHIVED RECORDING)
    KRISTAN HAWKINS: And today we may very well be confronting a brand-new frontier of abortion - no-test online chemical abortion distribution - in essence, death by mail delivered to your doorstep.
    MCCAMMON: So she'd like to see states pass more restrictive laws surrounding abortion pills.
    CORNISH: What about people in states like Texas - right? - that does have a restrictive law around abortion?
    MCCAMMON: Right. That state, of course, has a law banning most abortions after about six weeks. Another law just took effect this month that also puts restrictions on abortion pills, prescribing them - allowing them to be prescribed just up to seven weeks instead of the 10 allowed by the FDA and prohibiting the mailing of the pills. It's not clear how enforceable that is, particularly if patients are seeing doctors out of state or even overseas.

"As controversial 'abortion reversal' laws increase, researcher says new data shows protocol can work" (April 4, 2018)[edit]

Ariana Eunjung Cha (April 4, 2018). "As controversial 'abortion reversal' laws increase, researcher says new data shows protocol can work". Washington Post.

  • San Diego physician George Delgado published anecdotes in 2012 from seven women who had changed their minds after taking one of two pills to terminate their pregnancies. Using an unproven protocol, he wrote, they were able to stop or “reverse” the abortions. The sensational claim was quickly embraced by conservative lawmakers pushing measures requiring clinics to inform women of this option.
    Several states have now adopted a version of this legislation; Idaho is the latest, following Utah, South Dakota, Arizona and Arkansas. The laws have alarmed many medical groups, including the American College of Obstetricians and Gynecologists, which says no “credible” evidence supports the idea of reversing a medical abortion.
  • Of the 547 patients who took progesterone within 72 hours of taking mifepristone and had outcomes that were known, there were 257 live births. Another four women remained pregnant with what seemed to be viable fetuses, but were lost to follow-up tracking after their 20th week of pregnancy. The overall rate of a pregnancy continuing, Delgado wrote, was 48 percent.
  • Delgado concludes that the use of progesterone to stop a medical abortion “appears to be both safe and effective.”
    Daniel Grossman, a professor at the University of California at San Francisco who focuses on reproductive health issues, has been one of the most vocal critics of abortion-reversal laws. He says “it makes some biological sense” that flooding the body with progesterone could counter the effect of the first abortion pill. But, he continues, there's also logic to the argument that progesterone is elevated in a normal pregnancy and so a pharmaceutical dose won't make much difference.
    In addition, he said, “mifepristone by itself is not a very effective abortion-causing agent. If you use it just by itself there's a good chance the pregnancy will continue on its own.” Indeed, his own work has shown that women who took only mifepristone had a 25 percent chance of the pregnancy continuing. Such a finding is why the second abortion pill is typically given.
    Grossman, whose research focuses on improving access to safe abortion in the United States and other parts of the world, said it's too soon to draw any conclusions from Delgado's latest paper. Whether medical abortions can be stopped or reversed is a question that should be studied, but in a rigorous way removed from the politics of abortion, he said.
  • “The really concerning part for me is that states are passing laws and essentially forcing physicians to inform women about a treatment that is experimental,” he said. Only a small fraction of the roughly 150,000 U.S. women who have medical abortions annually change their minds, he noted. “But it’s not zero, and I do think that women who change their minds should be given the best available information about what they should do.”
  • Delgado acknowledged that the journal in which his work appeared is co-sponsored by the Watson Bowes Research Institute, which is focused on antiabortion issues and therefore may be viewed more skeptically than other peer-reviewed journals. He said he would have liked to offer the paper to some mainstream publications but was not confident he would have gotten a fair look.
    “Quite frankly, with all of the prejudicial statements a lot of people have been putting out, I felt like it would lead to editors not wanting to consider the article and delay things,” he said.
    Delgado agrees that more research needs to be done. Once he secures funding, he said, he hopes to begin a randomized clinical trial in the next few months. He compares the skepticism about abortion reversal to the early questions about cardiopulmonary resuscitation when that technique was first introduced.
    “It hadn't been studied formally in a big way, but we saw it was saving lives and had no alternatives. Were you going to wait when someone was dying in front of you?” he said.
    Delgado, who is on the board of the American Association of Pro-Life Obstetricians and Gynecologists, said “the science is good enough that, since we have no alternative therapy and we know it's safe, we should go with it.”

"Wyoming Becomes First State to Outlaw Abortion Pills" (March 17, 2023)[edit]

David W. Chen and Pam Belluck, (March 17, 2023). "Wyoming Becomes First State to Outlaw Abortion Pills". The New York Times.

  • The law is the only one in the nation to prohibit the use separate from an overall abortion ban and is part of a growing effort by conservative states to target the pills.
    Wyoming on Friday became the first state to explicitly ban the use of pills for abortion, adding momentum to a growing push by conservative states and anti-abortion groups to target medication abortion, the method now used in a majority of pregnancy terminations in the United States.
    Wyoming’s new law comes as a preliminary ruling is expected soon by a Texas judge that could order the U.S. Food and Drug Administration to withdraw its approval of mifepristone, the first pill in the two-drug medication abortion regimen. Such a ruling, if it stands, could upend how abortion is provided nationally, affecting states where abortion is legal as well as states with bans and restrictions.
  • Gov. Mark Gordon of Wyoming, a Republican, signed that state’s medication abortion ban on the same day that he said he would allow another more sweeping measure banning abortion to become law without his signature. That law, which takes effect on Sunday, would ban abortion under almost all circumstances, making it a felony to provide an abortion.
    “I have acted without bias and after extensive prayer, to allow these bills to become law,” Mr. Gordon wrote in a letter to Wyoming’s secretary of state released on Friday evening.
    Mr. Gordon said in the letter that he withheld his signature from the broader abortion ban because he feared it would complicate matters in an ongoing legal battle over an earlier abortion ban passed by Wyoming legislators.
    The broader ban outlaws medication abortion as well, and the abortion pill measure, called the Prohibiting Chemical Abortions Act, would mostly have the effect of adding additional penalties for medication abortion providers.
  • Wyoming’s abortion pill law would take effect on July 1 and would make it illegal to “prescribe, dispense, distribute, sell or use any drug for the purpose of procuring or performing an abortion.” Doctors or anyone else found guilty of violating this law would be charged with a misdemeanor, punishable by up to six months in prison and a $9,000 fine. The law explicitly says that pregnant patients will be exempt from charges and penalties.
    Wyoming has only one clinic that has been providing abortions, Women’s Health & Family Care Clinic in Jackson, which provides only medication abortion, not the surgical procedure.
    “The impact of that legislation not only infringes on our constitutional rights, it actually causes harm,” said Dr. Giovannina Anthony, an obstetrician-gynecologist at the clinic. “Criminalizing evidence-based medicine is really what this boils down to, and that, in the end, honestly, will lead to maternal deaths and horrible outcomes for both mothers and babies.”
  • Adam Schwend, Western regional director for Susan B. Anthony Pro-Life America, an anti-abortion network, thanked Mr. Gordon for enacting the medication abortion ban, saying that “Wyoming’s new law will limit the abortion industry’s ability to jeopardize the health and safety of women and girls.”
    Mr. Schwend added that the law will help make Wyoming “one of the most pro-life states in the country.”
    Earlier versions of the medication abortion bill had named specific drugs: mifepristone and two brand-name versions of it as well as misoprostol, the second drug used in the medication abortion regimen.
    But doctors testified in objection, pointing out that misoprostol, in particular, had many other medical uses, including helping pregnant patients successfully give birth. The doctors raised concerns that pharmacists would be fearful of stocking any of the drugs, and some Republicans said names of abortion medications could simply be changed to get around the law. As a result, the final language was broadened to outlaw using any medication for abortion without mentioning specific drugs.
  • A bill introduced in Texas, a state that already bans abortion, includes many provisions that seek to close off any access to pills, including making it difficult for Texas patients to learn about or use abortion services outside of the state. The bill would make it illegal to manufacture, distribute or “provide an abortion-inducing drug in any manner to or from any person or location in this state.”
    It would also make it illegal to “create, edit, upload, publish, host, maintain, or register a domain name for an internet website, platform, or other interactive computer service that assists or facilitates a person’s effort in obtaining an abortion-inducing drug.”
  • In addition to Wyoming and states with near-total abortion bans, 15 states have enacted restrictions on access to medication abortion, according to the Guttmacher Institute, a research group supporting abortion rights. Those restrictions include requiring that the drugs be provided by a physician and requiring the patient have an in-person visit with a doctor. Several states, including Texas and Arizona, have outlawed the mailing of abortion pills, and bills to ban mailing pills have been introduced in at least three other states this year.
    “We are seeing efforts to further bar access to medication abortion because abortion opponents recognize that even with abortion bans in effect” patients are still able to obtain abortion pills, said Elizabeth Nash, state policy analyst for the Guttmacher Institute. “Now, abortion opponents have turned to the courts, attorneys general and state legislatures to further limit access to pills.”
    Since January, when newly elected legislatures began to convene for the first time since the Dobbs v. Jackson Women’s Health Organization decision ended the national right to an abortion, more than 500 bills in states across the country have been proposed that are related to abortion.
  • “These abortion bans should alarm everybody in every corner of our country,” said Mini Timmaraju, president of NARAL Pro-Choice America, which supports abortion rights. “This first-of-its-kind ban on medication abortion, as well as the total ban, are just the latest proof” of how far “anti-choice Republicans” will go to prohibit the procedure, she said.
    Under the other new Wyoming law, the Life Is a Human Right Act, performing an abortion or administering abortion medication would be considered a felony, punishable by up to five years in prison, and doctors would have their licenses revoked. The law bans abortion with narrow exceptions for rape, incest and dire risks to the pregnant patient’s life or health.
    “While other states are pushing an extreme abortion agenda, comparable to North Korea’s and China’s inhumane laws, Wyoming is a pro-life state, affirming that life is a human right and ensuring that women have real support,” said state Representative Rachel Rodriguez-Williams, the bill’s sponsor.
    Under the Wyoming Constitution, residents have the right to make their own health care decisions. So the new law stipulates: “Instead of being health care, abortion is the intentional termination of the life of an unborn baby.”

"Mifepristone With Buccal Misoprostol for Medical Abortion: A Systematic Review" (July 2015)[edit]

Chen MJ, Creinin MD (July 2015). "Mifepristone With Buccal Misoprostol for Medical Abortion: A Systematic Review". Obstetrics and Gynecology. 126 (1): 12–21. doi:10.1097/AOG.0000000000000897. PMID 26241251. S2CID 20800109.

  • Tabulation, integration, and results
    We included 20 studies with a total of 33,846 women through 70 days of gestation. We abstracted efficacy and ongoing pregnancy rates as an overall rate and by gestational age in days in reference to completed weeks (eg, 49 days or less, 50-56 days, 57-63 days, 64-70 days) and adverse effects when reported. The overall efficacy of mifepristone followed by buccal misoprostol is 96.7% (95% confidence interval [CI] 96.5-96.8%) and the continuing pregnancy rate is 0.8% (95% CI 0.7-0.9%) in approximately 33,000 pregnancies through 63 days of gestation. Only 332 women with pregnancies between 64 and 70 days of gestation are reported in the literature with an overall efficacy of 93.1% (95% CI 89.6-95.5%) and a continuing pregnancy rate of 2.9% (95% CI 1.4-5.7%). Currently available data suggest that regimens with a 24-hour time interval between mifepristone and buccal misoprostol administration are slightly less effective than those with a 24- to 48-hour interval. Rates of surgical evacuation for reasons other than ongoing pregnancy range from 1.8% to 4.2%. Severe adverse events like blood transfusion (0.03-0.6%) and hospitalization (0.04-0.9%) are uncommon.
    Conclusion
    Outpatient medical abortion regimens with mifepristone followed in 24-48 hours by buccal misoprostol are highly effective for pregnancy termination through 63 days of gestation. More data are needed to evaluate clinical outcomes with regimens containing mifepristone followed in 24 hours by buccal misoprostol and in pregnancies beyond 63 days of gestation.
    • p.12
  • The use of medical abortion for pregnancy termination is increasing in the United States. In 2011, approximately 239,400 medical abortions were per-formed, which was a 20% increase from 2008. The current U.S. Food and Drug Administration (FDA)–approved regimen for medical abortion consists of600 mg mifepristone orally followed in 48 hours by 400 micrograms misoprostol orally in pregnancies up to 49 days based on initial clinical trials. Studies since FDA approval in 2000 have accumulated evidence demonstrating increased efficacy in regimens with a lower dose of mifepristone and a higher dose of misoprostol, even in pregnancies past 49 days of gestation. The transition from oral to alternative routes of administration, including vaginal, buccal, and sublingual, is associated with increased efficacy and fewer side effects. National evidence-based clinical guide-lines in the United States, the United Kingdom, and other countries clearly identify that regimens other than the current FDA-approved regimen are superior based on higher efficacy and fewer adverse effects.
    • p.12
  • Vaginal misoprostol administration was routinely used in the United States until reports of severe infection with Clostridium sordellii after medical abortion surfaced, prompting a reevaluation of vaginal misoprostol and a search for alternative routes of misoprostol administration. Although the use of vaginal misoprostol was ultimately not the cause of these infections, continued safety evaluations from Planned Parenthood Federation of America showed that severe infection, albeit a rare complication, decreased after changing to a buccal misoprostol regimen in addition to screening for sexually transmitted infections or providing routine preventive antibiotic coverage as part of the medical abortion.
    With buccal administration, misoprostol is held in the buccal pouch between the teeth and gums for30 minutes before swallowing any remaining tablets. Buccal misoprostol is slowly absorbed, unlike oral misoprostol, which is rapidly absorbed and undergoes extensive first-pass metabolism. After a dose of oral misoprostol, plasma misoprostol acid levels peak quickly at 30 minutes and decrease rapidly by 120 minutes. In contrast, after buccal administration, plasma misoprostol acid levels rise gradually to peak concentration after a median time of 75 minutes and fall slowly over several hours.
    Within the last 10 years, buccal misoprostol use with mifepristone for medical abortion has become commonplace. However, the published literature did not contain abundant information about medical abortion outcomes with buccal misoprostol until recently.
    • p.13
  • Primary outcome definitions were similar across the included studies. All of the studies defined successful abortion as one in which the pregnancy was expelled from the uterus without need for surgical evacuation during the follow-up period for any reason. Ongoing pregnancy was defined in all studies as a viable gestation at follow-up ultrasound evaluation performed per study protocol or when clinically indicated except one study that defined a viable gestation as an increase in uterine size on follow-up examination consistent with an ongoing pregnancy.
    The overall efficacy and continuing pregnancy rate after mifepristone followed by buccal misoprostolis 96.6% and 0.8%, respectively, through 70 days of gestation in the 33,846 women who were included in this systematic review (Table 1). However, only 332 women are reported in the literature between 64 and 70 days of gestation from three trials with 304 of the patients from a single trial. The overall efficacy at 64–70 days of gestation is 93.1%. Ongoing pregnancy rate at 64–70 days of gestation is 2.9% as compared with 1.8% at 57–63 days of gestation.
    • pp.17-18
  • Success rates through 63 days of gestation from studies reporting a 24-hour interval between mifepristone and misoprostol differ significantly from the rates in studies with a 24- to 48-hour interval overall (94.2% compared with 96.8%, respectively, P,.001), among gestations 49 days or less (96.8% compared with 98.2%, respectively,P5.046) and gestations 50–63 days (92.1% compared with 96.3%, respectively,P5.009). Two studies included intervals of 36–48 hours and one for 48 hours. When these studies are excluded from the 24- to 48-hour group in the previous calculations, the results remain statistically significant for the overall (94.2% compared with 96.8%, respectively,P,.001), 49 days or less of gestation (96.8% compared with 98.2%, respectively,P5.04), and 50–63 days of gestation (92.1% compared with 96.3%, respectively, P5.008) calculations. The overall ongoing pregnancy rate through 63 days of gestation was not different among studies reporting a 24-hour or 24- to 48-hour interval between mifepristone and misoprostol (1.3% compared with 0.8%, respectively, P5.10).
    • pp.18-19
  • Several studies using buccal misoprostol allowed the option of repeat misoprostol at follow-up 1 week after mifepristone for persistent gestational sac; however, few report specific outcomes. Table 4 high-lights success rates after a repeat dose of misoprostolin reports that included these specific outcomes. In these study protocols, women with an ongoing pregnancy at follow-up were recommended to undergo uterine suction curettage, whereas women who had a nonviable pregnancy with a persistent gestational sac were given the options of expectant management, suction curettage, or a second dose of misoprostol. Overall, women who received a second dose of misoprostol experienced expulsion rates between 91.0% and 100.0%.
    Adverse outcomes after medical abortion for selected studies are shown in Table 5. Rates of surgical evacuation for reasons other than ongoing pregnancy range from 1.8% to 4.2% in women who received mifepristone followed by buccal misoprostol, which is lower than the 6.9% surgical evacuation rate reported in women who received mifepristone followed by oral misoprostol through 49 days of gesta-tion.2Blood transfusion and infection are uncommon, occurring in approximately 0.03–0.6% and 0.01–0.5%of patients, respectively. Adverse outcomes of emergency department visits (2.9–3.7%) and hospitalizations (0.04–0.9%) are inconsistently reported with variable rates across studies.
    • p.19
  • Over 30,000 women have now been included in studies examining mifepristone with buccal misoprostol for medical abortion since the first report using this regimen 10 years ago. These studies demonstrate that outpatient medical abortion regimens with mifepristone followed in 24–48 hours by buccal misoprostol are highly effective for pregnancy termination through 63 days of gestation. The complete abortion rate with this protocol is higher than the 92% rate with the FDA-approved regimen. Furthermore, surgical evacuation for reasons other than continuing pregnancy is also lower with buccal compared with oral misoprostol regimens. Side-effect rates vary across studies, which may be related to different ways of defining these events or different patient populations. Overall, the side-effect profile of both regimens is comparable, and regimens with buccal misoprostol have been shown to be well tolerated and acceptable to participants.
    • p.19
  • Despite the presence of data supporting buccal misoprostol in medical abortion, there are still gaps in the literature, specifically with use 24 hours after mifepristone. Based on the available literature, the overall efficacy of regimens with a 24-hour interval between mifepristone and buccal misoprostol is significantly lower than those with a 24- to 48-hourinterval (94.2% compared with 98.1%). Our ability to fully understand if buccal misoprostol is more effective with a dosing interval closer to 48 hours is limited by the relatively small number of women in protocols with a 24-hour dosing as compared with a 24- to 48-hour dosing interval. Moreover, published trials only include outcomes by gestational age in 129 and 49 patients between 50–56 and 57–63 days of gestation, respectively. There is also a paucity of data on the actual time interval at which women actually administer misoprostol when instructed to use buccal misoprostol in a 24- to 48-hour window after mifepristone. Only one study reported the actual time elapsed between mifepristone and buccal misoprostol dosing; the median time interval was 47–48 hours.
    Another obvious and important limitation of the available data is the relative lack of significant numbers of women who reported using mifepristone and buccal misoprostol beyond 63 days of gestation. Only 332 patients between 64 and 70 days of gestation are included in the literature, representing just 1.0% of the total number of women for which medical abortion outcomes with regimens containing buccal misoprostol are available. Based on current data, caution should be exercised when using buccal misoprostol in medical abortion regimens beyond 63 days in an outpatient setting until more evidence is available on efficacy rates and adverse effects
    • pp.19-20
  • Because regimens with mifepristone and buccal misoprostol are highly effective, large data sets are required to generate enough information to evaluate outcomes of a repeat misoprostol dose when abortion does not occur with initial treatment. These large data sets have been accumulated for regimens using vaginal misoprostol32; however, little information is available in the published literature about repeat dosing of buccal misoprostol (Table 4). These limited data do support the potential efficacy of a repeat dose of buccal misoprostol. Because most women who choose medical abortion have a strong desire to avoid surgery, further medical treatment instead of vacuum aspiration may be preferable as long as further medical management is beneficial. Although these studies did not report expulsion rates after expectant management, most women with a persistent gestational sac but absent gestational cardiac activity would eventually expel the pregnancy. Even so, a repeat dose of misoprostol may facilitate quicker expulsion and is a reasonable option for women.
    • p.20
  • To our knowledge, this systematic review includes all studies that utilize mifepristone and buccal misoprostol for early medical abortion. Of note, the evidence for these regimens is mainly derived from two large retrospective studies that contribute 76% of the data on clinical outcomes. To minimize heterogeneity of results, studies were grouped by the time interval between mifepristone and buccal misoprostol administration (ie, 24 hours and 24–48 hours) before analysis of over-all efficacy and ongoing pregnancy rates. Further studies are needed to evaluate whether regimens with mifepristone followed in 24 hours by buccal misoprostol are effective, especially in pregnancies greater than 49 days of gestation. More evidence regarding clinical outcomes for pregnancies more than 63 days of gestation is needed before this practice becomes standard of care.
    • p.20

"Medical versus surgical methods for first trimester termination of pregnancy: RHL commentary" (15 December 2006)[edit]

Chien P, Thomson M (15 December 2006). "Medical versus surgical methods for first trimester termination of pregnancy: RHL commentary". Reproductive Health Library. Geneva: World Health Organization. Archived from the original on 17 May 2010. Retrieved 1 June 2010.

  • The authors of the review concluded that prostaglandin used alone appeared to be less effective and more painful compared with surgical termination of pregnancy in the first trimester. Participants in the WHO study were recruited and randomized without prior confirmation of pregnancy. A pregnancy test was only performed on day of treatment and 54 (11%) patients were subsequently found to be not pregnant and therefore were excluded from the analysis. The exclusion of these patients can potentially result in an imbalance between the two groups studied.
  • Of the four different regimens used for medical termination of pregnancy reviewed in this review, use of a combination of mifepristone followed by a prostaglandin 48 hours later is the most commonly used regimen at the present time. Given the clinical importance of this topic, it is surprising to find that the literature search for this review only retrieved two primary studies comparing the combination of mifepristone and prostaglandin versus vacuum aspiration. Of the two different gestational periods studied in these two studies, it is now widely accepted that the efficacy rate for the combination of mifepristone and prostaglandin is higher for gestational ages up to nine weeks than for the longer gestational period of 10–13 weeks. The prostaglandin employed in the study by Henshaw et al. was vaginal gameprost pessary. This prostaglandin has now been replaced by vaginal misoprostol tablet owing to its cheaper cost. Indeed, the efficacy (defined as completion of abortion process without the need for surgical evacuation of uterus or suction termination of pregnancy) of 200 mg oral mifepristone followed by 800 μg vaginal misoprostol 1–3 days later for termination of pregnancy up to nine weeks gestation is at least 94%.
  • The main advantage of the medical method over surgical termination of pregnancy is the potential avoidance of an anaesthetic and complications such as cervical laceration and uterine perforation. Furthermore, the whole procedure can be undertaken either at home or in an outpatient setting. In under-resourced settings, these features can be an advantage as the direct health-care cost is lower compared with the surgical option. The drawback with the use of mifepristone and misoprostol is the need to follow-up patients to ensure that the abortion process is complete. Because of the high efficacy, safety and benefits of medical termination of pregnancy with mifepristone and misoprostol, the proportion of pregnancies of up to nine weeks' gestation terminated with this method increased from 19% in 1996 to 55% in 2005 in a major teaching hospital in Dundee, Scotland (unpublished data).
  • Although the prostaglandin used in the original primary studies was either PGE2 or gameprost, it is clear that satisfactory efficacy can also be achieved with misoprostol. The use of misoprostol instead of PGE2 or gameprost will also reduce the cost of treatment especially in under-resourced settings.
    There is sufficient evidence to show that the self-administration of these agents at home is feasible, safe and acceptable to patients. This approach will further open accessibility of the service and reduce the need to keep patients in hospital to provide a termination service.
  • Future research should be conducted using the mifepristone and misoprostol protocol. There is a need to examine the different dosages, routes and timing of administration of these therapeutic agents to determine the most appropriate treatment protocol. There is also a need to evaluate whether repeated doses of misoprostol can further improve the efficacy of a single dose of misoprostol for termination of pregnancy up to nine weeks' gestation. Furthermore, head-to-head randomized comparisons between the combination of mifepristone and misoprostol with methotrexate and misoprostol should be undertaken to assess the efficacy of the later therapeutic regimen as mifepristone is not available and licensed for use in some countries where termination of pregnancy is not legally available.

"Medical Abortion: What Is It, Types, Risks & Recovery" (October 21, 2021)[edit]

"Medical Abortion: What Is It, Types, Risks & Recovery". Cleveland Clinic. October 21, 2021. Last reviewed by a Cleveland Clinic medical professional on 10/21/2021.

  • What is a medical abortion?
    A medical abortion (or medication abortion) is a procedure in which medication (prescription drugs) is used to end a pregnancy. It does not require surgery and is performed through the ninth week of pregnancy. It involves taking two medications — mifepristone and misoprostol. Mifepristone works by blocking the hormone progesterone. Without progesterone, the pregnancy cannot continue to grow in the uterus. Misoprostol causes cramping and bleeding to empty the uterus.
  • When can someone get a medical abortion?
    Medical abortions are performed up to around nine weeks of pregnancy. It can be done as soon as you find out you are pregnant. Your healthcare provider will use an ultrasound to confirm you are pregnant and how long you have been pregnant. If you are beyond nine weeks of pregnancy, there are other options for ending the pregnancy. Your healthcare provider can talk to you about other options and help you decide which would be best for you.
  • Who should not get a medical abortion?
    Medical abortion is not a safe option for those who:
    *Are too far along in the pregnancy.
    *Have a pregnancy outside of the uterus (ectopic pregnancy).
    Have a blood clotting disorder or significant anemia.
    *Have chronic adrenal failure.
    Use long-term corticosteroids.
    Have an intrauterine device (IUD).
    Have an allergy to the medications used.
    Do not have access to emergency care.
    Can’t return for a follow-up visit.
  • Why is a medical abortion performed?
    Having a medical abortion is a highly personal decision based on your own circumstances. Women may choose medical abortions because of the risk of a congenital or inherited disease, to end an unwanted pregnancy or to complete an early miscarriage. It can also be an option for women with health complications where carrying the pregnancy could be life-threatening.
  • What are the different types of abortions?
    There are medical and surgical abortions. Some differences between the different types of abortions include:
    *Medical abortions (nine weeks of pregnancy or less): A woman will take two different medicines (usually within a 48-hour period). The medication is given by a healthcare provider and is either taken in the provider’s office or at home (or a combination of both). Your healthcare provider will give you specific instructions about how and when to take the medications.
    *Surgical abortions: In this type of abortion, a healthcare provider will surgically remove the embryo from the uterus. These types of abortions require mild sedation, local anesthesia (numbing an area) or general anesthesia (fully asleep). Some other terms for surgical abortions are in-clinic abortions, aspiration abortions and dilation and curettage (D&C) abortions. Some reasons women have a surgical abortion are personal preference, too far along in pregnancy or a failed medical abortion.
  • What happens during a medical abortion?
    Medical abortion involves taking medication orally or through the vagina. It does not require anesthesia or surgery. It works by using a combination of two drugs that, when used together, induce an abortion. Mifepristone works by blocking progesterone. Without progesterone, the uterine lining will thin, and the embryo will not stay attached. When misoprostol is taken, it causes the uterus to contract, bleed and expel the embryo.
  • The most severe side effects from a medical abortion start shortly after taking the second pill. After both doses of medication have been taken you can expect the following to occur:
    *Bleeding and cramping that starts between one and four hours after taking the second pill.
    *Heavy bleeding with blood clots for the next several hours.
    *Heavy cramping for several hours.
    *A low fever or chills that last about a day after taking the second pill. Others report feeling tired, nauseas and dizzy, and having diarrhea.
    A follow-up appointment will be scheduled to make sure there were no complications. Some healthcare providers may prescribe antibiotics, although infection from a medical abortion is uncommon.
  • What do you do to prepare for a medical abortion?
    You will need to meet with your healthcare provider for an evaluation and exam. This usually includes:
    A physical exam and confirmation of pregnancy.
    Ultrasound to view the pregnancy in the uterus.
    Determining length of pregnancy and that it’s not an ectopic pregnancy.
    Blood and urine tests.
    Explanation of the procedure, risks and side effects.
    You will have bleeding and cramping afterwards, so be prepared to stay home or in a comfortable location for a few days. Purchase a supply of absorbent pads to contain the bleeding, acetaminophen or ibuprofen for pain relief and a heating pad for cramping.
  • What can you expect after a medical abortion?
    Vaginal bleeding and cramping will be the biggest side effects. Other side effects from a medical abortion are:
    Nausea and vomiting.
    Fever.
    Chills.
    Diarrhea.
    Headache.
  • Does a medical abortion pain feel like labor pain?
    A medical abortion feels most like strong period cramps. The amount of cramping and pain varies among women. You can take most over-the-counter pain relievers to help with any discomfort or pain that you feel. Ask your healthcare provider what medications can be taken to help manage pain.
  • What are the benefits of a medical abortion?
    The benefits of a medical abortion are:
    You can get one as soon as you know you are pregnant.
    There is no surgery or anesthesia involved.
    You can be at home once the cramping and bleeding occurs.
    It might feel more natural.
    You can have a support system with you.
  • What are the disadvantages of a medical abortion?
    The disadvantages of a medical abortion are:
    Heavy and painful bleeding for a few days.
    Can’t be performed after nine weeks of pregnancy.
    The process is longer (over the course of days versus a few hours).
  • Before taking the medications for abortion, make sure you are willing to complete all doses that are prescribed to you. Skipping a dose or not following the instructions can pose serious health risks.
    Risks of a medical abortion are:
    *Incomplete abortion.
    *Heavy bleeding that will not stop.
    *Infection.
    *Fever.
    *Diarrhea and digestive pain.
    *Allergic reaction to the medications.
  • What are signs of an infection after a medical abortion?
    The biggest signs of an infection after a medical abortion are unpleasant odors from the vagina and fever that lasts more than 24 to 48 hours.
  • When using the combination of mifepristone and misoprostol, it is found to be about 98% effective. It is generally most effective in pregnancies that haven’t reached seven weeks gestation.
  • Your healthcare provider will want to see you for a follow-up appointment within two or three weeks. In this appointment, they are likely to:
    *Perform a pelvic exam.
    *Look for signs of infection.
    *Discuss how much bleeding you had, when it stopped, the color and if there were clots.
    *Check your uterus with an ultrasound.
    *Talk about contraceptives to avoid future pregnancies, if you choose to do so.
  • The amount of time it takes to recover from a medical abortion will vary. In some cases, you may be resuming normal activities within a day or two. Avoid any activities that cause you pain. You will likely have a range of emotions — relief, sadness, stress or guilt. These feelings are common and expected. It may be helpful to speak with a mental health professional, such as a counselor or therapist, about how you are feeling. Your healthcare provider may be able to give you recommendations on mental health professionals who can help you.
  • The amount of bleeding to expect depends on the person and how far along you were in pregnancy. Heavier bleeding is expected for one to two days. Bleeding will start to subside gradually over the course of two to three weeks. Healthcare providers may recommend sanitary pads until the bleeding stops. This helps you see the volume of blood and the clots more easily. Your risk for infection increases with the use of tampons during this time.
  • You should wait at least two to three weeks to have sex after a medical abortion. This is to prevent infection in the vagina. You should not insert anything into your vagina during this time, including tampons.
  • You will be able to get pregnant once ovulation has occurred again. Your normal menstruation cycle should return within four to six weeks after a medical abortion. Your first period may be slightly irregular due to hormonal changes from the procedure. Medical abortion should not affect future pregnancies unless there were complications.
  • You should work closely with your healthcare provider throughout the process of your medical abortion. Discuss all of the concerns you have and make sure you understand the process and what to expect.
    Contact your healthcare provider if any of the following occur afterwards:
    *Severe bleeding — soaking more than two thick pads within an hour.
    *Fever that lasts more than 24 hours.
    *Foul-smelling vaginal discharge.
    *Severe abdominal or back pain.
    *You do not get your period after two months.
    *You have symptoms of pregnancy.

"The abortion provider that Republicans are struggling to stop" (May 19, 2022)[edit]

Cohen RM (May 7, 2022). "The abortion provider that Republicans are struggling to stop". Vox. Retrieved May 19, 2022.

  • In 2018, more than two decades after Dutch physician Rebecca Gomperts first became an activist to deliver abortion pills around the world, she turned to the United States. For years she had dedicated her life to working in countries where the procedure was illegal, and was firm in her refusal to avoid the US, where safe, legalized access was still available. “I think this is a problem the US has to solve itself,” she explained in 2014.
    But following the election of President Donald Trump, the desperate requests she received from Americans went up, and the cost barriers in the US were glaring.
    So Gomperts launched a new nonprofit organization based in Austria — Aid Access — with the goal of providing affordable and accessible abortion services to people in the US.
    Over the past four years, Aid Access says it has delivered abortion medication — mifepristone and misoprostol — to more than 30,000 Americans across all 50 states, including the 19 conservative states that currently ban telemedicine abortion.
    The organization plays a unique role in the US reproductive rights ecosystem by successfully exploiting legal loopholes that make it easier for an overseas doctor to care for American patients in restrictive states — a role that could become even more key if Roe v. Wade is struck down.
  • For now, the biggest one may be the big tech platforms. Aid Access needs to spread awareness about its services, and quickly. The pills, when shipped from overseas, can take two to three weeks to arrive, and Aid Access prescribes the two medications up to the first 10 weeks of pregnancy. But because it operates outside the formal US health care system, Aid Access says it has been penalized by search engines and social media giants that have tried to tackle the spread of Covid-19 misinformation.
    Aid Access still pops up on Google if you search the organization’s name, but most users had come to the site while searching for terms like “abortion by mail” and “abortion pills.” Following a series of algorithm updates beginning in May 2020, Aid Access says it no longer shows up in top results for general medication abortion searches — and that ads from its sister organization, Women on Web, which serves countries all over the world, are frequently removed or rejected from Facebook and Instagram for dubious reasons, like “language ... that is likely to offend users.”
    Republicans might not be able to stop Aid Access right now, but it appears that Silicon Valley can.
  • Gomperts and the women she prescribes pills for operate in something of a legal gray area. As a result of being registered to practice medicine in Austria, she is subject to Austrian law, and therefore exempt from specific rules and regulations affecting doctors in the US, like state requirements for ultrasounds or 72-hour waiting periods. And while personal imports of drugs from other countries are usually against US law, the Food and Drug Administration (FDA) has said it generally avoids going after individuals who bring medicines in for personal use.
    It’s a model Gomperts developed first in 2005 with Aid Access’s older sister organization. Since its founding, Women on Web says it has delivered abortion pills to more than 100,000 women across the world, reaching pregnant patients in countries with restrictive laws, like Sudan, Hungary, and Brazil. In 2018, Gomperts set up Aid Access under a separate corporate structure, to serve the US while protecting Women on Web from the aggressive US anti-abortion movement.
  • Activists note that medication abortion is far safer than many painkillers easily purchased over the counter, and the World Health Organization maintains that individuals can self-administer the drugs without direct supervision of a health care provider during their first trimester. New Lancet research published in February affirmed the safety of the Aid Access model, which also provides the medication at significantly lower cost than in-person surgical abortions or even the new crop of US startups like Hey Jane, Abortion on Demand, and Carafem.
  • Christie Pitney, a midwife who fills prescriptions for Aid Access patients in California, Massachusetts, Oregon, and DC, said that while patients in some states with trigger bans may have to switch from US-based providers like Pitney to Gomperts, Aid Access will keep serving them. “We’ll still be here,” she said.
    “We’re pretty nonplussed, to be honest,” Pitney told Vox. “I don’t see a route [to stopping us]. It’s not to say that it’s impossible, I just don’t see a route for politicians to eliminate access to Aid Access; they just don’t have the jurisdiction to criminalize an international doctor.”
  • Despite the unique strategy Aid Access and Women on Web deploy, over the past two years, the organizations say they have been fighting against search engine algorithms that deprioritize their services, and opaque social media policies that limit or block their posts.
    Earlier this year, in an interview with the New York Review of Books, Gomperts said that “the algorithms of Google are suddenly becoming the de facto gatekeeper to access to safe abortion services in the US.” When Google set out to correct Covid-19 misinformation and started elevating more health sites that were officially government-sanctioned, Gomperts said it had the side effect of demoting sites like hers.
    Searches like “abortion by mail” and “online abortion” no longer led users to Gomperts’s groups, she says. Women on Web, for example, says it saw a 90 percent drop in daily global traffic after Google rolled out a new update on May 4, 2020. A subsequent update brought back some of what had disappeared, doubling its now-minuscule traffic, but then a third algorithmic update six months later took 40 percent of what remained. “We’re back to pretty low,” said Venny Ala-Siurua, the executive director.
    Ala-Siurua told Vox that deprioritization in internet search results remains one of their biggest barriers. Google “keep[s] pushing up traditional health providers, brick-and-mortar clinics, but they’re missing what’s happening in the digital world today,” she said. “The algorithm is not neutral. It was built and written usually by white men in the Bay Area who might not really be in tune with what the needs are here.”
    Aid Access isn’t alleging Google is intentionally restricting access to its site specifically, but Gomperts told the New York Review of Books that they might eventually launch a lawsuit over this. “The algorithms are making it much harder to find the places where you can obtain these medicines,” she said. “That is what people don’t realize: It’s Google that is filtering people’s access to information.”
    Lara Levin, a Google spokesperson, told Vox that their search ranking systems “are designed to return relevant results from the most reliable sources, and on critical topics related to health matters, we place an even greater emphasis on signals of reliability.” Levin added that no update is made to benefit or penalize any one site. “We give site owners and content producers ample notice of relevant updates along with actionable guidance,” she said.
  • The Facebook and Instagram accounts for Women on Web have had spending restrictions placed on them for more than a year, after their ads were flagged or hidden by other users who oppose their work or who found their content “to be offensive ... violent, [or] about a sensitive topic.” Some of their ads for medication abortion have also been rejected, with rationales like “Ads must not promote the sale or use of unsafe supplements, as determined by Facebook in its sole discretion.” One Women on Web Instagram post that read, “You can now order abortion pills BEFORE you are pregnant,” and included a link for advanced provision was taken down for not following “community guidelines.”
    Facebook did not respond to a request for comment on the Women on Web ads specifically, but pointed Vox to company policies from Meta (Facebook and Instagram’s parent company) including ad prohibitions for direct sales of prescription drugs, and for ads promoting reproductive health products or services to people under age 18. In November 2021, Facebook also announced it would remove ad targeting options for topics people may perceive as “sensitive” — including health-related causes.
  • The algorithmic battles playing out reflect broader challenges faced by tech companies, which are under pressure to crack down on misinformation and propaganda and to take clearer stands on polarized political issues that users may be researching. The last few years have also brought greater attention to the ways in which machine learning and AI more broadly can reflect bias and discrimination, even while purporting to be objective and neutral.
    “We have to be careful not to frame questions as one of adapting to technology,” said David Broniatowski, a professor at George Washington University who has studied anti-vaccination communities online. “The technology is out in the world, so we should ask how to remake technology so we can achieve goals that are of best benefit to society.”
  • Aid Access has faced one regulatory challenge, in 2019, when the FDA sent the group a cease-and-desist letter, claiming that its generic mifepristone drug represented a “misbranded and unapproved” drug that posed risk to consumers. (The FDA approved one brand of mifepristone, Mifeprex, in 2000, and in 2019 approved a generic version.)
    Aid Access, in turn, sued the FDA, alleging the agency was impeding Americans’ constitutional right to an abortion and that its drugs were, in fact, approved. Aid Access also maintained that the FDA had no legal jurisdiction over Gomperts. The case was dismissed in part because the FDA never took action following its letter.

"The FDA made mail-order abortion pills legal. Access is still a nightmare" (May 19 2022)[edit]

Craven J (March 21, 2022). "The FDA made mail-order abortion pills legal. Access is still a nightmare". Vox. Retrieved May 19, 2022.

  • Telehealth companies focused on abortion access use a straightforward model. Once a patient decides on a service that’s legally allowed to ship to their state — like Hey Jane, Choix, Just the Pill, or Carafem — they fill out a medical history questionnaire, learn about the treatment, and sign a few consent forms. Then, within hours, they’ll hear back from a physician if they’re eligible to manage the procedure at home; the pills arrive in one to five days. “Abortion is something that is underserved,” said Kiki Freedman, the CEO and co-founder of Hey Jane. “Being able to access something more conveniently, more discreetly, more affordably, and more robustly is beneficial.”
    That’s in an ideal scenario in a progressive state like California or New York. Unfortunately, the process was more complicated for Emma and others who live in states where abortion access is legally hindered. Texas and Indiana ban medication abortion starting at about seven and 10 weeks, respectively. Thirty-two states require a physician to administer the medication, while 19 states require the prescribing clinician to be physically present when the pills are taken — legalities that amount to a de facto ban on receiving abortion care via telehealth. These laws don’t affect the safety of the procedure, which is safer than Tylenol, but, instead, construct barriers to accessing abortion.
  • If the Supreme Court deals a blow to Roe v. Wade this summer, as many expect it to do, these obstacles will get worse. While telehealth startups focused on reproductive health are hoping to play a role in expanding access, state laws and societal structures such as poverty and lack of access to health care prevent these companies from helping those most in need of their services should Roe be overturned. Nineteen states, including Texas and most of the Deep South, require two or more in-person visits to access medication abortion, while eight others require at least one visit; in 2021, six states, including Texas, passed explicit laws against receiving medication abortion through telehealth.
  • “It’s great that we have so many more options with things like telehealth, but even right now, that’s not available to every single person across this country,” said Renee Bracey Sherman, the executive director of We Testify, an advocacy organization for people who have abortions. “What feels challenging is this idea that people are looking for a panacea to just fix it all. And they’re like, ‘Great! If we just have pills mailed, then everything will be fine. That’s the solution to the crisis around Roe.’ But it is not the solution.”
  • Sending the pills directly to consumers sidesteps several everyday challenges encircling abortion access. Nearly 90 percent of US counties lack an abortion clinic, according to the most recent data from the Guttmacher Institute; clinics, for various reasons, continue to close. Multiple states in the South and Midwest rely on doctors from out of state, limiting the number of abortions a clinic can provide. Five states — including Mississippi, North Dakota, and West Virginia — have one clinic left.
    Mifepristone and misoprostol now are used in more than half of the country’s abortions. And interest in medication abortion is rising — by choice and out of necessity. Many birthing people don’t discover they’re pregnant until the five- or six-week mark, about a week or two after a missed period, which only leaves roughly a four-week window to perform a medication abortion.
  • “Getting abortion medication in the mail, or just expanding access to abortion medication period, could potentially be a game-changer in a United States, where abortion is illegal in some places and inaccessible in lots of places,” said Mary Ziegler, a law professor at Florida State University and the author of Abortion and the Law in America: Roe v. Wade to the Present.
  • The convenience for people who can’t afford to travel to a clinic, take time off from work, or find child care is unmatched. The more traumatic aspects of visiting an in-person clinic are removed, too: There are no protesters to navigate, no apprehension about being recognized at a small community clinic, and removal from the potential threats of violence clinics often face. Appointment wait times are also shorter, and the cost can be a bit cheaper than in-clinic services, which can cost anywhere between $400 and $1,000, with the price increasing depending on factors such as gestational age of the fetus.
  • Abortion medication by mail is also an alternative for people who’ve had bad experiences with clinicians, those who don’t want an ultrasound, or to discuss their decision any further — all of which rang true for Emma.
  • Access to abortion-inducing drugs may seem like the future of care in America, but it’s been an option for birthing people elsewhere in the world for quite some time. In spite of the criminalization of abortion, in most Latin American countries, misoprostol is available over the counter for other medical purposes, and many people have used it to induce abortion without serious complications. (It’s worth noting that even as American states work to curtail access, several countries in Latin American countries — including Colombia, Mexico, and Argentina — have made the procedure more accessible.)
    According to Grossman, advocates in Latin America have also developed robust models of care, such as telephone hotlines and other digital networks, to support people throughout the process of ending their pregnancies with medication. Aides help people access the medication and explain how they should use it. In some scenarios, a helper can be physically present to determine if the patient needs to get to a health care facility or if the treatment worked.
    Before abortion was decriminalized in Uruguay, Iniciativas Sanitarias, a reproductive health advocacy group, developed a harm reduction model to assist people who wanted to terminate their pregnancies. They provided safety information and support to people considering self-managing an abortion, including how to use misoprostol. “For example, for [those] beyond 11 or 12 weeks, if they have a bleeding disorder, or are taking blood thinners, it’s not an appropriate method,” said Grossman. “So if people have accurate information, they have access to good quality medications, and they know about the warning signs that should prompt them to seek medical care, I think that self-managed abortion can be very safe and effective,” he added.
  • [T]elehealth and medication-by-mail are much less likely to reach people who are incarcerated, unhoused, live on low incomes, don’t have an HSA/FSA, or internet access — groups disproportionately made up of Black and brown people.
    It’s crucial, advocates say, that the current hierarchies to abortion access aren’t replicated as well-intentioned companies search for solutions.
    “That FDA decision is not actually making a difference in the people’s lives who need it most because they simply cannot have [the pills] mailed,” said Bracey Sherman, of We Testify.
  • “States are going continue passing laws to limit access to medication abortion,” said Ziegler, the Florida State law professor. “But they’re also going to have a very hard time identifying when those laws are being broken or enforcing laws, especially against actors who don’t live in the state, and especially if they’re actually serious about not punishing pregnant people.”

"Mifepristone and misoprostol administered simultaneously versus 24 hours apart for abortion: a randomized controlled trial" (April 2007)[edit]

Creinin MD, Schreiber CA, Bednarek P, Lintu H, Wagner MS, Meyn LA (April 2007). "Mifepristone and misoprostol administered simultaneously versus 24 hours apart for abortion: a randomized controlled trial". Obstetrics and Gynecology. 109 (4): 885–894. doi:10.1097/01.AOG.0000258298.35143.d2. PMID 17400850. S2CID 43298827.

  • OBJECTIVE: Mifepristone and oral misoprostol are typically used for medical abortion in women up to 49 days of gestation, with a 36- to 48-hour interval between the medications. Alternative routes of misoprostol administration allow for use beyond 49 days of gestation. We designed this randomized, non inferiority trial to compare the efficacy, adverse effects, and acceptability of misoprostol 800 mcg vaginally administered simultaneously with, or 24 hours after, mifepristone 200 mg orally for abortion in women up to 63 days of gestation.
    • p.885
  • CONCLUSION: Mifepristone 200 mg and misoprostol800 mcg vaginally used simultaneously is as effective for abortion as compared with regimens using a 24-hourdosing interval.
    • p.885
  • Medical abortion techniques have evolved over the past 2 decades based on scientific advances. The original mifepristone and misoprostol regimens included 600 mg of oral mifepristone, followed 36 – 48 hours later by 400 mcg of oral misoprostol in women up to 49 days of gestation. Large, prospective, randomized trials support equal efficacy with regimens using a lower dose of mifepristone (200 mg). Additionally, alternative methods of administration of misoprostol, including vaginal, buccal, and sublingual, allow for use of the medications for gestations beyond 49 days of gestation.
    • pp.885-886
  • Over the past 5 years, multiple studies have focused on the time interval between medications. Regimens with oral misoprostol are not very effective when the time interval decreases below the recommended 36 – 48 hours. Buccal regimens appear effective with dosing intervals as little as 24 hours in women up to 56 days of gestation. The largest trials include vaginal misoprostol, with which efficacy is maintained in women up to 63 days of gestation when the time interval is as little as 6 – 8 hours. Decreasing the time interval allows most women to complete a medical abortion in less than 1 day. Additionally, because approximately 50% of women have vaginal bleeding during the 48-hour interval between mifepristone and misoprostol administration with the standard regimen, administering the drugs on the same day would decrease undesirable adverse effects like bleeding.
    The natural progression in the evaluation of the effect of time between mifepristone and vaginal misoprostol administration is simultaneous administration of the agents. Such studies appear scientifically rational based on available pharmacokinetic and clinical data. Vaginal administration appears to act as a depot of misoprostol acid. Typically, cramping be-gins approximately 2 hours and bleeding about 3 to 31⁄2hours after misoprostol placement. Significant serum levels of misoprostol acid are still present 4 hours after administration based on the pharmacokinetic profile, thereby rationalizing simultaneous application.
    • p.886
  • Pilot trials were performed with the primary objective of evaluating 24-hour expulsion rates after simultaneous administration of mifepristone 200 mg and vaginal misoprostol 800 mcg. These trials included 120 women, with 40 women in each of the gestational age ranges of 49 days or less, 50–56, and 57– 63 days of gestation. The expulsion rates of 90%, 88%, and 85%, respectively, were similar to those seen in regimens with intervals of 6 – 8 hours, demonstrating the potential efficacy of these drugs for medical abortion when administered simultaneously. We performed this prospective, randomized, multicenter trial to compare the efficacy, adverse effects, and acceptability of misoprostol 800 mcg vaginally administered simultaneously with, or 24 hours after, mifepristone 200 mg orally in women up to 63 days of gestation. This study is designed as a non inferiority trial, with efficacy as the primary outcome variable.
    • p.886
  • The efficacy of treatment in women with simultaneous administration was non inferior to that in women who administered the medications 24 hours apart (Table 2) (P.003). If the women who were lost to follow-up were included as treatment failures, the outcomes were still equivalent (data not shown).However, the success rates with mifepristone followed by a single dose of misoprostol were different(Table 2) (91% versus 94%, respectively,P.1 for non inferiority). There was no trend for decreasing success overall or with mifepristone and a single dose of misoprostol with increasing gestational age within study groups (P.3 for all comparisons). There was also no difference for overall efficacy within study groups by study site (data not shown)
    • pp.890-891
  • Cramping began after a median of 2.5 hours(range 0 to 143 hours) and 1.7 hours (range –24 to 115hours) after misoprostol administration in groups 1and 2, respectively (P.001). Bleeding began after a median of 3.7 hours (range 0 to 74 hours) and 2.0hours (range –23 to 24 hours), respectively (P.001).Pad count data were available for 549 (99.1%) and544 (99.6%) women in groups 1 and 2, respectively. For these women, 31.5% and 36.8% reported that the heaviest amount of bleeding they experienced was soaking at least two pads in 1 hour (P.07). There was also no difference in the number of women who reported that the heaviest amount of bleeding exceeded two pads in 1 hour (9.7% versus 10.1%,P.8).Bleeding and spotting duration was not different between groups, lasting a median of 10 and 15 days, respectively, for women in group 1, and 10 and 14days, respectively, for women in group 2 (Table 3).
    • p.891
  • Adverse effects are presented in Table 4. Women in group 1 had statistically significantly higher rates of nausea, diarrhea, and warmth or chills after misoprostol administration. Bleeding, cramping, and accept-ability information are presented in Table 3. Complete pre- and post treatment VAS assessments were available for 533 (96%) and 527 (97%) women in groups 1 and 2, respectively. The median level of pain reported on the post-questionnaire was 64 mm and 62mm, respectively. The indicated level of pain was 3mm higher in group 1 and 2 mm lower in group 2than that anticipated on pretreatment VAS assessment in both groups. The findings were similar for bleeding, with a median post treatment severity of bleeding of 63 mm and 64 mm for groups 1 and 2, respectively, and the differences as compared with pretreatment estimation of bleeding, 8 mm and 7 mmlower, respectively.
    Serious adverse events occurred in 17 (1.5%)women. Four women (0.4%) received a transfusion, all in group 2, with gestational ages at initiation of treatment of 50, 51, 57, and 63 days. One subject in group 1 had a heterotopic pregnancy and had surgery for the tubal gestation after a successful medical abortion. Two other women had hospitalizations for events unrelated to the medical abortion. In addition to these serious events, 10 women (0.9%), five in each group, were diagnosed with acute pelvic infection after the medical abortion but were treated as outpatients. One of these infections (in group 2) occurred after a suction aspiration for an incomplete abortion.
    • p.891
  • We have demonstrated that simultaneous administration of mifepristone and vaginal misoprostol is at least as effective as administration of the medications 24 hours apart. The sample size was calculated to evaluate non-inferiority for the overall study sample and was not large enough to determine noninferiority at each gestational age range. However, even with smaller samples within each gestational age range, the abortion rates within each gestational age range were almost noninferior, with Pvalues of .051 to .08 (Table 2), suggesting that larger trials would likely demonstrate equivalence. The point difference between the two treatment groups was 3%,the value declared a priori for noninferiority of the overall complete abortion rates. Given that the standard treatment group had a single-dose efficacy below 95%,the sample was not large enough to demonstrate this 3% difference to be noninferior.
    The complete abortion rates and adverse effect rates11in the standard treatment groups were similar to those previously published for this regimen, inferring external validity. In a prior trial comparing dosing intervals of 6 – 8 hours and 23–25 hours, women in the shorter interval group experienced fewer adverse effects and were less likely to experience significant bleeding.Further shortening the interval to simultaneous dosing does not appear to create these same benefits in relation to adverse effects or bleeding. It is possible that the lack of a decrease is, in reality, the result of women experiencing adverse effects from both the mifepristone and misoprostol when administered simultaneously. Importantly, the differences, albeit statistically significant, are relatively small and are not likely to have clinical relevance as evidenced by the high and equal satisfaction in both treatment groups.
    • p.892
  • When this study was initiated, the “evidence-based” use of vaginal misoprostol was very common in the United States. In December 2005, Fischer et al28re-ported four deaths in the United States from Clostridium sordellii infection in women who had received mifepristone and vaginal misoprostol. A fifth infectious death, related to C perfringens, was reported at a Centers for Disease Control and Prevention meeting in May 2006. One theory about infection and medical abortion is that mifepristone causes immunosuppression; however, more widespread and serious infections would be occur-ring with more common organisms. In our current study, mild infection was diagnosed in less than 1% of subjects, a rate that is too low to support the idea of significant immunosuppression. Another theory is that use of the misoprostol vaginally increases the likelihood of infection with rare organisms. Such a finding would obviate the importance of this study. Additional recent reports have linked C sordellii infection to the deaths of eight women who recently had delivered infants either vaginally or by caesarean, two women who had miscarriages, and one woman who was infected during her menstrual period. Obviously, neither mifepristone nor vaginal misoprostol was routinely used in these cases. For now, the evidence does not allow any inference as to whether the use of vaginal misoprostol as opposed to other routes impacts this risk. It is unclear if these rare infectious deaths with medical abortion are a direct effect of the medications used or a result of the process of medical abortion caused by the medications.
    • p.892
  • We, as providers and policy makers, may not be able to globally categorize how women assess risks and benefits of pregnancy options, and it is likely that such decisions are complex and personal. If there really is an increased risk of death with medical as compared with early surgical abortion, that difference is likely 1 per 100,000 with medical abortion and 1per million with early surgical abortion. For perspective, the mortality risk with a term delivery is 1 per 10,000. The risk of death is small regardless of pregnancy outcome, but the experience of each process for the woman is vastly different. The current study shows that women can use regimens with vaginal misoprostol without any time delay between medications with efficacy that is similar to those with a delay. Studies with a 6 – 8 hour interval demonstrate fewer adverse effects than those with a 24-hour interval. For women, what is the relative value of all of these differences? Would women prefer a vaginal route with fewer adverse effects or the ability to have their abortion completed sooner? Are changes in mortality from very, very rare to very, very, very rare more relevant to a woman than significant decreases in adverse effects or timing issues? These are questions we need to understand better to provide the best options for women.
    • pp.892-893

"Medical abortion in early pregnancy" (2009)[edit]

Creinin MD, Gemzell-Danielsson K (2009). "Medical abortion in early pregnancy". In Paul M, Lichtenberg ES, Borgatta L, Grimes DA, Stubblefield PG, Creinin MD (eds.). Management of unintended and abnormal pregnancy: comprehensive abortion care. Oxford: Wiley-Blackwell. pp. 111–34. ISBN 978-1-4051-7696-5.

  • The phrase medical abortion commonly refers to use of medications up to 63 days’ gestation to effect abortion, although some regimens are effective beyond 63 days. Medical abortion allows a woman to have a safe, effective abortion without a surgical procedure. Since the early 1990s, millions of women in Europe, China, and North America have used mifepristone in combination with a prostaglandin analog for early abortion. However, in many regions of the world mifepristone is not available, prompting use of alternative regimens, including methotrexate in combination with misoprostol and misoprostol alone. This chapter reviews accumulated research on these medical methods of abortion and presents guidelines for their use in clinical practice.
    • p.111
  • Although using medications to induce abortion dates back centuries, effective medical regimens have emerged only in the last 50 years. In the early 1950s, Thiersch and col-leagues experimented with the folic acid antagonist, 4-aminopteroylglutamic acid (aminopterin) in mice, rats, and humans. Aminopterin was noted to induce embryonic demise and resorption in mice and rats during the first week of gestation. Oral aminopterin was then used to induce medically indicated abortions in women less than 3 months’ gestation. Ten of 12 women aborted.
    In the 1970s, natural prostaglandins such as PGE2andPGF2αwere found to induce early abortion effectively. However, regimens that resulted in high efficacy also caused intolerable side effects, including nausea, vomiting, diarrhea, fever, and pain. Prostaglandin analogs developed in the mid-1970s acted more selectively on the myometrium, allowing use of lower doses to effect abortion, but their instability limited long-term use. By 1980, more stable analogs proved efficacious, including the vaginal suppository, gemeprost (16,16-dimethyl-trans-2-PGE1methyl ester) [4–6], and the injectable analog, sulprostone (16-phenoxy-tetranor PGE2 sulfonylamide). Gastrointestinal side effects were less severe with the analogs than with natural prostaglandins, but they still occurred commonly, thus limiting their clinical utility.
    • pp.111-112
  • Although medical contraindications to abortion with mifepristone, methotrexate, or misoprostol alone are few, social or psychological considerations are more common. Women are not optimal candidates for medical abortion if they:
    wish to minimize participation in their abortion;
    are anxious to have the abortion over quickly;
    cannot return for follow-up visits;
    or cannot communicate easily with the provider because of language or comprehension barriers (phone interactions are more common with medical than with surgical abortion patients).
    Due to the risk of teratogenicity in an ongoing pregnancy, women also must intend to have a surgical abortion should the medical method fail. Other nonmedical considerations include access to a telephone in case of an emergency and distance from emergency medical treatment (e.g., suction curettage for hemorrhage). A few reports have examined use of medical abortion by adolescents, with outcomes similar to older women.
    • p.123
  • As with all abortion methods, the informed consent process must assure that a woman is certain about her decision to have an abortion and that she understands the alternatives available and their risks and benefits (Chapter 5). Patient uncertainty warrants a delay, even if waiting means that she will be unable to choose an early medical option. The process of medical abortion is quite similar regard-less of the agent used, although the timing and efficacy may vary. Patient education includes explaining the medical abortion process and ways in which it differs from surgical abortion (Chapter 10). Heavier bleeding and more severe cramping may occur as compared to surgical abortion; describing the bleeding and cramping as comparable to a miscarriage, rather than menses, helps to prepare some patients. Mean days of bleeding are higher with medical (14 days) than surgical abortion (9 days), but days of spotting (about 10) are similar. Increasing gestational age predicts more bleeding or spotting days after medical, but not surgical, abortion.
    In contrast to surgical abortion, patients experience pas-sage of the products of conception firsthand, and women may wonder if they will identify the tissue. The pregnancy and the decidua may pass at the same time or separately. The decidualized endometrium commonly appears thick and solid as it passes either in fragments or as a complete decidual cast. The gestational sac and placenta frequently pass intact, often with adherent clot (Figure 9.3). The clots maybe quite large and obscure the pregnancy tissue. However, some patients may see a tiny sac or conceptus, particularly if the pregnancy is more than 7 weeks’ gestation. Using true-to-size illustrations that show early products of conception may help prepare the patient for this event.
    • p.124
  • Mifepristone in combination with misoprostol or another prostaglandin analog is the most effective and efficient abortifacient combination. Acceptable gestational age limits for using mifepristone depend on the type and route of ad-ministration of the prostaglandin analog. Regimens using mifepristone with gemeprost are effective through 63 days’ gestation. When mifepristone is combined with oral miso-prostol 400μg, complete abortion occurs in more than 90%of women through 49 days’ gestation. Using misoprostol800μg vaginally results in high efficacy through 63 days’ gestation or more. Although less studied, buccal or sub-lingual misoprostol administration appears to have similar efficacy to vaginal regimens, albeit with more side effects. Unlike vaginal administration, regimens with buccal miso-prostol may not be effective with time intervals of less than 24 hours.
    • p.129

"Medical management of first-trimester abortion" (March 2014)[edit]

Creinin MD, Grossman DA (March 2014). "Medical management of first-trimester abortion". Contraception. American College of Obstetricians and Gynecologists; Society of Family Planning. 89 (3): 148–161. doi:10.1016/j.contraception.2014.01.016. PMID 24795934.

  • Over the past three decades, medical methods of abortion have been developed throughout the world and are now a standard method of providing abortion care in the United States. Medical abortion, which involves the use of medications rather than a surgical procedure to induce an abortion, is an option for women who wish to terminate a first-trimester pregnancy. Although the method is most commonly used up to 63 days of gestation (calculated from the first day of the last menstrual period), the treatment also is effective after 63 days of gestation. The Centers for Disease Control and Prevention estimates that 64% of abortions are performed before 63 days of gestation. Medical abortions currently comprise 16.5% of all abortions in the United States and 25.2% of all abortions at or before 9 weeks of gestation. Mifepristone, combined with misoprostol, is the most commonly used medical abortion regimen in the United States and Western Europe; however, in parts of the world, mifepristone remains unavailable. This document presents evidence of the effectiveness, benefits, and risks of first-trimester medical abortion and provides a framework for counseling women who are considering medical abortion.
    • p.148
  • Mifepristone, a derivative of norethindrone, binds to the progesterone receptor with an affinity greater than progesterone itself but does not activate the receptor, thereby acting as an antiprogestin. Its known actions on a uterus in pregnant women include decidual necrosis, cervical softening, and increased uterine contractility and prostaglandin sensitivity. Human studies have suggested that uterine contractility does not increase until 24–36 h after mifepristone administration. At this point, the sensitivity of the myometrium to the stimulatory effects of exogenous prostaglandins increases fivefold. However, more recent studies have shown high efficacy when vaginal misoprostol is administered less than 15 min after mifepristone. The effectiveness of such a regimen cannot be attributed to the actions of the misoprostol because misoprostol alone has a much lower efficacy than mifepristone. Accordingly, these studies suggest that some or all of these actions occur sooner than previously believed or that the effects of mifepristone that are important and necessary for its abortifacient activity remain incompletely understood.
    As a progesterone receptor antagonist, mifepristone also has several other potential medical applications, including emergency contraception; cervical ripening and labor induction; and treatment of symptomatic uterine leiomyomas, endometriosis, Cushing syndrome, breast cancer, early pregnancy loss, and glaucoma.
    • pp.148-149
  • Misoprostol is an inexpensive prostaglandin E1 analogue in a tablet form that is stable at room temperature. It is approved by the US Food and Drug Administration (FDA) for oral administration to prevent gastric ulcers in individuals who take antiinflammatory drugs on a long-term basis, and it is included in the FDA-approved labeling of mifepristone for use in abortion. It is used off-label in other regimens for abortion, labor induction, treatment of early pregnancy loss, prevention and treatment of postpartum hemorrhage, and cervical priming before uterine procedures, such as hysteroscopy. Pharmacokinetic evaluations of misoprostol absorption when administered by various routes have been performed. Routes that result in a longer duration of action (i.e., buccal and vaginal) also appear to result in greater efficacy compared with oral administration. Similarly, those routes with rapid and

significant absorption (i.e., sublingual) also have high efficacy, but the greater maximum concentration results in more adverse effects. Misoprostol-only medical abortion regimens are significantly less effective than those that use a combination of mifepristone and misoprostol.

    • p.149
  • Methotrexate in combination with misoprostol was adopted in the United States and Canada as an alternative to mifepristone regimens before mifepristone was available. However, methotrexate rarely is used anymore in the United States for medical abortion because of the greater availability and efficacy of mifepristone regimens. Methotrexate blocks dihydrofolate reductase, an enzyme involved in producing thymidine during DNA synthesis. Methotrexate exerts its action primarily on the cytotrophoblast rather than the developing embryo, which inhibits syncytialization of the cytotrophoblast. Thus, methotrexate stops the process of implantation rather than weakening the implantation site directly. In contrast, the antiprogestin mifepristone has no direct effect on the trophoblast.
    Tamoxifen has been used in some studies of early abortion in combination with misoprostol. However, randomized trials have demonstrated no benefit of using tamoxifen–misoprostol over methotrexate–misoprostol or misoprostol alone regimens.
    Two small studies from China suggest that multiple daily administrations of letrozole followed by misoprostol, 800 mcg vaginally, may be another effective option for medical abortion, but more research is needed regarding this regimen.
    • p.149
  • The FDA-approved regimen, as detailed in the mifepristone package labeling, is based on the original regimen registered in France 25 years ago. This regimen includes mifepristone, 600 mg orally, followed approximately 48 h later by a prostaglandin analogue, usually misoprostol 400 mcg orally. The FDA-approved regimen includes this treatment with a follow-up visit approximately 14 days after mifepristone administration. If clinical history indicates that the woman had a confirmed abortion, a pelvic examination is performed to confirm uterine involution. If clinical history and physical examination do not confirm expulsion, ultrasonography is performed. Suction aspiration at the follow-up evaluation is not specified as necessary unless the pregnancy is ongoing.
    The efficacy of the FDA-approved regimen is approximately 92% in women with gestations up to 49 days. Complete abortion rates are higher with earlier gestations; approximately 96–98% in gestations of up to 42 days, 91–95% in gestations from 43 days to 49 days, and less than 85% in gestations beyond 49 days. When abortion does not occur within 3–4 h after oral misoprostol administration, use of an additional dose does not improve efficacy.
    • p.149
  • Additional “evidence-based” regimens have been developed to improve medical abortion in terms of expense, safety, speed, and adverse effects. Regimens that use low doses of mifepristone (200 mg) have similar efficacy and lower costs compared with those that use mifepristone at 600 mg. Based on efficacy and the adverse effect profile, evidence-based protocols for medical abortion are superior to the FDA-approved regimen. Vaginal, buccal and sublingual routes of misoprostol administration increase efficacy, decrease continuing pregnancy rates and increase the gestational age range for use as compared with the FDA-

approved regimen. By changing the route of misoprostol administration, the timing between mifepristone and misoprostol dosing can be varied to allow women more flexibility to accommodate personal situations, such as work and childcare. Regimens that use vaginal misoprostol can be provided simultaneously with mifepristone to terminate gestations of up to 63 days. A 6–8-h interval between mifepristone administration and vaginal misoprostol administration is as effective as a 24-h interval and results in significantly fewer adverse effects. Buccal and sublingual misoprostol can be administered as early as 24 h after mifepristone administration. Women can safely and effectively self-administer misoprostol at home as part of a medical abortion regimen.

    • pp.149-150
  • Features of medical and surgical abortion
    Medical abortion
    *Usually avoids invasive procedure
    *Usually avoids anesthesia
    *Days to weeks to complete
    *Available during early pregnancy
    *High success rate (approximately 95%)
    *Bleeding commonly not perceived as light
    * Requires follow-up to ensure completion of abortion
    *Patient participation throughout a multiple-step process
    Surgical abortion
    * Involves invasive procedure
    *Allows use of sedation if desired
    *Complete in a predictable period of time
    *Available during early pregnancy
    *High success rate (99%)
    *Bleeding commonly perceived as light
    *Does not require follow-up in most cases
    *Patient participation in a single-step process.
    • p.150
  • Only when a woman has considered her options and decided to have an abortion does the discussion about the different methods become an issue. Most women who seek early abortion will be eligible for medical and surgical methods. The general advantages and disadvantages of each approach should be explained early in the counseling process (Box 1). Even for women who think they are unsure about the method, most will have some preference after counseling. Studies that have compared abortion method preferences have included groups of patients who choose their method and those who are randomized to their method. The applicability of these studies to current US medical abortion practice is limited given that no studies included the mifepristone−misoprostol regimen, and in two studies, surgical abortion was performed only under general anesthesia. Generally, women are satisfied with the method they choose but, when randomized, prefer surgical abortion to medical abortion.
    • p.150
  • Most women choose medical abortion because of a desire to avoid surgery, a perception that medical abortion is safer than surgical abortion, and a belief that medical abortion is more natural and private than a surgical procedure. Compared with surgical abortion, medical abortion takes longer to complete, requires more active patient participation, and is associated with higher reported rates of bleeding and cramping. With medical abortion, expulsion of the products of conception most likely will occur at home, but a few women will still require surgical evacuation to complete the abortion. An early surgical abortion takes place most commonly in one visit and involves less waiting and less doubt about when the abortion occurs compared with medical abortion. In addition, women who undergo surgical abortion will not see any products of conception or blood clots during the procedure.
    • p.150
  • Bleeding and cramping will be experienced by most women undergoing medical abortion and are necessary for the process to occur. Adverse effects commonly associated with mifepristone use include nausea, vomiting, diarrhea, head-ache, dizziness, and thermoregulatory effects. The incidence of each adverse effect is based on the regimen used (especially the prostaglandin analogue), the dose and route of administration of the prostaglandin analogue and the gestational age. Gastrointestinal adverse effects are less common when misoprostol is administered vaginally as compared with regimens that use oral, buccal, or sublingual misoprostol. Buccal and sublingual administration cause similar adverse effects, with the sublingual route associated with a higher rate of chills.
    • p.150
  • Counseling should emphasize that the woman is likely to have bleeding that is much heavier than menses (and potentially with severe cramping) and is best described to patients as comparable with a miscarriage. The woman should understand how much bleeding is considered too much. An easy reference for the patient to use is the soaking of two maxi pads per hour for 2 consecutive hours. Patients should be advised to call their health care providers if they experience this level of bleeding.
    • p.150
  • Overall, large series demonstrate that less than 1% of women will need emergency curettage because of excessive bleeding. Moreover, the risk of clinically significant bleeding and transfusion may be lower in women who undergo medical abortion of gestations up to 49 days compared with those who undergo medical abortion of gestations of more than 49 days; this risk will vary based on the regimen used.
    • p.152
  • One randomized trial found that ibuprofen taken when needed was more effective than acetaminophen to reduce pain associated with medical abortion. Nonsteroidal antiinflammatory drugs inhibit the synthesis of new prostaglandins, but they do not block the action of prostaglandin receptors and should not inhibit the action of a prostaglandin used for medical abortion. In a retrospective analysis of nonsteroidal antiinflammatory drugs and complete abortion, in 416 women who received misoprostol after methotrexate for medical abortion of gestations up to 56 days, the use of ibuprofen did not interfere with the action of misoprostol to induce uterine contractions and expulsion of the products of conception. One randomized trial found that multiple doses of ibuprofen given prophylactically at the time of misoprostol administration did not significantly reduce pain associated with medical abortion compared with ibuprofen taken when needed.
    • p.152
  • The overall rate of surgical evacuation with medical abortion varies greatly based on the regimen used, the gestational age of the pregnancy, and many other factors. In most studies of medical abortion of gestations up to 63 days with mifepristone 200 mg followed by misoprosto Guidelines for intervention vary for women who have a persistent gestational sac on ultrasonography without evidence of embryonic cardiac activity or continuing development. Patients with a persistent gestational sac 1 week after treatment can safely receive another dose of misoprostol or continue with expectant management. Studies indicate that even with a retained sac 2 weeks after mifepristone, intervention is unnecessary and that expulsion will typically occur in the ensuing weeks. Women who prefer not to wait longer may choose to have a surgical evacuation at any time. Most commonly, women who are awaiting delayed expulsion will no longer feel pregnant or have medication-induced symptoms; patients will be waiting for the onset of bleeding or cramping similar to anticipating the start of menses. Health care providers must differentiate these women from those who have incomplete expulsion of the pregnancy tissue with symptoms, such as prolonged and irregular bleeding episodes. l, less than 5% of patients undergo surgical evacuation.
    • p.152
  • Continuing pregnancies are typically reported in less than 1% of women who begin medical abortion at or before 63 days of gestation with evidence-based regimens. Ongoing pregnancy may be treated with uterine aspiration or a repeat dose of vaginal misoprostol. In an analysis of data from two randomized trials with 14 cases of ongoing pregnancy with gestational cardiac activity, treatment with a repeat dose of misoprostol, 800 mcg administered vaginally, resulted in expulsion of the products of conception in five cases (36%); in an additional four cases (29%), gestational cardiac activity was no longer present at the next follow-up visit. If gestational cardiac activity persists at follow-up after a second dose of misoprostol, uterine aspiration should be performed. Repeat doses of buccal misoprostol to treat ongoing pregnancy have not been studied.
    • p.152
  • In women who receive mifepristone and vaginal misoprostol, emergency curettage within the first 24 h of treatment is rare, occurring in 0.2% of patients. Clinicians who wish to provide medical abortion services either should be trained in surgical abortion or should be able to refer to a clinician trained in surgical abortion.
    • p.152
  • Women are candidates for medical abortion with mifepristone and misoprostol if they meet the gestational age criteria for the regimen and have no contraindications to the medical abortion process. Women with twin gestations can be treated with the same regimens as those with singleton gestations. Medical contraindications are infrequent.
    Most studies exclude women with anemia who have Hb levels of less than 9.5 g/dL or less than 10 g/dL; accordingly, the safety of medical abortion in women with anemia is unknown. Although the transfusion rates associated with medical abortion are low (0.05%), they exceed those reported for surgical abortion in early pregnancy (0.01%).
    Other medical contraindications to abortion with mifepristone regimens include confirmed or suspected ectopic pregnancy, intrauterine device (IUD) in place, current long-term systemic corticosteroid therapy, chronic adrenal failure, known coagulopathy or anticoagulant therapy, and intolerance or allergy to mifepristone. Most clinical trials also have excluded women with severe liver, renal or respiratory disease or uncontrolled hypertension or cardio- vascular disease (angina, valvular disease, arrhythmia or cardiac failure).
    • pp.152-153
  • Women are not good candidates for medical abortion if they are unable or unwilling to adhere to care instructions, desire quick completion of the abortion process, are not available for follow-up contact or evaluation or cannot understand the instructions because of language or comprehension barriers.
    • p.153
  • Confirmation of pregnancy is necessary before attempting abortion, regardless of method. Preoperative assessment of Hb or hematocrit is indicated when anemia is suspected. Rh testing is standard of care in the United States, and RhD immunoglobulin should be administered if indicated. Other laboratory evaluations are not indicated but may be required by local and state legislation.
    • p.153
  • The upper gestational age limit at which a medical abortion regimen is still an option varies based on the types, dosages, and routes of administration of the medications. Complete abortion rates with all regimens are highest for women with earlier gestations and are clinically similar in women with pregnancies up to 42 days of gestation. After 49 days of gestation, evidence-based regimens have advantages over the FDA-approved regimen and are medically preferable (Table 2). After 49 days of gestation, the efficacy of the FDA-approved regimen decreases significantly, and the likelihood of continuing pregnancy increases. However, regimens using vaginal, sublingual and buccal misoprostol provide efficacy rates when used up to 63 days of gestation that exceed the approximately 92% efficacy of the FDA-approved regimen when used up to 49 days of gestation. Moreover, the continuing pregnancy rates with these alternative methods of administering misoprostol remain low, at approximately 1% or less for vaginal, buccal and sublingual regimens up to 63 days of gestation. The amount of published data on sublingual regimens is relatively small compared with vaginal regimens.
    • p.153
  • The use of the mifepristone–misoprostol regimen has been evaluated for medical abortion in women with pregnancies beyond 9 weeks of gestation, most commonly with regimens that involve the use of vaginal misoprostol and in an in-patient setting. In a published review of more than 1000 women who were observed as inpatients after misoprostol treatment, primarily by the vaginal route, the efficacy rate exceeded 92% for women with pregnancies through 13 weeks of gestation (with a rate of 97% at 9–10 weeks of gestation), steadily decreasing to 92% for those with gestations at 12–13 weeks. Continuing pregnancy rates were less than 1% for women with gestations through 11 weeks. The published experience with sublingual misoprostol in this gestational age range is relatively small.
    A more recent US multicenter trial evaluated 629 women with pregnancies from 57 days of gestation to 70 days of gestation who received mifepristone with buccal misoprostol in an outpatient setting. Success rates were 94% for women with gestations from 57 days to 63 days and 93% for those with gestations from 64 days to 70 days, and acceptability was high and similar for both gestational age groups. However, the continuing pregnancy rate was 3% for both groups.
    • p.153
  • Uterine infection with medical abortion is uncommon, and limited data exist to support the prophylactic use of antibiotics in medical abortion. In a systematic review of 65 studies of heterogeneous design (prospective, retrospective, and randomized), the overall frequency of diagnosed or treated infection after medical abortion in more than 46,000 patients was 0.9%. In these studies, as in most surgical abortion studies, the diagnostic criteria for infection were variable, which possibly led to an overestimation of infection. Although concern regarding serious, rare and deadly infection with clostridial bacteria in women who undergo medical abortion has been raised, it has since become evident that no specific connection exists between clostridial organisms and medical abortion. Investigations have found these organisms also are associated with other obstetric and gynecologic processes and procedures, including spontaneous abortion, term delivery, surgical abortion, and cervical cone or laser treatment for cervical dysplasia. In addition, it is now recognized that clostridial species are a more common cause of pelvic infection than previously believed.
    • p.153
  • Large retrospective analyses of medical abortion safety conducted by Planned Parenthood Federation of America, Inc, since 2001 showed a decrease over time in the serious infection rate (defined as receipt of intravenous antibiotics, hospitalization, sepsis, or death) with a change from vaginal to buccal misoprostol (from 0.093% to 0.020%) and a further decrease (to 0.006%) when routine provision of a 1-week treatment course of doxycycline was started on the day of mifepristone administration. Because the study used continuous prior time periods as the comparator, the addition of a treatment course of antibiotics cannot be separated from the effect of the switch in the route of misoprostol administration. In a subsequent report, the risk of serious infection in Planned Parenthood clinics increased to 0.013% in 2009 and 0.019% in 2010 [54], a rate equal to the rate noted before routine doxycycline provision.
    • pp.153-154
  • [N]o strong data exist to support the universal use of prophylactic antibiotics for medical abortion.
    • p.154
  • A US study found that women’s reported last menstrual period combined with clinical estimation of gestational age was accurate and would have resulted in medical abortion erroneously offered to only 1.6% of women after 63 days of gestation. Because efficacy of some regimens decreases significantly with increasing gestational age, the clinical relevance of erroneous gestational age assignment will vary based on the regimen used.
    • p.155
  • A potential concern when providing early abortion services is the possibility of an undiagnosed extrauterine gestation. The ectopic pregnancy rate in the general population is approximately 19–21 per 1000 pregnancies and may be slightly higher (21–24 per 1000 pregnancies) among patients who receive Medicaid. However, ectopic pregnancy rates in studies of women who seek abortion are consistently lower. A study of surgical abortion in U.S. women with pregnancies less than 6 weeks of gestation found the ectopic pregnancy rate to be 5.9 per 1000 pregnancies. Similarly, the largest study of medical abortion patients published involved 16,369 women with pregnancies of 49 days of gestation or less, 21 of whom were excluded from the analysis because of an ectopic pregnancy, yielding an ectopic pregnancy rate of 1.3 per 1000 pregnancies. Although ectopic pregnancy in a population of women who seek early abortion is rare, women with significant medical risk factors or history (i.e., unilateral pain and vaginal bleeding) should have a pretreatment ultrasonography.
    • p.155
  • The introduction of medical abortion into widespread clinical practice has required continued emphasis on follow-up because failure rates for medical abortion are higher than those for surgical techniques, and misoprostol is potentially teratogenic. Initial reports showed that mifepristone and misoprostol can be integrated into clinical practice with low rates of patients lost to follow-up. However, further reports reported loss-to-follow-up rates as high as 45% in clinical settings.
    • p.155
  • When the clinician and the patient think that expulsion has occurred based on symptomatology, they are correct 96–99% of the time. However, a systematic review found that women’s self-assessment alone or combined with clinical assessment had low sensitivity (33−85%) and low positive predictive value (6−66%) to detect ongoing pregnancy. Follow-up after receiving mifepristone and misoprostol for medical abortion is important, although an in-clinic evaluation is not always necessary.
    • p.155
  • The FDA-approved regimen includes an evaluation at 2 weeks after mifepristone administration to assess for history of bleeding and evidence of uterine involution on pelvic examination. However, other options that allow evaluation sooner with a high degree of accuracy to detect ongoing pregnancy include in-clinic transvaginal ultrasound examination 1 week after treatment; serum human chorionic gonadotropin (hCG) level measurement before and 1 week after treatment; and telephone follow-up at 1 week, with subsequent urine pregnancy testing at 2 weeks or 4 weeks after treatment. Although urine pregnancy testing alone with standard high- or low-sensitivity tests has not been shown to be a viable alternative, newer semiquantitative urine hCG tests have shown promise in accurately identifying ongoing pregnancies after medical abortion.
    • p.155
  • In research trials, when a transvaginal ultrasound examination shows no evidence of a gestational sac 1 week after mifepristone use, only 1.6% of women will need a subsequent surgical evacuation.
    • p.155
  • In a trial that randomized women to follow-up in the form of in-clinic transvaginal ultrasound examination or serum hCG testing, 24.5% of patients were lost to follow-up, with no significant differences reported in unplanned visits and interventions by 2 weeks (6.6% vs. 8.2%, respectively) or in dilation and curettage rates by 4 weeks (4.4% and 1.4%, respectively).
    • p.156
  • Another study examined follow-up rates for women that chose ultrasound examination or hCG testing. The loss-to-follow-up rate was somewhat higher among women who chose hCG testing (33.7% vs. 22.9%), but in multivariable analysis, follow-up method was not associated with loss to follow-up. Instead, loss to follow-up was found to be based on patient factors, such as living at least 10 miles from the clinic, prior pregnancy, unemployment, and a history of induced abortion.
    When patients are required to go to a facility for assessment of medical abortion outcome, approximately 25% are lost to follow-up, which indicates the need for development of other follow-up methods.
    • p.156
  • Many health care providers may offer women only one option for misoprostol administration, even though all routes are not the same. Vaginal routes of administration enable the patients to complete the medical abortion process sooner because of the ability to use the misoprostol 6 h or less from the time of mifepristone administration. Early studies with mifepristone regimens demonstrated that women preferred a shorter interval between medications. Other research indicates women prefer oral routes of administration to vaginal administration.
    A US study with 139 participants allowed the women to choose between buccal and vaginal misoprostol administration. The women were fully informed of the efficacy rates, the timing interval allowed for the two routes, and adverse effect rates based on available literature. Almost all women (94%) chose vaginal misoprostol and 74% of these women used the misoprostol at 6 h or less after the mifepristone, which indicates that timing was a significant factor in their choice.
    • p.156
  • Because teratogenicity of medical abortifacients becomes an important issue if the pregnancy continues, patients must be counseled before medical abortion treatment of the need for a surgical abortion in the event of a continuing pregnancy. No evidence exists to date of a teratogenic effect of mifepristone. Evidence suggests that misoprostol can result in congenital anomalies when used during the first trimester, possibly because of mild uterine contractions that lead to decreased blood flow during organogenesis. Anomalies associated with misoprostol use that have been described in the literature include

defects in the frontal or temporal bones and, most commonly, limb abnormalities with or without Möbius syndrome (mask-like facies with bilateral sixth and seventh nerve palsy and frequently coincident micrognathia). A case–control study from Brazil compared 96 infants with Möbius syndrome matched with 96 infants with neural tube defects. Exposure to misoprostol during the first trimester was 49% and 3%, respectively [odds ratio (OR), 29.7; 95% confidence interval (CI), 11.6–76]. Six cases of limb reduction abnormalities in fetuses examined after failed abortion with methotrexate and misoprostol also have been reported. Methotrexate exposure also is characterized by a variety of malformations, including growth restriction, limb defects, and craniofacial anomalies, among others. Because misoprostol is the common agent used with every medical abortion regimen, health care providers must counsel all women regarding potential teratogenic effects.

    • p.156
  • Future fertility with medical abortion has been evaluated within only a 1-year period after medical abortion in a group of 93 women who received methotrexate and misoprostol for abortion. Although none of the women were actively attempting to achieve pregnancy, 25% became pregnant, a rate higher than the calculated rate expected for this group of women using contraception. By comparison, another report indicated a pregnancy rate of 13% within 1 year after a first surgical abortion.
    A comparative study from China enrolled more than 14,000 nulliparous women to compare outcomes of pregnancies after medical or surgical abortion and pregnancies in women with no history of abortion. Women who had a prior mifepristone abortion were less likely to have preterm birth compared with those women who had never been pregnant (adjusted OR, 0.77; 95% CI, 0.61–0.98), and the frequencies of low birth weight infants and mean lengths of pregnancy were similar in both groups. No significant differences were reported in risk of preterm delivery, frequency of low birth weight infants, or mean infant birth weight in the comparisons of women with previous mifepristone abortion and women with surgical abortion. In a registry-based study from Scotland, no association was found between prior abortion and subsequent preterm birth during the period 2000−2008, when 68% of abortions were medical.
    • pp.156-157
  • In addition to physicians, advanced practice clinicians, such as nurse–midwives, physician assistants, and nurse practitioners, possess the clinical and counseling skills necessary to provide first-trimester medical abortion. In a randomized controlled trial in Nepal, women randomized to receive medical abortion under the care of a staff nurse had a statistically equivalent risk of complete abortion compared with those under the care of a physician, and no serious adverse events were reported. This evidence indicates that medical abortion also can be provided safely and effectively by nonphysician clinicians, and in some states, advance practice clinicians are allowed to provide medical abortion. However, many states require that a physician perform an abortion and prohibit provision of medical abortion by nonphysician clinicians.
    • p.157
  • Women who chose telemedicine medical abortion were significantly more likely to say they would recommend the service to a friend compared with women who had an in-person visit with a physician (OR 1.72; 95% CI, 1.26–2.34). In an analysis of this clinic system’s service-delivery statistics, after telemedicine was introduced, a significant reduction in second-trimester abortion was reported, and women in remote parts of the state were more likely to obtain an abortion than before. Medical abortion can be provided safely and effectively via telemedicine with a high level of patient satisfaction; moreover, the model appears to improve access to early abortion in areas that lack a physician health care provider. Despite the medical evidence, several states have passed legislation that bans the use of telemedicine to provide abortion.
    • p.157
  • Almost all contraceptive methods can be provided immediately after uncomplicated first-trimester medical abortion, and all are considered Category 1 for provision after first-trimester abortion according to the U.S. Medical Eligibility Criteria (meaning there is no restriction for use). Oral contraceptives, patch, ring, depot medroxypro-gesterone acetate, and subdermal implants all may be started on the day of misoprostol administration. However, this requires an additional visit to the clinic to start depot medroxyprogesterone acetate and implants, and research is exploring whether these methods can be

administered on the day of mifepristone without reducing the efficacy of medical abortion.

    • p.157
  • The optimal timing of IUD insertion has been evaluated in two randomized studies. One study randomized women to insertion of a copper IUD 1 week after mifepristone vs. 4−6 weeks later. Significantly more women in the early- insertion group received an IUD (97% vs. 76%, pb.001). Another study randomized women to insertion of either a copper or levonorgestrel-containing IUD 5−9 days after mifepristone vs. 3−4 weeks later. Fewer women in the delayed group attended the follow-up visit to insert the IUD (1.5% vs. 11%, p=.03). In both studies, no significant difference was found in expulsion rates by group; however, the delayed-insertion groups had expulsion rates of 7−11%, which is higher than the expulsion rate noted with immediate IUD insertion after surgical abortion. The risk of expulsion of an IUD needs to be weighed against the risk that the patient will not return for a delayed insertion. Sterilization may be performed once abortion is confirmed.
    • p.157
  • The following recommendations are based primarily on good and consistent scientific evidence (Level A):
    Based on efficacy and adverse effect profile, evidence-based protocols for medical abortion are superior to the FDA-approved regimen. Vaginal, buccal, and sublingual routes of misoprostol administration increase efficacy, decrease continuing pregnancy rates, and increase the gestational age range for use as compared with the FDA-approved regimen.
    Regimens that use low doses of mifepristone (200 mg) have similar efficacy and lower costs compared with to those that use mifepristone at 600 mg.
    Women can safely and effectively self-administer misoprostol at home as part of a medical abortion regimen.
    Medical abortion also can be provided safely and effectively by nonphysician clinicians.
    Follow-up after receiving mifepristone and misoprostol for medical abortion is important, although an in-clinic evaluation is not always necessary.
    Misoprostol-only medical abortion regimens are significantly less effective than those that use a combination of mifepristone and misoprostol.
    • pp.157-158
  • The following recommendations are based primarily on limited scientific evidence (Level B):
    Because teratogenicity of medical abortifacients becomes an important issue if the pregnancy continues, patients must be counseled before medical abortion treatment of the need for a surgical abortion in the event of a continuing pregnancy.
    Before medical abortion is performed, gestational age should be confirmed by clinical evaluation or ultrasound examination.
    Nonsteroidal antiinflammatory drugs, such as ibuprofen, are not contraindicated in women who undergo a medical abortion and are appropriate first-line agents for pain management.
    Buccal administration of misoprostol may result in a lower risk of serious infection compared with vaginal administration.
    Medical abortion can be provided safely and effectively via telemedicine with a high level of patient satisfaction; moreover, the model appears to improve access to early abortion in areas that lack a physician health care provider.
    • p.158
  • The following recommendations are based primarily on consensus and expert opinion (Level C):
    Women who undergo medical abortion may need to access emergency surgical intervention, and it is medically appropriate to provide referral to another health care provider. However, state or local laws may have additional requirements.
    Clinicians who wish to provide medical abortion services either should be trained in surgical abortion or should be able to refer to a clinician trained in surgical abortion.
    No strong data exist to support the universal use of prophylactic antibiotics for medical abortion. Rh testing is standard of care in the United States, and RhD immunoglobulin should be administered if indicated.
    • p.158

"Medical abortion reporting of efficacy: the MARE guidelines" (August 2016)[edit]

Mitchell D. Creinin, Melissa J. Chen; (August 2016). "Medical abortion reporting of efficacy: the MARE guidelines". Contraception. 94 (2): 97–103. doi:10.1016/j.contraception.2016.04.013. PMID 27129936.

  • Although the term medical abortion had most commonly referred to the use of abortion-inducing medication for early pregnancy termination without primary surgical intervention, more recently, the phrase has been used to refer to labor induction abortions as well. Accordingly, we consider early medical abortion to refer to procedures in the first trimester.
    • p.97
  • Reports of using medical agents to cause early abortion first appeared in the 1950s, but the modern era of medical abortion research started in the early 1980s with the discovery of test agents that were ultimately developed into mifepristone. Over the past 30 years, research has evolved, with the use of various drugs including mifepristone, methotrexate, tamoxifen, letrozole and various prostaglandin analogs to induce early abortion. The first drug with a labeled indication for medical abortion, mifepristone, was initially approved in China and France more than two decades ago. The United States Food and Drug Administration approved mifepristone in 2000 for use in combination with the prostaglandin analog misoprostol for abortion through 49 days gestation.
    • p.97
  • Over the more than 25 years since mifepristone first became available for women to obtain a medical abortion, researchers have continued to evaluate alternative regimens to improve efficacy and the patient experience. Professional and national organizations now lead the way in promoting the best science by providing evidence-based recommendations for the preferred medical abortion treatment options. Although many individual studies are methodologically strong, the heterogeneity of design, conduct and reporting hinders synthesis of data from multiple studies. Importantly, many studies do not stratify outcomes by week of gestation. These issues became evident during data collation for creation of the 2014 Medical Management of First Trimester Abortion Practice Bulletin written collaboratively by the American College of Obstetricians and Gynecologists and the Society of Family Planning. More recently, a systematic review including approximately 30,000 patients who received mifepristone and buccal misoprostol found that only 57% had data identifying week of gestation for a stratified evaluation of overall efficacy; only 51% had such information for evaluation of continuing pregnancy.
    • p.97
  • Well-performed and reported research trials provide the basis for evidence-based guidelines and do more than simply inform providers and patients about more cost-effective or therapeutically effective options — they also affect access to care. Methodologically strong research can counter ideologically motivated arguments for legal restrictions on medical abortion regimens and gestational age limits. The medical community can use this evidence to oppose such legislation.
    • p.97

"Improving Access to Abortion via Telehealth" (May 16, 2019)[edit]

Megan K. Donovan "Improving Access to Abortion via Telehealth". Guttmacher Institute. May 16, 2019. Retrieved April 21, 2020.

  • HIGHLIGHTS
    * Medication abortion can be safely and effectively administered via telehealth, which can help extend care to remote and otherwise underserved communities.
    * Numerous policy barriers, some specific to abortion and others not, currently limit the reach of telehealth abortion.
    * As new telehealth-related policies emerge and investments and infrastructure continue to grow, it is essential that abortion care is not overlooked—or purposefully excluded.
  • Under the traditional clinic-based model, a patient visits a health center and receives abortion care in person from an on-site clinician. In 2008, however, Planned Parenthood of the Heartland pioneered telehealth access to abortion when it began using telehealth at health centers in Iowa not regularly staffed by a clinician providing abortion care. Today, Planned Parenthood health centers offer medication abortion via telehealth in at least 10 states, and some independent abortion providers have also begun integrating telehealth. Under this site-to-site model, the process is similar to the in-person model in that a patient must still visit a health center for a consultation and screening with on-site staff. However, a patient who is eligible and opts for medication abortion is then connected to a clinician at another health center via videoconference. During this interaction, the clinician reviews the patient’s medical records, answers any questions and remotely authorizes the medication.
    This model has been proven to be safe and effective, and qualitative research indicates both patients and providers find it to be a positive experience. In Alaska, where Planned Parenthood of the Greater Northwest and the Hawaiian Islands began offering telehealth abortion in 2011, providers indicated that use of this model not only increased patient choice, but also resulted in patients being seen sooner and closer to home. This is consistent with findings from Iowa, where the creation of the telehealth program was associated with improved access to medication abortion—particularly for patients who lived more than 50 miles from the nearest clinic offering surgical abortion—and increased odds of obtaining abortion care in the first trimester.
  • Another telehealth abortion model is currently being piloted and studied by Gynuity Health Projects, with special approval from the U.S. Food and Drug Administration (FDA). The TelAbortion Study began in 2016 and is now open to participants in eight states. Under this direct-to-patient model, someone seeking abortion care does not need to visit a health center but instead consults with a clinician via videoconference from a location of her choosing, such as her own home. Any required tests, such as an ultrasound and blood work, are completed at a local laboratory or health care facility and the pills are mailed directly from the study clinician to the patient. After using the medication, the patient completes follow-up testing locally to ensure the pregnancy has terminated and has another video consultation with the abortion provider. Data from the first four pilot states (Hawaii, New York, Oregon and Washington) suggest this method is a feasible, safe and acceptable option for patients.
  • Although telehealth offers one clear way to expand access to medication abortion, the politicization that isolates abortion from other types of health care also limits its reach and could stand in the way of further expansion and innovation. Overcoming the following obstacles is a necessary precursor to realizing the full potential of abortion provision using telehealth.
    State telehealth abortion bans. Seventeen states currently require the prescribing clinician to be physically present when medication abortion is dispensed, effectively banning the use of telehealth. Removing these restrictions would allow providers to expand medication abortion services to patients in these states using the site-to-site model pioneered by Planned Parenthood, and it would be a necessary precondition to implementation of the direct-to-patient model used in the TelAbortion Study.
  • FDA restrictions. Mifepristone (one of the two drugs used in the FDA-approved medication abortion regimen) is subject to an FDA-imposed and medically unwarranted Risk Evaluation and Mitigation Strategy (REMS), which requires the medication to be dispensed only by certified prescribers and only in clinics, medical offices or hospitals. As a result, and unlike most other safe and effective medications, it cannot be sold at pharmacies.
    The FDA is authorized to design and impose a REMS "for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks." Given mifepristone’s extensive safety record since it was approved for use in the United States in 2000, the REMS restrictions are not justified, which is why leading medical organizations such as the American Medical Association and the American College of Obstetricians and Gynecologists support their removal.
    If the FDA removed the REMS, medication abortion providers could go beyond the site-to-site telehealth model and offer the direct-to-patient model currently being piloted through the TelAbortion Study. Patients could receive the medication by mail directly from the clinician (as they do under the current study) or receive a prescription after their telehealth consultation and fill that prescription at a local or online pharmacy, enhancing patient choice.
  • Telehealth across state lines. Realizing the full potential of telehealth requires figuring out how to make it work most effectively throughout the United States. But by and large, the regulation of medicine and medical practice is the purview of individual states. Laws and policies governing clinician licensing, prescribing authority, insurance reimbursement, malpractice and many patient protections differ among states in ways big and small, creating a complex patchwork for providers to navigate.26 Moreover, some state laws serve as explicit barriers to telehealth, such as rules that require an established physician-patient relationship or an in-person exam before a prescription can be furnished remotely.
    As a result, the entire health care industry continues to grapple with how best to support and enhance telehealth systems that extend across state lines. For example, one response to the licensing issue is to enter into multistate compacts, which allow a provider licensed in one state to receive reciprocity or expedited licensing in the other states participating in the agreement. As policymakers devise solutions to these sorts of challenges to help telehealth realize its full potential, it is critical that abortion care is not excluded from the policies they put in place.
    In this context, restrictive policies specific to abortion further complicate the extent to which clinicians can extend care into other states using telehealth. Lawmakers hostile to abortion have imposed a variety of onerous and unnecessary restrictions on abortion providers and patients over the decades, and the applicability of these policies must be assessed for every new state in which a clinician wishes to serve. In other words, telehealth is not an automatic work-around or solution to many state abortion restrictions, which must be lifted in order to expand access to abortion care, whether via telehealth or otherwise.
  • Funding. Of course, it takes money to incorporate new technologies and infrastructure and to change how entire systems operate and health care is delivered. Due to the segregation of abortion services from other health care, some of the standard ways health care providers access new funds and technology—such as through hospital networks or incentives from insurers—already exclude many abortion providers. In addition, a tactic frequently pursued by antiabortion policymakers is to exclude abortion providers and abortion care from public funding streams.
    Ensuring that abortion providers can acquire the technology and build the infrastructure they need to provide telehealth services requires, at the very least, ensuring that they are not excluded from dedicated telehealth resources such as public grants. Larger changes that would help to ensure abortion providers have the resources and financial stability to incorporate innovations such as telehealth include reintegrating them into broader health care networks, reversing existing funding restrictions and defending against new encroachments.
  • Affordability. Cost is one of the biggest factors that make it difficult to obtain abortion care in the United States, and existing barriers to insurance coverage of abortion combined with emerging telehealth policies could exacerbate inequities in who can access telehealth abortion.Whether and how insurers cover telehealth services varies considerably and continues to evolve across state Medicaid programs, private insurance plans, and other federal and state health insurance programs. For example, some states encourage or mandate that insurance plans include telehealth services, but this does not necessarily mean that a telehealth service is reimbursed at the same rate as an in-person service.
    Moreover, even if a health plan covers telehealth services generally, it may not cover telehealth abortion. The Hyde Amendment and similar federal policies block millions of people from having insurance coverage of abortion under Medicaid and other federal programs. Many states also bar private insurance coverage of abortion in the Affordable Care Act marketplaces or throughout the private insurance market. Realizing the full potential of telehealth abortion, especially for low-income and otherwise marginalized patients, requires eliminating existing financial barriers and ensuring that abortion is explicitly covered under and adequately reimbursed by public and private health insurance plans.
  • Challenges and limitations notwithstanding, telehealth abortion has the potential to greatly expand access for individuals and communities across the country. Fully realizing this potential requires overcoming multiple obstacles, some specific to abortion and others related more generally to telehealth. In addition, if the conservative majority in the U.S. Supreme Court takes action in coming years to undermine abortion rights and the state policy landscape becomes all the more polarized, telehealth would be a significant—perhaps vital—way to extend the capacity and reach of the abortion providers still operating. Both in preparation for that day and to expand abortion access now, policymakers must take action to remove existing restrictions and ensure that abortion is included in telehealth-related policies and funding opportunities.

"Women's Experiences Using Telemedicine to Attend Abortion Information Visits in Utah: A Qualitative Study" (September 2019)[edit]

Ehrenreich K, Kaller S, Raifman S, Grossman D (September 2019). "Women's Experiences Using Telemedicine to Attend Abortion Information Visits in Utah: A Qualitative Study". Women's Health Issues. 29 (5): 407–413.

  • Introduction: Utah requires abortion patients to wait at least 72 hours between attending mandatory information sessions and having an abortion. In 2015, Planned Parenthood Association of Utah began offering telemedicine as a way for patients to attend state-mandated information visits. The purpose of this study was to evaluate patients’ experiences using telemedicine to attend abortion information visits.
    • p.407
  • Main Findings: Women reported telemedicine helped to minimize the burdens of cost, travel, and time associated with attending two in-person visits. Those who lived near a clinic that offered in-person information sessions reported the additional benefit of maintaining privacy by not being seen at the clinic. Overall, women reported that telemedicine was easy to use and felt the nurse was attentive to their emotions over video. A minority of women said they would have preferred an in-person visit, but the burdens of attending in person led them to choose telemedicine.
    Conclusions: The findings from this study indicate that telemedicine is highly acceptable to patients as a mode of attending state-mandated information visits for abortion. Although telemedicine does not eliminate the logistical and financial burdens previously found to be associated with Utah’s 72-hour waiting period and two-visit requirement, telemedicine may reduce the burdens associated with two-visit requirements for abortion and should be adopted in states that require face-to-face information sessions.
    • p.407
  • Telemedicine, the delivery of health care services at a distance using information and communication technology, has become an increasingly integral part of health care provision, including for abortion. Over the past decade, abortion providers have begun using telemedicine with videoconferencing to deliver information and to administer medication abortion services remotely. A study in Iowa found that telemedicine provision of medication abortion was safe, effective, and well-liked by patients (Grindlay, Lane, & Grossman, 2013; Grossman & Grindlay, 2017; Grossman, Grindlay, Buchacker, Lane, & Blanchard, 2011). It was also associated with a decrease in second trimester abortions, suggesting that telemedicine may enable early access to services, when risks and costs are lower (Grossman, Grindlay, Buchacker, Potter, & Schmertmann, 2013). Planned Parenthood Association of Utah (PPAU) began using telemedicine to complete Utah’s mandated information visit in January 2015. Tele-medicine used for information visits involves receiving state mandated information about pregnancy and abortion from a health care provider during a live, interactive videoconference session. This model of synchronous videoconferencing uses a direct-to-patient model, where patients are connected to a health care provider through their personal devices. The purpose of this study was to describe women’s experiences using telemedicine for their abortion information visits, including their perceptions and reactions to Utah’s mandated waiting period and information visit.
    • p.408


  • Women who said that the privacy of telemedicine was important to them mainly described how it helped them to avoid their local clinics. Although these women expressed that this privacy improved their abortion experience, these examples suggest that telemedicine may reinforce internalized or anticipated stigma of abortion for some, as previously found in a qualitative study on telemedicine and medication abortion (Grindlay et al., 2013). Interestingly, our participants did not discuss cybersecurity as a concern related to the telemedicine platform, as previously found among a sample of women receiving medication abortion via telemedicine (Grindlay et al., 2013). Rather, our participants referred to the privacy of tele- medicine as a reason they chose, or liked, this method.
    • p.412
  • Similar to previous findings that telemedicine for medication abortion provision facilitated a more patient-centered approach to care (Grindlay & Grossman, 2017), our participants were highly satisfied with their patient–provider interaction over telemedicine. Although one participant was not satisfied with her interaction, women’s descriptions that nurses put them at ease and were attentive to their emotions over video were consistent across all other interviews.
    • p.412
  • This study indicates that women were highly satisfied with their experiences using telemedicine for information visits and that telemedicine aided in decreasing anticipated burdens associated with the cost, travel, and social consequences for our participants. Telemedicine may not be the preference for all women, and it is important to provide both telemedicine and in-person options when possible. Our findings have implications for other states that have state-mandated information visits and waiting periods, suggesting that telemedicine could allow abortion patients to fulfill these requirements and decrease some of the burdens of multiple in-person visits. The use of telemedicine for abortion care clearly extends beyond the provision of medication abortion (Grindlay & Grossman, 2017; Grindlay et al., 2013; Grossman & Grindlay, 2017; Grossman et al., 2011; Grossman et al., 2013), and should be adopted in states that require face-to-face information sessions for abortion.
    • p.412

"Medabon - Combipack of Mifepristone 200 mg tablet and Misoprostol 4 x 0.2 mg vaginal tablets - Summary of Product Characteristics (SmPC)" (February 3, 2020)[edit]

[https://www.medicines.org.uk/emc/files/pil.3380.pdf "Medabon - Combipack of Mifepristone 200 mg tablet and Misoprostol 4 x 0.2 mg vaginal tablets - Summary of Product Characteristics (SmPC)". Electronic Medicines Compendium (EMC). February 3, 2020. Retrieved January 19, 2021.

  • Medabon is a combination therapy containing two medicines called mifepristone and misoprostol.
    Medabon is recommended for the medical termination of a pregnancy no later than 63 days after the first day of your last menstrual period.
    Mifepristone is an anti-hormone that acts by blocking the effects of progesterone, a hormone which is needed for pregnancy to continue. Misoprostol is a prostaglandin, which is a substance that increases contraction of the womb that will help expel the pregnancy. The two drugs can therefore cause termination of pregnancy and must be used one after the other to give the best possible chance for the treatment to work.
    • p.1
  • Do not use Medabon
    - if your pregnancy has not been confirmed by gynecological examination, ultrasound scan or biological tests
    - if the first day of your last period was more than 63 days ago (if there is any doubt, the doctor can check the age of your pregnancy with a scanner)
    - if your doctor suspects an extra-uterine pregnancy (the egg is implanted outside the womb)
    - if you are allergic to mifepristone, misoprostol (or any other prostaglandins) or any of the other ingredients of this medicine (listed in section6)
    - if you suffer from severe asthma which cannot be adequately treated with medication
    - if you have hereditary porphyria (an inherited disorder of the blood)
    - if you suffer from chronic adrenal failure.
    • pp.1-2
  • In some circumstances the treatment may not be suitable for you or you may need extra care, so please tell your doctor if
    - if you have undergone genital cutting or circumcision
    - if you cannot easily get emergency medical help in the 2 weeks after you use Medabon
    - you have a heart complaint
    - your heart has been fitted with an artificial valve
    - you have a risk factors for heart diseases, such as high blood pressure or high blood cholesterol levels (increased fat content in your blood)
    - you suffer from asthma
    - you suffer from an illness that may affect the clotting of your blood
    - you have liver or kidney disease
    - you are anaemic or otherwise malnourished.
    • p.2
  • Caution should be exercised when Medabon is used with medicines containing the following active substances:
    - immunospressants such as cyclosporine, tacrolimus, sirolimus, everolimus (used to prevent the body from rejecting a transplanted organ)
    - alfentanil, fentanyl (used to relieve pain)
    -ergotamine, diergotamine (used to treat migraines)
    - quinidine (used to help keep the heart beating normally)
    - some agents used during general anesthesia.
    • p.2
  • You should not drink grapefruit juice when you are treated with Medabon.
  • There is little information on the risks to the unborn baby. Failure of pregnancy termination (continuing pregnancy) after taking Medabon after the first medicine (mifepristone) has been associated with a 3-fold increased risk of birth defects, in particular facial paralysis, head and limb malformations. If you decide to continue with the, careful pre-natal monitoring and ultrasound examinations, with a special attention to the limbs and head, in a specialised clinic must be carried out.
  • Medabon may pass into breast milk and be taken in by your baby. You should stop breast-feeding once you have used the treatment.
  • Important: It is possible for you to become pregnant again very soon after the pregnancy termination is complete. It is recommended that you avoid becoming pregnant again before your next menstrual period after taking Medabon, and use a method of contraception within 3 to 9 days of using the mifepristone tablet (see also in section 3. ‘After treatment you should be aware that’).
  • You should know that mifepristone and misoprostol may make you dizzy. Do not drive a car or operate machinery until you know how this medication affects you.
  • p.3
  • 3. How to use Medabon
    - For pregnancies that have occurred with an intrautrine contraceptive device (coil) in place, this must be removed prior to administering Medabon.
    - It is recommended that you do not travel too far away from the prescribing hospital/clinic until the follow-up (see ‘Third step below’), in case in an emergency you need to return to the hospital/clinic. In an emergency or if you are worried for any reason, you can contact or return to the hospital/clinic before the appointment time. You will be given the telephone number to call for emergencies or any problems.
    • p.3
  • First step
    - Take one tablet of mifepristone 200 mg to swallow with some water.
    - If you vomit shortly after administration of mifepristone, please inform the doctor.
    - If you experience symptoms such as severe abdominal pain, fainting, fast heartbeat, fever lasting more than 4 hours after taking the tablet, please tell your doctor.
    -In rare cases, the pregnancy may be expelled before you use the misoprostol tablets. It is essential that you still have a follow-up consultation to confirm that a complete pregnancy termination has occurred (see ‘Third step’ below).
    • pp.3-4
  • Second step
    - 36 to 48 hours after taking mifepristone, the four misoprostol vaginal tablets are inserted into the vagina.
    - If you receive misoprostol in a clinic, you may be asked to stay for 3 hours after the misoprostol vaginal tablets are inserted or until you feel comfortable and able to return home.
    - If you use the misoprostol vaginal tablets at home, follow the same insertion instructions as given above. Please make sure that you empty your bladder and clean your hands thoroughly before inserting the misoprostol vaginal tablets. Push the four vaginal tablets one at a time up into the vagina as far as you can using your finger.
    - After the misoprostol vaginal tablets have been inserted into the vagina, remain lying down for 30 minutes.
    - The pregnancy may be expelled within a few hours or during the next few days after misoprostol treatment.
    • p.4
  • Third step
    - To confirm you are no longer pregnant, a follow-up is required 14 – 21 days after the mifepristone tablet was swallowed.
    - A special type of pregnancy test after about 2 weeks is required, to confirm the pregnancy has ended. Some women may need to have a scan to confirm the pregnancy has ended.
    - A follow up consultation can take place remotely by phone, video call, text messaging or other form of communication with your healthcare professional.
    - It is important that you keep this follow-up appointment to check that your pregnancy has been completely expelled and you are well.
    • p.4
  • After treatment you should be aware that
    - Uterine bleeding usually starts 1 to 2 days after taking the mifepristone tablet. The bleeding lasts 2 or 3 weeks (on average 13 days). If the bleeding is heavy and prolonged, contact the doctor immediately.
    - The presence of these bleedings is not related to the success of the method. If pregnancy continues or expulsion is incomplete, you will be offered a surgical method for terminating the pregnancy.
    - If the pregnancy continues and you decide to keep it, discuss this with your doctor who will arrange careful pre-natal monitoring and ultrasound examinations.
    - Important: It is possible for you to become pregnant again very soon after the pregnancy termination is complete. It is recommended that you avoid getting pregnant again soon after the termination. You should therefore start using a method of contraception within 3 to 9 days of taking the mifepristone tablet. Discuss contraceptive options with your doctor.
    • p.4

"MIFEPREX (mifepristone) Tablets Label"[edit]

"MIFEPREX (mifepristone) Tablets Label". FDA. Retrieved June 30, 2022.

  • If Mifeprex* results in incomplete abortion, surgical intervention may be necessary. Prescribers should determine in advance whether they will provide such care themselves or through other providers. Prescribers should also give patients clear instructions on whom to call and what to do in the event of an emergency following administration of Mifeprex.
  • Mifeprex tablets each contain 200 mg of mifepristone, a synthetic steroid with antiprogestational effects. The tablets are light yellow in color, cylindrical and biconvex, and are intended for oral administration only. The tablets include the inactive ingredients colloidal silica anhydrous, corn starch, povidone, microcrystalline cellulose, and magnesium stearate.
    Mifepristone is a substituted 19-nor steroid compound chemically designated as 11ß-[p-(Dimethylamino)phenyl]-17ß-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one. Its empirical formula is C29H35NO2. Its structural formula is:
    The compound is a yellow powder with a molecular weight of 429.6 and a melting point of 191-196°C. It is very soluble in methanol, chloroform and acetone and poorly soluble in water, hexane and isopropyl ether.
  • The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results.
    Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins.
    Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol. Antiandrogenic activity was observed in rats following repeated administration of doses from 10 to 100 mg/kg.
  • Following oral administration of a single dose of 600 mg, mifepristone is rapidly absorbed, with a peak plasma concentration of 1.98 mg/l occurring approximately 90 minutes after ingestion. The absolute bioavailability of a 20 mg oral dose is 69%.
  • Mifepristone is 98% bound to plasma proteins, albumin and  1-acid glycoprotein. Binding to the latter protein is saturable, and the drug displays nonlinear kinetics with respect to plasma concentration and clearance. Following a distribution phase, elimination of mifepristone is slow at first (50% eliminated between 12 and 72 hours) and then becomes more rapid with a terminal elimination half-life of 18 hours.
  • Metabolism of mifepristone is primarily via pathways involving N-demethylation and terminal hydroxylation of the 17-propynyl chain. In vitro studies have shown that CYP450 3A4 is primarily responsible for the metabolism. The three major metabolites identified in humans are: (1) RU 42 633, the most widely found in plasma, is the N-monodemethylated metabolite; (2) RU 42 848, which results from the loss of two methyl groups from the 4-dimethylaminophenyl in position 11ß; and (3) RU 42 698, which results from terminal hydroxylation of the 17-propynyl chain.
  • By 11 days after a 600 mg dose of tritiated compound, 83% of the drug has been accounted for by the feces and 9% by the urine. Serum levels are undetectable by 11 days.
  • The effects of age, hepatic disease and renal disease on the safety, efficacy and pharmacokinetics of mifepristone have not been investigated.
  • Safety and efficacy data from the U.S. clinical trials and from two French trials of mifepristone are reported below. The U.S. trials provide safety data on 859 women and efficacy data on 827 women with gestation durations of 49 days or less (dated from the first day of the last menstrual period). In the two French clinical trials, safety evaluable data are available for 1800 women, while efficacy information is available for 1681 of these women. Success was defined as the complete expulsion of the products of conception without the need for surgical intervention. The overall rates of success and failure, shown by reason for failure, for the U.S. and French studies appear in Table 1.
    In the U.S. trials, 92.1% of the 827 subjects had a complete medical abortion, as shown in Table 1. In 52 women (6.3%) expulsion occurred within two days, and resulted from the action of mifepristone (600 mg) alone, unaided by misoprostol, an analog of prostaglandin E2. All other women without an apparent expulsion took a 400 µg dose of misoprostol two days after taking mifepristone. Many women (44.1%) in the U.S. trials expelled the products of conception within four hours after taking misoprostol and 62.8% experienced expulsion within 24 hours after the misoprostol administration. There were 65 women (7.9%) who received surgical interventions: 13 (1.6%) were medically indicated interventions during the study period, mostly for excessive bleeding; five (0.6%) interventions occurred at the patient’s request; 39 women (4.7%) had incomplete abortions at the end of the study protocol; and eight (1.0%) had ongoing pregnancies at the end of the study protocol.
    Women who participated in the U.S. trials reflect the racial and ethnic composition of American women. The majority of women (71.4%) were Caucasian, while 11.3% were African American, 10.9% were East Asian, and 4.7% were Hispanic. A small percentage (1.7%) belonged to other racial or ethnic groups. Women aged 18 to 45 were enrolled in the trials. Nearly two-thirds (66.0%) of the women were under 30 years old with a mean age of 27 years.
    In the French trials, complete medical abortion occurred in 95.5% of the 1681 subjects, as shown in Table 1. In 89 women (5.3%), complete abortion occurred within two days of taking mifepristone (600 mg). About half of the women (50.3%) in the French trials expelled the products of conception during the first four hours immediately following administration of misoprostol and 72.3% experienced expulsion within 24 hours after taking misoprostol. In total, 4.5% of women in the French trials ultimately received surgical intervention for excessive bleeding, incomplete abortions, or ongoing pregnancies at the end of the protocol.
  • Mifeprex is indicated for the medical termination of intrauterine pregnancy through 49 days’ pregnancy. For purposes of this treatment, pregnancy is dated from the first day of the last menstrual period in a presumed 28 day cycle with ovulation occurring at mid-cycle. The duration of pregnancy may be determined from menstrual history and by clinical examination. Ultrasonographic scan should be used if the duration of pregnancy is uncertain, or if ectopic pregnancy is suspected.
    Any intrauterine device ("IUD") should be removed before treatment with Mifeprex begins.
    Patients taking Mifeprex must take 400 µg of misoprostol two days after taking mifepristone unless a complete abortion has already been confirmed before that time (see DOSAGE AND ADMINISTRATION).
    Pregnancy termination by surgery is recommended in cases when Mifeprex and misoprostol fail to cause termination of intrauterine pregnancy (see PRECAUTIONS).
  • Administration of Mifeprex and misoprostol for the termination of pregnancy (the "treatment procedure") is contraindicated in patients with any one of the following conditions:
    - Confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass (the treatment procedure will not be effective to terminate an ectopic pregnancy);
    - IUD in place (see INDICATION AND USAGE);
    - Chronic adrenal failure;
    - Concurrent long-term corticosteroid therapy;
    - History of allergy to mifepristone, misoprostol or other prostaglandin;
    *Hemorrhagic disorders or concurrent anticoagulant therapy; *Inherited porphyrias.
  • Because it is important to have access to appropriate medical care if an emergency develops, the treatment procedure is contraindicated if a patient does not have adequate access to medical facilities equipped to provide emergency treatment of incomplete abortion, blood transfusions, and emergency resuscitation during the period from the first visit until discharged by the administering physician.
    Mifeprex also should not be used by any patient who may be unable to understand the effects of the treatment procedure or to comply with its regimen. Patients should be instructed to review the Medication Guide and the PATIENT AGREEMENT provided with Mifeprex carefully and should be given a copy of the product label for their review. Patients should discuss their understanding of these materials with their health care providers, and retain the Medication Guide for later reference (see PRECAUTIONS).
  • Vaginal bleeding occurs in almost all patients during the treatment procedure. According to data from the U.S. and French trials, women should expect to experience bleeding or spotting for an average of nine to 16 days, while up to 8% of all subjects may experience some type of bleeding for 30 days or more. Bleeding was reported to last for 69 days in one patient in the French trials. In general the duration of bleeding and spotting increased as the duration of the pregnancy increased.
    In some cases, excessive bleeding may require treatment by vasoconstrictor drugs, curettage, administration of saline infusions, and/or blood transfusions. In the U.S. trials, 4.8% of subjects received administration of uterotonic medications and nine women (1.0%) received intravenous fluids. Vasoconstrictor drugs were used in 4.3% of all subjects in the French trials, and in 5.5% of women there was a decrease in hemoglobin of more than 2 g/dL. Blood transfusions were administered in one of 859 subjects in the U.S. trials and in two of 1800 subjects in the French trials. Since heavy bleeding requiring curettage occurs in about 1% of patients, special care should be given to patients with hemostatic disorders, hypocoagulability, or severe anemia.
  • Patients should be scheduled for and return for a follow-up visit at approximately 14 days after administration of mifepristone to confirm that the pregnancy is completely terminated and to assess the degree of bleeding. Vaginal bleeding is not evidence of the termination of pregnancy. Termination can be confirmed by clinical examination or ultrasonographic scan. Lack of bleeding following treatment, however, usually indicates failure. Medical abortion failures should be managed with surgical termination.
  • Mifeprex is available only in single dose packaging. Administration must be under the supervision of a qualified physician (see DOSAGE AND ADMINISTRATION).
    The use of Mifeprex is assumed to require the same preventive measures as those taken prior to and during surgical abortion to prevent rhesus immunization.
    There are no data on the safety and efficacy of mifepristone in women with chronic medical conditions such as cardiovascular, hypertensive, hepatic, respiratory or renal disease; insulin-dependent diabetes mellitus; severe anemia or heavy smoking. Women who are more than 35 years of age and who also smoke 10 or more cigarettes per day should be treated with caution because such patients were generally excluded from clinical trials of mifepristone.
    Although there is no clinical evidence, the effectiveness of Mifeprex may be lower if misoprostol is administered more than two days after mifepristone administration.
  • Patients should be fully advised of the treatment procedure and its effects. Patients should be given a copy of the Medication Guide and the PATIENT AGREEMENT. (Additional copies of the Medication Guide and the PATIENT AGREEMENT are available by contacting Danco Laboratories at 1-877-4 Early Option) (1-877-432-7596). Patients should be advised to review both the Medication Guide and the PATIENT AGREEMENT, and should be given the opportunity to discuss them and obtain answers to any questions they may have. Each patient must understand:
    - the necessity of completing the treatment schedule, including a follow-up visit approximately 14 days after taking Mifeprex;
    - that vaginal bleeding and uterine cramping probably will occur;
    - that prolonged or heavy vaginal bleeding is not proof of a complete expulsion;
    - that if the treatment fails, there is a risk of fetal malformation;
    - that medical abortion treatment failures are managed by surgical termination; and
    - the steps to take in an emergency situation, including precise instructions and a telephone number that she can call if she has any problems or concerns.
  • Another pregnancy can occur following termination of pregnancy and before resumption of normal menses. Contraception can be initiated as soon as the termination of the pregnancy has been confirmed, or before the woman resumes sexual intercourse.
  • Clinical examination is necessary to confirm the complete termination of pregnancy after the treatment procedure. Changes in quantitative human Chorionic Gonadotropin (hCG) levels will not be decisive until at least 10 days after the administration of Mifeprex. A continuing pregnancy can be confirmed by ultrasonographic scan.
    The existence of debris in the uterus following the treatment procedure will not necessarily require surgery for its removal.
    Decreases in hemoglobin concentration, hematocrit and red blood cell count occur in some women who bleed heavily. Hemoglobin decreases of more than 2 g/dL occurred in 5.5% of subjects during the French clinical trials of mifepristone and misoprostol.
    Clinically significant changes in serum enzyme (serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase, gamma-glutamyltransferase (GT)) activities were rarely reported.
  • Although specific drug or food interactions with mifepristone have not been studied, on the basis of this drug’s metabolism by CYP 3A4, it is possible that ketoconazole, itraconazole, erythromycin, and grapefruit juice may inhibit its metabolism (increasing serum levels of mifepristone). Furthermore, rifampin, dexamethasone, St. John’s Wort, and certain anticonvulsants (phenytoin, phenobarbital, carbamazepine) may induce mifepristone metabolism (lowering serum levels of mifepristone).
    Based on in vitro inhibition information, coadministration of mifepristone may lead to an increase in serum levels of drugs that are CYP 3A4 substrates. Due to the slow elimination of mifepristone from the body, such interaction may be observed for a prolonged period after its administration. Therefore, caution should be exercised when mifepristone is administered with drugs that are CYP 3A4 substrates and have narrow therapeutic range, including some agents used during general anesthesia.
  • No long-term studies to evaluate the carcinogenic potential of mifepristone have been performed. Results from studies conducted in vitro and in animals have revealed no genotoxic potential for mifepristone. Among the tests carried out were: Ames test with and without metabolic activation; gene conversion test in Saccharomyces cerevisiae D4 cells; forward mutation in Schizosaccharomyces pompe P1 cells; induction of unscheduled DNA synthesis in cultured HeLa cells; induction of chromosome aberrations in CHO cells; in vitro test for gene mutation in V79 Chinese hamster lung cells; and micronucleus test in mice.
    The pharmacological activity of mifepristone disrupts the estrus cycle of animals, precluding studies designed to assess effects on fertility during drug administration. Three studies have been performed in rats to determine whether there were residual effects on reproductive function after termination of the drug exposure.
    In rats, administration of the lowest oral dose of 0.3 mg/kg/day caused severe disruption of the estrus cycles for the three weeks of the treatment period. Following resumption of the estrus cycle, animals were mated and no effect on reproductive performance was observed. In a neonatal exposure study in rats, the administration of a subcutaneous dose of mifepristone up to 100 mg/kg on the first day after birth had no adverse effect on future reproductive function in males or females. The onset of puberty was observed to be slightly premature in female rats neonatally exposed to mifepristone. In a separate study in rats, oviduct and ovary malformations in female rats, delayed male puberty, deficient male sexual behavior, reduced testicular size, and lowered ejaculation frequency were noted after exposure to mifepristone (1 mg every other day) as neonates.
  • Over 620,000 women in Europe have taken mifepristone in combination with a prostaglandin to terminate pregnancy. Among these 620,000 women, about 415,000 have received mifepristone together with misoprostol. As of May 2000 a total of 82 cases have been reported in which women with on-going pregnancies after using mifepristone alone or mifepristone followed by misoprostol declined to have a surgical procedure at that time. These cases are summarized in Table 2.
  • Several reports in the literature indicate that prostaglandins, including misoprostol, may have teratogenic effects in human beings. Skull defects, cranial nerve palsies, delayed growth and psychomotor development, facial malformation and limb defects have all been reported after exposure during the first trimester. Teratology studies in mice, rats and rabbits at doses of 0.25 to 4.0 mg/kg (less than 1/100 to approximately 1/3 the human exposure level based on body surface area) were carried out. Because of the antiprogestational activity of mifepristone, fetal losses were much higher than in control animals. Skull deformities were detected in rabbit studies at approximately 1/6 the human exposure, although no teratogenic effects of mifepristone have been observed to date in rats or mice. These deformities were most likely due to the mechanical effects of uterine contractions resulting from decreased progesterone levels.
  • The indication for use of Mifeprex in conjunction with misoprostol is for the termination of pregnancy through 49 days' duration of pregnancy (as dated from the first day of the last menstrual period). These drugs together disrupt pregnancy by causing decidual necrosis, myometrial contractions and cervical softening, leading to the expulsion of the products of conception.
  • It is not known whether mifepristone is excreted in human milk. Many hormones with a similar chemical structure, however, are excreted in breast milk. Since the effects of mifepristone on infants are unknown, breast-feeding women should consult with their health care provider to decide if they should discard their breast milk for a few days following administration of the medications.
  • Safety and effectiveness in pediatric patients have not been established.
  • The treatment procedure is designed to induce the vaginal bleeding and uterine cramping necessary to produce an abortion. Nearly all of the women who receive Mifeprex and misoprostol will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Those adverse events that occurred with a frequency greater than 1% in the U.S. and French trials are shown in Table 3.
    Bleeding and cramping are expected consequences of the action of Mifeprex as used in the treatment procedure. Following administration of mifepristone and misoprostol in the French clinical studies, 80 to 90% of women reported bleeding more heavily than they do during a heavy menstrual period (see WARNINGS, Bleeding for additional information). Women also typically experience abdominal pain, including uterine cramping. Other commonly reported side effects were nausea, vomiting and diarrhea. Pelvic pain, fainting, headache, dizziness, and asthenia occurred rarely. Some adverse reactions reported during the four hours following administration of misoprostol were judged by women as being more severe than others: the percentage of women who considered any particular adverse event as severe ranged from 2 to 35% in the U.S. and French trials. After the third day of the treatment procedure, the number of reports of adverse reactions declined progressively in the French trials, so that by day 14, reports were rare except for reports of bleeding and spotting.
  • No serious adverse reactions were reported in tolerance studies in healthy non-pregnant female and healthy male subjects where mifepristone was administered in single doses greater than threefold that recommended for termination of pregnancy. If a patient ingests a massive overdose, she should be observed closely for signs of adrenal failure.
    The oral acute lethal dose of mifepristone in the mouse, rat and dog is greater than 1000 mg/kg (about 100 times the human dose recommended for termination of pregnancy).
  • Treatment with Mifeprex and misoprostol for the termination of pregnancy requires three office visits by the patient. Mifeprex should be prescribed only by physicians who have read and understood the prescribing information. Mifeprex may be administered only in a clinic, medical office, or hospital, by or under the supervision of a physician, able to assess the gestational age of an embryo and to diagnose ectopic pregnancies. Physicians must also be able to provide surgical intervention in cases of incomplete abortion or severe bleeding, or have made plans to provide such care through others, and be able to assure patient access to medical facilities equipped to provide blood transfusions and resuscitation, if necessary.
    Day One: Mifeprex Administration
    Patients must read the Medication Guide and read and sign the PATIENT AGREEMENT before Mifeprex is administered.
    Three 200 mg tablets (600 mg) of Mifeprex are taken in a single oral dose.
    Day Three: Misoprostol Administration
    The patient returns to the healthcare provider two days after ingesting Mifeprex. Unless abortion has occurred and has been confirmed by clinical examination or ultrasonographic scan, the patient takes two 200 µg tablets (400 µg) of misoprostol orally.
    During the period immediately following the administration of misoprostol, the patient may need medication for cramps or gastrointestinal symptoms (see ADVERSE REACTIONS). The patient should be given instructions on what to do if significant discomfort, excessive bleeding or other adverse reactions occur and should be given a phone number to call if she has questions following the administration of the misoprostol. In addition, the name and phone number of the physician who will be handling emergencies should be provided to the patient.
    Day 14: Post-Treatment Examination
    Patients will return for a follow-up visit approximately 14 days after the administration of Mifeprex. This visit is very important to confirm by clinical examination or ultrasonographic scan that a complete termination of pregnancy has occurred.
    According to data from the U.S. and French studies, women should expect to experience bleeding or spotting for an average of nine to 16 days. Up to 8% of women may experience some type of bleeding for more than 30 days. Persistence of heavy or moderate vaginal bleeding at this visit, however, could indicate an incomplete abortion.
    Patients who have an ongoing pregnancy at this visit have a risk of fetal malformation resulting from the treatment. Surgical termination is recommended to manage medical abortion treatment failures (see PRECAUTIONS, Pregnancy).
    Adverse events, such as hospitalization, blood transfusion, ongoing pregnancy, or other major complications following the use of Mifeprex and misoprostol must be reported to Danco Laboratories.

"Mifepristone U.S. Post-Marketing Adverse Events Summary through 12/31/2018" (December 31, 2018)[edit]

"Mifepristone U.S. Post-Marketing Adverse Events Summary through 12/31/2018". Food and Drug Administration. December 31, 2018.

  • The following information is from United States (U.S.) post-marketing reports received by FDA of adverse events that occurred among patients who had taken mifepristone for medical termination of pregnancy. Because FDA has eliminated duplicate reports, and in some cases, reclassified the adverse event terms for individual cases after reviewing the narrative details, the numbers provided here may differ from the numbers of the reports that may be obtained through Freedom of Information Act requests. These events cannot with certainty be causally attributed to mifepristone because of information gaps about patient health status, clinical management of the patient, concurrent drug use, and other possible medical or surgical treatments and conditions. The estimated number of women who have used mifepristone in the U.S. for the medical termination of pregnancy through the end of December 2018 is approximately 3.7 million women, an increase of approximately 179,000 since June 2018.
    • p.1
  • The fatal cases are included regardless of causal attribution to mifepristone. Deaths were associated with sepsis in eight of the 24 reported fatalities 7 cases tested positive for Clostridium sordellii, and one case tested positive for Clostridium perfringens). Seven of the eight fatal sepsis cases reported vaginal misoprostol use; one case reported buccal misoprostol use. Fifteen of the sixteen remaining U.S. deaths involved two cases of homicide, two cases of combined drug intoxication/overdose (this includes a case previously categorized as “drug overdose of undetermined intent and cardiac arrest” which was changed based on autopsy information received), two cases of ruptured ectopic pregnancy, and one case each of the following: substance abuse/drug overdose; methadone overdose; drug intoxication; suspected homicide; suicide; delayed onset toxic shock-like syndrome; hemorrhage; unintentional overdose resulting in liver failure; and a case of natural death due to severe pulmonary emphysema. In the sixteenth case, the cause of death could not be established despite performance of an autopsy; tissue samples were negative for C. sordellii. There were 11 additional reported deaths in women in foreign countries who used mifepristone for medical termination of pregnancy. These fatal cases were associated with the following: sepsis (Clostridium sordellii identified in tissue samples) in a foreign clinical trial; sepsis (Group A Streptococcus pyogenes); a ruptured gastric ulcer; severe hemorrhage; severe hemorrhage and possible sepsis; “multivisceral failure;” thrombotic thrombocytopenic purpura leading to intracranial hemorrhage; toxic shock syndrome (Clostridium sordellii was identified through uterine biopsy cultures); asthma attack with cardiac arrest; respiratory decompensation with secondary pulmonary infection 30 days after mifepristone in a patient on the lung transplant list with diabetes, a jejunostomy feeding tube, and severe cystic fibrosis; and a case of Clostridium septicum sepsis (from a published literature report).
    • p.1
  • As stated in the approved Mifeprex (mifepristone) labeling, bleeding or spotting can be expected for an average of 9-16 days, and may last for up to 30 days. Excessive vaginal bleeding usually requires treatment by uterotonics, vasoconstrictor drugs, curettage, administration of saline infusions, and/or blood transfusions.
    • p.2

"Questions and Answers on Mifeprex". FDA. December 16, 2021.[edit]

  • 1. What is mifepristone and how does it work?
    Mifepristone is a drug that blocks a hormone called progesterone that is needed for a pregnancy to continue. Mifepristone, when used together with another medicine called misoprostol, is used to end a pregnancy through ten weeks gestation (70 days or less since the first day of the last menstrual period). The approved mifepristone dosing regimen is:
    On day one: 200 mg of mifepristone taken by mouth
    24 to 48 hours after taking mifepristone: 800 mcg of misoprostol taken buccally (in the cheek pouch), at a location appropriate for the patient
    About seven to fourteen days after taking mifepristone: follow-up with the health care provider
  • 2. When did the FDA approve mifepristone for medical termination of pregnancy?
    The FDA first approved Mifeprex (mifepristone) in September 2000 for medical termination of pregnancy through seven weeks gestation and this was extended to ten weeks gestation in 2016. FDA approved a generic version of Mifeprex, Mifepristone Tablets, 200 mg, in April 2019. The agency’s approval of this generic reflects the FDA’s determination that Mifepristone Tablets, 200 mg, is therapeutically equivalent to Mifeprex and can be safely substituted for Mifeprex. Like Mifeprex, the approved generic product is indicated for the medical termination of intrauterine pregnancy through 70 days gestation. The labeling for the approved generic version of Mifeprex is consistent with the labeling for Mifeprex.
  • 3. Who should not take mifepristone, in a regimen with misoprostol, for medical termination of pregnancy?
    An individual should not take mifepristone, in a regimen with misoprostol, for medical termination of pregnancy if it has been more than 70 days since the first day of their last menstrual period, or if they:
    have an ectopic pregnancy (a pregnancy outside of the uterus)
    have problems with the adrenal glands (the glands near the kidneys)
    are currently being treated with long-term corticosteroid therapy (medications)
    have had an allergic reaction to mifepristone, misoprostol or similar drugs
    have bleeding problems or are taking anticoagulant (blood thinning) drug products
    have inherited porphyria (a rare disorder that can affect the liver and other organs)
    have an intrauterine device (IUD) in place (it must be removed before taking mifepristone)
  • 4. Is it safe to use mifepristone?
    Yes. Mifepristone is safe when used as indicated and directed and consistent with the Mifepristone Risk Evaluation and Mitigation Strategy (REMS) Program. The FDA approved Mifeprex more than 20 years ago based on a thorough and comprehensive review of the scientific evidence presented and determined that it was safe and effective for its indicated use. As of 2016, it can be used for medical termination of pregnancy up to 70 days of gestation. The FDA’s periodic reviews of the postmarketing data for Mifeprex and its approved generic have not identified any new safety concerns with the use of mifepristone for medical termination of pregnancy through 70 days gestation. As with all drugs, the FDA continues to closely monitor the postmarketing safety data on mifepristone for the medical termination of pregnancy.
  • 6. What serious adverse events have been reported after the use of mifepristone for medical termination of pregnancy through ten weeks gestation?
    As with all approved drugs, when the FDA receives new information regarding adverse events, the agency reviews the new information and, as appropriate, takes necessary action. This could include, for example, providing updates to health care providers and their patients so that they have information on how to use a drug safely.
    It is common for the FDA to receive reports of serious adverse events for prescription drugs after they are approved. Many drugs are associated with serious adverse events that are known at the time of approval and considered when the FDA makes its approval decision. The FDA continuously reviews reports of adverse events to, among other things, determine whether they are known risks or whether they are signals of emerging safety concerns.
    The FDA has received reports of serious adverse events in patients who took mifepristone. As of June 30, 2022, there were 28 reports of deaths in patients associated with mifepristone since the product was approved in September 2000, including two cases of ectopic pregnancy (a pregnancy located outside the womb, such as in the fallopian tubes) resulting in death; and several fatal cases of severe systemic infection (also called sepsis). The adverse events cannot with certainty be causally attributed to mifepristone because of concurrent use of other drugs, other medical or surgical treatments, co-existing medical conditions, and information gaps about patient health status and clinical management of the patient. A summary report of adverse events that reflects data through June 30, 2022, is here. The FDA has reviewed this information and did not identify any new safety signals. The FDA intends to update this summary report as appropriate.
  • 10. Why is there a REMS for this product?
    The FDA’s determination as to whether a REMS is necessary for a particular drug is a drug-specific evaluation. The agency considers whether (based on premarketing or postmarketing risk assessments) there is a particular risk or risks associated with the use of the drug that, on balance, outweigh its benefits and whether additional risk mitigation measures beyond the FDA-approved labeling are necessary to ensure that the drug’s benefits outweigh its risks.
    The goal of the Mifepristone REMS Program is to mitigate the risk of serious complications associated with mifepristone when used for medical termination of pregnancy through ten weeks gestation by, among other things, requiring that prescribers have the necessary qualifications to assess whether patients are appropriate candidates for the drug and to provide necessary intervention in case of complications (or have made plans to provide such care through others), ensuring that mifepristone is only dispensed by certified pharmacies or by or under the supervision of certified prescribers, and requiring that patients be informed of the risks of the treatment regimen.
  • 11. What are the restrictions on prescribing and dispensing mifepristone for medical termination of pregnancy through ten weeks gestation?
    When the agency reviewed and approved the original new drug application for Mifeprex (mifepristone) in 2000, it concluded that certain restrictions were necessary to ensure the safe use of the drug. These restrictions were approved as a risk evaluation and mitigation strategy (REMS) in 2011 and have been modified since then.
    These REMS requirements also apply to the approved generic version of Mifeprex. Mifeprex and the approved generic version of Mifeprex are subject to a single, shared system REMS, known as the Mifepristone REMS Program. This program sets the requirements that must be followed to ensure safe use of both Mifeprex and the approved generic version of Mifeprex.
    Under the Mifepristone REMS Program:
    Mifepristone must be prescribed by a health care provider that meets certain qualifications and is certified under the Mifepristone REMS Program.
    In order to become certified to prescribe mifepristone, health care providers must complete a Prescriber Agreement Form.
    The Patient Agreement Form must be reviewed with and signed by the patient and the health care provider, and the risks of the mifepristone treatment regimen must be fully explained to the patient before prescribing mifepristone.
    The patient must be provided with a copy of the Patient Agreement Form and mifepristone Medication Guide (FDA-approved information for patients).
    Mifepristone may only be dispensed by or under the supervision of a certified prescriber, or by a certified pharmacy on a prescription issued by a certified prescriber.
    To become certified to dispense mifepristone, pharmacies must complete a Pharmacy Agreement Form.
    Certified pharmacies must be able to ship mifepristone using a shipping service that provides tracking information.
    Certified pharmacies must ensure mifepristone is dispensed to the patient in a timely manner.
    Each REMS is required to have a plan for periodic assessments by the sponsor, which are reviewed by the agency to determine whether the REMS is meeting its goals or whether certain goals or elements of the REMS must be modified. FDA may require applicants to modify a REMS if the agency determines that an element is no longer necessary to ensure that the benefits of the drug outweigh the risks or to minimize the burden on the health care delivery system.
  • 12. How does the Mifepristone REMS Program ensure safe use of the drug?
    The Mifepristone REMS Program requires that in order for patients to receive mifepristone, it must be prescribed by a certified prescriber who meets certain qualifications. Under the Mifepristone REMS Program, mifepristone must be dispensed by or under the supervision of a certified prescriber or by certified pharmacies on prescriptions issued by certified prescribers. The Mifepristone REMS Program is a closed system, meaning prescribers, pharmacies, and distributors are certified or authorized and verified under the REMS prior to distribution or dispensing of the drug. The Mifepristone REMS Program ensures that mifepristone is only distributed to health care providers and pharmacies that have agreed to the REMS requirements.
  • 13. How does the Mifepristone REMS Program approved in January 2023 differ from the previous REMS requirements?
    Prior to the modifications to the Mifepristone REMS Program in January 2023, there were periods when the in-person dispensing requirement was not being enforced. First, from July 13, 2020, until January 12, 2021, the FDA was enjoined from enforcing the in-person dispensing requirement by an injunction issued in the ACOG v. FDA litigation. On April 12, 2021, the agency stated its intent to exercise enforcement discretion with respect to the in-person dispensing requirement during the COVID-19 public health emergency.
    In 2021, after conducting a comprehensive review of the Mifepristone REMS Program, the FDA determined, based on the available data and information, that the REMS must be modified to reduce burden on the health care delivery system and to ensure the benefits of the product outweigh the risks. On December 16, 2021, the FDA announced that the modifications to the Mifepristone REMS Program would consist of:
    Removing the requirement that mifepristone be dispensed only in certain health care settings, specifically clinics, medical offices, and hospitals (referred to as the “in-person dispensing requirement”)
    Adding a requirement that pharmacies that dispense the drug be certified
    Consistent with the typical process for REMS modifications, the FDA sent REMS Modification Notification letters to the applicants for Mifeprex and the approved generic version of Mifeprex, Mifepristone Tablets, 200 mg. Following receipt of these letters, the applicants prepared a proposed REMS modification and submitted it to their respective applications. Those submissions were reviewed and approved on January 3, 2023. The REMS document and materials are available on the FDA website at: http://www.accessdata.fda.gov/scripts/cder/rems/index.cfm.
  • 15. What qualifications must health care providers have to become certified to prescribe mifepristone for medical termination of pregnancy through ten weeks gestation?
    Health care providers who would like to become certified to prescribe mifepristone must have the ability to date pregnancies accurately and the ability to diagnose ectopic pregnancies. Health care providers must also be able to provide any necessary surgical intervention or have made arrangements for others to provide for such care. Health care providers must be able to ensure that patients have access to medical facilities for emergency care, and must agree to other responsibilities, including reviewing and signing the Patient Agreement Form with the patient and providing each patient with a copy of the signed Patient Agreement Form.
    Some states allow health care providers other than physicians to prescribe medications. Health care providers should check their individual state laws.
  • 16. Are patients required to see a health care provider in person before obtaining mifepristone for medical termination of pregnancy through ten weeks gestation?
    No. The Mifepristone REMS Program does not require patients to see a health care provider in person before obtaining mifepristone for medical termination of pregnancy through ten weeks gestation. Mifeprex and the approved generic Mifepristone Tablets, 200 mg, are indicated, in a regimen with misoprostol, to terminate a pregnancy up to 70 days gestation and contraindicated for certain patients, including those with an ectopic pregnancy. The FDA has determined that it is not necessary for the REMS to mandate how providers clinically assess patients for duration of pregnancy and for ectopic pregnancy. The prescription labeling for Mifeprex and the approved generic provide guidance to prescribers regarding how they can confirm the gestational age of the pregnancy and confirm that the pregnancy is located in the uterus. Aspects of a patient’s medical history that may constitute contraindications to medical abortion may be elicited without direct physical contact with the certified prescriber and can be done in different types of health care settings, thus certified prescribers are not necessarily required to be physically present with the patient when they prescribe mifepristone. As explained above (Question 15), health care providers certified under the Mifepristone REMS Program must also be able to provide any necessary surgical intervention or have made arrangements for others to provide for such care and must be able to ensure that patients have access to medical facilities for emergency care.
  • 17. What information did the FDA consider when it reviewed the Mifepristone REMS Program in 2021?
    To determine whether a modification to the Mifepristone REMS Program was warranted, the FDA conducted a comprehensive review of the published literature, other relevant safety and adverse event data, and information provided by advocacy groups, individuals and the applicants related to the modifications that were under consideration. Our review also included an examination of literature references provided by plaintiffs in the Chelius v. Becerra litigation.
  • 18. Prior to the FDA’s action in January 2023, how was mifepristone dispensed to patients?
    Prior to the FDA’s action on the REMS modification applications submitted by the applicants for Mifeprex and the approved generic version of Mifeprex, Mifepristone Tablets, 200 mg, the Mifepristone REMS Program required certified prescribers to dispense mifepristone directly to the patient in a clinic, medical office, or hospital. The requirement to dispense directly to the patient in one of these settings was referred to as the “in-person dispensing requirement.”
    There were periods when the in-person dispensing requirement was not being enforced. First, from July 13, 2020, until January 12, 2021, the FDA was enjoined from enforcing the in-person dispensing requirement by an injunction issued in a lawsuit, ACOG v. FDA filed in the U.S. District Court for the District of Maryland. On April 12, 2021, the agency stated its intent to exercise enforcement discretion with respect to the in-person dispensing requirement during the COVID-19 public health emergency.
    During the periods when the in-person dispensing requirement was not being enforced, the applicants for Mifeprex and the approved generic version of Mifeprex, Mifepristone Tablets, 200 mg, used mail order pharmacies to receive and hold mifepristone on behalf of the certified prescribers who purchased the product. Pursuant to a prescription for Mifeprex or its approved generic, the mail order pharmacy would ship the product to a named patient.
  • 21. What steps are required for pharmacy certification?
    The pharmacy certification requirement ensures that pharmacies are aware of and agree to follow applicable REMS requirements and ensures that mifepristone is only dispensed pursuant to prescriptions that are written by certified prescribers.
    To become certified to dispense mifepristone, pharmacies must: (1) be able to receive Prescriber Agreement Forms by email and fax; (2) be able to ship mifepristone using a shipping service that provides tracking information; (3) designate an authorized representative to carry out the certification process on behalf of the pharmacy; and (4) ensure the authorized representative oversees implementation and compliance with the Mifepristone REMS Program, which includes, among other requirements, the completion of a Pharmacy Agreement Form.
  • 23. Is mifepristone available for over-the-counter use?
    No. Mifepristone for medical termination of a pregnancy through ten weeks gestation is currently only available by prescription. An applicant seeking to switch mifepristone for medical termination of pregnancy through ten weeks gestation from prescription to nonprescription (also referred to as over-the-counter) status would need to submit this information to the FDA for evaluation. In order for a drug product to be approved for nonprescription use (including switching a prescription drug product to nonprescription marketing), the applicant must provide sufficient information demonstrating that the drug can be used safely and effectively by consumers without the supervision of a licensed health care practitioner.
  • 28. Has FDA ever taken action regarding the sale of mifepristone online?
    The FDA has sent warning letters to websites selling unapproved and misbranded mifepristone and misoprostol over the internet, including AidAccess and Rablon.
    There have also been several criminal cases related to the online sale of mifepristone for medical termination of pregnancy. We are aware of three cases about which the Agency can speak publicly. The first is United States v. O’Neil, in the U.S. District Court for the District of Maryland. Information about two more individual prosecutions are available here: March 28, 2017: Former Atlantic County, New Jersey, Man Charged with Smuggling and Dispensing Misbranded Drugs | FDA and here: New York Woman Sentenced for Selling Abortion-Inducing Pills Illegally Smuggled Into US | USAO-WDWI | Department of Justice. The FDA also issued a Final Debarment Order for Ursula Wing, debarring her for a period of five years from importing or offering for import any drug into the United States. This debarment was based on her felony conviction related to her importation and distribution of unapproved and misbranded mifepristone and misoprostol over the internet.
  • 29. Was the Mifepristone REMS Program modified in 2023 in response to the Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization?
    No. The agency’s comprehensive review of the Mifepristone REMS Program, which led to the 2021 decision that a modification is required, is related to the litigation in Chelius v. Becerra. In accordance with the typical process for REMS modifications, the FDA sent REMS Modification Notification letters to the applicants for Mifeprex and the approved generic version of Mifeprex, Mifepristone Tablets, 200 mg. Following receipt of these letters, the applicants prepared a proposed REMS modification and submitted it to their respective applications. The FDA has reviewed the REMS modification supplements submitted by the applicants in the Mifepristone REMS Program and approved a REMS modification that removes the in-person dispensing requirement and adds pharmacy certification.
  • 30. Was the Mifepristone REMS Program modified in 2023 in response to state abortion laws?
    No. The agency’s comprehensive review of the Mifepristone REMS Program, which led to the 2021 decision that a modification is required, is related to the litigation in Chelius v. Becerra. In accordance with the typical process for REMS modifications, the FDA sent REMS Modification Notification letters to the applicants for Mifeprex and the approved generic version of Mifeprex, Mifepristone Tablets, 200 mg. Following receipt of these letters, the applicants prepared a proposed REMS modification and submitted it to their respective applications. The FDA reviewed the REMS modification supplements submitted by the applicants in the Mifepristone REMS Program and, on January 3, 2023, the FDA approved a REMS modification that removes the in-person dispensing requirement and adds pharmacy certification.
  • 31. What happens if a state refuses to allow mifepristone to be prescribed for medical termination of pregnancy?
    We are coordinating with the Department of Justice and others across the government on these legal issues. Any questions regarding preemption of state law should be directed to the Department of Justice.
  • 33. What action did the FDA take on the Mifepristone REMS Program in January 2023?
    In response to the REMS Modification Notification letters sent on December 16, 2021, to the applicants for Mifeprex and the approved generic Mifepristone Tablets, 200 mg, the applicants submitted supplemental applications to modify the Mifepristone REMS Program to remove the in-person dispensing requirement and add pharmacy certification. The FDA reviewed the applicants’ supplemental applications, as amended, and has approved a modification to the Mifepristone REMS Program. Under the Mifepristone REMS Program, as modified, Mifeprex and its approved generic can be dispensed by certified pharmacies or by or under the supervision of a certified prescriber.
    The Mifepristone REMS Program continues to require the Patient Agreement Form and certification of health care providers who prescribe mifepristone.
  • 34. What was the process for approving the current REMS modification?
    In 2021, in order to determine whether a modification to the Mifepristone REMS Program was warranted, the FDA conducted a comprehensive review of the published literature, other relevant safety and adverse event data, and information provided by advocacy groups, individuals, and the applicants related to the modifications that were under consideration. After conducting this review, the FDA determined that the REMS must be modified to remove the in-person dispensing requirement and add pharmacy certification. In accordance with the typical process for REMS modifications, the FDA sent REMS Modification Notification letters to the applicants for Mifeprex and the approved generic version of Mifeprex, Mifepristone Tablets, 200 mg. Following receipt of these letters, the applicants prepared a proposed REMS modification and submitted it to their respective applications. The approved REMS document and materials are available here.
  • 35. Why did the FDA conduct a review of the Mifepristone REMS Program in 2021?
    REMS require applicants to prepare and submit periodic assessments, which are reviewed by the agency to determine whether the REMS is meeting its goals or whether certain goals or elements of the REMS must be modified.
    The agency’s comprehensive review of the Mifepristone REMS Program, which led to the agency’s December 16, 2021, decision that a modification is required, was related to the litigation in Chelius v. Becerra. On May 7, 2021, the FDA and the plaintiffs in Chelius filed a joint motion to stay that litigation, which involves the single, shared system REMS for Mifeprex and its approved generic, Mifepristone Tablets, 200 mg. The court granted the stay on May 7, 2021.
    In accordance with the stay, and in conjunction with the regular periodic assessments of the REMS, the agency reviewed the elements of the Mifepristone REMS Program in 2021.
  • 36. Was there a change in the frequency of reported adverse events during the pandemic when the in-person dispensing requirement was not enforced?
    No. There were periods when the in-person dispensing requirement was not being enforced. First, from July 13, 2020, until January 12, 2021, the FDA was enjoined from enforcing the in-person dispensing requirement by an injunction issued in the ACOG v. FDA litigation. On April 12, 2021, the agency stated its intent to exercise enforcement discretion with respect to the in-person dispensing requirement during the COVID-19 public health emergency. The FDA analyzed postmarketing data to determine if there was a difference in adverse events between periods when in-person dispensing was and was not enforced. Based on this review, the agency concluded that there did not appear to be a difference in adverse events between periods when in-person dispensing was and was not enforced.

“Information about Mifepristone for Medical Termination of Pregnancy Through Ten Weeks Gestation” (February 7, 2022)[edit]

“Information about Mifepristone for Medical Termination of Pregnancy Through Ten Weeks Gestation”. FDA. (February 7, 2022).

  • Mifeprex (mifepristone) and its generic Mifepristone Tablets, 200 mg (collectively mifepristone) are approved, in a regimen with misoprostol, to end an intrauterine pregnancy through ten weeks gestation (70 days or less since the first day of a patient’s last menstrual period). The FDA first approved Mifeprex in 2000 and approved a generic version of Mifeprex, Mifepristone Tablets, 200 mg in 2019.
  • Mifeprex and its generic Mifepristone Tablets, 200 mg, are available under a single, shared system risk evaluation and mitigation strategy (REMS), known as the Mifepristone REMS Program, which sets forth the requirements that must be followed for mifepristone for medical termination of pregnancy through ten weeks gestation.
    Under the Mifepristone REMS Program, mifepristone must be dispensed by or under the supervision of a certified prescriber or by certified pharmacies for prescriptions issued by certified prescribers. Under the Mifepristone REMS Program, mifepristone may be dispensed in-person or by mail.
  • Mifeprex was approved in 2000 with restrictions to assure its safe use. Mifeprex was deemed to have in effect an approved REMS under the Food and Drug Administration Amendments Act of 2007. In 2019, at the same time the FDA approved the generic version of Mifeprex, the agency approved a single, shared system REMS for mifepristone products for the medical termination of intrauterine pregnancy through 70 days gestation (known as the Mifepristone REMS Program).
    In 2021, after conducting a review of the Mifepristone REMS Program, the FDA determined that the available data and information support modification of the REMS to reduce burden on the health care delivery system and to ensure the benefits of the product outweigh the risks. The Mifepristone REMS Program was modified on January 3, 2023. Under the Mifepristone REMS Program:
    *Mifepristone must be prescribed by a health care provider that meets certain qualifications and is certified under the Mifepristone REMS Program.
    *In order to become certified to prescribe mifepristone, health care providers must complete a Prescriber Agreement Form.
    *The Patient Agreement Form must be reviewed with and signed by the patient and the health care provider, and the risks of the mifepristone treatment regimen must be fully explained to the patient before mifepristone is prescribed.
    * The patient must be provided with a copy of the Patient Agreement Form and mifepristone Medication Guide (FDA-approved information for patients).
    *Mifepristone may only be dispensed by or under the supervision of a certified prescriber, or by a certified pharmacy on a prescription issued by a certified prescriber.
    * To become certified to dispense mifepristone, pharmacies must complete a Pharmacy Agreement Form.
    *Certified pharmacies must be able to ship mifepristone using a shipping service that provides tracking information.
    *Certified pharmacies must ensure mifepristone is dispensed to the patient in a timely manner.
  • Mifepristone prescribed under the Mifepristone REMS Program will be dispensed to you by your health care provider (or someone under the supervision of your health care provider), or by a pharmacy to which your health care provider has submitted your prescription. You can ask your health care provider whether they are certified in the Mifepristone REMS Program (or working under the supervision of someone who is). The FDA does not recommend purchasing mifepristone outside of the Mifepristone REMS Program – e.g. buying it online or personally transporting it from a foreign country. If a person does so, they would be bypassing important safeguards specifically designed to protect their health. Prescription medicines that are approved for use in the United States have been reviewed for safety, effectiveness, and quality by the FDA, and are subject to FDA-regulated manufacturing controls, including inspection of manufacturing facilities. Generally, prescription medicines purchased from foreign sources are not the FDA-approved versions. The FDA does not have regulatory oversight of prescription medicines from outside the legitimate U.S. drug supply chain; therefore, the FDA cannot ensure the safety, effectiveness, or quality of those medications.

"Rates of serious infection after changes in regimens for medical abortion" (July 2009)[edit]

Mary Fjerstad, James Trussell, Irving Sivin, E. Steve Lichtenberg, and Vanessa Cullins. (July 2009). "Rates of serious infection after changes in regimens for medical abortion". The New England Journal of Medicine. 361 (2): 145–151. doi:10.1056/NEJMoa0809146. PMC 3568698. PMID 19587339.

  • BACKGROUND—From 2001 through March 2006, Planned Parenthood health centers throughout the United States provided medical abortion (abortion by means of medication) principally by a regimen of oral mifepristone followed 24 to 48 hours later by vaginal misoprostol. In response to concern about serious infections, in early 2006 Planned Parenthood changed the route of misoprostol administration from vaginal to buccal and required either routine provision of antibiotics or universal screening and treatment for chlamydia; in July 2007, Planned Parenthood began requiring routine treatment with antibiotics for all medical abortions.
    • p.145
  • METHODS—We performed a retrospective analysis assessing the rates of serious infection after medical abortion during a time when misoprostol was administered vaginally (through March 2006), as compared with rates after a change to buccal administration of misoprostol and after initiation of additional infection-reduction measures.
    RESULTS—Rates of serious infection dropped significantly after the joint change to buccal misoprostol from vaginal misoprostol and to either testing for sexually transmitted infection or routine provision of antibiotics as part of the medical abortion regimen. The rate declined 73%, from 0.93 per 1000 abortions to 0.25 per 1000 (absolute reduction, 0.67 per 1000; 95% confidence interval [CI], 0.44 to 0.94; P<0.001). The subsequent change to routine provision of antibiotics led to a further significant reduction in the rate of serious infection — a 76% decline, from 0.25 per 1000 abortions to 0.06 per 1000 (absolute reduction, 0.19 per 1000; 95% CI, 0.02 to 0.34; P = 0.03).
    CONCLUSIONS—The rate of serious infection after medical abortion declined by 93% after a change from vaginal to buccal administration of misoprostol combined with routine administration of antibiotics.
    • p.145
  • The Planned Parenthood Federation of America (PPFA) is a federation of 97 independent local affiliates operating 880 health centers throughout the United States; roughly 300 of those health centers provide medical abortion. In 2008, a total of 96,738 women received medical abortions (abortion by means of medication), representing 32% of first-trimester abortions in Planned Parenthood health centers. Extensive data gathering during the use of

mifepristone and vaginal misoprostol indicated that efficacy (successful medical abortion without the need for surgical intervention) was 98.5%; a subsequent audit of abortions performed with the use of buccal rather than vaginal misoprostol showed virtually identical efficacy.

    • pp.145-146
  • Antibiotics have been routinely administered at the time of surgical abortions since the publication of a meta-analysis showing that their use resulted in a 42% reduction in postabortion infection rates. When medical abortion was first introduced, there was little concern about the risk of infection, because there is no use of instruments in the cervix or uterus unless the procedure fails. However, it is clear that serious infections do occur.
    Data are lacking to compare the rates of serious infection with antibiotic treatment and the rates without such treatment among women undergoing medical abortion. The Food and Drug Administration (FDA) states that it “does not have sufficient information to recommend the use of prophylactic antibiotics for women having a medical abortion.” The current American College of Obstetricians and Gynecologists Practice Bulletin on medical abortion states that no data exist to support the routine use of preventive antibiotics for medical abortion.
    • p.146
  • By late 2005, four women in the United States and one in Canada had died from a rare bacterial infection, with Clostridium sordellii, after medical abortion with mifepristone and misoprostol. In contrast, no such deaths had been reported in Europe, where medical abortion had been available longer and far more women had used it. One hypothesis for the difference was that vaginal administration of misoprostol was very common in the United States but not so common in Europe. Another hypothesis was that periprocedural antibiotics were routinely provided in the United Kingdom but not in the United States.
    • p.146
  • Prompted by the deaths that occurred after medical abortion and internal data that show a higher-than-expected rate of serious infection, PPFA changed its medical abortion protocol at the end of March 2006. Vaginal administration of misoprostol was discontinued and replaced by buccal (or, much less commonly, oral) administration, and all health centers were required to use one of the following two regimens, with the intention of reducing the risk of infection: the routine administration of antibiotics or universal testing for chlamydia (and for gonorrhea when considered appropriate), with treatment dependent on test results. After reviewing the rates of serious infection among health centers that were using these two infection-reduction regimens, PPFA in July 2007 required all health centers to provide routine preventive antibiotic treatment.
    • p.146
  • We obtained information about all patients who had a medical abortion from all 78 Planned Parenthood affiliates that provided this service at any time during the entire study period. A quarterly survey has been conducted by an administrator since 2001 to determine the number of patients undergoing medical abortion and the number of health centers providing it. In addition, all Planned Parenthood affiliates send a yearly report to the national office detailing the number of each clinical procedure provided (including medical and surgical abortions), and that report was used to verify the number of medical abortions in the quarterly surveys. Concordance between the two sources is high, with the annual reports containing 1.3% fewer cases than the quarterly reports; we used the caseload reported in the quarterly report, because the administrator of that report had much more frequent contact with the health professionals who reported these data than did the national office, collected data on a quarterly rather than an annual basis, and collected information only about medical abortions.
    • p.146
  • The provisions of FDA approval stipulate that any physician who orders, provides, or supervises the provision of mifepristone must sign an agreement with the sole U.S. distributor of mifepristone (Danco Laboratories) to report all serious adverse events associated with its use. Serious adverse events include all ongoing pregnancies (pregnancies that continue after the use of mifepristone or misoprostol), hemorrhage requiring emergency treatment, serious infections, hospitalizations, potentially life-threatening events, and death. Danco submits all such reports to the FDA. Staff members at Planned Parenthood health centers were trained in accurate and complete reporting of serious adverse events. Adverse- event reports are centrally tracked and monitored. Planned Parenthood health centers are audited on site for internal accreditation by the PPFA. Since 2005, concurrent with the starting date of our analysis, the accreditation process has included auditing to verify that adverse events related to the use of mifepristone for medical abortions are submitted as required.
    • p.147
  • Follow-up visits routinely scheduled 1 to 2 weeks after ingestion of mifepristone provide an additional opportunity to evaluate whether a serious adverse event has occurred. The importance of the follow-up visit is emphasized to patients, and staff members are required to make three attempts to reach patients who have not returned for follow-up by the end of 2 weeks. However, information on the proportion of women who did not return for follow-up was not available through quarterly or yearly reports. The required attempts to contact patients uncovered several reports of emergency procedures at hospitals that meet the criteria for serious adverse events. In addition, surveillance by the Centers for Disease Control and Prevention (CDC) through multiple channels to identify deaths from infection-related causes after medical abortion did not find any cases other than those already known.
    • p.147
  • After March 2006, PPFA changed the route of administration of misoprostol from vaginal to buccal (200 mg of mifepristone followed 24 to 48 hours later by 800 μg of buccal misoprostol) or, much less commonly, to oral administration. In addition, Planned Parenthood health centers that provide medical abortion were required either to screen all patients for chlamydia (and gonorrhea if endemic rates or the patient’s history or symptoms indicated the need) or to routinely provide prophylactic use of doxycycline (100 mg orally twice a day for 7 days, starting the same day as mifepristone administration) to all women. Doxycycline was chosen because it provides treatment against chlamydia, the most commonly reported sexually transmitted infection (STI) in the United States, and most gonorrhea strains; doxycycline also has in vitro efficacy against C. sordellii. Theoretically, it might prevent an ascending infection and sepsis. Patients who had a positive test for an STI were treated with the standard CDC treatment recommendations, consisting of doxycycline for chlamydia (100 mg orally twice daily for 7 days), and ceftriaxone for gonorrhea (125 mg intramuscularly in a single dose).
    • pp.147-148
  • We conducted analyses of events for the years 2005 to mid-2008 during four periods. Period 1 (January 1, 2005, through March 31, 2006) was the baseline 15-month period during which vaginal misoprostol and standard antiseptic measures were used for the abortion of fetuses through 63 days of gestation. Period 2 (April 1, 2006, through June 30, 2007) was the 15-month period during which buccal misoprostol was used through 56 days of gestation (or, much less commonly, oral misoprostol was used through 49 days of gestation); some Planned Parenthood clinics used the infection-reduction measure of universal screening for STI and treatment when screening was positive, whereas others routinely provided antibiotics consisting nearly uniformly of 100 mg of oral doxycycline twice a day for 7 days. Period 3 (July 1, 2007, through December 31, 2007) was the 6-month period during which buccal misoprostol was used through 56 days of gestation and all health centers routinely provided the doxycycline regimen. Period 4 (January 1, 2008, through June 30, 2008) was the 6-month period during which buccal misoprostol was used through 63 days of gestation and all health centers routinely provided the doxycycline regimen.
    • p.148
  • During the course of the study, 243,692 women underwent medical abortion at Planned Parenthood centers. After the exclusion of 15,869 women who did not meet eligibility criteria (<7%), the analysis population included 227,823 women, among whom 92 serious infections were reported.
    During Period 1 in the analysis population, a total of 72,195 women underwent medical abortion; serious infections were reported in 67 women (0.93 per 1000 abortions). One death occurred in early 2006, from C. perfringens; this was the only death during the study periods. Rates of serious infection for each group in this and each subsequent period are shown in Table 1 and Figure 1.
    The 93% relative decrease in the rate of serious infection between Period 1 and Period 4 was an absolute reduction of 0.86 per 1000 (95% confidence interval [CI], 0.64 to 1.12; P<0.001). The rate of serious infection declined significantly between Periods 1 and 2 (absolute reduction of 0.67 per 1000; 95% CI, 0.44 to 0.94; P<0.001) and between Periods 2 and 3 (absolute reduction of 0.19 per 1000; 95% CI, 0.02 to 0.34; P = 0.03). Between Periods 3 and 4, the change in the rate of serious infection was not significant (absolute increase of 0.01 per 1000; 95% CI, 0.0 to 0.15; P>0.99).
    • pp.148-149
  • (Between Periods 1 and 2, there were significant declines in the rates of serious infection in both Group 1 and Group 2, but the relative decline was significantly greater in Group 2 (93% decline) than in Group 1 (61% decline) (relative risk ratio, 0.19; 95% CI, 0.04 to 0.89; P = 0.04). Between Periods 2 and 3, there were further declines in both Group 1 (significant) and Group 2 (nonsignificant), but the relative declines did not differ significantly (75% and 100%, respectively; P = 0.07); the combined relative risk in Period 3 as compared with Period 2 was 0.24 (95% CI, 0.03 to 0.97). In Group 1, the rate of serious infection fell from 1.15 per 1000 in Period 1 to 0.11 per 1000 in Period 3. Of this absolute decline in rate of 1.04 per 1000, 33% occurred between Periods 2 and 3.
    • p.149
  • We observed significant and clinically important reductions in the risk of serious infections among patients who had undergone medical abortion after a change from vaginal to buccal administration of misoprostol and after the adoption of routine preventive treatment with antibiotics. Although the observational design of our study precludes a determination of cause and effect, it is plausible that the changes in practice patterns could explain the

reductions in the rate of serious infection. Because PPFA instituted more than one measure at a time, it is difficult to estimate from our analyses the relative values of different interventions. However, the fact that Planned Parenthood health centers adopted two infection-reduction measures in Period 2 allows further exploration of this issue.
In Group 1 — the group of health centers that used the screen-and-treat strategy in Period 2— one third of the decline in the rate of serious infection from Period 1 to Period 3 occurred between Periods 2 and 3, when the only regimen change was from screen-and-treat to routine antibiotic coverage. Moreover, the relative decline in the reported rate of serious infection from Period 1 to Period 2 was significantly greater in Group 2 than in Group 1 (in the analysis including all cases). These findings indicate that routine provision of antibiotics was associated with a greater reduction in serious infection than was the use of the screen- and-treat method. This finding could be explained by the fact that, with the screen-and-treat strategy, not all those who test positive return for treatment; also, even among those who do return for treatment, treatment is delayed for at least 2 days while they await test results.
Between Period 3 and Period 4, the only change in the regimen was an increase in the maximum gestational age at the time of medical abortion, from 56 to 63 days. Because there was no significant increase in the rate of serious infection from Period 3 to Period 4, it is unlikely that a decline in the maximum gestational age from 63 days in Period 1 to 56 days in Period 2 explains the decline over time in the rates of serious infection observed in both groups.
The rate of serious infection in Period 1 was substantially higher than the rates previously published, even in one study that used Planned Parenthood data. (This finding, along with the deaths from C. sordellii after medical abortion, prompted the changes in Period 2.) It is likely that previously reported rates are underestimates and that apparent increases from previously reported data reflect improved reporting of serious adverse events to PPFA. Specifically, the official Planned Parenthood medical standards and guidelines were changed in 2004 to require that all serious adverse events be reported centrally; also, as stated earlier, since 2005, the accreditation process has included auditing to verify that adverse events related to the use of mifepristone are submitted as required.

    • pp.149-150
  • A potential concern is that serious infections might have been more likely to be underreported during Periods 2 through 4, since the intense scrutiny that occurred during Period 1 (after the reports of deaths from clostridial infections) had waned. However, we consider this unlikely, since national conference calls and meetings that were focused on the risk of infection were ongoing during the time of the study.
    • p.150
  • Although a randomized clinical trial would be the preferred approach to determine whether the use of buccal rather than vaginal administration of misoprostol might reduce the rate of serious infection and whether a strategy of routine antibiotic coverage is superior to a strategy of screening before treating, this study design would not have been feasible. Given the low rates of serious infection, such a design would have required a prohibitively large sample. The large population that receives care at Planned Parenthood centers allowed the discerning of changes over time in the rates of serious infection after medical abortion. In summary, the current report shows that changes in PPFA policies for medical abortion that involve replacing vaginal administration of misoprostol with buccal administration and, later, providing routine antibiotics coupled with a highly monitored, systemwide surveillance network were associated with significant reductions in the rates of serious infections.
    • p.150

"Self-administered versus provider-administered medical abortion" (9 March 2020)[edit]

Gambir, Katherine; Kim, Caron; Necastro, Kelly Ann; Ganatra, Bela; Ngo, Thoai D. (9 March 2020). "Self-administered versus provider-administered medical abortion". The Cochrane Database of Systematic Reviews. 3: CD013181. doi:10.1002/14651858.CD013181.pub2. ISSN 1469-493X. PMC 7062143. PMID 32150279.

  • The advent of medical abortion has improved access to safe abortion procedures. Medical abortion procedures involve either administering mifepristone followed by misoprostol or a misoprostol‐only regimen. The drugs are commonly administered in the presence of clinicians, which is known as provider‐administered medical abortion. In self‐administered medical abortion, drugs are administered by the woman herself without the supervision of a healthcare provider during at least one stage of the drug protocol. Self‐administration of medical abortion has the potential to provide women with control over the abortion process. In settings where there is a shortage of healthcare providers, self‐administration may reduce the burden on the health system. However, it remains unclear whether self‐administration of medical abortion is effective and safe. It is important to understand whether women can safely and effectively terminate their own pregnancies when having access to accurate and adequate information, high‐quality drugs, and facility‐based care in case of complications.
  • This review shows that self‐administering the second stage of early medical abortion procedures is as effective as provider‐administered procedures for the outcome of abortion success. There may be no difference for the outcome of ongoing pregnancy, although the evidence for this is uncertain for this outcome. There is very low‐certainty evidence for the risk of complications requiring surgical intervention. Data are limited by the scarcity of high‐quality research study designs and the presence of risks of bias. This review provides insufficient evidence to determine the safety of self‐administration when compared with administering medication in the presence of healthcare provider supervision.
    Future research should investigate the effectiveness and safety of self‐administered medical abortion in the absence of healthcare provider supervision through the entirety of the medical abortion protocol (e.g. during administration of mifepristone or as part of a misoprostol‐only regimen) and at later gestational ages (i.e. more than nine weeks). In the absence of any supervision from medical personnel, research is needed to understand how best to inform and support women who choose to self‐administer, including when to seek clinical care.
  • Medical abortion used to end pregnancies has been successful and safe when women have access to appropriate information and resources. In provider‐administered medical abortion, drugs are taken in the presence of trained healthcare providers. Access to medical abortion drugs has increased and has given women more control over their abortion procedures through self‐administration. In self‐administered medical abortion, the woman takes the drug(s) without the supervision of a healthcare provider after receiving appropriate information and resources. This is the first review of the published evidence on whether self‐administration of medical abortion is a safe and successful way to end pregnancies. We compared the success and safety of self‐administered medical abortion versus provider‐administered medical abortion.
  • Women who self‐administer medical abortion drugs in early pregnancy (up to nine weeks gestational age) experience similar rates of completed abortion as women who undergo provider‐administered procedures in low‐to‐middle and high‐resource settings. Evidence about safety is uncertain.
  • [w]omen’s access to medical abortion remains constrained in part by government regulations and medical provision guidelines as to where and how the procedure can be administered, and by whom. The trend is well‐established that women, especially those in low‐resource and legally‐restricted settings, are increasingly obtaining abortifacients through informal and unreliable channels, including pharmacies, drug sellers, and online services without prescription, which may place them at greater risk of receiving poor‐quality drugs, inadequate information, and no referrals for management of complications.
  • There is a growing body of research demonstrating that women can manage their own abortions with little or no healthcare provider supervision, so long as they receive accurate and adequate information, high‐quality drugs, and have access to facility‐based care in case of complications. Additionally, women overwhelmingly prefer to administer abortion drugs at home, with self‐administered medical abortion becoming increasingly common for greater control and privacy around the procedure.
    While home‐based medical abortion has been shown to be effective, safe, and acceptable to women compared to clinic‐based procedures, it remains unclear whether self‐administered medical abortion is as effective, safe, and acceptable compared to procedures administered under healthcare provider supervision (i.e. provider‐administered medical abortion). To fill this evidence gap, we reviewed the evidence on the comparative effectiveness, safety, and acceptability of self‐administered versus provider‐administered medical abortion, in any setting.
  • Self‐administration seeks to expand access to medical abortion by allowing women to take the medical abortion drug(s) in the privacy of their own homes and with support from their friends, partners, or family, if desired, and is therefore often reported as more acceptable than having medical abortion in a health facility. Furthermore, self‐administration is empowering for women as the process allows them to have a role in managing their own health, specifically having a choice in and control over their pregnancy termination procedures. It also reduces the burden on the healthcare system, particularly in low‐resource settings, where there are insufficient providers to administer safe abortions, as well as reducing the burden on women, who may have significant socio‐economic constraints to accessing facility‐based abortions, including transportation and medical costs. It may be beneficial to prioritize facility‐based abortion care for circumstances of pregnancy requiring special attention and equipment, including advanced pregnancies, high‐risk pregnancies, and the management of abortion complication. Regardless of the location of medical abortion, all women must have access to accurate information and healthcare services, if needed.
  • Despite being preventable, most unsafe abortions account for 8% to 18% of all maternal mortality. In these settings, unsafe abortion can be attributed in part to inadequate healthcare infrastructure, the lack of trained providers, and poor knowledge about lawful access to safe termination services, as well as legal restrictions and stigma associated with abortion. Given that the mifepristone‐misoprostol regimen is known to be highly effective and has been shown to be easily self‐administered with little or no healthcare provider supervision, self‐administration of medical abortion may be a key strategy to significantly improve abortion‐related morbidity and mortality in low‐resource settings. It may also reduce the burden on the healthcare system where there are insufficient trained providers to administer safe abortions, and it can increase access to safe procedures for marginalized women who are at risk of unsafe abortions.
    Furthermore, there is inconclusive evidence about whether clinical supervision is necessary and whether self‐administration of medical abortion is as safe and effective. The efficacy and acceptability of home use of misoprostol is well documented, but research on self‐use of mifepristone, as part of a combined mifepristone‐misoprostol regimen, is still nascent. It is important to understand whether women can safely and effectively terminate their own pregnancies using medical abortion without healthcare provider supervision, and whether a strategy of informed choice over restricted provision meets their needs. This review will contribute to filling this evidence gap by evaluating whether self‐administered medical abortion is as effective, safe, and acceptable as provider‐administered medical abortion.
  • Home‐based medical abortion has previously been shown to be safe, effective, and acceptable to women seeking early termination, which can provide women with convenience and choice. While self‐administration of medical abortion has further potential to expand access to safe abortion for unintended pregnancies and to alleviate burdens on health systems where trained healthcare providers are limited, it has remained unclear whether medical abortion procedures that are self‐administered by the women are as safe, effective, and acceptable as those that are provider‐administered. In this review, we have assessed the evidence base on women’s role in administering their own medical abortions by comparing the effectiveness, safety, and acceptability of self‐administered medical abortion versus provider‐administered medical abortion in any setting.
  • Overall, most women were satisfied or highly satisfied with the medical abortion method they received. Women who self‐administered were more satisfied or highly satisfied and more likely to choose their medical abortion procedure again compared to those who underwent the provider‐administered procedure, although the findings were not statistically significant. Furthermore, compliance with the medical abortion protocol was higher among women who self‐administered, allaying a main concern about self‐administration. These studies showed that women who self‐administered took the drugs on time and correctly and were more likely to return to the clinic to confirm their abortion status compared to those in the provider‐administered group.
  • This review is the first to systematically assess the evidence base on the role of women administering their own medical abortion procedures. We build on the evidence from a prior systematic review on home‐based medical abortion and extend the research objective to a comparison of the administrator of the procedure rather than simply location. Just as home‐based medical abortion was found to be comparable to a clinic‐based procedure in terms of effectiveness, safety, and acceptability, this review found self‐administration of medical abortion to be as effective, safe, and acceptable as provider administration. However, we are very uncertain of the evidence for safety. This review supports the literature that women prefer to self‐administer abortions, based on convenience, privacy, and access to support.
    Some studies have suggested that self‐administered medical abortion is associated with higher failure rates, although failures are more likely to be a result of misuse of abortifacients or of deviation from the protocol rather than a consequence of self‐administration. A large proportion (98.33%) of women in the self‐administered group in this review had high adherence to the medical abortion protocol. The inclusion of a low‐sensitivity pregnancy test as a component of self‐assessment may decrease the likelihood of complications and the need for clinic follow‐up. Providing women with a low‐sensitivity pregnancy test as well as accurate and digestible information that complies with WHO‐recommended guidelines should be a crucial aspect to preventing failure in either self‐administered or provider‐administered medical abortion.
  • We demonstrate that women may administer their medical abortion procedure effectively, although there is uncertainty about safety outcomes. We also demonstrate that self‐administration is highly acceptable, with almost all women (91.2%) opting to self‐administer again if they had a future abortion. Policy‐makers should review international and national guidelines on medical abortion methods to consider whether to offer women at nine weeks gestation or less and with access to the support and information they want or need, the choice to return to the clinic for misoprostol or to take the drug at home. In this way, the number and cost of clinic visits for the woman would be reduced, and the strain on overburdened healthcare systems would be alleviated.
    However, a shift toward medical methods for early abortion occurring outside a clinic setting and partially administered by women comes with a variety of health service delivery implications to prevent any health complications, albeit rare. First, there is a need to expand healthcare provider training in monitoring, supervision, and referral for medical abortion, particularly in low‐resource settings, to ensure safe and standardized procedures. Second, a need exists for knowledge‐sharing with women around correct and appropriate use of medical abortion regimens to increase their ability to obtain accurate and reliable information, and to increase their ability to self‐assess before, during, and after the termination process. Healthcare providers must also receive adequate training to appropriately diagnose complications and prevent unnecessary surgical interventions. Given inequitable access to safe and effective abortion is a downstream consequence of inequitable access to contraceptives, post‐abortion care regimens must emphasize family planning counseling and services to substantially reduce unintended pregnancies and pregnancy‐related morbidity and mortality, including that from unsafe abortion. Not only does self‐administered medical abortion have the potential to improve access to safe abortion, it can potentially reduce the burden on health systems, especially in settings where there are inadequate number of trained healthcare providers.
  • This review fills the evidence gap by demonstrating that women can effectively administer the second stage of their own abortions by self‐administration of abortion drugs, and therefore may not require full supervision from a healthcare provider during this stage of the drug regimen. However, more research is required to determine whether self‐administration is as safe as provider‐administration. In the absence of medical supervision, research is needed to understand how best to inform and support women who choose to self‐administer, including when to seek clinical care. To improve access and ease burdens on the health system, it is important to study which types of healthcare providers can be involved during the medical abortion process to ensure that the provision of the procedure is efficient and of high quality. Further research is needed to understand to what extent healthcare providers are trained according to the WHO guidelines on medical abortion procedures, and to what extent they are being implemented in practice.
    Misoprostol is becoming ubiquitous across low‐resource settings where abortion laws are restrictive. In many of these countries, surveys in pharmacies suggest that women are buying misoprostol to terminate pregnancies and that they are not receiving adequate information, high‐quality drugs, or robust referrals. There is therefore a need to assess the self‐administration of a misoprostol‐alone regimen to understand its safety and effectiveness, along with operational research to understand how to train these outlets to dispense quality drugs and support women during the abortion process.

“A Drug that Eases Miscarriages is Difficult for Women to Get” (January 10, 2019)[edit]

Mara Gordon, Sarah McCammon, “A Drug that Eases Miscarriages is Difficult for Women to Get”, NPR, (January 10, 2019)

  • Mifepristone causes a woman to have what's essentially a very heavy period, and there is a small risk of excessive bleeding.
    It's been heavily regulated since it was approved by the Food and Drug Administration for medication abortions in 2000. Government restrictions make it difficult for women who are miscarrying to get it.
  • In June, the New England Journal of Medicine published results of a study that showed the combination of mifepristone and misoprostol was more effective than misoprostol alone to help women expel a miscarriage, or what's known as an early pregnancy loss. That's when a pregnancy is not viable in the first trimester.
    Before these findings were published, women who were miscarrying usually had three options: a surgical procedure to remove the miscarriage, misoprostol alone, or waiting for the miscarriage to pass on its own.
    Research shows that women tend to prefer the surgery or medication, but since a single dose of misoprostol fails about 30 percent of the time, many women are forced to return to their doctors for a second dose or to get the surgery.
  • "It ends up adding insult to injury," says Courtney Schreiber, an OB-GYN in the Department of Obstetrics and Gynecology at the University of Pennsylvania and the lead author of the New England Journal study. "The misoprostol alone has really not been a therapeutic intervention."
    In Schreiber's study, which followed 300 women who were miscarrying, the combination of mifepristone and misoprostol was more effective in helping patients expel the miscarriage. The overall success rate was 90 percent for patients who took both medications, and 76 percent for those who who got misoprostol alone.
    "It offers them a sense of control over their own bodies and their own process when they feel that they've already lost an element of control," Schreiber says.
  • Miscarriage is common. The Centers for Disease Control and Prevention estimates that over 1 million American women have a first trimester pregnancy loss each year. The American College of Obstetricians and Gynecologists now officially recommends the two-drug regimen. Yet access to mifepristone is restricted in a way that makes it difficult for physicians to prescribe.
    "We clearly need to provide mifepristone," says Dr. Karen Meckstroth, director of the Women's Options Center at the University of California, San Francisco. "How do we get it?"
  • Mifepristone is regulated by the Food and Drug Administration under what's called a Risk Evaluation and Mitigation Strategy, a designation the agency uses for extra safety oversight that affects how a medication is distributed. But most physicians and the FDA itself consider mifepristone safe; the FDA approved the medication for use in 2000. The REMS is in place, abortion-rights advocates say, for political reasons: It limits access to a medication commonly used for abortion.
    The REMS restrictions mean that mifepristone is not available in commercial pharmacies; a doctor can't prescribe it for pickup at a CVS or Walmart. Instead, a woman must travel to a clinic or hospital that is designated as a mifepristone supplier under an agreement with the drug's manufacturer, Danco Laboratories. The patient must also sign a form that says she understands what the medication is for and understands its risks.
  • No definitive data exist on the number of clinics in the U.S. that stock mifepristone, according to Rachel Jones, a researcher with the Guttmacher Institute who studies the drug, but academic medical centers and clinics that provide abortions tend to be the places where doctors can prescribe it. Danco representatives say they can't provide information on the number and types of sites that stock mifepristone because of confidentiality agreements.
  • But for some physicians who oppose abortion, the restrictions on mifepristone may provide "an appropriate pause," says Dr. Christina Francis, an OB-GYN and chair of the American Association of Pro-Life Obstetrician Gynecologists. She says the restrictions on mifepristone help ensure women who take it are under the care of qualified physicians who understand how to use the medication.
    "I don't see it as imposing an undue barrier on physicians," Francis says.
  • In Albuquerque, N.M., for example, women's health providers have developed a special protocol that helps women who are miscarrying get mifepristone.
    "We immediately ... saw this as a superior way of providing care," says Dr. Lisa Hofler, the chief of family planning at the University of New Mexico School of Medicine. Hofler runs a clinic that stocks mifepristone but doesn't routinely provide prenatal care. Since many miscarriages are discovered when women get their first ultrasound in pregnancy, she and her colleagues have developed a workflow that lets women who are diagnosed during a prenatal visit elsewhere get same-day appointments for mifepristone in the clinic.
    Other women's health providers are working to make mifepristone available in the locations where miscarriage is diagnosed, like primary care offices and emergency rooms.
    But because many think of mifepristone as the "abortion pill," it can be difficult to get it stocked — even when its intended use is for miscarriages.
  • Kristyn Brandi, an OB-GYN at Rutgers New Jersey Medical School in Newark, says she currently can't prescribe mifepristone to her patients, even though she practices at an academic medical center that gets referrals from across New Jersey.
    "Some people are worried about the politics around the medication and how that could create repercussions for the hospital," Brandi says.
  • While Hofler is happy she can provide women with care that is backed by research, she says women shouldn't have to go to special clinics to get mifepristone. She's hopeful that a change in access will reduce the shame women feel about both miscarriage and abortion.
    "People can talk about miscarriage, but it's stigmatized in the undercurrents," Hofler says. "Society still views this as a failing of the woman."
  • In October 2017, the American Civil Liberties Union sued the FDA on behalf of Dr. Graham Chelius, a family physician in Kauai, Hawaii, who says he would like to prescribe mifepristone. His hospital doesn't stock the medication and it isn't available on the island.
    "The FDA restrictions on mifepristone are motivated by politics, not science," says Julia Kaye, the lead attorney in the ACLU's lawsuit. Several professional societies — including the California Academy of Family Physicians — are also listed as plaintiffs in the case.
    The ACLU is in the midst of negotiations with the government about technical aspects of the case, Kaye says, and she doesn't expect arguments to begin for at least several months.
    "Restrictions continue to be necessary to ensure the safe use of the drug," an FDA spokesperson wrote in an email statement to NPR.

"Controversial 'Abortion Reversal' Regimen is Put to the Test" (March 22, 2019)[edit]

Mara Gordon, "Controversial 'Abortion Reversal' Regimen is Put to the Test". "Shots". NPR. (March 22, 2019).

  • Proponents of "abortion pill reversal" say it can stop a medication-based abortion in the first trimester, if the progesterone is administered in time.
    But Creinin says the progesterone treatments are ineffective at best in halting an abortion that has already begun. And, Creinin says, promotion of the treatment can be potentially harmful by giving pregnant women misleading information that an abortion can be undone.
    Though critics of abortion pill reversal say the term is an unproven misnomer, it has been such a compelling phrase that it's already been written into the laws of a number of states.
    Legislators in Arkansas, Idaho, South Dakota and Utah have made it a legal requirement in recent years that doctors who provide medical abortions must tell their patients that "reversal" is an option, although they are not prevented from also telling patients if they think the treatment doesn't work.
    Medical researchers such as Creinin and the American College of Obstetricians and Gynecology are concerned by that trend.
    "You create a law based on no science — absolutely zero science," Creinin says.
    Proponents of the technique say they do have evidence. But it's anecdotal, Creinin says, or comes from studies that lack rigorous controls. It's time, Creinin says, for a formal study that can be definitive.
    "I want to own that," he says.
  • So what happens if a woman takes mifepristone, then changes her mind and wants to continue with the pregnancy?
    If the change of heart comes in the first hour after she's swallowed that initial medicine, her doctor might help her induce vomiting. If she hasn't yet absorbed the first drug, the process may be stopped before it starts.
    The bigger question, and one for which the data are murkier, is: What happens if a woman takes the first medicine but never goes on to take misoprostol, the second drug in the regimen?
    According to the American College of Obstetricians and Gynecology, "as many as half of women who take only mifepristone continue their pregnancies." (If the pregnancy does continue, mifepristone isn't known to cause birth defects, ACOG notes.)
  • "People do change their minds all the time," Delgado says.
    Hoping to help the woman, Delgado gave her progesterone — a medication that has many uses, including as a treatment for irregular vaginal bleeding and as part of hormone replacement therapy during menopause. If progesterone is useful in these other ways, Delgado figured, it might stop the action of the progesterone-blocker mifepristone, and halt an abortion.
    Delgado says the pregnancy of that first patient continued uneventfully, which he credits to the progesterone.
  • In 2012, Delgado co-authored a report in the Annals of Pharmacotherapy on the experiences of six pregnant women who received mifepristone and then injections of progesterone. Four of the women, the paper said, were able to carry their pregnancies to term.
    In a statement released in August 2017, ACOG said the results of the study, a type known as a case series that didn't include a comparison group, "is not scientific evidence that progesterone resulted in the continuation of those pregnancies." ACOG's statement also said: "Case series with no control group are among the weakest forms of medical evidence."
    In 2018, Delgado and colleagues in his network of health providers published a larger case series, this one involving 754 patients, in the journal Issues in Law and Medicine. The paper concluded that the reversal of mifepristone's effects with progesterone "is safe and effective."
    The researchers acknowledged that the study didn't randomly assign women to receive a placebo or mifepristone. A study like that, called a randomized placebo-controlled trial, would provide strong evidence. But Delgado and his colleagues wrote that doing this kind of trial "in women who regret their abortion and want to save the pregnancy would be unethical."
    "There's no alternative treatment," he says. "You can't always wait for the [randomized, controlled trials]. If it's lifesaving, there's no alternative."
  • One of Delgado's most outspoken critics, Dr. Daniel Grossman, an OB-GYN at the University of California, San Francisco, says all of the published studies supporting this use of progesterone have been marred by methodological flaws that inflate the "success rate" of the reversal treatment.
    Last October, Grossman and Kari White, a sociologist at the University of Alabama, Birmingham who studies family planning issues, wrote an editorial in the New England Journal of Medicine criticizing Delgado's research methodology, saying he used flawed statistics and didn't set rigorous criteria for the characteristics patients had to fulfill to be included in the study.
    "A systematic review we coauthored in 2015 found no evidence that pregnancy continuation was more likely after treatment with progesterone as compared with expectant management among women who had taken mifepristone," they wrote.
    "I think there's a big bias against abortion pill reversal," Delgado says in response. "ACOG typifies that bias by coming out with strong statements. ... This is a new science, but we have a substantial amount of data, and it's been proven to be safe."
  • Grossman says he's furious that states are forcing abortion providers to give their patients inaccurate information related to abortion care.
    What's more, Grossman says, "these laws take an extra step ... and essentially are encouraging patients to be a part of clinical research that isn't really being appropriately monitored. ... This is really an experimental treatment."
    Progesterone hasn't been evaluated by the Food and Drug Administration for reversing a medication abortion. Doctors are permitted to prescribe drugs for uses not approved by the FDA as part of the practice of medicine. It's known as off-label use.
    Until Delgado published his 2018 paper, Delgado told his patients they were receiving a "novel treatment." He says he believes there is now enough research to support the routine off-label prescription of progesterone for women who don't want to complete a medication-based abortion.
    "Now we have a substantial amount of data. There is no alternative. And it's been proven to be safe," Delgado says. "Why not give it a chance?"
  • Although Creinin disagrees that the evidence supports this use of progesterone, he is sympathetic to the idea that women who seek an abortion may not be certain about the decision at their first appointment. Creinin says he supports policies that allow women as much control as possible over the decision about whether or not to terminate a pregnancy.
    "There are people who change their minds," Creinin says. "That's a normal part of human nature."
    UCSF's Grossman agrees.
    He encourages abortion providers, when possible, to send the mifepristone and misoprostol home with the patient, if she requests it. That way, she can start the protocol only if and when she's ready, rather than make the decision in a clinic where she might feel rushed. (FDA rules about mifepristone say the pill can only be dispensed in certain types of clinics — usually clinics that provide abortions. And some states have additional restrictions on how and where the drugs can be prescribed and taken.)
  • Creinin's study, approved by the UC Davis institutional review board in December, has been registered with ClinicalTrials.gov, which tracks medical research.
    The study is slated to involve 40 women who are between 44 and 63 days of pregnancy and are seeking to have a surgical abortion. As a condition of the research, the women would have to be willing to take mifepristone, the initial pill that would normally trigger a medical abortion, and then a placebo or progesterone.
    Two weeks later, researchers will see if there's any difference in the rates of continued pregnancy. If progesterone can prevent the effects of mifepristone, Creinin says, he'll find that more women in the group that got progesterone are still pregnant, with a pregnancy that's progressing.
  • Creinin is skeptical that progesterone will have any effect, since it is thought that mifepristone irreversibly blocks progesterone in the body.
    But if it does have a clinically significant effect, he says, "I want to know that."
    Creinin hopes that his work will help medical researchers better understand if this kind of treatment can actually help women who change their minds after taking mifepristone for a medication abortion.
    If the results show the progesterone doesn't work, Creinin hopes that it will discourage state legislators from mandating that doctors tell their patients about an ineffective treatment.

"Safety Problems Lead To Early End For Study Of 'Abortion Pill Reversal'" (December 6, 2019)[edit]

Mara Gordon (December 5, 2019). "Safety Problems Lead To Early End For Study Of 'Abortion Pill Reversal'". NPR.

  • Advocates for abortion pill reversal have succeeded in having it written into law as an option to be discussed in mandatory pre-abortion counseling in several states, including Kentucky, Nebraska and Oklahoma.
    Opponents have said there wasn't sufficient evidence to support the approach. Now, there's evidence that it could cause harm.
    "Encouraging women to not complete the regimen should be considered experimental," says Dr. Mitchell Creinin, a professor of obstetrics and gynecology at UC Davis and the lead researcher on the study. "We have some evidence that it could cause very significant bleeding."
  • Proponents of the abortion-reversal treatment offer the hormone progesterone to patients after they have taken mifepristone but have then decided they don't want to complete the abortion. A group of researchers published a small case series about the protocol, claiming it prevents the abortion from taking place.
    The research has been criticized for having serious methodological flaws. Most OB-GYNs — including the professional group the American College of Obstetricians and Gynecologists — oppose the practice, saying it's "not supported by science."
    At least seven states, however, legally require abortion providers to tell patients about progesterone treatment for stopping a medication-based abortion midway through.
    This advice, Creinin says, may put patients at risk for life-threatening bleeding.
    "It's not that medical abortion is dangerous," he says. "It's not completing the regimen, and encouraging women, leading them to believe that not finishing the regimen is safe. That's really dangerous."
  • Although Creinin acknowledges that his study was limited by its premature termination and small sample size, he hypothesizes that taking mifepristone without misoprostol may be especially risky later in the first trimester of pregnancy. All three patients with severe bleeding were at least 56 days into their pregnancies.
    The women who experienced hemorrhage included one who received progesterone and two who received a placebo. Of the remaining participants, two left the study because of side effects and completed their planned surgical abortions.
    Women in both the progesterone and placebo groups had some evidence that their pregnancies continued. Four patients who took mifepristone and then received progesterone had pregnancies with cardiac activity on ultrasound. Two patients who got the placebo also had gestational cardiac activity.
    Creinin says that because the study was cut short, it wasn't big enough to answer the question it set out to. There simply aren't enough data, he says, to know if the progesterone treatment is effective at preventing a medication-based abortion from taking place.
    "Does progesterone work? We don't know," he says. "We have no evidence that it works."

"Unsafe abortion: the silent scourge" (2003-12-01)[edit]

Grimes DA (2003-12-01). "Unsafe abortion: the silent scourge"]. British Medical Bulletin. 67 (1): 99–113. doi:10.1093/bmb/ldg002. PMID 14711757.

  • Pharmacological abortion has transformed the landscape over the past decade. In recent years, the term for drug-induced abortion in early pregnancy has been ‘medical’ abortion. This ambiguous term has caused needless confusion and thus needs to be replaced with a more descriptive term. For example, in many cultures, ‘medical’ abortion implies that performed by medical personnel, such as physicians or midwives. Thus, in some countries, a vacuum aspiration performed by a physician would be deemed a ‘medical’ abortion, as compared with an abortion induced by a lay person.
    Several approaches to pharmacological abortion are used, depending on the local availability of drugs. The best appears to be the combination of mifepristone followed by misoprostol. A popular regimen includes an oral dose of mifepristone 200 mg by mouth followed 1–3 days later with vaginal misoprostol, up to 800 μg. The optimal regimen has not been established, and research is under way to evaluate different doses and routes of administration (e.g. buccal or sublingual misoprostol). Regimens of mifepristone and misoprostol have been found safe and effective in both developed and developing countries27.
    Where mifepristone is not available, another alternative is methotrexate 50 mg/m2 as a single intramuscular injection, followed some days later by misoprostol. This rivals the success of mifepristone–misoprostol, although the process is slower. Although many clinicians use blood tests to ensure normal liver function before administering single-dose methotrexate, the necessity of this practice is unclear. Another option more widely available is misoprostol alone. Reports suggest that the success of this approach is not as high as with the combined drug regimens, and gastrointestinal toxicity and fever become problems with repetitive doses.
  • Several pharmacological approaches are used for labour induction. Intra-amniotic instillation of hypertonic saline (200 cc of 20%) or urea (80 g) remain safe and effective regimens. Augmentation by oxytocin, prostaglandin and osmotic cervical dilators shortens abortion times greatly. An advantage of hypertonic abortifacients is the lower risk of an abortus with signs of life; a disadvantage is a small risk of coagulopathy.
    Uterotonic agents alone are effective abortifacients. One alternative is high-dose intravenous oxytocin, given in increasing concentrations. This avoids the gastrointestinal distress associated with prostaglandins but requires many vials of oxytocin, which may be prohibitively expensive in developing countries. With scheduled breaks in the oxytocin infusion, water intoxication is avoided. Misoprostol alone, given by different routes and in different doses, can be effective as well. An advantage is the low cost and wide availability of misoprostol; a disadvantage is dose-related gastrointestinal side-effects and fever. In countries where available, mifepristone administered before uterotonic agents dramatically reduces induction-to-abortion times.

"Medical methods for first trimester abortion: RHL commentary" (September 3, 2004)[edit]

Grossman D (3 September 2004). "Medical methods for first trimester abortion: RHL commentary". Reproductive Health Library. Geneva: World Health Organization. Archived from the original on 28 October 2011.

  • Medical methods for first trimester abortion have been demonstrated to be both safe and effective. Regimens that combine mifepristone or methotrexate with a prostaglandin such as misoprostol are more efficacous than a prostaglandin alone. In the case of regimens that combine mifepristone with a prostaglandin, the dose of mifepristone may be reduced from 600 mg to 200 mg without affecting efficacy; in 4 trials that compared the efficacy of the 200-mg dose with the 600-mg dose of mifepristone the relative risk (RR) of failure was 1.07 with the 95% confidence interval (CI) being 0.87–1.32. In combination with mifepristone, vaginally administered misoprostol in a 800-µg dose , appears to be more efficacious compared with a prostaglandin E1 analogue 0.5 mg. When mifepristone is used with misoprostol to terminate pregnancies of up to 63 days’ gestation, misoprostol administered vaginally is more efficacious than when administered orally (2 trials, RR 4.41 of failure with oral misoprostol compared with vaginal adminstration, 95% CI 2.32–8.38). Data were insufficient in the meta-analysis to determine the effect of gestational age on the efficacy of the various regimens. Oral administration of misoprostol was found to be associated more frequently with nausea and diarrhoea compared with vaginal administration (2 trials, RR 1.13, 95% CI 1.0–1.25; RR 1.80, 95% CI 1.49–2.18, respectively). With regard to the timing of administration of the prostaglandin following the administration of mifepristone on day 0, one trial indicated that misoprostol administered on day 3 was less effective compared with its administration on day 1 (RR of failure 1.94, 95% CI 1.05–3.58). However, in the three trials included in the review (but not pooled), there was no difference in efficacy when comparing prostaglandin administration on day 3 with day 2, day 2 with day 1, and day 2 with day 0.
  • Several research questions remain unanswered regarding medical methods for first trimester abortion. With regimens that include mifepristone, more well-designed studies are needed to determine the optimal dose of misoprostol administered via the sublingual (more side-effects) or buccal routes in order to minimize side-effects while maintaining efficacy. More data comparing oral and vaginal misoprostol after mifepristone among women in early pregnancy (≤49 or ≤56 days) would be helpful to clarify the relative efficacy of these regimens in this period.
    As the Cochrane Review notes, additional studies comparing the efficacy of the mifepristone and methotrexate regimens are needed. One non-blinded randomized trial found the regimens to be equally effective, although methotrexate took significantly longer to complete the abortion process.
  • Until mifepristone is widely available at an affordable price more research is needed to perfect medical abortion regimens using methotrexate and misoprostol alone, including studies to test further oral methotrexate and to evaluate alternative routes of administration for misoprostol. While these studies are less relevant in countries with access to mifepristone, they are critical to improving services in developing countries without such access. These studies are also difficult to perform in countries where abortion is legally restricted. Similarly, well-designed trials are needed to evaluate medical methods of late first trimester abortion (between 9 and 12 weeks of gestation) in order to increase access to services in areas with few surgical abortion providers.
    Further research also is needed to evaluate the extent to which medical abortion regimens—regardless of the medications used—can be simplified for use in under-resourced settings. A recent randomized controlled trial found that the interval between mifepristone and vaginal misoprostol may be shortened to 6–8 hours without affecting efficacy, and more studies of varying intervals—including immediate misoprostol administration—would be welcome. Several non-randomized trials have demonstrated the safety, efficacy and acceptability of home use of misoprostol after mifepristone. Further research is needed to prospectively evaluate clinical determination of gestational age and abortion completion without the use of ultrasound, as well as the possible use of low sensitivity urine pregnancy tests to confirm completion. Well-designed studies of the management of incomplete abortion after medical abortion regimens are also needed, including trials to assess the utility of repeat dosing of misoprostol.

"Mifepristone and misoprostol: Recommended regimen" (January 30, 2020)[edit]

"Mifepristone and misoprostol: Recommended regimen". Ipas. (January 30, 2020. Last reviewed: January 30, 2020)

  • Recommended regimen for 13-24 weeks gestation:
    Mifepristone 200mg orally followed 1-2 days later by misoprostol 400mcg buccally, sublingually or vaginally every three hours until fetal and placental expulsion.
    If the woman is stable and it is convenient for her to do so, providers should allow her at least four hours after fetal expulsion to expel the placenta before intervening.
  • Mifepristone combined with misoprostol is the preferred regimen for medical abortion at or after 13 weeks gestation, as it is highly efficacious, resulting in a short induction-to-abortion interval with an excellent safety profile (Borgatta & Kapp, 2011; Wildschut et al., 2011; World Health Organization [WHO], 2018). Mifepristone combined with misoprostol has a consistently shorter induction-to-abortion interval and higher expulsion rate at 15 (Ngoc et al., 2011), 24 (Constant et al., 2016) and 48 hours when compared to misoprostol alone (Dabash et al., 2015).
  • A 2013 systematic review evaluating the effect of dosing interval between mifepristone and misoprostol on induction-to-abortion interval included 20 randomized controlled trials and nine observational studies (Shaw, Topp, Shaw, & Blumenthal, 2013). Based on the results of three randomized controlled trials, the review found that when mifepristone was given 12-24 hours before misoprostol, the induction-to-abortion interval was slightly longer (median 7.3 hours, range 7 to 8.5) than when mifepristone was administered 36 to 48 hours before misoprostol initiation (6.8 hours, range 6.3 to 7.2), but the abortion rate at 12 and 24 hours was the same (Shaw et al., 2013). In studies examining simultaneous administration of mifepristone and misoprostol, median expulsion times in the simultaneous group ranged from 10 to 13 hours, compared to 5 to 8 hours in women who waited 24 to 36 hours between mifepristone and misoprostol; however, rates of expulsion at 48 hours were equivalent in the two groups (Abbas et al., 2016; Chai et al., 2009).
  • Although an early, large case series used an initial loading dose of vaginal misoprostol (Ashok, Templeton, Wagaarachchi & Flett, 2004), a more recent small, randomized controlled trial assigned 77 women to receive a loading dose of misoprostol vaginally (600mcg, followed by 400mcg every six hours) and 80 women to receive a no-loading dose regimen (400mcg every six hours) (Pongsatha & Tongsong, 2014). Median induction-to-abortion intervals and rates of complete abortion at 24 and 48 hours did not differ between groups, but the loading dose group suffered significantly more misoprostol-related side effects. Recent clinical trials that did not use loading doses of misoprostol showed average induction-to-abortion intervals of 8-10 hours and similar or better success rates as studies with loading doses (Abbas et al., 2016; Dabash et al., 2015; Louie et al., 2017; Ngoc et al., 2011). Therefore, a high initial dose of misoprostol appears to confer no benefit on expulsion times.
  • Route: In clinical trials of medical abortion at or after 13 weeks, misoprostol 400mcg vaginally or sublingually has higher success and shorter induction-to-abortion intervals than oral dosing (Dickinson, Jennings & Doherty, 2014; Tang, Chang, Kan & Ho, 2005). Buccal misoprostol has not been directly compared to other routes in a combined regimen for medical abortion at or after 13 weeks, but has similar efficacy as other routes of administration in abortion before 13 weeks (Kulier et al., 2011; Raymond, Shannon, Weaver, & Winikoff, 2013). Studies that use buccal misoprostol as part of a combined mifepristone-misoprostol regimen show an average induction-to-abortion interval of 8-10 hours (Abbas et al., 2016; Dabash, 2015; Louie et al, 2017; Ngoc et al., 2011; Blum et al., 2019)
    Dose: Misoprostol 400mcg has higher expulsion rates, shorter induction-to-abortion intervals and similar side effects compared to 200mcg, regardless of route of administration (Brouns, van Wely, Burger, & van Wijngaarden, 2010; Shaw et al., 2013).
    Timing: In one randomized trial examining two regimens of misoprostol-only medical abortion at or after 13 weeks gestation, the induction-to-abortion interval was shorter and the expulsion rate at 24 hours was higher when misoprostol was given every three hours compared to every six hours; rates of adverse events were similar (Wong, Ngai, Yeo, Tang, & Ho, 2000).
    Number of doses: A prospective cohort study of 120 women between 13 and 22 weeks gestation who received mifepristone followed 24 hours later by misoprostol 400mcg buccally every 3 hours until fetal and placental expulsion reported a complete abortion rate of 99% without additional intervention (Louie et al., 2017). The median number of misoprostol doses necessary was four (range 2 to 6) and no adverse events were reported. In a similar prospective study of 306 women between 13-22 weeks, 90.2% required five or fewer doses of misoprostol (Platais et al., 2019).
    Quality of evidence: The recommendation is based on multiple randomized clinical trials and a Cochrane meta-analysis comparing different mifepristone and misoprostol doses, dosing intervals and routes of administration in the second trimester (Wildschut et al., 2011). Most randomized controlled trials of medical abortion at or after 13 weeks do not include women with pregnancies greater than 21 weeks gestation.
  • In a prospective study of women between 13-18 weeks gestation utilizing mifepristone and misoprostol, most women expelled the fetus and placenta at about the same time, with a median time between fetal and placental expulsion of 15 minutes (range 0-4.5 hours) and 15.5% requiring a manual removal of the placenta (Blum et al., 2019). One retrospective cohort study measured intervention rates for placental removal in 233 women receiving a feticidal agent and repeated doses of misoprostol to induce abortion for pregnancies between 18-23 weeks gestation (Green et al., 2007). Following fetal expulsion, the placenta was allowed to expel spontaneously; operative intervention was performed only for excessive bleeding following fetal expulsion or to expedite hospital discharge after a minimum of four hours had elapsed since fetal expulsion. The overall intervention rate for retained placenta was 6%, and most removals were to expedite discharge. The study found no increase in morbidity for women managed expectantly during this time frame.

"'I didn't feel judged': exploring women's access to telemedicine abortion in rural Australia" (March 2020)[edit]

Ireland S, Belton S, Doran F (March 2020). "'I didn't feel judged': exploring women's access to telemedicine abortion in rural Australia". Journal of Primary Health Care. 12 (1): 49–56. doi:10.1071/HC19050. PMID 32223850.

  • INTRODUCTION: Regardless of geographical location, safe and legal abortion is an essential reproductive health service. Accessing an abortion is problematic for women in rural areas. Although telemedicine is globally established as safe and effective for medical abortion in urban settings, there is a paucity of research exploring access to telemedicine abortion for women in rural locations.
    • p.49
  • RESULTS: Rural women had severely limited access to abortion care. The five domains of the Patient-Centred Access model demonstrated that when women with the prerequisite personal skills and circumstances are offered a low-cost service with compassionate staff and technical competence, telemedicine can innovate to ensure rural communities have access to essential reproductive health services.
    DISCUSSION: Telemedicine offers an innovative model for ensuring women’s access to medical abortion services in rural areas of Australia and likely has similar applicability to international non-urban contexts. Strategies are needed to ensure women with lower literacy and less favourable situational contexts, can equitably access abortion services through telemedicine.
    • p.49
  • In Australia and other parts of the world, provision of telemedicine in rural areas is considered to increase access to health and medical services. Telemedicine may be beneficial to rural populations by eliminating the spatial distance between people and the health services they need. Certainly,

geographical remoteness is an important health determinant, with widening disparities in health outcomes and behaviours between urban and rural dwelling populations. This means that telemedicine is a promising approach to improving the health outcomes of rural populations and that successful provision models are worthy of scrutiny.

    • p.49
  • What is already known: Access to abortion services is problematic for women living in rural areas. Although telemedicine is safe and effective for medical abortion in urban settings, there is a paucity of research exploring access to telemedicine abortion by women in rural locations.
    What this study adds: Despite medical abortion being within the scope of rural primary health-care services, our study provides evidence that women in rural areas continue to have limited access to abortion. Telemedicine abortion bridges this access gap to essential reproductive health-care services for rural communities. Specific strategies are needed to ensure that vulnerable population subgroups can equitably access telemedicine in rural areas.
    • p.50
  • The World Health Organization recognises that access to safe and legal abortion is an essential reproductive health service, yet access to abortion services, even in developed wealthy Western countries, remains problematic. There is an established track-record of medical abortion safely provided by telemedicine in numerous countries including Brazil, the United States, Finland, Norway, Ireland and Canada. Some research notes the likely utility of telemedicine to extend abortion access into rural settings, but none specifically explores non- urban women’s access and perceptions around abortion by telemedicine. Although Australia is a wealthy and developed country, women living in rural areas find access to abortions difficult and would likely benefit from innovative telemedicine services to address their unmet needs.
    • p.50
  • Australian abortion health services are primarily found in urban centres and are largely outsourced to private providers; it is a profit-driven item of health care. Medical abortion has had a convoluted access entry point and, although being within their scope of practice, is not widely used in primary health care by general practitioners (GPs). There is no Medicare- (universal health insurance) specific reimbursement for a medical abortion performed in primary care. Similar to New Zealand, Australia has a complex legal environment that has inhibited abortion provision, but there are an estimated 19 legal abortions performed per 1000 women aged 14–45 years. Unlike some countries, there is not an underbelly of unsafe, illegal abortions in Australia. Australian telecommunication infrastructure (mobile and landline networks) supports the delivery of telemedicine in both urban and rural areas, but Medicare rules limit doctors’ ability to fund this practice.
    • p.50
  • Many of the women interviewed had initial face-to face contact with GPs in their remote and regional home town. Although medical abortion is within the practice scope and knowledge domain of GPs in Australia, women reported that none of the doctors they attended were helpful or familiar with pro-

viding this essential health care; and nor were they able to offer alternative services to women. Some women were referred from one health service to another, before using their own initiative and skills to identify and access the telehealth service. Two women reported returning to their GPs and edu- cating them about telehealth and medical abortion services. Some women incorrectly reasoned that medical abortion could not be provided by their town’s GP because of their non-urban location.

    • pp.52-53


  • Women reported that the telemedicine service was affordable and overwhelmingly the cheapest option available to them. They reported costs of $AUD250–350. One woman reported that her alternative option for a surgical abortion was $AUD1500. Affordability was a crucial determinant for these women, many of whom had a low income and dependants to support. Indirect costs such as time away from work, childcare and transport were absorbed by the woman, but were perceived as having far less impact then either travelling away for a surgical abortion or the alternative of going through with an unwanted pregnancy. All the women accessed some sort of social capital by disclosing their decision to stop the pregnancy to either a trusted friend or family member. Some of the screening tests incurred an additional fee, but this was outside the control of the telemedicine service. Most women were able to undertake these screening tests free-of-charge under the universal Medicare insurance scheme. No women reported using private health insurance to pay for screening tests or the service fees.
    • p.53
  • This qualitative exploration of rural women’s access and perceptions around abortion by telemedicine addresses an identified knowledge gap in international literature. The five domains of the Patient- Centred Access model demonstrated that when women with the prerequisite personal skills and circumstances are offered a low-cost service with compassionate and technically competent staff, telemedicine can innovate to ensure rural communities have access to essential reproductive health services. The rural women who participated in our research were able to access telemedicine abortion without a referral, but they reported many difficulties in gaining abortion information and services from local GPs. The reasons for this are likely due to a complex interplay of systemic and personal factors including financial Medicare disincentives, health provider abortion stigma and burdens from the additional administrative and training prerequisites required to legally prescribe Australian abortion medication. Similar barriers have been reported by Dawson et al. who explored reasons for the low uptake of medical abortion provision by Australian GPs. Although none of these service provision barriers are specifically related to the challenges of geography, they disproportionally affect rural women who have either fewer choices or often no home town abortion service at all, and thus contribute heavily to the inequity of rural abortion access. In our research, access to the telemedicine service required women to have high digital literacy and self-efficacy, alongside other favourable situational personal circumstances such as transport.
    • p.54
  • Although our analysis offers cause for celebrating the innovations of telemedicine in meeting reproductive health challenges, it may also inadvertently perpetuate known health inequities for certain rural population cohorts, especially minority, Indigenous, marginalised or socially vulnerable women, who may be in the greatest need for access to reproductive health services but who lack the personal skills and favourable circumstances to access telemedicine. Addressing telemedicine’s ‘paradoxical inequity’ is therefore a crucial challenge, especially in the current global context where many nations’ health inequities are widening. Our findings suggest the need for further scrutiny over how to safeguard access to telemedicine for marginalised and vulnerable populations, particularly those with low digital literacy.
    • p.55

"Medication Abortion Now Accounts for More Than Half of All US Abortions" (February 24, 2022)[edit]

Rachel K. Jones, Elizabeth Nash, Guttmacher Institute Lauren Cross, Guttmacher Institute Jesse Philbin, Guttmacher Institute Marielle Kirstein, Guttmacher Institute "Medication Abortion Now Accounts for More Than Half of All US Abortions". Guttmacher Institute. (February 24, 2022).

  • In 2000, the US Food and Drug Administration (FDA) approved mifepristone as a method of abortion. Taken along with misoprostol, the two-drug combination is known as medication abortion or the "abortion pill." New research from the Guttmacher Institute shows that 20 years after its introduction, medication abortion accounted for more than half of all abortions in the United States.
    Guttmacher Institute’s periodic census of all known abortion providers show that in 2020, medication abortion accounted for 53% of US abortions. That year is the first time medication abortion crossed the threshold to become the majority of all abortions and it is a significant jump from 39% in 2017, when Guttmacher last reported these data. Preliminary data originally published in February 2022 showed that medication abortion accounted for 54% of all abortions in the US.
  • As medication abortion has become the most common method of abortion, there is still the potential to further increase access—which is why the method has become a main target of anti-abortion politicians and activists seeking to restrict care.
  • Currently, medication abortion is approved for use up to 10 weeks of pregnancy. The FDA approved that limit based on research the agency reviewed at the time. However, additional research shows provision beyond 10 weeks is safe and effective and some providers administer medication abortion "off label" after that point in pregnancy.
  • Medication abortion can be completed outside of a medical setting—for example, in the comfort and privacy of one’s home. Pills can be provided at a clinic or delivered directly to a patient through the mail. The latter option can be especially useful in addressing logistical burdens abortion patients often face when they have to visit a provider to obtain care, such as arranging for child care and time off work and paying for transportation costs. And, in areas of the country that are rural or underserved by providers, medication abortion can save a patient hundreds of miles of travel.
  • Throughout the more than 20 years that it has been used in the United States, medication abortion has been proven to be overwhelmingly safe and effective.
    *A comprehensive review of the science related to the provision of abortion care in the United States conducted by the National Academies of Sciences, Engineering, and Medicine confirmed that medication abortion has a very low rate of serious complications and is effective at ending an early pregnancy.
    *Subsequent research has demonstrated that direct-to-patient medication abortion provided via telemedicine—where the patient remotely consults with a provider and pills are shipped through the mail—is likewise safe and effective and works well for patients.
  • A number of factors have transformed the landscape around medication abortion in recent years. While the use of medication abortion has been steadily increasing since it was first approved, the COVID-19 pandemic likely accelerated that trend. Since the start of the pandemic in early 2020, there has been increased attention on the benefits of telehealth—and abortion has very much been a part of that conversation.
    Another factor improving access has been an increase in evidence-based policies that allow non-physician medical professionals—such as physician assistants and advanced practice nurses—to provide medication abortion. Broadening the pool of qualified providers is in line with expert guidance. There has also been an increase in clinics that only provide medication abortion and not procedural care.
    Despite its long-standing safety record, mifepristone has been subject to a medically unwarranted Risk Evaluation and Mitigation Strategy (REMS) imposed by the FDA with the drug’s approval in 2000. Under the requirements of this restriction, the medication had to be dispensed only by certified prescribers, patients had to sign an agreement stating they were told about potential side effects of the medication and pills had to be dispensed in clinics, medical offices or hospitals (not pharmacies).
    In April 2021, the FDA announced it would allow abortion pills to be mailed to patients for the duration of the pandemic. This action meant patients could obtain an abortion without making one (or several) in-person visits to a health care facility and risking unnecessary exposure to COVID-19. The change also allowed online-only abortion providers to mail pills to patients in more states.
  • Because medication abortion is a great option for patients and can be taken safely and effectively outside of a clinic setting, it has long been a target of abortion opponents. The lifting of mailing restrictions has predictably encouraged abortion opponents to quickly enact additional burdensome and medically unnecessary restrictions on medication abortion. These attacks have been paired with renewed efforts to misrepresent the method’s safety record and otherwise attempt to stigmatize it and deter its use.
  • As part of that larger strategy, anti-abortion policymakers have long pursued state-level restrictions to limit access to medication abortion, a push that may further intensify this year. As of February 2022:
    *In 32 states, clinicians who administer medication abortion are required to be physicians, even though medical professionals with different titles and specialties are otherwise allowed to prescribe medications, oversee treatments and manage patients’ health.
    *This is an effort to limit the availability of medication abortion, which particularly affects patients in rural or underserved areas where there may not be consistent access to a physician.
    *Texas prohibits the use of medication abortion starting at seven weeks of pregnancy, which is a politically determined limit at odds with current medical guidance. Indiana bans its use at 10 weeks, which corresponds to current FDA guidance, but prevents expanded access in the future.
    *In 19 states, the clinician providing a medication abortion must be physically present when the medication is administered, thereby prohibiting the use of telemedicine to prescribe medication for abortion.
    *In three states, mailing abortion pills to patients is currently banned (Arizona, Arkansas and Texas); mailing bans in another three states (Montana, Oklahoma and South Dakota) have been blocked by courts.
    * In January 2022, South Dakota approved regulations that would have required patients to make four trips to a clinic in order to obtain a medication abortion. Enforcement of these regulations has been blocked pending the outcome of litigation.
    *Already this year (as of February 22, 2022), 16 state legislatures have introduced bans or restrictions on medication abortion, including legislation that would ban the use of medication abortion in seven states (Alabama, Arizona, Illinois, Iowa, South Dakota, Washington and Wyoming), specifically prohibit the mailing of abortion pills in five states (Georgia, Kentucky, Maryland, Massachusetts and Nebraska) and bar the use of telehealth to provide medication abortion in eight states (Georgia, Iowa, Kentucky, Massachusetts, Minnesota, Nebraska, South Dakota and Tennessee).
  • Before abortion was legalized across the country in 1973, quality of care and health risks were widespread concerns for patients without legal access to the procedure. Given general medical advancements in the past 50 years and mifepristone’s safety record during more than 20 years of use, a larger worry among medical professionals and advocates today is the potential legal risk to patients, providers and anyone who assists someone in obtaining a medication abortion in states where it may be banned or criminalized. Actions that pose a risk for prosecution could include obtaining pills through alternative channels, such as online providers and clinics across state lines.
    Such a scenario is likely to further exacerbate existing racist and discriminatory law enforcement practices that target and disproportionately criminalize Black, brown and other people of color for their pregnancy outcomes. Furthermore, people of color account for the majority of abortion patients in the United States and they will be the most severely affected by denial of abortion care.

"The Availability and Use of Medication Abortion" (Apr 19, 2023)[edit]

"The Availability and Use of Medication Abortion". Kaiser Family Foundation. Published: Apr 19, 2023. Retrieved May 19, 2022.

  • On June 24th, 2022, the Supreme Court ruled on the Dobbs v. Jackson Women’s Health Organization, overturning Roe v. Wade. States can now set their own policies protecting or banning abortion without any federal standard protecting access to abortion. This has created a new focus on medication abortion as an option for expanding access to people facing barriers to abortion care.
    Medication abortion, also known as medical abortion or abortion with pills, is a pregnancy termination protocol that involves taking two different drugs, Mifepristone and misoprostol, that can be safely used up to the first 70 days (10 weeks) of pregnancy according to the U.S. Food and Drug Administration (FDA). The World Health Organization has authorized use to 12 weeks of pregnancy. Since the FDA first approved the drug in 2000, its use in the United States has quickly grown. By 2021, over half of abortions in the US were medication abortions. The medication abortion drug regimen approved by the FDA is available in many states across the nation, however, dispensing these pills for the purpose of terminating a pregnancy is now banned in some states. This factsheet provides an overview of medication abortion, how it is used and regulated, the role of the drug in self-managed abortions, and an analysis of the intersection of federal and state regulations pertaining to its provision and coverage.
  • The most common medication abortion regimen in the United States involves the use of two different medications: mifepristone and misoprostol. Mifepristone, also known as the abortion pill, or RU-486 is sold under the brand name Mifeprex and through a generic manufactured by GenBioPro in the United States. Mifepristone works by blocking progesterone, a hormone essential to the development of a pregnancy, and thereby preventing an existing pregnancy from progressing. Misoprostol, taken 24–48 hours after mifepristone, works to empty the uterus by causing cramping and bleeding, similar to an early miscarriage. A follow-up visit can be scheduled a week or two later, to confirm that the pregnancy was terminated via ultrasound or blood test. The FDA has found that medication abortion is a safe and highly effective method of pregnancy termination. When taken, medication abortion successfully terminates the pregnancy 99.6% of the time, with a 0.4% risk of major complications, and an associated mortality rate of less than 0.001 percent (0.00064%).
    The FDA first approved Mifeprex in 2000. In 2016, the FDA updated and approved a new evidence-based regimen and drug label, which guides current clinical practice. This regimen approves use of medical abortions for up to 70 days (10 weeks) of pregnancy (Table 1). Until 2019, mifepristone was only sold under the brand name Mifeprex, manufactured by Danco Laboratories. In 2019, the FDA approved GenBioPro, Inc.’s application for generic mifepristone.
  • While the combined regimen of mifepristone and misoprostol for medication abortion is recommended, there is a second medication abortion protocol using misoprostol–only that is more commonly used internationally and currently not approved by the FDA. The regimen is also recommended for up to 70 days (10 weeks) of pregnancy. It involves taking 800 µg (4 pills) of misoprostol sublingually or vaginally every three hours for a total of 12 pills. Research has shown the misoprostol-only regimen to be a safe and highly effective method of pregnancy termination, however it may result in a higher incidence of side effects, particularly diarrhea, fever and chills. When taken, the misoprostol-only regimen successfully terminates the pregnancy approximately 80-100% of the time, with a complication rate of less than 1%. Some U.S. telehealth organizations have been providing the misoprostol-only regimen as an option for medication abortion for a number of years.
  • In 2011, the FDA added a Risk Evaluation and Mitigation Strategy (REMS) to the dispensing requirements for mifepristone permitting only medical providers who had obtained certification from the manufacturer to prescribe and directly dispense the drug. This requirement has had the effect of limiting the number of clinicians able to prescribe medication abortions, but also necessitated an in-person visit to a health care setting and meant patients could not obtain the medication from a retail pharmacy or by mail.
    On December 16, 2021, the FDA removed the in-person dispensing requirement for mifepristone and expanded the distribution to include certified pharmacies in addition to certified clinicians. This change removed the requirement to dispense the medication in person and expanded the opportunity for telehealth in states that have not banned abortion. Despite the change to the in-person requirement, prescribers are still required to be certified by the manufacturers. On January 3, 2023, the FDA approved a protocol for pharmacies, allowing those that have been certified by the manufacturers to dispense mifepristone directly to patients. Table 2 shows the change in REMS from 2011 to 2021.
  • State laws that ban or restrict abortion apply to medication abortion just as they apply to abortion procedures. There are currently large swaths of the country, mostly in the South and Midwest that ban abortion. Even though the federal FDA has approved mifepristone as safe and effective, following the Dobbs decision, the availability of medication abortion today depends on state laws. Even before the Dobbs decision, however, some states restricted access to medication abortion either by blocking the use of telehealth abortions by mandating in-person visits for abortions, imposing requirements for in-person dispensing, or limiting the kinds of clinicians who could dispense the pills (only permitting MDs to dispense). In many states these laws are now superseded by state laws that ban abortion.
  • There are other ways that state laws also affect use of and access to medication abortion. Some states require that patients be counseled about unsubstantiated claims about the ability to reverse an abortion after mifepristone is ingested. For example, Nebraska, a state that hasn’t banned abortion, requires patients to be counselled that medication abortion may be reversed if given a high dose of progesterone after taking mifepristone—despite a lack of scientific evidence to support this claim. Similarly, Utah requires counseling that mifepristone alone is not always effective in ending a pregnancy and that patients may still have a viable pregnancy after taking mifepristone despite its record of effectiveness. Similar laws were passed in Arizona, North Dakota, and Kansas, with courts blocking the laws in Arizona and North Dakota, and the Governor vetoing the bill in Kansas. Prior to banning abortion Arkansas, Idaho, Kentucky, Oklahoma, South Dakota had similar requirements. Research demonstrates that APCs, such as nurse practitioners, physician assistants, or nurse-midwives, can dispense abortion pills as safely as physicians can, but they are only permitted to do so in 20 states and DC.
  • Telehealth can be used to expand access to health services in areas where the number of clinicians who provide abortion care is limited. Many patients, particularly those who live in rural communities, must travel long distances to obtain abortion services even in states where abortion is still permitted, which has raised interest in the potential of telehealth to expand access medication abortion. Because the updated FDA label now allows for telehealth, mifepristone has emerged as an option for patients who are either unable to travel to clinic or for other reasons wish to have an abortion in the privacy of their own home, if permitted by state law.
    As part of efforts to limit abortion access, some states have taken action to block the use of telehealth for abortion. Among the states that have not banned abortion, eight states have at least one restriction that requires at least one trip to the clinic, and effectively ban telehealth for medication abortion (Figure 1).
  • According to a recent study, the median self-pay price for medication abortion significantly increased from $495 in 2017 to $560 in 2020. Although Danco Laboratories does not make the cost of Mifeprex public, providers report that Mifeprex pills alone cost them around $90 a pill. GenBioPro, the manufacturer of the generic mifepristone drug also does not report the cost of their pill but has stated that they want to drive down costs for those who choose medication abortion. Private insurance coverage of abortion services is variable and depends on the type of insurance plan, the policy holder’s state of residence, and employer coverage decisions. Federal Medicaid funding only pays for abortions when the pregnancy is a result of rape or incest or a threat to the pregnant person’s life. Sixteen states have opted to use their own state funds to pay for abortions, including medication abortions, for Medicaid enrollees. For those who do not have abortion coverage, there are limited means of financial support, promoted on both Danco and GenBioPro’s website. The National Abortion Federation, as well as local abortion funds are sometimes able to cover some of the cost of an abortion (including travel) for a pregnant person. Outside of these funding sources or a sliding fee scale clinic, there are few options to help with abortion costs.
  • Although the overall rate of abortion has declined over the past two decades, the use of medication abortion as a share of all abortions has greatly increased over the years. According to Danco Laboratories, by 2016, over 2.75 million women in the United States had used Mifeprex since its FDA approval in 2000. Data from the Centers for Disease Control and Prevention (CDC) show medication abortions have increased steadily over the past 15 years. A 2022 Guttmacher Institute Report found that medication abortion accounted for 53% of all nonhospital abortions.
  • Self-managed abortion, sometimes referenced as “self-induced” or “at-home” abortion, is when a person ends a pregnancy outside the medical care setting, typically by ordering abortion pills online. Patients may seek to manage their own abortion for many reasons, including state bans, clinic access barriers, cost, transportation, time limitations, and privacy. There are different medication protocols that can be used for a self-managed abortion. As detailed in this JAMA review, an individual can take the FDA-approved medication abortion regimen of mifepristone and misoprostol pills or misoprostol pills alone.
    There are a number of companies that offer self-managed abortion services using different approaches. Some companies have a clinician that reviews a customer’s medical information and may have a telehealth visit. Other companies, such as AidAccess based outside the United States, will mail abortion medications to an individual without requiring a clinician visit. Plan C Pills operates a website that provides a list of online retailers in every state and includes information about clinician involvement, price, ship time, product quality, as well as information about how to take the drugs and resources for financing assistance. Prices differ between companies, but typically costs are lower than average charges for a clinic abortion as there is typically no involvement with a bricks and mortar clinic. One 2017 study found the median cost of mifepristone-misoprostol products ordered online is approximately $205.
  • The use of medication abortion has grown significantly since its approval by the FDA in 2000. The FDA update of the REMS could expand the availability of medication abortion and broaden the use of telehealth dispensing. However, state abortion bans, specific bans on telehealth for medication abortion, and state-level requirements for in-person dispensation of mifepristone and for in-person counseling visits and ultrasounds that are not medically recommended will continue to restrict access in many states.

"Medical abortion in the late first trimester: a systematic review" (February 2019)[edit]

Kapp N, Eckersberger E, Lavelanet A, Rodriguez MI (February 2019). [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367561/ "Medical abortion in the late first trimester: a systematic review". Contraception. 99 (2): 77–86. doi:10.1016/j.contraception.2018.11.002. PMC 6367561. PMID 30444970.

  • Results
    The search strategy returned 3384 articles, nine of which met inclusion criteria. Medical abortion, as compared with surgical abortion, was effective in the late first trimester (94.6% versus 97.9% complete abortion). A combined regimen of mifepristone and misoprostol was significantly more effective than misoprostol alone (90.4 versus 81.6% complete abortion). Complete abortion rates for all regimens investigated ranged from 78.6% to 94.6%. Success rates were higher with repeat dosing of misoprostol both in combination regimens and alone, and with vaginal compared with oral administration for repeat dosing.
    Conclusion
    A limited body of evidence indicates a range of efficacy of medical abortion in the late first trimester and highlights the need for well-designed trials in this gestational age range.
    Implications
    This review highlights the need for research focused on the late first trimester to strengthen the body of evidence. The available evidence is limited but offers reassurance that adverse events are rare for later first trimester abortion. Importantly, new research demonstrates that efficacy remains unchanged in the 10th gestational week regardless of whether the medication is taken in a facility or at a woman's home.
  • Medical abortion is an effective and acceptable option for abortion care. Given the few medical requirements for safe provision of medical abortion drugs, and that the abortion process may generally be managed by the woman, a growing proportion of induced abortions in the United States (US) and internationally are medical abortions. Unsafe abortion remains a significant threat to women's lives and health. Improved access to medical abortion, including by expanding the gestational ages at which it can safely be used is one strategy to reduce unsafe abortion, particularly where trained surgical providers are limited.
  • The most effective medical abortion regimen combines mifepristone with misoprostol; however, variation exists in dose, timing and route of administration of the two drugs. A large body of evidence, practice internationally, and recommendations by the World Health Organization (WHO) supports the efficacy of a 200 mg dose of mifepristone, followed by 800 mcg of misoprostol in pregnancies up to 63 days gestational age and recent data supports extending its use to 70 days gestation. These protocols are highly effective, with treatment failure occurring in approximately 2–5% of cases. Gestational age is known to affect the efficacy of all regimens, with decreasing efficacy after nine weeks gestation, which is why regimens recommend routinely repeating misoprostol doses starting in the late first trimester. Home administration of misoprostol has similar effectiveness as clinic administration up to 63 days gestation and is endorsed as a safe and acceptable practice in the WHO guidance. Studies of later gestational age ranges would need also to demonstrate similar efficacy, acceptability and rates of adverse events with home administration of medical abortion drugs.
  • The ideal regimen for medical abortion in the later part of the first trimester has yet to be determined. The objective of this review is to synthesize available information on medical abortion during the gestational age range of>63 to≤84 days gestational age. We conducted a review to compare the efficacy, safety and acceptability of medical abortion with surgical abortion; compare evidence on the dosage, route and frequency of misoprostol administration alone or following mifepristone; and compare management of medical abortion at home to within facilities. This systematic review is part of the evidence synthesis for WHO guidance related to the use of medical abortion in the clinical management of abortion care. An improved understanding of the efficacy, safety and acceptability of medical abortion in the later part of the first trimester should strengthen recommendations for medical regimens, and improve the information provided to women considering medical abortion.
  • Two articles meeting inclusion criteria compared vacuum aspiration with medical abortion (200 mg of mifepristone followed by 800 mcg of vaginal misoprostol between 36–48 h later) using a partially-randomized study design. In both of these studies, women with a preference between aspiration or medical methods received it; those without a preference were randomized between the two and data from all participants was combined, by method received. Only one of these studies reported on efficacy, finding the proportion of women having a complete abortion following a medical abortion was 94.6% as compared with 97.9% following vacuum aspiration, while rates of ongoing pregnancy were 1.5% and 0%, respectively.
    Safety outcomes included the following: the Ashok trial reported slightly higher rates of heavy bleeding with medical abortion (2.0% vs 0.8%), as compared with vacuum aspiration, but lower rates of pelvic infection (4.4% vs 8.2%). In the Robson study, there were four transfusions, and 11 suspected pelvic infections, which were not reported by treatment group, and four unplanned hospitalizations among those randomized to medical abortion. Side effects, including nausea, vomiting and diarrhea, were higher among women undergoing medical abortion in both studies. Acceptability was the primary outcome of the Robson study: vacuum aspiration was found to be more acceptable than medical abortion in women randomized to treatment group in both studies, and this preference for surgical treatment was greater at higher gestational ages.
  • One small study conducted in Tunisia was identified that compared the combination regimen with misoprostol alone, among women with pregnancies with a gestational age range of 9–12 weeks. Women were randomized to either mifepristone, 200 mg, followed 48 h later by 400 mcg oral misoprostol or to misoprostol alone (800 mcg vaginal administration). After 2 weeks, a quarter of women in both the combination regimen and misoprostol-only groups required a second dose of misoprostol to achieve a complete abortion rate of 80% vs. 78%, respectively; the remaining 19.2% and 32.5% were treated with uterine curettage. Ongoing pregnancy at two-week follow-up was half as common with the combined regimen (9.6%) compared with the misoprostol alone group (18.4%); however, curettage for persistent sac was reportedly no different between the two groups (9.5% vs. 8.1%, respectively). Side effects and acceptability were similar among the two treatment groups.
  • Two studies investigated the effect of differences in misoprostol dose and route of administration following mifepristone. Hamoda et al. conducted a randomized controlled trial of 340 women presenting for medical abortion with pregnancies up to 13 weeks gestational age. All women received 200 mg of mifepristone, and then were randomized to receive 600 mcg of misoprostol sublingually or 800 mcg vaginally. Misoprostol dosing was repeated at 3 h for all women, and 3 h later a third dose was given if abortion had not occurred. In terms of efficacy between 9–12 weeks gestation, there was no significant difference in the need for surgical evacuation for women in the sublingual and vaginal groups; however, only the sublingual group had ongoing pregnancies (n=2) and were offered surgical treatment while none occurred in the vaginal group. Women receiving misoprostol sublingually, as compared to vaginally, were more likely to experience the side effects of diarrhea (70.5% vs. 52.1%) and shivering among all gestational ages (data not disaggregated). Satisfaction scores were high in both groups (70% vs 68% were satisfied).
    Another trial randomized 1112 women presenting for medical abortion between 8–16 weeks gestation in 12 Shanghai hospitals to four treatment groups: 1) 200 mg mifepristone followed by 600 mcg misoprostol vaginally at 24 h, repeated every 3 h; 2) 200 mg mifepristone followed by 600 mcg misoprostol vaginally at 24 h, repeated orally every 3 h; 3) 200 mg mifepristone followed by 600 mcg misoprostol sublingually at 24 h; and 4) 100 mg mifepristone q 24 h for 2 doses followed by 600 mcg misoprostol vaginally every 12 h. The complete abortion rates among the gestational age group of 8–10 weeks was significantly lower in group 4, at 78.2%, than the other groups (≈93%, ≈89%,≈87%, respectively); ongoing pregnancy rates were similar between groups (2.2–2.9%). Average number of repeated doses was not reported by gestational age range. No differences in complete abortion were found between groups at higher gestational ages.
  • Three studies compared different misoprostol-only regimens for late first trimester abortion. A randomized trial of women presenting for medical abortion in Iran with pregnancies up to 16 weeks investigated the effect of differing misoprostol doses. Women with an indication for induced abortion (but without evidence of a failed or threatened abortion) were randomized to either 200 or 400 mcg of misoprostol vaginally every 6 h for up to four doses. Complete abortion rates at 48 h were not significantly different between the two groups (74.5% vs 76%, p=.086); although data were not disaggregated by gestation age, average was about 11 weeks.
    A second prospective cohort study conducted in Mozambique compared efficacy of medical abortion with 200 mcg or 400 mcg misoprostol given vaginally every 12 h. Complete abortion rates were low overall at 48 h at which point vacuum aspiration was performed among those incomplete, but higher among women receiving 400 mcg (30%) than 200 mcg (25%). Van Bogaert, et al. compared 400 mcg of sublingual misoprostol followed by 800 mcg of misoprostol vaginally or orally every 8 h among a prospective cohort. Complete abortion rates were higher among the vaginal group when compared with the oral group (93.4% vs 86.9%) with 42% of the women requiring repeat misoprostol. The only factor in a linear regression associated with need for repeat misoprostol doses was increasing gestational age.
  • One article investigating the management of abortion outside of health care facilities met inclusion criteria. In a comparative, non-randomized study conducted in Kazakhstan, investigators compared clinic- based versus at home administration of mifepristone (200 mg) in women with pregnancies up to 70 days of gestational age. Women were given the option to take mifepristone in the clinic or at home followed by home-administered sublingual misoprostol, 600 mcg. Out of a total sample of 290 women, 16 had pregnancies between 64 and 70 days gestational age. Ten of these took mifepristone at home, and six in the clinic. Most women (15/16) had a successful medical abortion; there was one ongoing pregnancy (1/16). There were no serious adverse events. Chills, diarrhea and nausea were the most common side effects. Overall, satisfaction rates were high among both groups with 98.4% of the home group and 99.0% of the clinic group reporting being very satisfied or satisfied.
  • Available evidence of efficacy and safety of medical abortion in the late first trimester is limited and highlights the need for well-designed trials in this gestational age range. Complete abortion rates for all regimens investigated ranged from 78.6% to 94.6%. Success rates were in the higher range when misoprostol dosing was repeated, both in combination regimens and alone, and when vaginal compared with oral administration was used. Ongoing pregnancy rates were lowest with the combination regimen, mifepristone and misoprostol. This limited body of evidence offers reassurance that adverse events are rare during medical abortion in the late first trimester.
    Overall, safety issues reported with medical abortion in the late first trimester were rare. An increased risk of heavy bleeding appears more likely with medical abortion as compared with vacuum aspiration and appears to be greater as gestational age increases. As with most studies of abortion, overall satisfaction and acceptability were high among participants; one exception may be for women randomized between methods, vacuum aspiration was significantly more acceptable than medical abortion.
    Importantly, new research is investigating the safe expansion of abortion management into a woman's home in this gestational age range. Although only one prospective study compared home use of medical abortion with clinic administration of mifepristone in gestations up to 70 days and was included in this review, other research is supportive. Two comparative, prospective studies, which had a comparison arm outside the gestational age range of this review and did not meet inclusion criteria, investigated the efficacy of medical abortion between 64–70 days compared with 57–63 days. One study with a total of 714 women found no significant difference in abortion efficacy between groups, with 94.8% and 91.9% (RR 0.79 CI 0.61–1.04) reporting complete abortions in the earlier and later gestational age groups, respectively. The rate of surgical intervention for excessive/prolonged bleeding was significantly greater for the later gestational age (0.5% in 57–63 days versus 2.5% in 64–70 days). A similarly-designed study in the US enrolled 729 women using 200 mg mifepristone followed 24–48 h later by 800 mcg buccal misoprostol. Rates of successful abortion did not differ between the two groups (93.5% vs 92.8%, respectively) nor did ongoing pregnancy (3.1% vs 3.0%). There were no differences in major adverse events. These studies demonstrate that efficacy remains unchanged in the 10th gestational week regardless of whether the mifepristone and misoprostol are taken in a facility or at a woman's home. Whether home administration at gestations later than 70 days has similar efficacy, adverse events and acceptability is a subject for future research.
  • Expanding the gestational ages at which medical abortion can be safely offered can increase access to quality abortion services. Current evidence supports the home use of mifepristone and misoprostol up to 70 days gestation, and emphasizes the need for routine, repeated misoprostol dosing beyond 70 days. Although medical abortion has great potential that is only becoming realized, uterine aspiration methods should remain an important option for women, as it is associated with high satisfaction and possibly with lower rates of adverse events of excessive bleeding. Further research of medical abortion in the late first trimester should aim to determine whether the gestational age range for home use is appropriate beyond 70 days gestation, and to investigate whether efficacy can be improved with misoprostol-only regimens by increasing the dose or timing interval; however, future research should be carefully designed to avoid introducing the most common biases we encountered in the literature, namely: selection, detection and performance biases. Ensuring access to safe abortion services is an important strategy to reduce maternal morbidity and mortality. Increasing the gestational age at which medical abortion is offered is one way to safely increase access to a critical health service.

"Women in states that ban abortion will still be able to get abortion pills online from overseas" (June 27, 2022)[edit]

Kimball S (June 27, 2022). "Women in states that ban abortion will still be able to get abortion pills online from overseas". CNBC. Retrieved June 30, 2022.

  • The Supreme Court on Friday overturned the landmark 1973 Roe v. Wade ruling that protected abortion as a constitutional right across the U.S. — allowing states to impose partial or full bans on the procedure.
    At least eight states immediately banned all forms of abortion, including medical abortions using the pill, within hours of the high court’s decision. Health-care providers who perform abortions, and in some cases people who help patients get the procedure, would face criminal prosecutions and yearslong prison sentences. In Missouri, for example, anyone who performs an abortion faces up to 15 years in prison.
    However, the states prohibit the prosecution of women who receive abortions, according to the text of the legislation in the eight states. That suggests many women with unwanted pregnancies who cannot travel out of state for an abortion will likely end their pregnancies alone at home with abortion pills purchased online through international telehealth companies like Aid Access.
  • “Under certain circumstances, it will be possible for women to get medication abortion from these internet providers and self manage their abortion, so it will provide some access to some people but not enough,” said Dr. Jennifer Villavicencio with the American College of Obstetricians and Gynecologists.
    “People can, with the right information, safely manage their own abortion in the first trimester,” she said.
  • The abortion pill, mifepristone, is approved in the U.S. to end pregnancies before the 10th week. The Food and Drug Administration first approved the medication in 2000, but required women to obtain it in person under a program that monitors certain drugs for safety risks.
    Abortion rights advocates fiercely criticized the FDA requirements, arguing that mifepristone had a long and proven track record as a safe and effective way to end an early pregnancy.
  • Aid Access will be one of the few options left for many women in U.S. states that have banned the procedure. The organization’s European doctors face little legal risk from state laws in the U.S.. However, health-care providers in the U.S. that offer abortions pills through telehealth into states that have banned the procedure would potentially face legal consequences.
    In telehealth, the patient’s location generally governs the laws that need to be followed, said Amanda Allen, senior counsel and director at the Lawyering Project. For example, a health-care provider based in New York, where abortion is legal, that offers the pill through telehealth to a patient in Texas would be subject to that state’s law, Allen said. The provider could face criminal penalties and their medical license could come under scrutiny, she said.
    “Unfortunately, that is going to mean very, very few choices for people in these ban states,” Allen said. “Telemedicine is not going to be a Band-Aid to the situation,” she said.
  • Abortion bans went into effect in Arkansas, Kentucky, Louisiana, Missouri, Oklahoma, South Dakota, Utah and Alabama on Friday. Idaho, Tennessee and Texas will implement bans in 30 days. Bans in Mississippi, North Dakota and Wyoming are set to take effect after a certification process.
    Nearly all of these 14 states specifically outlaw the prescription or administration of any drug to terminate a pregnancy, while in other states the bans are written so broadly that they include the pill as well.
    “They all apply throughout pregnancy to any method of abortion so medication abortion would not be available to people in those states,” said Elizabeth Nash, an expert on state abortion laws at the Guttmacher Institute. That means women will have two options — cross state lines or order pills online.
    “People are increasingly using online access,” Nash said, “but we’re going to see unfortunately how many more people will seek care that way.”
  • Websites such as Plan C Pills are also providing information on how patients are finding ways to obtain the abortion pill. In some cases, people are setting up telehealth consultations in states such as California, where abortion is protected, through services where a video visit is not required so they do not have to provide their location. They then set up a virtual mailbox on the internet, have the abortion pill mailed to that address and then have the package forwarded to their home, according to Plan C’s website.
    There are also several internet companies that mail generic abortion pills directly to people’s addresses without prescriptions or consultations. The medication costs anywhere from $200 to more than $400 depending on the website. Plan C has ordered medication from several of these companies, tested them at a lab and found they were real abortion pills, said Elisa Wells, the group’s co-founder. Plan C published results from its tests in the journal Contraception in 2017.
    However, the pills have not been inspected by the FDA, so their safety and effectiveness is not guaranteed by a U.S. regulator. It’s also unclear who runs these companies and where they are based. The FDA has in the past sought to shut down such websites.
    “There is never a guarantee, but based on our test purchases and initial laboratory testing, the sites we list on our website appear to provide real pills of adequate quality,” Wells said.
  • Dr. Abigail Aiken, an expert on reproductive health at the University of Texas at Austin, said pills from online websites would have to be regularly tested to ensure they are authentic. Aiken said it is important to make sure the pills come in a blister pack that is properly sealed, because exposure to air can affect the medication’s effectiveness. She also said the advantage of Aid Access, as opposed to other websites, is it has a staffed help desk to answer patient questions and provide information about the process.
    Aiken and Aid Access published a study in The Lancet in February that examined the records of nearly 2,800 people in the U.S. who used abortion pills prescribed by the group from March 2018 to 2019. About 96% of respondents reported they successfully ended their pregnancy without surgical intervention. One percent of patients reported serious side effects in which they needed medical treatment, including blood transfusion and intravenous antibiotics. No deaths were reported.
  • Women who take the abortion pill should have access to a phone and transportation to a medical facility in the event serious complications do occur, according to the National Abortion Federation. However, it’s unclear how much access women in banned states will have to that health care if they are one of the rare patients who has complications from the pill.
    Robin Marty, the operations director of West Alabama Women’s Center, said in some cases women who have had complications from the pill or thought they were having complications have been refused care at emergency rooms at some hospitals in Alabama.
    “Anyone who is having any sort of pregnancy complication needs to understand that there is nothing that they need to say to a doctor when they go in other than ’I’m pregnant — I’m scared and I think I’m having a miscarriage,″ Marty said. “That is all the information that they need to provide. Doctors owe them an examination. Emergency rooms owe them medical care.”
  • The abortion pill is about 97% effective at ending pregnancy though it’s most successful when taken at 49 days or earlier, according to a report by the American College of Obstetricians and Gynecologists.

"California Board of Nursing Sanctions Unproven Abortion 'Reversal' (Updated) - Rewire" Aug 17, 2017)[edit]

Nicole Knight, "California Board of Nursing Sanctions Unproven Abortion 'Reversal' (Updated) - Rewire". Rewire. (Aug 17, 2017)

  • California’s Board of Registered Nursing has approved a course on abortion pill “reversal,” giving credence to the unproven notion that it’s scientifically possible to undo a medication abortion.
    A spokesperson for the state Department of Consumer Affairs, a consumer watchdog agency that includes the Board of Registered Nursing, confirmed that an abortion “reversal” class met the department’s scientific standard for nursing education and the “letter of the law.”
    The approval paves the way for anti-choice organizations to teach so-called abortion reversal to nurses for state continuing education credit. Jor-El Godsey, president of Heartbeat International, one of the nation’s largest anti-choice groups, told Rewire the organization has “prioritized training nurses on this innovative medical intervention.”
    “Every nurse needs to know the truth about abortion—including the truth that a woman can change her mind in some cases even after beginning a chemical abortion,” he said in an emailed statement.
  • [S]imply failing the take the second medication can also forestall a medication abortion, according to a systematic review of medical literature. “Claims of medication abortion reversal are not supported by the body of scientific evidence,” the Arizona chapter of the American Congress of Obstetricians and Gynecologists said in a 2015 statement. Reproductive rights advocates contend that abortion “reversal” pushes a false narrative of abortion regret. Republican-led states like Arizona that enacted laws requiring doctors to discuss the idea of abortion “reversal” with patients are now on the hook for significant legal fees after losing in court, as Rewire reported this week.
    Earlier this year, the Louisiana Department of Health issued a report concluding there is “insufficient evidence to suggest that there is a sound method to reverse a medication-induced abortion.” Louisiana Republicans had asked the department to investigate the possibility of abortion “reversal.”
    California regulators for years allowed national anti-choice groups to teach similar unproven ideas to nurses in continuing education classes, as Rewire first reported last year. When Heartbeat International, for example, taught the abortion reversal class at a national conference in 2015, it touted in printed materials that it was approved by the state of California to do so.
    Last fall, following Rewire’s reporting, California’s governor signed a bill to crack down on continuing education providers and require the courses to hew to “scientific knowledge or technical skills required for the practice of nursing.” The law, sponsored by state Sen. Jerry Hill (D-San Mateo), also requires the state to routinely audit continuing education providers, something it hadn’t been doing.
  • On Thursday, Michelle M. Cave, spokesperson for the California Department of Consumer Affairs, told Rewire the Board of Registered Nursing approved the abortion reversal course because it met one of the criteria below:
    Be related to the scientific knowledge and/or technical skills required for the practice of nursing, or
    Be related to direct and/or indirect patient/client care. Learning experiences are expected to enhance the knowledge of the Registered Nurse at a level above that required for licensure. Courses related to the scientific knowledge for the practice of nursing include basic and advanced courses in the physical, social, and behavioral sciences, as well as advanced nursing in general or specialty areas. Content which includes the application of scientific knowledge to patient care in addition to advanced nursing courses may include courses in related areas, i.e., human sexuality; death, dying, and grief; foreign languages ( conversational); therapeutic interpersonal relationship skills; pharmacology; and those related to specialty areas of nursing practice. Courses in nursing administration, management, education, research, or other functional areas of nursing relating to indirect patient/client care would be acceptable. Courses which deal with self-improvement, changes in attitude, financial gain, and those courses designed for lay people are not acceptable for meeting requirements for license renewal.
    The Board of Registered Nursing, Cave noted, reviews “course content for evidence based scientific research.”
  • Last year, after hearing of the abortion reversal course, the board issued a cease and desist letter to Heartbeat International at the recommendation of Sen. Hill. But Cave told Rewire the board lacked the authority to send the letter and has since rescinded it.
    After publication, Sen. Hill told Rewire, “I am concerned about the action by the board and the Department of Consumer Affairs’ response to it, and will be following up on this matter. It is in fact, the board’s responsibility to determine what is and what is not relevant and appropriate to the practice of nursing and the continuing education for registered nurses.”
    Godsey contends Heartbeat International has seen abortion “reversal” work. “There are now 300 mothers nationally who have safely and successfully stopped their abortions after taking the first pill in the chemical abortion process, and that is good news regardless of one’s views on abortion,” he told Rewire.
  • Rebecca Griffin, associate director, California programs, of NARAL Pro-Choice America, said abortion pill reversal claims are unsupported by the body of scientific evidence.
    “It’s irresponsible to promote a procedure that isn’t grounded in good medicine and perpetuates offensive ideas about women’s ability to make informed reproductive health decisions,” she told Rewire in an email.

"Online abortion pill interest soars after the demise of Roe v. Wade" (July 1, 2022)[edit]

Korn J (July 1, 2022). "Online abortion pill interest soars after the demise of Roe v. Wade". CNN. Retrieved July 4, 2022.

  • Traffic to telehealth abortion platforms has skyrocketed in the last several days and weeks, up 456% when the draft opinion was leaked in May compared to the previous month and an additional 20% month over month in June when the final Supreme Court verdict was announced, according to Similarweb data. These platforms reached 5.3 million web visits in June, pushing abortion pill startups to rapidly expand to match growing demand.
    On June 24th, the day the decision was released, visits to telehealth abortion platforms soared to 436,727, up 2,585% from the day before, according to Similarweb. The next day, traffic rose more than 50%.
  • Since Roe v. Wade was overturned, Choix has seen a 600% jump in web traffic, according to the company. In the less than four days following the decision, Just The Pill had over 260 appointment requests made online, up from the usual 20 to 25 a day, according to the company. Hey Jane saw site traffic grow nearly tenfold and patient demand more than double when compared to last month’s average. The abortion pill startup is treating 25 times more patients daily than 15 months ago, according to the company, as it pushes to expand beyond its current six state reach.
    Carafem, an organization that offers both telemedicine appointments and by-mail abortion pills in several states, said it has seen a spike in web traffic, double the number of phone calls and a “large increase in demand” for abortion care.
  • Just The Pill is launching a new initiative, “Abortion Delivered,” which will use mobile clinics to deliver medication abortion to cater to “the major influx of people who will now need care,” said Dr. Julie Amaon, medical director of Just The Pill and Abortion Delivered, in a statement. “We are undaunted. We will bring care to the people who most need it, and we will defy reproductive repression by providing more affordable and accessible care.”
    The mobile clinics will operate on state borders to reduce travel issues for patients coming from more restrictive states. By working outside the boundaries of a traditional building the effort will be able to adapt more quickly to shifting legislation, according to Dr. Amaon.
  • Remote care from services like Choix and Hey Jane cost about half the national average, according to the companies. They also partner with abortion funds to offer patients financial assistance if needed. Even so, these pills still cost between $249 and $289, including consultation fees, medication, shipping and provider check-ins.
  • “Over the last year, we’ve seen telemedicine abortion platforms grow to be a primary battleground in the fight for abortion rights,” said Sneha Pandey, a Similarweb data expert analyst. “Numerous states are moving to ban all forms of abortion, including 19 states that have already banned telemedicine abortions, but this is a largely unregulated space. The availability of telehealth and mail order abortion makes an outright ban incredibly difficult to enforce.”

"Medical methods for first trimester abortion" (2011)[edit]

Kulier R, Kapp N, Gülmezoglu AM, Hofmeyr GJ, Cheng L, Campana A (2011). "Medical methods for first trimester abortion". The Cochrane Database of Systematic Reviews. 11 (11): CD002855. doi:10.1002/14651858.CD002855.pub4. PMC 7144729. PMID 22071804. S2CID 205167182.

  • Safe and effective medical abortion methods are available. Combined regimens are more effective than single agents. In the combined regimen, the dose of mifepristone can be lowered to 200 mg without significantly decreasing the method effectiveness. Vaginal misoprostol is more effective than oral administration, and has less side effects than sublingual or buccal.
  • Surgical abortion by vacuum aspiration or dilatation and curettage has been the method of choice for early pregnancy termination since the 1960s. Medical abortion became an alternative method of first trimester pregnancy termination with the availability of prostaglandins in the early 1970s followed by the development of anantiprogesterone in the 1980s. Large uncontrolled studies suggested that early medical abortion with mifepristone and a prostaglandin would be an effective method for pregnancy termination (Urquhart 1997).
    Various drugs have been used for first trimester medical abortion. The most widely researched are prostaglandins (PGs) alone, mifepristone alone, methotrexate alone, mifepristone with prostaglandins and methotrexate with prostaglandins. Prostaglandins soften the cervix, cause uterine contractions and are used orally or vaginally for ripening of the cervix before surgical or for medical abortion. The most commonly used prostaglandins are gemeprost given vaginally and misoprostol administered either orally (including buccal and sublingual) or vaginally. Misoprostol is a prostaglandin analogue registered for use in nonsteroidal anti‐inflammatory drug (NSAID) induced gastric ulcer prevention and treatment. It has a strong uterotonic effect and is used to induce pregnancy terminations illegally in some parts of the world (Blanchard 1999, Costa 1998) as well as legally, in areas where mifepristone is not available. The reported complete abortion rate for misoprostol alone varies between 61% for single and 93% for repeat doses (Bugalho 1996, Carbonell 1997b). Gemeprost used alone appears to be less effective in inducing complete abortion than when used in combination with mifepristone (Norman 1992).
    Mifepristone, an antiprogestogen, blocks the receptors for progesterone and glucocorticosteroid and increases the sensitivity of the uterus to prostaglandins (Bygdeman 1985). This blockage results in the breakdown of maternal capillaries in the decidua, the synthesis of prostaglandins by the epithelium of decidual glands and inhibition of prostaglandin dehydrogenase (WHO 1997).
  • Side‐effects of medical methods are heavy bleeding, pain, nausea, vomiting and diarrhoea, varying in severity according to the protocols and gestational age (Henshaw 1994). In two randomised controlled trials included in the Cochrane review of the subject, compared to surgical procedures, medical methods are associated with a longer duration of bleeding (Say 2002, updated 2010).
    Failed abortion is an infrequent but important complication of medical abortion. Both methotrexate and misoprostol may lead to fetal anomalies if the pregnancy persists, as described by some (Grimes 1997). However, other reports state that none of the malformations reported could be conclusively related to medications used for medical abortion (Wiebe 2006).
    Some women prefer medical to surgical abortion. 'More natural', 'being easier', more private', and 'can be done earlier in pregnancy' were reasons to opt for a medical method by some women (Creinin 1996b). Characteristics such as the method being more new, less invasive and the possibility of verifying the expulsion were reported by others (Bachelot 1992).
    Medical methods for first trimester abortion are already widely available in some countries and increasingly available throughout the world. It is therefore important to identify the best available agents and regimen for use. Comparison of medical methods with surgical evacuation in the first trimester is the subject of another review: Say 2002, updated 2010.
  • The literature on different medical abortion methods is vast, but contains relatively few randomised controlled trials comparing the different regimens.
  • An important aspect of this review is the overall very low rate of major complications reported among the various medical abortion regimens. The most common complication is the need for blood transfusion (about 0.2%) (see table 'characteristics of included studies'). The reported self‐limiting side‐effects of medical abortion regimens are mainly due to the prostaglandins (nausea, vomiting, diarrhoea). The dose, route and type of prostaglandin used may influence the occurrence of side effects, as higher doses and oral administration are associated with an increase in nausea and vomiting.

"Mifegymiso Product Monograph" (April 15, 2019)[edit]

Linepharma International Limited (April 15, 2019). "Mifegymiso Product Monograph" (PDF). Health Canada.

  • Mifegymiso (mifepristone tablet/misoprostol tablets) is indicated for medical termination of a developing intra-uterine pregnancy with a gestational age up to 63 days as measured from the first day of the Last Menstrual Period (LMP) in a presumed 28-day cycle.
    • p.3
  • Limitations of use:
    Mifegymiso is not intended for routine use as a contraceptive. Prior to prescribing Mifegymiso, health professionals must:
    * Ensure that patients have access to emergency medical care in the 14 days following administration of mifepristone;
    * Schedule follow-up 7 to 14 days after patients take mifepristone to confirm complete pregnancy termination;
    * Exclude ectopic pregnancy and confirm gestational age by an appropriate method.
    * Counsel each patient on the risks and benefits of Mifegymiso, including bleeding, infection and incomplete abortion;
    * Obtain the patient’s informed consent to take the drug; Mifegymiso should be prescribed by health professionals with adequate knowledge of medical abortion and/or who have completed a Mifegymiso education program.
  • p.4
  • CONTRAINDICATIONS
    Mifegymiso should not be prescribed to patients who:
    * have a confirmed or suspected ectopic pregnancy;
    * have an intrauterine device (IUD) in place;
    * have unconfirmed gestational age;
    * have chronic adrenal failure;
    *are on concurrent long term systemic corticosteroid therapy;
    *have haemorrhagic disorders or using concurrent anticoagulation therapy;
    *have inherited porphyria;
    *have uncontrolled asthma;
    *have known hypersensitivity to mifepristone, misoprostol, other prostaglandins, or any of the excipients used in Mifegymiso. For a complete listing, see the DOSAGE FORMS, COMPOSITION AND PACKAGING
  • p.4
  • It is important that all patients be followed by a health professional 7 to 14 days after taking mifepristone to confirm safety and complete pregnancy termination (see WARNINGS AND PRECAUTIONS, Genitourinary, Failures and Monitoring and Laboratory Tests).
    • p.5
  • Return to fertility: Patients should be advised of their immediate return to fertility after Mifegymiso administration. To avoid the potential exposure of a subsequent pregnancy to mifepristone and misoprostol, it is recommended that conception be avoided during the next menstrual cycle. Reliable contraceptive methods should therefore commence as early as possible (see WARNINGS AND PRECAUTIONS, Special Populations, Pregnant Woman).
    • p.5
  • Genitourinary
    Gestational age should be confirmed by an appropriate method. Ultrasound imaging is recommended before prescribing Mifegymiso when an ectopic pregnancy is suspected or gestational age is uncertain. Health professionals should remain alert to the possibility that a patient who is undergoing a medical abortion could have an undiagnosed ectopic pregnancy, since some of the symptoms of a medical abortion may be similar to those of a ruptured ectopic pregnancy. The presence of an ectopic pregnancy may have been missed even if the patient underwent ultrasonography prior to being prescribed Mifegymiso.
    • p.6
  • Failures in clinical studies occurred in 2.7 to 5.1% of cases prior to 63 days of gestation (see CLINICAL TRIALS). The rate of failure increases with advancing gestational age. Reasons for failure requiring a surgical termination of pregnancy included persistent non-viable pregnancies, continuing pregnancies and persistent heavy vaginal bleeding. Follow-up is mandatory to ensure that the expulsion is completed. In the event of an ongoing pregnancy, pregnancy termination should be completed by another method (see WARNINGS AND PRECAUTIONS, Special Populations, Pregnant Woman). Animal studies have shown that, if a pregnancy continues after exposure to mifepristone or misoprostol, fetal abnormalities may occur (see TOXICOLOGY, Reproductive and developmental studies).
    • p.6
  • Bleeding occurs in almost all cases and is not proof of complete expulsion (see CLINICALTRIALS). Prolonged heavy vaginal bleeding may occur and can be a sign of incomplete expulsion. Bleeding can lead to a significant decrease in hemoglobin levels and may necessitate a blood transfusion.
    Persistent bleeding should be monitored closely.
    The patient should have access to emergency medical care until complete termination of pregnancy is confirmed at a follow-up visit.
    • p.6
  • Cases of serious bacterial infection, including very rare cases of fatal septic shock, have been reported following the use of mifepristone and misoprostol. A sustained fever of 38oC or higher, severe abdominal pain or pelvic tenderness in the days after a medical abortion may be an indication of infection.
    • p.6
  • Heavy bleeding requiring curettage occurred in some patients in clinical trials. Patients with anemia should be treated with caution. Patients with severe anemia were excluded from clinical trials and administration of Mifegymiso in these patients is not recommended.
    • p.7
  • During clinical trials, pregnancies occurred between embryo expulsion and the resumption of menses. To avoid the potential exposure of a subsequent pregnancy to mifepristone and misoprostol, conception should be avoided during the next menstrual cycle. Reliable contraceptive precautions should commence as early as possible after Mifegymiso administration.
    • p.7
  • Rare serious cardiovascular accidents have been reported following administration of prostaglandins including misoprostol. Mifegymiso has not been studied, and is therefore not recommended, in women with cardiovascular disease.
    • p.7
  • Patients with suspected acute adrenal failure were excluded from trials and therefore should be treated with caution. If treatment with Mifegymiso is required, therapy should be adjusted. The safety and efficacy have not been studied in women suffering from malnutrition. Treatment with Mifegymiso is therefore not recommended.
    • p.7
  • The safety and efficacy have not been studied in women suffering from hepatic failure. Treatment with Mifegymiso is therefore not recommended.
    • p.7
  • Seizures have been reported with prostaglandins and prostaglandin analogues, and therefore this possibility should be considered when treating patients with a history of a seizure disorder.
    • p.8
  • The safety and efficacy have not been studied in women suffering from renal failure. Treatment with Mifegymiso is therefore not recommended.
    • p.8
  • Due to the antiglucocorticoid activity of mifepristone, the efficacy of corticosteroid therapy, including inhaled corticosteroids, may be decreased temporarily following intake of mifepristone. Therapy should be adjusted. Bronchospasm may occur with some prostaglandins and prostaglandin analogues. Caution should be exercised in patients with a history of asthma (see CONTRAINDICATIONS).
    • p.8
  • Reproductive studies conducted in rabbits and monkeys have shown that if a pregnancy continues after exposure to mifepristone, abnormalities in fetal skull, brain and developmental markers may occur (see TOXICOLOGY, Reproductive and developmental studies). A review of births from 105 pregnancies exposed during first trimester of pregnancy to mifepristone alone (46 cases) or to both mifepristone and misoprostol (59 cases) has been published1. There were 94 live births (90.4%) and 10 (9.6%) miscarriages (including one with major malformation). Elective termination of pregnancy was performed after the subsequent diagnosis of trisomy 21 in one case. The overall rate of major congenital malformations was 4.2% (95% CI: 1.2 – 10.4%), with two cases among 38 patients exposed to mifepristone alone and two cases among 57 patients exposed to both mifepristone and misoprostol.
    • p.8
  • Use of misoprostol has been associated with birth defects. When used alone to induce an abortion, the following effects of misoprostol have been reported: malformations of limbs, abnormalities of fetal movements and of cranial nerves (hypomimia, abnormalities in suckling, deglutition, and eye movements).
    Misoprostol was shown to be embryotoxic in rabbits, rats and mice, when exposure occurred during embryogenesis. There was also an increase in skeletal abnormalities in rabbits and cleft palate in mice (see TOXICOLOGY, Reproductive and developmental studies).
    • pp.8-9
  • Due to the risk of failure of the medical method of pregnancy termination an Mifegymiso use should be avoided during breast-feeding.
    Mifepristone is lipophilic and may be excreted in the mother's milk. Misoprostol is rapidly metabolised in the mother to misoprostol acid, which is biologically active and is excreted in breast milk. This could cause undesirable effects such as diarrhea in breastfeeding infants. d to the unknown risk to the fetus, follow-up is mandatory (see WARNINGS AND PRECAUTIONS, Boxed Serious Warnings and Precautions). Should a failure of Mifegymiso be diagnosed at follow-up (viable ongoing pregnancy), it is recommended that pregnancy termination should be completed by another method.
    • p.9
  • There are insufficient data in patients less than 15 years old to establish efficacy and safety. Mifegymiso is not indicated in the prepubertal population.
    Patients 15 to 17 years of age had similar efficacy to that seen in the adult population. More pain than expected was reported more frequently in this population, as well as vomiting, compared with adults (see CLINICAL TRIALS). Careful counselling should be provided to adjust patients’ expectations from the procedure and identification of safety issues requiring immediate medical attention.
    • p.9
  • Follow-up must take place within a period of 7 to 14 days after administration of Mifegymiso to verify that expulsion has been completed (i.e. clinical examination, ultrasound scan or beta-hCG measurement).
    • pp.9-10
  • Bleeding was occasionally observed after mifepristone alone. Misoprostol administration resulted in vaginal bleeding, abdominal pain and cramping. In some patients, persistent or heavy vaginal bleeding required treatment with intravenous fluids or blood transfusion. On average, bleeding lasted for 11.4 days and was heavier than a normal period for 2.2 days.
    Infectious complications, including sometimes fatal sepsis, have been observed. Patients typically presented with abdominal pain or discomfort, fever or general malaise (including weakness, nausea, vomiting or diarrhoea) more than 24 hours after taking misoprostol. Clostridium sordellii infection was observed in some women without abdominal pain or fever, that progressed rapidly to multi-organ failure and death.
    • p.10
  • Mifegymiso was studied in three open-label multi-center prospective studies. In these studies, a total of 1,596 women were included in the safety analysis. The mean age of women who received mifepristone and misoprostol was 26.0, 26.7 and 25.4 years for Studies 1, 2 and 3, respectively. Treatment-emergent adverse events reported in clinical trials are reported in Table 2. Nausea and vomiting tended to increase slightly with advancing gestational age.
    • p.11
  • Of the 1,000 women enrolled in Study 3, 67 were less than 18 years of age. The reported frequent adverse events are detailed below. Women less than 18 years old reported vomiting more frequently than women 18 years and older.
    • p.11
  • No interaction studies have been performed with mifepristone and misoprostol.
    • p.12
  • Due to the irreversible nature of the CYP binding and the slow elimination of mifepristone from the body, such interaction may be observed for a prolonged period after its administration. Therefore, caution should be exercised when mifepristone is administered with drugs that are CYP3A4 substrates and have narrow therapeutic range, including some agents used during general anaesthesia.
    Due to the antiglucocorticoid activity of mifepristone, the efficacy of corticosteroid therapy, including inhaled corticosteroids, may be temporarily decreased following intake of mifepristone. Therapy should be adjusted.
    • p.12
  • Grapefruit juice may inhibit mifepristone’s metabolism, increasing its serum levels.
    • p.13
  • The concomitant use of St. John’s wort may increase mifepristone metabolism, lowering its serum levels.
    • p.13
  • Before starting Mifegymiso, patients must be informed of the following:
    * Mifepristone and misoprostol must be taken in sequence according to instructions.
    * Follow-up within 7 to 14 days after intake of mifepristone to confirm pregnancy termination and complete abortion is required.
    * Return to fertility is expected immediately after Mifegymiso administration and reliable contraceptive methods should be started as early as possible.
    * Failure of Mifegymiso may require surgical termination of pregnancy (see CLINICAL TRIALS).
  • p.13
  • 200 mg of mifepristone (1 tablet) should be taken orally, followed 24 to 48 hours (1 to 2 days) later by the administration of misoprostol.
    Mifepristone should be administered as directed by the prescribing health professional.
    Misoprostol:
    800 mcg of misoprostol (4 tablets, each tablet containing 200 mcg) should be taken in a single intake by buccal route (kept between the cheek and the gum for 30 minutes before any remaining fragments are swallowed with water).
    There are no data available on the effect of food intake on the absorption of mifepristone or misoprostol.
    • pp.13-14
  • If it is less than 48 hours since the patient took Step 1 but after the time and date on the Patient Information Card, clinical trial data indicates that health professionals can instruct patients to take the Misoprostol tablets (Step 2) right away.
    • p.14
  • Mifepristone
    No cases of overdose have been reported.
    In the event of massive ingestion of mifepristone signs of adrenal failure may occur. Signs of acute intoxication may require specialist treatment including the administration of dexamethasone.
    Misoprostol
    Cumulative total daily doses of 1600 mcg have been tolerated, with only symptoms of gastrointestinal discomfort reported.
    Possible symptoms of an overdose are sedation, tremor, convulsions, dyspnoea, abdominal pain, diarrhea, fever, palpitations, hypotension or bradycardia. Hypertension and tachycardia have also been reported.
    There is no specific antidote. Treatment should be symptomatic and supportive. Consider administration of activated charcoal in the event of a potentially toxic ingestion. Activated charcoal may reduce absorption of misoprostol if given within one or two hours after ingestion.
    • pp.14-15
  • When mifepristone blocks progesterone receptors, the endometrium can no longer sustain the growing embryo. Without the effect of progesterone, the lining of the uterus breaks down, and bleeding begins. Mifepristone also triggers an increase in prostaglandin levels and dilates the cervix, facilitating abortion. Misoprostol then induces contractions of the smooth muscle fibers in the myometrium, relaxation of the uterine cervix and evacuation of intrauterine content.
    • p.15
  • Mifepristone is a synthetic steroid with antiprogestational action as a result of competition at the progesterone receptors.
    Mifepristone binds to human progesterone receptors with nanomolar affinity. In animals, oral administration was shown to inhibit the action of endogenous or exogenous progesterone in multiple species.
    In women administered 1 mg/kg or greater, mifepristone antagonises the endometrial and myometrial effects of progesterone. During pregnancy it sensitises the myometrium to the contraction-inducing action of prostaglandins. During the first trimester, administration of mifepristone allows cervical dilatation.
    In vitro studies showed mifepristone to also bind to the glucocorticoid and androgen receptors with high affinity, comparable to that for the progesterone receptor. In toxicological studies in rats and monkeys up to a duration of 6 months, mifepristone produced effects related to its antihormonal (antiprogesterone, antiglucocorticoid and antiandrogenic) activity.
    In man the antiglucocorticoid action is manifested at a dose equal to or greater than 4.5 mg/kg by a compensatory elevation of ACTH and cortisol.
    • p.15
  • Misoprostol is a synthetic analogue of prostaglandin E1. At the recommended dosage, misoprostol induces contractions of the smooth muscle fibers in the myometrium and relaxation of the uterine cervix. The uterotonic properties of misoprostol facilitates cervical opening and evacuation of intrauterine content.
    • p.15
  • Absorbtion:
    After oral administration of a single dose of 200 mg, mifepristone is rapidly absorbed. The peak concentration of 2.3 to 2.7 mg/L is reached after 0.75 hours (mean of 49 subjects). The half-life of mifepristone is 36.5 to 38.3 hours.
    The absolute bioavailability of a low oral dose of 20 mg is 69%.
    • p.16
  • Distribution: Mifepristone is 99% bound to plasma proteins, albumin and 1-acid glycoprotein in man. Binding to the latter protein is saturable, and the drug displays nonlinear kinetics with respect to plasma concentration and clearance. Animal studies found mifepristone to be widely distributed, initially having high extravascular concentration, but shifting to greater erythrocyte concentration over 24 hrs. Studies in pregnant animals have shown mifepristone to cross the placental barrier.
    • p.16
  • Metabolism: Metabolism of mifepristone is primarily via pathways involving N-demethylation and terminal hydroxylation of the 17 propynyl chain. In vitro studies have shown that CYP450 3A4 is primarily responsible for the metabolism. The three major metabolites identified in humans are: (1) N-monodemethylated metabolite, the most widely found in plasma; (2) N- didemethylated mifepristone, which results from the loss of two methyl groups from the 4- dimethylaminophenyl in position 11 ß; and (3) terminal hydroxylation of the 17-propynyl chain.
    • p.16
  • Excretion: Elimination of mifepristone is slow at first (50% eliminated between 12 and 72 hours) and then becomes more rapid with a terminal elimination half-life of 18 hours. Mifepristone shows non-linear pharmacokinetics. Eleven days after a 600 mg dose of tritiated compound, 83% of the drug has been accounted for in the feces and 9% in the urine. Serum levels are undetectable at 11 days.
    • p.16
  • Absorption: When administered orally, misoprostol is rapidly absorbed and metabolized. Peak concentrations around 1.1 ng/mL were reached about 15 minutes after a 400 microgram dose in the fasting state. Plasma concentrations of its main degradation metabolite, misoprostol acid, reach their peak of 2 - 2.5 ng/mL after a 2 microgram/kg oral dose within approximately 30 minutes and rapidly decline thereafter. As a result, uterine contractility increases and then

plateaus after about one hour. Absorption is almost complete, measured at levels between 64 - 73% from urinary data. While not compared directly with oral administration, buccal administration has been found to result in peak concentrations comparable to those following vaginal administration, which have been found in turn to be lower and later than those for oral administration.

    • p.16
  • Distribution: Serum protein binding of labeled misoprostol acid was studied in man and was similar in young (81-88%) and elderly (81-89%) subjects. Accumulation in erythrocytes was not seen.
    Metabolism: Metabolism of misoprostol to misoprostol acid is rapid with no intact misoprostol found in plasma consistent with an in vitro half-life of 6.4 minutes for the de-esterification of misoprostol in human plasma at 37ºC.
    Excretion: Elimination of misoprostol and its metabolites is also rapid with a plasma elimination half-life of 21 minutes in man. 1-4% of misoprostol acid is excreted in the urine.
    • p.17
  • Mifegymiso should be stored between 15-25°C in its original outer carton in order to protect from light. Keep out of the sight and reach of children.
    * When separated, mifepristone should be stored between 15-30°C; in the mifepristone (Green) box, in order to protect from light.
    * When separated, misoprostol should be stored between 15-25°C; in the misoprostol (Orange) box.
  • p.17
  • Mifepristone tablets are white to off white, round, biconvex with “MF” embossed on one side. Each tablet contains 200 mg of mifepristone and the following non-medicinal ingredients: colloidal silica anhydrous, magnesium stearate, maize starch, microcrystalline cellulose and povidone K30.
    Mifepristone is packaged in a PVC/PVDC/Aluminum blister of 1 tablet presented in a green box of one tablet.
    • p.17
  • Misoprostol tablets are white, round flat with “ML” debossed on one side and “200” on the other side. Each tablet contains 200 mcg of misoprostol and the following non-medicinal ingredients: hydrogenated castor oil, hypromellose, microcrystalline cellulose and sodium starch glycolate.
    Misoprostol tablets are packaged in dual-faced aluminum strips and presented in an orange box

of four (4) tablets.

    • p.17-18
  • Proper name or common name: mifepristone
    Chemical name: (11β,17β)-11-[4-(Dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one
    CAS Registry Number: 84371-65-3
    Molecular formula and molecular mass: C29H35NO2; 429.6 g/mol
    • p.19
  • The compound is a yellow powder with a melting point of 191-196 °C. It is highly soluble in methanol and methylene chloride, and poorly soluble in water.
    • p.19
  • Proper name or common name: misoprostol
    Chemical name: (±)-Methyl (1R,2R,3R)-3-hydroxy-2-[(E)-(4RS)-4-hydroxy-4-methyl-1-octenyl]-5- oxocyclopentaneheptanoate (USP)
    CAS Registry Number: 59122-46-2
    Molecular formula and molecular mass: C22H38O5; 382.54g/mol
    • pp.19-20
  • Misoprostol is a clear, colorless to yellowish oily liquid. Practically insoluble in water, soluble in ethanol (96%), sparingly soluble in acetonitrile.
    • p.20
  • Results from the three phase 3 pivotal trials are summarized in Table 5 to Table 9. Clinical efficacy in the three pivotal trials was defined as complete abortion without surgical intervention. In the three studies, women presenting at follow-up with an on-going viable pregnancy were offered surgical termination of pregnancy. Ultrasound was performed in 96.7% of patients in clinical trials. Women presenting with a persistent gestational sac at first follow-up visit could opt for surgical intervention or wait and follow-up at a next visit for a spontaneous resolution on Day 15 to 36 post-mifepristone. In studies 2 and 3, women with a persistent gestational sac at the first follow-up visit could also choose to receive a second dose of 800 mcg buccal misoprostol. Of the 12 women choosing a second misoprostol dose, 9 had a complete abortion without surgery at next follow-up visit and 3 required a surgical intervention.
    • pp.21-22
  • The results from the three trials indicate that a regimen of 200 mg oral mifepristone followed by 800 mcg buccal misoprostol is efficient for the termination of a pregnancy with a gestational age of 63 days or less. Stratification of the efficacy by age and ethnicity revealed no clinically meaningful difference in termination of pregnancy outcome. In trials 2 and 3, patients with a gravidity of 4 or more tended to have a higher failure rate in the 50 to 63 days of gestational age group (failure rate 3.1-3.4% vs 6.3%, in women with gravidity of 1-3 (N = 465) or 4 and over (N = 142)), but not in women with a gestation of 49 days or less (failure rate 1.9-2.5% vs 2.3% in women with gravidity of 1-3 (N = 592) or 4 and over (N = 172)).
    • p.22
  • Of the 1,000 women enrolled in Study 3, 67 were less than 18 years of age. The number of participants is stratified by age below:
    In that population, all women (100 %) had termination of pregnancy without the need for a surgical intervention. Women less than 18 years old tended to rate pain intensity higher and to report more frequently “feeling more pain than expected” than women 18 years and older.
    • p.23
  • This retrospective observational study conducted in 15 clinics in Australia reported the outcome of 5,730 patients having termination of pregnancy of less than 63 days since last menstrual period with a regimen of 200 mg mifepristone followed 24-48 hours later by 800 μg buccal misoprostol. 121 patients of less than 18 years of age were enrolled and one woman (0.8%) received a surgical intervention for retained products of conception. No other serious adverse events were reported in pediatric patients.
    • pp.23-24
  • This observational study conducted in women’s health clinics in Australia reported the outcome of 10,822 patients having termination of pregnancy of 63 days since last menstrual period or less with a regimen of 200 mg mifepristone followed 24-48 hours later by 800 μg buccal misoprostol. In the study, 138 women of less than 18 years of age were enrolled and 2.8% reported a method failure and required a surgical termination of pregnancy. Two patients reported an incomplete abortion and one patient a continuing pregnancy. All three required surgical termination of pregnancy. No serious haemorrhage or infection was reported in pediatric patients.
    • p.24
  • Mifepristone is an orally active antiprogestogen which acts by competing with progesterone for receptor binding. It also possesses antiglucocorticoid and antiandrogenic activity. It is devoid of estrogenic, antiestrogenic, mineralocorticoid and antimineralocorticoid properties. Its ability to block the action of progesterone on the pregnant uterus provides a medical approach to termination of early pregnancy. In normally menstruating women, the effect of mifepristone depends on the timing of administration. When administered in the first half of the luteal phase, menstrual induction occurs independently of luteolysis; mifepristone administration during the mid-luteal phase produced bleeding within a few days in most women but there was a second bleed at the time of expected menses in about two-thirds. The first episode of bleeding occurred in the presence of elevated progesterone and estrogen concentrations. Administration during the late luteal phase resulted in bleeding within 1 to 3 days, shortening the luteal phase of the treatment cycle and lengthening of the subsequent follicular phase. Administration on the first 3 days of the menstrual cycle had no effect on cycle length but when given in the late follicular

phase, mifepristone prolonged the follicular phase by preventing the development of a normal LH surge and delaying the new surge for about 15 days.

    • p.24
  • In the first trimester of pregnancy, mifepristone induced uterine activity in virtually all women 36 and 48 hours after administration, and increased the sensitivity of myometrium to exogenous prostaglandins (PG). The accompanying increase in decidual PGF2 production was attenuated by indomethacin, but the increase in uterine activity was not: thus, mechanisms other than an increase in decidual PG production contribute to the abortifacient effect of mifepristone. Mifepristone administration also resulted in cervical ripening in pregnant women.
    • pp.24-25
  • Misoprostol is a synthetic analogue of prostaglandin E1. At the recommended dosages, misoprostol induces contractions of the smooth muscle fibers in the myometrium and relaxation of the uterine cervix. The uterotonic properties of misoprostol should facilitate cervical opening and evacuation of intrauterine content. In the event of an early termination of pregnancy, the combination of misoprostol used in a sequential regimen after mifepristone leads to an increase in the success rate and accelerates the expulsion of the conceptus. Among other effects, misoprostol inhibits the acid gastric secretion and increases the digestive peristaltism.
    Uterine contractility following administration of misoprostol via the buccal route was investigated with an intrauterine pressure transducer in women seeking termination of pregnancy. Results indicated that the average time to onset of increased tone and first uterine contraction were 41.2 and 67.1 minutes, respectively. Sustained uterine activity was observed on average after 90.0 minutes and peak uterine activity after 264.0 minutes.
    • p.25
  • The pharmacokinetic properties of mifepristone have been studied mostly following oral administration in healthy women, although studies were also conducted in pregnant women and a few male volunteers. Plasma concentrations of mifepristone and its metabolites were measured by radioimmuno- and radioreceptor assays, or high performance liquid chromatography (HPLC), and pharmacokinetic parameters calculated employing one- and two-compartment models as well as non-compartmental analysis.
    The pharmacokinetics of mifepristone and its metabolites are not linear. Following oral administration of single doses of mifepristone 100, 400, 600 and 800 mg to healthy female volunteers maximum plasma concentrations were about 2.5 mg/L (2,500 ng/mL) and differed between the 100 and 800 mg doses only 2 hours after ingestion. After a single 600 mg dose maximum plasma concentration was about 2 mg/L (2,000 ng/mL) at 1.35 hours. High doses of 10 and 25 mg/kg in healthy female and male volunteers produced maximum plasma concentrations of progesterone receptor-reactive material of 5.17 to 7.5 mg/L. Maximum plasma concentrations were attained 0.7 to 1.5 hours after oral administration. The parent drug and its metabolites were still detectable 6 to 7 days after a single dose using HPLC and for 10 days using radioimmunoassay.
    • pp.25-26
  • Total plasma clearance of mifepristone was reported to be 3 L/h. Following oral administration of tritiated mifepristone to healthy volunteers, 90% of the dose was recovered in the feces over a period of 6 to7 days. As mifepristone was completely absorbed, the principal route of elimination was biliary. The urinary route was secondary and renal clearance was negligible relative to total clearance. In studies employing long sampling periods, the elimination half-life of mifepristone was reported to be 24 to 54 hours.
    • p.27
  • After oral administration, misoprostol is rapidly absorbed (Tmax: 30 minutes) and converted to its pharmacologically active metabolite, misoprostol acid. Its plasma half-life is 1.5 hrs. After administration of radio-labeled misoprostol, approximately 80% of radioactive products are eliminated in the urine and feces, respectively. Approximately 56 % of the product is eliminated in the urine within 8 hours after intake.
    • p.27
  • Pharmacokinetic exposure data for misoprostol was limited, making it challenging to compare the doses used in animal studies to those proposed for human use.
    • p.30
  • A retrospective analysis of human data also determined there to be a link between misoprostol exposure during pregnancy and congenital malformation.
    • p.32
  • Mifepristone was tested for genotoxicity using both in vitro and in vivo studies. It showed no evidence of genotoxicity and carcinogenicity studies were not conducted.
    • p.32
  • Misoprostol was tested for genotoxicity using both in vitro and in vivo studies and showed no evidence of genotoxicity. The carcinogenicity potential of misoprostol has been evaluated in both mice and rats. There was no indication of a carcinogenic effect in either species.
    • p.32
  • No evidence of phototoxicity was observed with mifepristone being tested up to a concentration of 8 μg/mL in Balb/c 3T3 fibroblasts, the limit of solubility under the conditions of the assay.
    • p.32

"The Science Behind the "Abortion Pill"" (June 23, 2017)[edit]

Becky Little (June 23, 2017). "The Science Behind the "Abortion Pill"". Smithsonian Magazine.

  • Roe v. Wade may have legalized abortion in America 45 years ago, but the fight it ignited is far from over. While abortion is still legal, many states have since passed laws that restrict access to abortion to varying degrees—making it more expensive, difficult or even illegal in specific circumstances to terminate a pregnancy. Today abortion clinics are disappearing at a record pace, and Medicaid payouts to Planned Parenthood are in jeopardy.
    As a result, many women do not have access to a safe clinical abortion.
  • “The fact that a clinic exists in her state doesn’t help a woman who lives far away from that clinic and has no way to get there,” says Susan Yanow, a reproductive health consultant for the international nonprofit Women Help Women (WHW). Seven states—Kentucky, North Dakota, South Dakota, Missouri, Mississippi, Wyoming and West Virginia—currently have only one abortion provider, and Kentucky may soon be the only state with none.
    Now some women are once again taking the procedure outside the doctor's office, outside the law, and into their own hands. While the days of the infamous wire coat hanger aren't quite over, many women are turning to a safer method made possible by modern medicine: the “abortion pill.”
    For those with access to a clinic, the abortion pill has become an increasingly popular way to legally terminate an early pregnancy. The Food and Drug Administration mandates that medication can only be prescribed by a healthcare provider "who meets certain qualifications"; 19 states also require that a physician be there physically to supervise the procedure.
    Anti-abortion activists argue against the safety of using this method outside a doctor's office, and have even argued that states should require stricter medical supervision for abortion medication. “These drugs are dangerous. They are deadly. If they are mishandled, they result in serious injury,” Kristi Hamrick, spokeswoman for the antiabortion group Americans United for Life, recently told The Washington Post. (Hamrick is not a physician.)
  • But women who can't get the medication legally can and do buy it illegally, either online or in Mexico. In fact, this is fast becoming the primary option for women who lack others: In 2015, more than 700,000 Google users in the U.S. typed in queries about self-induced abortions, including “buy abortion pills online” and “free abortion pills,” according to the New York Times. In May 2016, Glamour magazine chronicled the stories of women seeking these pills in “The Rise of the DIY Abortion.”
    That’s why, in April, WHW launched its first website to assist American women undergoing medical abortions on their own. “The new Trump administration and anti-abortion legislatures in many states are moving swiftly to push abortion out of reach,” said Kinga Jelinska, the group’s executive director, in a statement announcing the move. The new website, Abortionpillinfo.com, provides women with confidential, one-on-one counseling on how to safely use their abortion medication—regardless of where they may have obtained it.
    It isn't clear just how many women are seeking abortion medication outside of a clinic. To protect its clients, WHW does not disclose how many inquiries its trained counselors receive. But in the past several years, many women have been charged for buying or taking it illegally, with several facing felony charges and jail time. As use of the abortion pill spreads outside the doctor’s office and into murky legal waters, we asked: How does this procedure work? And how safe is it?
  • While it's used by many abortion clinics, the name “abortion pill” is a bit misleading. Medical clinics actually administer two different types of medication: one mifepristone pill (which goes by the brand name Mifeprex), and four misoprostol tablets.
    How does it work? The first dose—a 200 mg mifepristone pill—begins the process by blocking the body’s progesterone, a hormone that is needed to continue a pregnancy in its early stages. “Whenever a woman has a period, part of what stimulates that period is the withdrawal of progesterone,” says Dr. Lauren Thaxton, an obstetrician-gynecologist in Albuquerque, New Mexico who has been performing abortions for six years
    By blocking this hormone, the first pill helps break down the uterine lining that a woman normally sheds during her period, so that the embryo can detach from the uterine wall. After that happens (generally one to two days after taking the first mifepristone pill), a woman dissolves four 200 mcg misoprostol tablets in her mouth. This second medication, which is also used to induce labor, helps expel the detached embryo.
  • Misoprostol “is in a class of medications called prostaglandins,” says obstetrician-gynecologist Dr. Daniel Grossman, who is the director of Advancing New Standards in Reproductive Health and co-author of a recent paper exploring the possibility of moving early abortion medication over the counter. “One of the effects of prostaglandins [is] that they cause what’s called cervical ripening—meaning causing the cervix to soften, open up, and become thinner. And it also causes the uterus to contract.”
    Misoprostol was first developed in the U.S. in 1973 to treat peptic ulcers, which it did by preventing harsh gastric secretions. But it had known, major side-effects on a pregnant uterus. In the 1980s, French researchers developed mifepristone, also known as RU-486, a pill that could be taken in sequence with misoprostol to induce an abortion. France legalized this regimen in 1988, and China, Great Britain and Sweden soon followed suit.
    In the U.S., reproductive rights activists hoped the FDA would adopt the method in the '90s, but anti-abortion activists helped delay its approval until 2000. When the U.S. first legalized abortion medication, it was available up to seven weeks after pregnancy. Women receiving it had to visit a clinic three times—once to take the mifepristone, a second time to take the misoprostol, and a third time for a follow-up.
    In 2016, the FDA extended the pregnancy period to 10 weeks and reduced the number of required visits to two, meaning that women could now take the misoprostol at home (though some states have restricted that as well). Today there are even clinics that aim to de-stigmatize the process by offering a "spa-like experience," like a Maryland Carafem health center that offers hot tea and robes to women seeking medical abortions.
  • One to two weeks after taking the medication, the woman returns to the clinic to make sure the pregnancy has passed. When taken between nine and 10 weeks into a pregnancy, mifepristone and misoprostol are 93 percent effective at inducing an abortion, according to Planned Parenthood. The earlier they are taken, the more effective they are.
    In 2014, almost half of U.S. hospital and clinical abortions performed before nine weeks were medication abortions, according to estimates from the Guttmacher Institute, a research and policy organization for reproductive rights. But if WHW’s new counseling services, Google queries and the increase in articles on DIY abortions are any indication, many more medical abortions may be happening outside the clinic.
  • Cara Harshman, a freelance writer and marketer in San Francisco, had her (legal) medication abortion in January. In an interview, she said that her symptoms of cramps, bleeding and nausea lasted for about five days after taking the misoprostol. By the time she had her follow-up appointment, she was stable and feeling healthy. She wrote about her experience on the Facebook group Pantsuit Nation in an essay she then re-published on Medium and Shout Your Abortion.
  • The only health issue that came up during Harshman’s abortion was a blood test showing she was Rh negative, a rare blood type, meaning she had to receive a shot of the medication RhoGAM after taking the misoprostol. According to Thaxton, most women are Rh positive. But “if a woman is Rh neg, pregnant and having bleeding,” she needs to receive RhoGAM “to prevent alloimmunization in future pregnancies, which is a condition wherein the mother develops an immune response to fetal red blood cells,” Thaxton wrote in an email.
    “Overall [a medication abortion] is extremely safe,” says Thaxton, who is also a member of Physicians for Reproductive Health. Common symptoms include nausea, cramping and heavy bleeding, similar to what women experience during a miscarriage. Thaxton generally tells her patients that if they soak through four maxi pads in two hours, that's too much bleeding, and they should consult their physician. “There’s a rare risk of [too much] bleeding—sometimes bleeding requiring a blood transfusion—and that can be related to the risk that the pregnancy has incompletely passed,” she says.
    To prevent this, abortion providers will counsel women about whether they have a history of bleeding disorders before prescribing this method. There’s also a small risk of infections like endometritis (inflammation of the uterine lining) or the contraction of the bacterium Clostridium Sordellii, both of which can also occur after childbirth. However, Thaxton said that the instances of infections after medication abortions are “extremely, extremely rare.”
    “Women are always screened for health conditions that might make a surgical abortion a safer option than the abortion pill,” Thaxton wrote in an email. “But for the vast majority of women, the abortion pill is a safe, private, effective way to have an abortion."
    Both mifepristone and misoprostol are available to purchase online without a prescription, even though doing so is illegal under federal law (laws regarding inducing an abortion vary by state). Many women who have to resort to this method use only misoprostol, because it is easier to get on its own and is available over (or under) the counter in many Latin American countries.
    Texas women have been getting misoprostol at Mexican pharmacies for years, The New York Times reported in 2013; while abortion in Mexico is legally restricted, the medication is sold over the counter for ulcers.
    Research has found that a larger amount of misoprostol is needed to induce an abortion on its own, and it’s usually less effective than the combined method. During the first 12 weeks of pregnancy, a woman who takes three 800 mcg doses of misoprostol orally at least three hours apart has an 85 percent chance of having a complete abortion, according to a 2007 study in the International Journal of Gynecology and Obstetrics.
    Yet some studies suggest that inducing an abortion using misoprostol alone is no less safe than the combined method. The World Health Organization recommends misoprostol as a safe alternative when mifepristone isn't available, and Grossman says he would use the misoprostol-only method if he didn't have access to mifepristone as well.
  • Over-the-counter abortion medication may sound pretty far-fetched in a country like the U.S., where even standard birth control requires a prescription in almost every state. Yet the fact that women are already managing their medication abortions on their own has led some to wonder: Could the abortion pill(s) ever be sold over-the-counter, as Grossman's study explored?
    In a recent Guardian op-ed, he writes that limited research suggests women who take abortion medication on their own are doing so safely, adding that “there is no question that use of these medications has contributed to a reduction in abortion-related mortality worldwide.” Abortion medication, he argues, could one day meet the FDA’s requirements for over-the-counter drugs. In fact, the research group Gynuity Health Projects is already conducting an FDA-approved research project called TelAbortion to test the safety of women using mail-order medication and online consultation to perform their abortions at home.
    Of course, future research will be needed to test these hypotheses. But even if the pill's at-home safety is confirmed, if history tells us anything, it's that efforts to make abortion more accessible will be fought every step of the way.

“Does misoprostol, the other abortion drug, work on its own?” April 8, 2023)[edit]

Berkeley Lovelace Jr., “Does misoprostol, the other abortion drug, work on its own?”, NBC News, (APRIL 8, 2023)

  • Medication abortions using both mifepristone and misoprostol are the most common method for ending an early pregnancy, according to Guttmacher Institute, a research group that advocates for abortion rights. In 2020, more than half of abortions in the U.S. were medication abortions, according to the group.
    Mifepristone is given first, followed by misoprostol one to two days later. Mifepristone blocks a hormone called progesterone, which the body needs to support a pregnancy. Misoprostol causes the uterus to contract and empty. As a two-drug regimen, the medications successfully end a pregnancy nearly 100% of the time, according to a 2015 study published in the journal Obstetrics & Gynecology.
    Friday's ruling, issued by U.S. District Judge Matthew Kacsmaryk, would prevent health care providers from prescribing mifepristone for medication abortions. That would mean misoprostol will need to be used as a stand-alone treatment for women who want to end a pregnancy, experts say.
    “It could be very problematic for women seeking abortion in states where it’s permitted,” said Arthur Caplan, the head of the Division of Medical Ethics at NYU Langone Medical Center in New York City.
    Using only misoprostol to end an early pregnancy is not unheard of. In some countries, mifepristone is not available, and misoprostol is the only option for medication abortion.
    But misoprostol used alone for abortion is not as effective as mifepristone and misoprostol used together, according to Dr. Abigail Aiken, an abortion researcher at the LBJ School Of Public Affairs at the University of Texas in Austin.
    Studies on the effectiveness of misoprostol alone for abortion vary, Aiken said, but typically range from 84% to 98%.
    Aiken co-authored a study published in February in the journal Perspectives on Sexual and Reproductive Health that looked at misoprostol as a stand-alone treatment for abortion in the U.S. That study found it was 88% effective.
    “So it is a dip in effectiveness,” Aiken said.
    Dr. Rachel Blake, an obstetrician-gynecologist at Beth Israel Deaconess Medical Center in Boston, said that the lower effectiveness carries an increased risk of incomplete abortions.
    “That’s the main thing we worry about,” Blake said.
    In those cases, patients may be at risk for vaginal bleeding, infection and damage to the uterus, she said. Sometimes patients may need to take an extra dose of the medication to empty the uterus entirely or need surgery to complete the abortion, she added.
    It can be “emotionally traumatic” for patients, Blake said, “because they’ve chosen this method for abortion.”
    Studies also suggest that misoprostol alone, compared to the two-drug regimen, can sometimes cause more severe side effects, possibly because people may end up taking more of the drug, said Dana Johnson, a researcher at the University of Texas in Austin who studies misoprostol use.
  • However, Johnson said that misoprostol is safe when used appropriately.
    She pointed to international studies, including by research and advocacy group Ibis Reproductive Health, which found more than 500 participants were able to use the medication safely and successfully from home.
  • Dr. Kristyn Brandi, an abortion provider and fellow at the American College of Obstetricians and Gynecologists, said the change in drug regimen will pose a significant challenge to clinicians.
    “Clinicians are used to being able to prescribe this medicine because this is the standard of care for medication abortion,” said Brandi, referring to the combination of mifepristone and misoprostol.
    With access to only misoprostol, she said, clinicians may need to provide patients with an extra dose of misoprostol, schedule a follow-up with patients over the phone, or ask patients to come back to the office an additional day to make sure the medication worked as intended.
    Many clinicians are likely to have trouble reconciling with the fact that they would be “forced to prescribe a treatment that we know is not the best treatment,” Brandi said.
    ”It will take time for clinicians to adjust,” she said.
    Blake said the ruling will also further exacerbate disparities in abortion care.
    “The combination is very safe and effective for this indication, and so taking this off the market would essentially put people at risk of access to abortion medications, access to abortion care, especially for marginalized persons, Black and brown people, people living in poverty, people who don’t have citizenship status in the United States,” she said.
    People who are wealthy will likely be able to get surgical abortions, which are often more expensive than medication abortions and require people to visit an abortion clinic, she added.
    “From my perspective, that’s what I’m most concerned about,” she said.

"Mail-order abortion pills become next US reproductive rights battleground" (April 7, 2022)[edit]

Adrienne Matei (April 7, 2022). "Mail-order abortion pills become next US reproductive rights battleground". The Guardian. Retrieved June 30, 2022.

  • On Tuesday, Oklahoma became the latest state to pass a bill to make performing an abortion a felony, punishable, in this case, by 10 years in prison and a $100,000 fine. The bill is expected to be signed into law by the governor, creating an even larger group of people – about 7.7 million between Texas and Oklahoma – who will have to leave their home state if they want an abortion.
  • In July 2020, the US Food and Drug Administration announced that anyone seeking a medication abortion – that is, an abortion by taking pills, up to 10 weeks into a pregnancy, without the need for an operation – would no longer have to pick up the medication in person, or take it in a doctor’s presence.
    Its decision to stop enforcing in-person requirements for the abortion drug mifepristone was a response to the Covid-19 pandemic, but in December, in consensus with the medical community, it ended the requirement for good.
  • The FDA’s decision empowered a wave of certified virtual clinics. In the coming months, the FDA is expected to clarify how pharmacies, like Walgreens and CVS, can distribute mifepristone for the first time.
    The increased accessibility of abortion medication is a huge asset to people living in states that permit it – in fact, medication abortion accounted for 54% of all US abortions in 2020, up from 39% in 2017, according to research from the pro-choice Guttmacher Institute.
  • “We were overjoyed [at the FDA’s decision], because over the years we’ve been building evidence that continues to show that people who want to use [mifepristone] to end their pregnancy … they are very capable of being able to read the instructions and do so on their own,” says Liza Fuentes, a senior research scientist at the Guttmacher Institute.
    However, 19 states currently have laws requiring an in-person element to abortions, such as an ultrasound or an in-person counseling session, precluding a totally virtual experience. And some states, including Texas, Arizona, and Louisiana ban abortion telehealth services outright.
  • Already, says Rachel Rebouché, interim dean of Temple University’s law school, people seeking medication abortions can use social media to find advice on how to change their VPNs, have pills illicitly mailed to a FedEx drop-off point in a neighboring state, or how to have pills sent to someone else who can deliver them.
  • “You see states like Missouri trying to attach its laws to providers who are providing abortions outside of Missouri, but trying to think about how to civilly penalize those providers by saying ‘any provider who provides an abortion to a Missouri resident is bound by the laws of Missouri,’” says Rebouché.
    Experts anticipate the brunt of aggressive anti-abortion enforcement will be disproportionately borne by those with few resources – people of color, low-income families, and the young.
    Blue states are working to enshrine abortion rights within and beyond their borders, with some refusing to accept that state legislatures can impinge on the sovereignty of other states by enforcing laws beyond their own jurisdictions. California and Connecticut are both actively advancing abortion rights, working to shield “providers from legal liability and prevent them from being extradited” and by creating networks for travel for abortion and centers for abortion care, says Rebouché.
    “The inevitable reality is that even though there is legal liability at stake, mailing abortion medication and administering those pills at home can be really hard to detect,” she adds. “Some states will try to enforce [abortion bans] but others will not because it won’t be worth the cost and it’s going to be difficult to do.”

"Medical abortion - Mayo Clinic" (July 10, 2022)[edit]

"Medical abortion - Mayo Clinic". www.mayoclinic.org. Retrieved July 10, 2022.

  • Medical abortion is a procedure that uses medicine to end a pregnancy. A medical abortion doesn't require surgery or anesthesia. It can be started in a medical office or at home with follow-up visits to your health care provider. It's safest and most effective during the first trimester of pregnancy.
    Having a medical abortion is a major decision with emotional and psychological consequences. If you're considering this procedure, make sure you understand what it entails, side effects, possible risks, complications and alternatives.
  • The reasons for having a medical abortion are highly personal. You can choose medical abortion to complete an early miscarriage or end an unintended pregnancy. You can also choose to have a medical abortion if you have a medical condition that makes continuing a pregnancy life-threatening.
  • Potential risks of medical abortion include:
    *Incomplete abortion, which may need to be followed by surgical abortion
    *An ongoing pregnancy if the procedure doesn't work
    *Heavy and prolonged bleeding
    *Infection
    *Fever
    *Digestive system discomfort
  • If you decide to continue the pregnancy after taking medicine used in medical abortion, your pregnancy may be at risk of major complications.
    Medical abortion hasn't been shown to affect future pregnancies unless complications develop.
    Medical abortion isn't an option if you:
    *Are too far along in your pregnancy. You shouldn't attempt a medical abortion if you've been pregnant for more than nine weeks (after the start of your last period). Some types of medical abortion aren't done after seven weeks of pregnancy.
    *Have an intrauterine device (IUD) currently in place.
    *Have a suspected pregnancy outside of the uterus. This is called ectopic pregnancy.
    *Have certain medical conditions. These include bleeding disorders; certain heart or blood vessel diseases; severe liver, kidney or lung disease; or an uncontrolled seizure disorder.
    *Take a blood thinner or certain steroid medicines.
    *Can't make follow-up visits to your provider or don't have access to emergency care.
    *Have an allergy to the medicine used.
    *A surgical procedure called a dilation and curettage (D&C) may be an option if you can't have a medical abortion.
  • Before a medical abortion, your health care provider will likely:
    *Evaluate your medical history and overall health
    *Confirm your pregnancy with a physical exam
    *Do an ultrasound exam to date the pregnancy and check that it's not outside the uterus (ectopic pregnancy) and not a tumor that developed in the uterus (molar pregnancy)
    *Do blood and urine tests
    *Explain how the procedure works, the side effects, and possible risks and complications
    Making the decision to have an abortion might not be easy. Consider seeking support from your partner, a family member or a friend as you think about your options. Talk with your health care provider to get answers to your questions, help you weigh alternatives and consider the impact the procedure may have on your future.
    No health care provider is required to perform an elective abortion. In some places, an elective abortion may not be legal. Or there may be certain legal requirements and waiting periods to follow before having an elective abortion. If you're having an abortion procedure for a miscarriage, there are no special legal requirements or waiting periods required.
  • What you can expect
    Medical abortion doesn't require surgery or anesthesia. The procedure can be started in a medical office or clinic. A medical abortion can also be done at home, though you'll still need to visit your health care provider to be sure there are no complications.
  • Medical abortion can be done using these medicines:
    *Oral mifepristone (Mifeprex) and oral misoprostol (Cytotec). This is the most common type of medical abortion. These medicines are usually taken within seven weeks of the first day of your last period.
    Mifepristone (mif-uh-PRIS-tone) blocks the hormone progesterone, causing the lining of the uterus to thin and preventing the embryo from staying implanted and growing. Misoprostol (my-so-PROS-tol), a different kind of medicine, causes the uterus to contract and expel the embryo through the vagina.
    You may take the mifepristone in your provider's office or clinic. Then you might take the misoprostol at home, hours or days later.
    You'll need to visit your health care provider again about a week later to make sure the abortion is complete. This regimen is approved by the Food and Drug Administration (FDA).
  • Oral mifepristone and vaginal, buccal or sublingual misoprostol. With this type of medical abortion, you take a mifepristone tablet by mouth. The next step is to use a slowly dissolving misoprostol tablet placed in your vagina (vaginal route), in your mouth between your teeth and cheek (buccal route), or under your tongue (sublingual route).
    The vaginal, buccal or sublingual approach lessens side effects and may be more effective. To be most effective, these medicines must be taken within nine weeks of the first day of your last period.
  • Methotrexate and vaginal misoprostol. Methotrexate is rarely used for elective, unintended pregnancies, although it's still used for pregnancies outside of the uterus (ectopic pregnancies). This type of medical abortion must be done within seven weeks of the first day of your last period. It can take up to a month for methotrexate to complete the abortion. You receive methotrexate as a shot or a pill you take by mouth. The misoprostol is later used at home.
  • Vaginal misoprostol alone. Vaginal misoprostol alone can be effective when used before nine weeks of gestation of the embryo. But vaginal misoprostol alone is less effective than other types of medical abortion.
    The medicines used in a medical abortion cause vaginal bleeding and abdominal cramping. They may also cause:
    *Nausea
    *Vomiting *
    8Fever
    *Chills
    *Diarrhea
    *Headache
  • You may be given medicine to manage pain during and after the medical abortion. You may also be given antibiotics, although infection after medical abortion is rare.
    Your health care provider will let you know how much pain and bleeding to expect, depending on the number of weeks of your pregnancy. You might not be able to go about your usual daily routine during this time, but it's unlikely you'll need bed rest. Make sure you have plenty of absorbent sanitary pads.
    If you have a medical abortion at home, you'll need access to a health care provider who can answer questions by phone and access to emergency services. You'll also need to be able to identify complications.
  • After the procedure
    Signs and symptoms that may require medical attention after a medical abortion include:
    *Heavy bleeding — soaking two or more pads an hour for two hours
    *Severe abdominal or back pain
    *Fever lasting more than 24 hours
    *Foul-smelling vaginal discharge
  • After a medical abortion, you'll need a follow-up visit with your provider to make sure you're healing properly and to evaluate your uterine size, bleeding and any signs of infection. To reduce the risk of infection, don't put anything into your vagina for two weeks after the abortion.
    Your health care provider may ask if you still feel pregnant, if you saw the expulsion of the gestational sac or embryo, how much bleeding you had, and whether you're still bleeding. If your provider suspects an incomplete abortion or ongoing pregnancy, you may need an ultrasound and possibly a surgical abortion.
    After a medical abortion, you may have a mix of emotions, including relief, loss, sadness or guilt. If these feelings bother you, it might help to talk to a counselor about them.
  • Preventing pregnancy
    Ovulation usually occurs as soon as two weeks after a medical abortion, and another pregnancy is possible even before your period begins. Before the abortion, talk to your provider about contraception that you can start as soon as the procedure is over.

"Methotrexate". Medication Abortion. Ibis Reproductive Health.[edit]

  • Since 1953, methotrexate has been available in the United States as a treatment for cancer. A chemotherapeutic agent, methotrexate has also been used since the 1980s to treat ectopic (extra-uterine) pregnancies. However, when the political environment in the US delayed the approval and availability of mifepristone as a medication abortion regimen, providers and researchers began to investigate the possibility of expanding the use of methotrexate to early pregnancy termination. In 1993, investigators initiated the first study using low-dose methotrexate in combination with misoprostol for early abortion. Subsequent studies have shown that the methotrexate/misoprostol regimen constitutes an effective method of terminating early pregnancies.
  • As of 2014, methotrexate had been registered in more than 70 countries worldwide. In most countries, methotrexate is registered as a chemotherapeutic agent and/or for the treatment of ectopic pregnancies. In many settings, the use of methotrexate for medication abortion is “off-label” meaning that the methotrexate is being used for an unapproved purpose or indication. However, there is a body of research that demonstrates the safety and efficacy of the methotrexate/misoprostol medication abortion regimen and evidence based protocols have been established. Thus it is permissible for clinicians to use methotrexate for this purpose and professional organization guidelines also allow this practice.
  • Methotrexate is an anti-metabolite. By blocking the enzyme dihydrofolate reductase, methotrexate inhibits the production of thymidine, a requirement for DNA synthesis. Methotrexate interferes with cell growth and specifically interferes with rapidly dividing cells. Conditions that produce rapid cell division include neoplastic disease, autoimmune diseases, and pregnancy. Methotrexate primarily affects the cytotrophoblast and inhibits, rather than weakens, the implantation process.
  • The most common evidence-based protocol begins with either the intramuscular injection (50 mg/m²) or oral administration (50 mg) of methotrexate (Day 1). Three to seven days later the woman self-administers 800 micrograms of misoprostol vaginally at home. Follow-up with a provider occurs approximately one week after the methotrexate administration (Day 7). If the abortion has not occurred (as determined by vaginal ultrasound examination) the dose of misoprostol is repeated and the woman returns for final evaluation four weeks after the methotrexate administration (Day 28). However, if at the first follow-up visit (Day 7), embryonic cardiac activity is noted on ultrasound, the woman is given an additional dose of misoprostol and asked to return on Day 14. If the abortion is not complete on either the Day 28 or the Day 14 visit, vacuum aspiration is typically performed.
  • Approximately 95% of women will have a complete abortion when using methotrexate/misoprostol up to 49 days' gestation. Medication abortion completion rates with the methotrexate and misoprostol regimen decline with increasing gestational age, with completion rates of approximately 82% between 50 and 56 days' gestation.
    Although the overall efficacy of the methotrexate/misoprostol regimen is similar to that of mifepristone and misoprostol within 49 days' gestation, timing of completion is quite different. For approximately one fifth of patients, the abortion will occur up to four weeks after misoprostol administration. For women who do not experience a complete abortion an aspiration intervention may be required.
    Ongoing pregnancy occurs in fewer than 1% of cases. However, methotrexate is a known teratogen and in utero exposure to the medication leads to severe fetal abnormalities and/or fetal death. Thus if a woman experiences an ongoing pregnancy after taking methotrexate an aspiration termination is highly recommended.
  • Most women with an early pregnancy can use the methotrexate and misoprostol regimen. Although the regimen is most effective in the first seven weeks of pregnancy, women with pregnancies of up to 9 weeks' gestation may still use the methotrexate and misoprostol regimen safely and effectively. Accurate dating of the pregnancy is critical and can occur through either clinical assessment or ultrasound. Methotrexate has demonstrated efficacy in treating ectopic pregnancies and is thus the preferred regimen for women with suspected extra-uterine pregnancies. If the use of methotrexate and misoprostol results in an incomplete abortion, aspiration intervention may be necessary. Women considering the methotrexate and misoprostol regimen should we willing to undergo a vacuum aspiration, if indicated.
  • To date, no data is available on the effect of folate supplementation on the efficacy of the methotrexate/misoprostol regimen. Generally, patients are advised to discontinue the use of folate supplements for one week after methotrexate administration. Women may also be advised to discontinue consumption of leafy green vegetables, beans, and organ meats for two weeks after methotrexate administration. However, no studies have evaluated the necessity of dietary modifications.
  • Abdominal cramping and vaginal bleeding are hallmarks of the abortion process itself. Many women and clinicians report cramps and abdominal pain similar to those associated with a heavy menstrual period. Vaginal bleeding can vary significantly in both duration and severity, and many report that the bleeding resembles a heavy period or a spontaneous miscarriage. Bleeding can last for weeks; the mean duration of bleeding is 14 to 21 days.
  • Side effects of methotrexate include nausea, vomiting, diarrhea, fever or chills, headache, dizziness, and oral ulcers. Side effects of the misoprostol include nausea, vomiting, diarrhea, fever, and chills. In most cases, side effects can be managed with appropriate counseling and symptomatic treatments, such as oral analgesics (e.g. ibuprofren) for pain.
    In the high doses used in the chemotherapy regimen, methotrexate exposure during pregnancy has been associated with numerous fetal malformations. Several case reports indicate that methotrexate may have teratogenic effects in cases of incomplete abortion. Women electing to use the methotrexate/misoprostol regimen should be informed of the teratogenic effects of methotrexate and should be counseled on the importance of aspiration completion in the event that the medication abortion is unsuccessful.
  • When administered in the first seven weeks of pregnancy, the overall failure rate is approximately 5%. Most of these patients require an aspiration abortion to resolve an incomplete abortion, end a continuing pregnancy, or control bleeding. Extremely heavy or prolonged bleeding is rare; less than 1% of women required intervention for heavy bleeding. Ongoing pregnancy occurs in less than 1% of cases.
  • Methotrexate is commonly used to treat neoplastic diseases, rheumatoid arthritis, and psoriasis. Methotrexate is also used to treat ectopic pregnancies, Crohn's disease, systemic lupus, and severe asthma.

"Misoprostol". Medication Abortion. Ibis Reproductive Health.[edit]

  • Despite evidence demonstrating the safety and efficacy of the mifepristone/misoprostol regimen, political and commercial difficulties present challenges to widespread production and distribution of mifepristone. Beginning in the early 1990s, researchers revisited the possibility of using misoprostol alone as a method of terminating early pregnancies. A considerable body of evidence has now shown that misoprostol can be used as a single agent to induce an early abortion. Misoprostol is inexpensive, stable at ambient temperatures, easy to transport, easy to administer, and does not require refrigeration, even in hot climates. Thus misoprostol has the potential to significantly expand medication abortion access in developing countries and low resources settings.
    In recent years, misoprostol has been added to the World Health Organization’s List of Essential Medicines for incomplete abortion management and post-partum hemorrhage prevention and treatment. This has led to a number of efforts to increase community-based distribution of and widespread access to misoprostol, particularly in low resource settings. However, due to its use as an abortifacient, some governments have restricted or attempted to restrict access to and use of misoprostol. As a result, the availability and cost of misoprostol may vary widely, even in countries that have approved misoprostol for one or more indications. Misoprostol may be available in countries in which it has not been formally approved, typically through the black market or from community pharmacies or drug shops. The misoprostol available through unregulated markets may be of variable quality and cost.
    Because misoprostol is widely available, generally inexpensive, and stable at room temperature, misoprostol is a suitable abortifacient in low-resource settings, particularly when more effective alternatives are not available. Over the last decade there have also been a number of efforts to expand access to misoprostol in settings were abortion is severely legally restricted and safe services are limited in order to reduce harm from unsafe abortion practices.
  • Many women, particularly in countries and settings with restrictive abortion laws, attempt to terminate early pregnancies with misoprostol alone. Reports from Latin America suggest that women frequently use misoprostol to induce abortion early in pregnancy. However, without standardized information and instructions, women utilize misoprostol in a numerous ways, with a high degree of variation in both dosage and timing. Some of these regimens are not as effective as others. Providing both health service providers and individual women with information about the evidence-based regimen for misoprostol use is critical.
    As indicated on the map above, misoprostol is currently registered in over 100 countries worldwide. In most countries, misoprostol has been approved specifically for use in the prevention of non-steroidal anti-inflammatory drug-induced gastric ulcers. However, misoprostol is often used "off label" for its many obstetric and gynecological indications. In an increasing number of countries, misoprostol has been approved specifically for Ob/Gyn indications, including post-partum hemorrhage prevention, incomplete abortion management, and, in conjunction with mifepristone, early pregnancy termination.
  • In the US, misoprostol (brand name Cytotec®) has been approved by the US Food and Drug Administration (FDA) only for the prevention and treatment of gastric ulcers. However, clinicians routinely use misoprostol off-label for obstetric and gynecological purposes, including cervical ripening and labor induction. Further, the FDA has approved the use of misoprostol in conjunction with mifepristone for the termination of early pregnancies.
    Misoprostol-only regimens are not widely used in the US, where mifepristone and misoprostol, methotrexate and misoprostol, and aspiration abortion services are available. However, the off-label use of misoprostol as a single agent abortifacient has been documented, particularly among Latinas in the US. Further, as state-level restrictions have created significant barriers to accessing clinic-based abortion care, in recent years there has been a reported increased in self-induction with misoprostol in certain regions of the country.
  • Prostaglandins are naturally occurring fatty acids produced by many tissues in the body. Prostaglandin E1 causes myometrial contractions by interacting with specific receptors on myometrial cells. This interaction results in a cascade of events, including a change in calcium concentration, thereby initiating muscle contraction. Misoprostol is an analog of prostaglandin E1. By interacting with prostaglandin receptors, misoprostol causes the cervix to soften and the uterus to contract, resulting in the expulsion of the uterine contents. Misoprostol is relatively metabolically resistant and thus has prolonged action. Misoprostol is absorbed through mucosal surfaces and thus can be administered through a number of different routes.
  • Determining the optimal protocol for the use of misoprostol as a single agent abortifacient has been an active area of investigation. Researchers throughout Latin America and Asia have explored buccal, sublingual, and vaginal regimens, a variety of doses, and different dosing schedules. Overall, these studies have shown that misoprostol alone can be effectively used in different clinical environments, at different doses, and through different routes of administration.
    The results of these studies have informed the development of a consensus regimen for the use of misoprostol for the termination of an early pregnancy. The optimal regimen for pregnancies through nine weeks’ gestation is 800 micrograms of misoprostol followed 3-12 hours later with a second 800 microgram dose of misoprostol followed 3-12 hours later by a third 800 microgram dose (3 doses x 800 micrograms). These doses can be administered buccally (between the cheek and the gum), sublingually (under the tongue), or vaginally with equal efficacy. Importantly, all three doses should be administered the same way. If the woman uses the buccal or sub-lingual regimens, she should keep the pills in place for 30 minutes at which point she can swallow any pill remnants.
    However, there are other protocols that appear to be as effective. This includes the vaginal administration of 800 micrograms followed 24 hours later by a second dose of 800 micrograms administered vaginally. There is some evidence that the efficacy of this regimen can be enhanced if the misoprostol tablets are moistened with a few drops of clean water prior to vaginal insertion.
  • The best available evidence suggests that the optimal protocol has an overall completion rate of 75% to 85% when used in the first nine weeks of pregnancy. Efficacy appears to be at the higher end of this range when the pregnancy is at an earlier gestational age. In the roughly 15%-25% of cases where misoprostol administration does not lead to a complete abortion, additional intervention in required. Recent studies have shown that approximately 10% of women using misoprostol for early pregnancy termination will experience an ongoing pregnancy. A woman may take an additional 800 microgram dose of misoprostol or she may need an aspiration intervention. Reasons for aspiration intervention include prolonged or excessive bleeding, incomplete abortion (remnants of fetal tissue in the uterus), or an ongoing pregnancy. An aspiration termination may also be performed at the request of the woman or the provider.
    The misoprostol-only regimen has the potential to expand access to safe abortion services in resource poor and developing country settings. However, the misoprostol-only regimen is not as effective as either the mifepristone/misoprostol or the methotrexate/misoprostol regimen. Further, the side effects associated with the misoprostol-only regimen, while tolerable, are generally more severe than those associated with the combined regimens.
  • Few contraindications to misoprostol use are described in the medical literature and most women with an intra-uterine pregnancy of nine weeks or less are eligible for misoprostol use. If a woman has a documented allergy to prostaglandins, in general, or misoprostol specifically, she should not use misoprostol. If an ectopic pregnancy is confirmed or strongly suspected, the woman should not use misoprostol. Finally, if a woman has an intrauterine device (IUD) in her uterus (an IUD in situ), the device should be removed before the administration of misoprostol.
    Women with uterine infections, severe anemia, cardiovascular and cerebrovascular diseases, coagulopathy or current therapy with anticoagulants, and hypertension were excluded from some clinical studies. In these cases, use of misoprostol should be evaluated on a case by case basis.
  • Abdominal cramping and bleeding are hallmarks of the abortion process itself. Many women report that cramps and abdominal pain are similar to those associated with a heavy menstrual period. Vaginal bleeding can vary significantly in both duration and severity and many women report that the bleeding resembles a very heavy period or an early miscarriage. The majority of studies conducted on the misoprostol-only regimen have reported that the mean duration of bleeding is approximately two weeks. Many women report passing blood clots, which can be large, and some women report passing gray or tan tissue (the products of conception). This tissue is usually less than one or two inches in length.
  • Reported side effects include nausea, vomiting, diarrhea, dizziness, headache, fever, chills, rashes, and pelvic pain. In most cases, these side effects are transient and resolve within 24 hours of misoprostol administration. Of women who report pelvic pain after using the misoprostol-only regimen, approximately 25% report that the pain was much stronger than menstrual pain. In most cases, side effects and pelvic pain can be managed with oral pain medications (like ibu profren).
    A number of case reports from Brazil have associated fetal exposure to misoprostol with an increased risk of limb and central nervous system abnormalities. However, the absolute risk associated with in uteromisoprostol exposure appears low. Women electing to use the misoprostol-only regimen should be informed of the possible teratogenic effects of misoprostol that may occur if the medication fails to induce an abortion and if the pregnancy is then carried to term.
  • Serious complications after misoprostol use are relatively rare. However, the woman should contact a provider if:
    1. She experiences fever or chills beyond 24 hours after misoprostol administration;
    2. She soaks more than two large maxi pads (or thick towels) an hour for two consecutive hours or if she experiences continuous bleeding for several weeks;
    3. She experiences an abrupt onset of heavy bleeding two weeks or more after having taken misoprostol; and/or
    4. She has no or scant bleeding in the seven days after misoprostol administration.
    In approximately 15%-20% of cases, the abortion is incomplete and either an additional dose of misoprostol or an aspiration intervention is required. As use of misoprostol leads to cervical dilation, mechanical dilation is generally unnecessary if an aspiration abortion is performed.
  • Few studies have directly assessed the acceptability of misoprostol-only regimens. Although side effects of greater severity are associated with the misoprostol-only regimen, the majority of patients report that the side effects are tolerable. Patient satisfaction with the vaginal regimen is high and the majority of patients state that they would use the misoprostol method for a future termination and would also recommend the method to others.
  • Misoprostol is used for a wide array of conditions including the prevention of NSAID-induced gastric ulcers. Misoprostol is also used for a variety of obstetric and gynecological health indications, including the induction of labor, cervical ripening, and second trimester abortion. Misoprostol is also effective in both preventing and treating postpartum hemorrhage and managing both incomplete and missed abortion. Because misoprostol is effective in managing incomplete abortion, the medication has become an integral part of post-abortion care.

"The Safety and Quality of Abortion Care in the United States" (2018)[edit]

National Academies of Sciences, Engineering; Division, Health Medicine; Board on Health Care Services; Board on Population Health Public Health Practice; Committee on Reproductive Health Services: Assessing the Safety Quality of Abortion Care in the U.S (2018). "The Safety and Quality of Abortion Care in the United States”, at NAP.edu. doi:10.17226/24950. ISBN 978-0-309-46818-3. PMID 29897702

  • Few women have contraindications to medication abortion (ACOG and SFP, 2014). The FDA-approved Mifeprex label states that the drug should not be used for women with confirmed or suspected ectopic pregnancy or undiagnosed adnexal mass; an IUD in place; chronic adrenal failure; concurrent long-term systemic corticosteroid therapy; hemorrhagic disorders or concurrent anticoagulant therapy; allergy to mifepristone, misoprostol, or other prostaglandins; or inherited porphyrias (FDA, 2016a).
    • pp.51-52
  • Since 2011, the distribution and use of Mifeprex has been restricted under the requirements of the FDA Risk Evaluation and Mitigation Strategy (REMS) program (see Box 2-1). (See Chapter 3 for additional details on REMS requirements for clinicians who prescribe Mifeprex.) Despite the restriction, use of the medication method is increasing, especially in early pregnancy. As noted in Chapter 1, the percentage of all abortions by medication rose by 110 percent between 2004 and 2013 and is expected to increase further (Jatlaoui et al., 2016). In 2014, medication abortions accounted for approximately 45 percent of all U.S. abortions performed <9 weeks’ gestation (Jones and Jerman, 2017).
    • p.52
  • It is common for medical procedures to result in side effects in addition to the intended outcome. Medication abortions involve cramping, pain, and bleeding, similar to the symptoms of a miscarriage (ACOG and SFP, 2014; Borkowski et al., 2015; FDA, 2016a). Vaginal bleeding is expected during and after an abortion and occurs in almost all patients during a medication abortion (FDA, 2016a). Bleeding generally starts as the tissue begins to separate from the endometrium and continues for several days after the abortion is complete. The heaviest bleeding occurs during and immediately following the passage of the gestational sac and lasts 1 to 2 days. Some bleeding and spotting may occur up to 9–16 days.
    Like bleeding, uterine pain and cramping are an expected and normal consequence of medication abortion (FDA, 2016a). Cramping can last from a half-day to 3 days (Ngo et al., 2011). Nonsteroidal anti-inflammatory drugs (NSAIDs) are typically recommended to manage the pain. Ibuprofen—after the onset of cramping—has been shown to reduce both pain and later analgesia use (Jackson and Kapp, 2011; Livshits et al., 2009). However, some women still report high levels of pain, and pain is commonly reported as the worst feature of the method. Prophylactic regimens for pain management are an area of active research (Dragoman et al., 2016).
    • p.54
  • Complications after medication abortion, such as hemorrhage, hospitalization, persistent pain, infection, or prolonged heavy bleeding, are rare—occurring in no more than a fraction of a percent of patients (Chen and Creinin, 2015; FDA, 2016a; Ireland et al., 2015; Kulier et al., 2011; Woodcock, 2016). Obesity (i.e., a body mass index [BMI] of 30 or greater) has not been found to increase the risk for adverse outcomes after medication abortion (Strafford et al., 2009). The Society of Family Planning suggests that medication abortion may be preferable to aspiration abortion when patients, including those with extreme obesity, are at risk of procedural and anesthetic complications (SFP, 2012).
    • p.55
  • There is no direct evidence suggesting that specific types of facilities (e.g., ambulatory surgery centers or hospitals) or facility factors (e.g., size of procedure room or corridor width) are needed to ensure the safety of medication abortion. Indeed, most women in the United States return home after taking mifepristone and take the misoprostol 28 to 48 hours later. As a result, medication abortions occur largely in nonclinical settings. Moreover, as described above, a body of research including systematic reviews (Chen and Creinin, 2015; Kulier et al., 2011; Raymond et al., 2013) and large cohort studies (Cleland et al., 2013; Ireland et al., 2015; Upadhyay et al., 2015) demonstrates that complications such as infection, hemorrhage requiring transfusion, or hospitalization occur in fewer than 1.0 percent of patients.
    • p.56
  • Some research has focused specifically on medication abortion outside the hospital or clinic setting. A variety of studies, for example, have assessed the self-administration of misoprostol after receiving mifepristone in a clinic. This largely observational research shows that home use of misoprostol produces outcomes similar to those of the clinic-supervised method (Clark et al., 2005; Fiala et al., 2004; Guengant et al., 1999; Løkeland et al., 2014; Ngoc et al., 2004; Shannon et al., 2005; Shrestha and Sedhai, 2014).
    Other research has assessed the safety and effectiveness of home use of both mifepristone and misoprostol (Chong et al., 2015; Conkling et al., 2015; Platais et al., 2016). In one U.S. prospective nonrandomized study, 400 women with pregnancies up to 63 days’ gestation were offered the choice of either clinic-supervised or home use of mifepristone. Of these women, 128 chose home administration, and 272 chose clinic administration; the women did not differ significantly in terms of gravidity, gestation, or other measured characteristics. The women choosing home use were slightly older (27.8 versus 26.0 years) and more likely to be doing paid work (78.9 versus 68.0 percent). Success rates did not differ between the groups (96.3 versus 96.9 percent), and the 2 patients who required hospitalization were in the clinic-supervised group. One patient was diagnosed with an incomplete abortion and underwent a follow-up dilation and curettage procedure, and the other was treated for severe nausea and vomiting (Chong et al., 2015). A related study found that among 301 women offered the choice of home use, the factor most cited by women who chose this option was flexibility in scheduling (Swica et al., 2013).
    • pp.56-57
  • The medication regimens for performing an induction abortion have evolved and improved in response to a growing body of research—most notably with respect to the combined use of mifepristone and misoprostol (Gemzell-Danielsson and Lalitkumar, 2008; Wildschut et al., 2011). The safety and efficacy of different medications and medication regimens for inducing abortion has been assessed in RCTs, retrospective analyses, prospective observational studies, and systematic reviews (Ashok et al., 2002, 2004; Constant et al., 2016; Goh and Thong, 2006; Gouk et al., 1999; Hamoda et al., 2003; Kapp et al., 2007; Mauelshagen et al., 2009; Ngoc et al., 2011; Sonalkar et al., 2017; Wildschut et al., 2011).
    • p.66
  • The expected side effects of induction abortions are similar to those described above for medication abortions at or before 10 weeks’ gestation: cramping, pain, and bleeding, as well as nausea, vomiting, diarrhea, chills, and headache (Borgatta, 2011; Ngoc et al., 2011; Wildschut et al., 2011). The side effects are a result of the medications that are used for induction, the abortion process itself, or the medications used to manage pain (Borgatta, 2011).
    The literature on complications resulting from induction abortions is limited by a variety of factors. The available research is a mix of study designs analyzing a variety of treatment protocols and patient populations that differ in important ways, including weeks’ gestation, parity, fetal anomaly, and the pharmaceutical regimens and agents used to induce labor (Goyal, 2009; SFP, 2011a). All of these factors may affect patient outcomes. Moreover, while the research on the outcomes of medication and aspiration abortions draws on the outcomes of thousands of patients, the study samples for research on inductions are relatively small and thus have limited statistical power. Nevertheless, the available evidence consistently finds that induction abortion rarely leads to serious complications, although they occur more often than in D&E procedures (Bryant et al., 2011; Grossman, et al., 2008; Mauelshagen et al., 2009; SFP, 2011b).
    • p.67
  • Clinical guidelines suggest that, regardless of abortion method, routine in-person follow-up care is not necessary. However, clinicians may choose to offer an in-person follow-up visit to women 7–14 days after the procedure to confirm the absence of ongoing pregnancy and to assess recovery (NAF, 2017a; WHO, 2014). In the case of medication abortion, which usually occurs in a nonclinical setting, confirmation of termination of the pregnancy is the primary concern after the abortion. The FDA advises that follow-up is needed to confirm complete termination of pregnancy, but that termination can be confirmed by medical history, clinical examination, hCG testing, or ultrasound (FDA, 2016a). Similarly, NAF advises that confirmation can be established by any of these methods in an office, by telephone, or through electronic communication (NAF, 2017a).
    • p.68
  • There is little research on how best to manage pain during an induction (Jackson and Kapp, 2011). Comparisons of different analgesic regimens are not available, and the optimal approach to effective treatment of pain is not well established (Wiebe and Renner, 2014). The options will depend on the provider’s resources and the particular clinical circumstances. Nulliparous women may require more analgesia compared with multiparous women (Ashok et al., 2004). The levels of pain in later-gestation induction abortions are said to be similar to those in normal delivery, but the committee found no studies documenting this (Smith et al., 2016; Viviand et al., 2003).
    • p.74
  • There is no evidence that the dispensing or taking of mifepristone tablets requires the physical presence of a clinician or a facility with the attributes of an ASC or hospital to ensure safety or quality. The effects of mifepristone occur after women leave the clinic, and extensive research shows that serious complications are rare. The risks of medication abortion are similar in magnitude to the risks of taking commonly prescribed and over-the-counter medications such as antibiotics and NSAIDs. In 35 states, however, only physicians are permitted to give women the mifepristone tablet(s) required to begin the process of medication abortion (RHN, 2017). In 19 states, the clinician (a physician or other provider if allowed) must be physically present to provide the medication, thus prohibiting the use of telemedicine to prescribe the medication remotely for abortion (Guttmacher Institute, 2017b). In 17 states, medication abortions must be performed in a facility that meets the structural standards of ASCs even though the abortion will occur outside the clinical setting, and there is no evidence to suggest that these regulations improve safety or quality.
    • p.79

"Mifepristone (Mifepristone Linepharma) followed by misoprostol (GyMiso) for medical termination of pregnancy of up to 49 days' gestation" (August 1, 2013)[edit]

"Mifepristone (Mifepristone Linepharma) followed by misoprostol (GyMiso) for medical termination of pregnancy of up to 49 days' gestation". RADAR Review. National Prescribing Service (NPS) MedicineWise. (August 1, 2013)

  • Medical termination of a pregnancy of up to 49 days' gestation using mifepristone (200 mg) followed by misoprostol (800 microgram) is a well-established regimen that is safe and effective.
  • Medical termination of a pregnancy using the combination of mifepristone followed by misoprostol is safe and effective. The alternatives of medical or surgical termination of pregnancy should be offered to a woman if both are available and suitable for her.
  • Mifepristone (also known as RU-486) is a synthetic steroid and progesterone antagonist that competes with progesterone and blocks progesterone receptors.
    In pregnant women mifepristone's action on the uterus can induce abortion. It causes dilatation of the cervix and increases the sensitivity of the myometrium to the action of prostaglandins.
    Misoprostol is a synthetic analogue of prostaglandin E1 that induces contractions of the smooth muscle fibres in the myometrium and relaxation of the uterine cervix.
    Mifepristone is followed 36–48 hours later with misoprostol to terminate a developing intrauterine pregnancy.5
  • Candidates for medical termination of pregnancy must be able to adhere to the treatment regimen (including follow-up visits) and have access to a telephone and transportation to a medical facility in case of emergency.
  • Medical abortion became an alternative method of first-trimester pregnancy termination in the 1980s with the availability of prostaglandins and anti-progesterones.
    The efficacy and safety of mifepristone followed by misoprostol for medical termination of pregnancy is well established. This combination of medicines has been in use for up to 20 years in many countries, including France, China, the UK and US.
    Mifepristone has been available in Australia since 2006 through the TGA Authorised Prescriber Scheme and was included on the Australian Register of Therapeutic Goods (ARTG) in 2012.
    Misoprostol was registered in Australia in 2012 for use orally or buccallya in combination with mifepristone for termination of pregnancy of up to 49 days' gestation.
  • Buccal administration of misoprostol involves the tablet being kept between the cheek and the gum for 30 minutes before any fragments are swallowed with water.
  • The efficacy and safety of mifepristone followed by misoprostol for termination of early pregnancy was established in four pivotal trials conducted in France, the UK and US. The overall rate of success was high, with complete termination of pregnancy achieved in 92–97% of women who were pregnant for up to 49 days.
    Subsequent clinical trials have demonstrated consistent efficacy of at least 93% with mifepristone (200 mg) followed by misoprostol (800 micrograms) 24–48 hours later.
  • In Australia medical termination of pregnancy using mifepristone followed by misoprostol is not approved by the TGA for use after 49 days of gestation. However, this combination of drugs is widely accepted and safely used overseas up to 63 days' gestation.
    Termination of pregnancy after 49 days' gestation using mifepristone followed by oral misoprostol has lower efficacy rates than termination up to 49 days — often less than 90%. A decline in efficacy was not observed using buccal misoprostol up to 63 days.
    Medical termination of pregnancy after 49 days' gestation is associated with slightly more adverse events, including bleeding, pain and a higher rate of complications.
  • Women can choose their preferred option if both alternatives for termination of pregnancy are suitable and available. Having a choice of method for termination of pregnancy may improve a woman's psychological outcome.
    In a UK study the most frequent reason for choosing medical abortion was to avoid some aspects of the operative process, particularly the anaesthetic (61%), or because women viewed the process as simpler and more natural (32%). Women who chose surgical termination of pregnancy generally wanted to avoid the awareness and involvement in the process of termination (49%) and were concerned about the pain (16%) or emotional impact (14%) of medical termination.
  • The most widely researched drugs for medical termination of early pregnancy are:
    mifepristone with prostaglandins (misoprostol or gemeprost)
    prostaglandins alone
    mifepristone alone
    methotrexate alone
    methotrexate with prostaglandins.
    Evidence suggests that combined regimens such as mifepristone followed by misoprostol are more effective than single agents. A combined regimen of mifepristone followed by misoprostol is faster and more effective than a combination of methotrexate followed by misoprostol.
    Different prostaglandins can be used with mifepristone for medical abortion, such as gemeprost, but misoprostol is superior because it is more cost effective, does not require refrigeration and offers different routes of administration.
    Buccal administration of misoprostol is absorbed more slowly than oral administration, but appears to induce higher overall uterine activity. Efficacy rates for mifepristone followed by misoprostol administered either orally or buccally are comparable for women at 43–49 days (94.7% vs 96.4%, respectively).
  • In general, medical termination of early pregnancy is considered to have similar efficacy to that of surgical termination. For example, vacuum aspiration, which is a common method for surgical terminations of early pregnancy, has similar efficacy to medical termination of pregnancy using mifepristone followed by misoprostol.
    However, surgical termination of early pregnancy appears to have higher rates of complete abortion, with less than 2–4% failure rate.
  • Satisfaction with both medical and surgical methods for termination of early pregnancy is high. The health outcomes appear to be similar with both methods, but many women have a strong preference for one approach.
    Recovery after medical and surgical termination of early pregnancy is estimated to be the same. For example, even though women who underwent vacuum aspiration required more time off work than those who underwent medical abortion (2.4 vs 1.3 days), the time taken for return to normal daily activities was similar for both groups.22
  • Medical termination of early pregnancy is an alternative to surgical termination and ideally both methods should be offered to ensure the woman understands that she has a choice.
    For a woman the choice between surgical and medical abortion involves balancing the benefits and risks of both methods (Table 1). The risk of surgery and anaesthesia is balanced against the risk of a medical method with a slightly lower efficacy, involving more pain and bleeding.
    Some women may feel more in control using a medical method, but this method may be perceived a more unpleasant option by others.
  • Expected consequences of medical abortion using mifepristone followed by misoprostol are heavy uterine bleeding and painful uterine contractions or cramps. Cramps are similar to those experienced during a menstrual cycle or labour. For most women the pain is adequately managed with OTC analgesics.
    Many of the side effects experienced during medical abortion are associated with misoprostol use. Common transient side effects from these drugs include:
    nausea: experienced by about 40–70% women
    vomiting: experienced by about 10–45% women
    diarrhoea: experienced by about 10–30% women
    headache, fever, chills and fatigue.
    Most women find the side effects acceptable. The rate of any serious adverse event or complication after medical termination of early pregnancy is low.
  • Bleeding associated with medical termination of pregnancy usually occurs within 4–6 hours of misoprostol administration in > 95% of women. Some vaginal bleeding may continue for an average of 10–16 days after mifepristone administration.
    Advise women experiencing heavy bleeding for > 2 days after misoprostol administration to seek medical advice. In 0.1–0.2% of women terminating pregnancy up to 49 days' gestation, the bleeding is heavy enough to cause anaemia and may require a blood transfusion.
    If persistent bleeding (even if light) is reported at the follow-up visit at 14–21 days, arrange a further appointment within a few days to assess cause. Persistent bleeding can be a consequence of incomplete abortion or an unnoticed extrauterine pregnancy and may require surgical intervention.
  • As with other types of abortion, cases of serious bacterial infection, including very rare cases of fatal septic shock, have been reported after use of mifepristone followed by misoprostol.
    Overall serious infection rates after medical abortion are estimated to be < 1%. The US FDA estimates reports of fatal sepsis are about 1 in 100,000.
    Fever, severe abdominal pain, nausea, vomiting or pelvic tenderness in the days after a medical abortion may indicate presence of an infection.
    There is currently insufficient evidence to recommend the use of prophylactic antibiotics for women having a medical abortion.
  • The overall failure rate of mifepristone followed by misoprostol is about 2–7%. Failure can be caused by incomplete abortion (about 2–4% of failures) or ongoing pregnancy (about 1% of failures).
    Surgical intervention is undertaken in ≤ 5% of women undergoing medical abortion for continuing viable pregnancy or, more commonly, incomplete abortion.
    The frequency of surgical evacuation of the uterus is reported to decrease with increasing experience of the clinical team with the medical method.
  • Follow-up is essential 14–21 days after mifepristone administration to verify that expulsion has completed, vaginal bleeding has stopped and to exclude complications such as infection.
    If medical termination fails and ongoing pregnancy is confirmed with an ultrasound, offer termination of pregnancy by a surgical method.
    There is unknown risk to the foetus after exposure to mifepristone, but use of misoprostol is associated with birth defects.
  • There does not appear to be an association between termination of pregnancy and risk of miscarriage, preterm birth or placenta praevia in subsequent pregnancies.
    Evidence does not support an association between termination of pregnancy and infertility, ectopic pregnancy or breast cancer.
    It appears that after one medical versus one surgical termination of pregnancy, obstetric risks for delivery in subsequent pregnancies are similar.
  • Women who choose medical termination using mifepristone followed by misoprostol over surgical termination are more likely to experience adverse events such as bleeding, abdominal pain, nausea and vomiting.
    There is a low and comparable incidence of serious complication rates with surgical and medical methods for termination of pregnancy. A Cochrane systematic review reported no significant difference in the rate of complications between surgical and medical methods of abortion in the first trimester, although there were few sufficiently powered randomised studies to identify different rates for rare events.
    A large registry-based cohort study of more than 42,000 women in Finland compared complication rates after medical and surgical termination of early pregnancy and reported that both methods were safe.
    The incidence of haemorrhage or incomplete abortion was higher in women undergoing medical termination, while complications requiring surgical treatment were more common after surgical termination of pregnancy. The rates of infection and serious morbidity did not differ between the groups.
  • Contraindications to mifepristone and misoprostol medical abortion include:
    chronic adrenal failure
    severe disease requiring steroid administration
    hypocoagulation diseases
    anticoagulant therapy
    allergy to mifepristone, misoprostol or other prostaglandin.
    This regimen is not recommended in women with anaemia, renal failure, hepatic impairment, malnutrition or cardiovascular disease.
    Before prescribing mifepristone and misoprostol ensure ectopic pregnancy is excluded, gestational age is confirmed as no more than 49 days and any intrauterine device is removed before treatment.
  • The PBAC recommended listing of mifepristone followed by misoprostol for medical termination of an intrauterine pregnancy of up to 49 days' gestation on the basis of similar effectiveness and cost compared with surgical termination of pregnancy.
  • Discuss pain relief using paracetamol or OTC analgesics. Evidence supports the pre-emptive use of ibuprofen for pain relief.
    In all instances, the use of mifepristone requires prior rhesus determination.
  • A single mifepristone tablet (200 mg) should be swallowed with water. Evidence suggests that 200 mg of mifepristone is as effective as higher doses (600 mg). In about 3% of pregnancies the products of conception will be expelled before misoprostol is administered.
  • Misoprostol should be taken 36–48 hours after mifepristone administration. Acceptable regimens for oral or buccal administration of misoprostol tablets (200 microgram tablet) are:
    800 micrograms (four tablets) in a single dose
    400 micrograms (two tablets) to be repeated after 2 hours.
    Advise the woman to stay at home and rest for 4–6 hours after taking misoprostol tablets or until the expulsion process is complete. Some women choose to be in the clinic for this part of the treatment. It is highly desirable that a support person is present who knows how to access emergency care if it is required.
  • If abortion has not occurred after the initial dose of misoprostol, an additional dose of misoprostol (up to 800 micrograms) can be prescribed from 1 to 7 days later.
  • Advise the woman to return to the clinic 14–21 days after mifepristone administration to ensure termination of pregnancy is complete.
  • If a woman chooses to terminate pregnancy using mifepristone followed by misoprostol, provide specific and clear instructions for this method.
    Discuss the mifepristone and misoprostol Consumer Medicine Information (CMI) leaflets with her.
    Provide a written list of the symptoms women may experience during medical termination of pregnancy and those that require urgent medical consultation.
    Advise a woman undergoing medical termination of pregnancy as follows.
    It is highly desirable to have a support person present who will stay with you until the abortion process is complete.
    Take mifepristone and oral misoprostol tablets with water 2 hours before or 2 hours after a meal.
    If using buccal administration of misoprostol, keep the tablet between the cheek and the gum for 30 minutes before swallowing any remaining fragments with water.
    After taking misoprostol tablets, stay at home and rest for 4–6 hours or until the expulsion process is complete.
    Vaginal bleeding will usually occur and the products of conception may be expelled within a few hours of taking misoprostol or during the next few days.
    Bleeding may last up to 10–16 days but should not be heavy for > 2 days.
    Ensure access to emergency care and a 24-hour phone service.
    Follow-up is essential within 14–21 days after taking mifepristone to confirm that the pregnancy is terminated.
    If ongoing pregnancy is confirmed, surgical termination of pregnancy is required due to risks of teratogenic effects from one or both drugs.
    Consider contraceptive options and, when appropriate, start contraception after the abortion process.

"The activists championing DIY abortions for a post-Roe v Wade world" (May 7, 2022)[edit]

Poppy Noor (May 7, 2022). "The activists championing DIY abortions for a post-Roe v Wade world". The Guardian. Retrieved June 30, 2022.

  • Mayhem – a pseudonym – is just one of many US activists vouching for self-managed abortions outside the gaze of the medical establishment. With a growing slate of abortion restrictions and the recent leak of a supreme court draft opinion indicating justices have already voted to overturn the constitutional right to abortion, activists like Mayhem say such measures aren’t just necessary, they are also better than what’s currently on offer. They are saying: abortion is your right – and you don’t need to depend on doctors or the state for it.
    When most people think of self-managed abortion, they think of back alleys, coat hangers or throwing oneself down the stairs; of last resorts, despair, shame. But that is no longer the reality. Today, self-managed abortion often means taking pills that are available over the counter in many countries, with little risk of death or serious complications. Other times, it means using herbs, or vacuum aspirators, like the Del-Em (a homemade suction device created by activists in the 70s), under the watchful eye of somebody experienced – like a midwife or a doula – who can advise if things go wrong.
  • Self-managed abortion is not a silver bullet. It carries with it the risk of prosecution, even though it is not illegal in most states. In April, a Texas woman was charged with murder for a self-induced abortion, even though there was no legal basis for the charges – as the district attorney admitted when he dropped the case. And not everybody wants to turn to a clandestine market for their abortion care. Some people feel more comfortable with a licensed practitioner. People want options. But for many, options are fast receding.
    Those who look outside the medical establishment will find, often through word of mouth, an underground movement of doctors, midwives, doulas and activists – some trained by formal institutions, others by practitioners in the network. They will find those who mostly undertake legal work – sharing information from the World Health Organization about how to use medication to induce an abortion, for example. They’ll also find some who do not – assisting with abortions later down the line, or giving medical advice when things go wrong.
  • The advent of medication abortion has made the work of these activists easier – because it is easily available. Medication abortion is safer than Tylenol – resulting in a successful termination 99.6% of the time when used appropriately, with less than a 1% risk of complications, according to the Kaiser Family Foundation. The safety of other means used outside a clinical setting hasn’t been sufficiently studied, but broadly speaking, existing data from recent years does not show elevated fatality rates from self-managed abortion.
  • Although the majority of abortions are completed with medication, only 21% of the US public know these pills exist. People can order them online but scam sites are common. So activists use in-person and virtual grassroots networks to share where to buy the pills, how to safely ingest them, what a normal response to them looks like and when to seek help. Crucially, they can explain the legal landscape – after all, if you turn up at the emergency room admitting you tried to cause your own abortion, you could face legal risk. But because medication abortion and complications from it look exactly the same, medically, as a miscarriage – people need not disclose they tried to induce their own abortion.
  • “It all comes down to someone assessing their own situation, and being able to make a decision about how to manage their reproductive care. There’s simply no medical reason that abortion pills shouldn’t be over the counter,” says a spokesperson for Mountain Access Brigade, a group that runs an abortion hotline in Appalachia and the south-east. “To make people jump through these hoops: to go to appointments, to have a mandatory ultrasound – these things are designed to humiliate, shame and coerce them into changing their mind,” she adds.
    “These pills are safer than aspirin. They’re safer than Viagra. We let people manage very complex conditions at home – such as diabetes. And yet these pills are so restricted,” says reproductive rights activist Susan Yanow. “People are afraid of them.”
  • Of course, some doctors worry about self-managed abortions. The abortion pill is considered safe only until 10 weeks. People can still use it effectively up to 14 weeks, but the risk of complications goes up.
    Doctors worry about people estimating the wrong date of conception; that they may still be pregnant after taking the medication without realizing; or they will experience complications and end up in need of urgent help.
    “I absolutely worry about people self-managing their abortions,” says Dr Mark Rosing, an obstetrician gynecologist who works in the Bronx, New York. “A patient could hemorrhage, develop a severe infection and even die,” he adds.

"Interruption of nonviable pregnancies of 24-28 weeks' gestation using medical methods: release date June 2013 SFP guideline #20133" (September 2013)[edit]

Perritt JB, Burke A, Edelman AB (September 2013). "Interruption of nonviable pregnancies of 24-28 weeks' gestation using medical methods: release date June 2013 SFP guideline #20133". Contraception. 88 (3): 341–349. doi:10.1016/j.contraception.2013.05.001. PMID 23756114.

  • The need to interrupt a pregnancy between 24 and 28 weeks of gestation is uncommon and is typically due to fetal demise or lethal anomalies. Nonetheless, treatment options become more limited at these gestations, when access to surgical methods may not be available in many circumstances. The efficacy of misoprostol with or without mifepristone has been well studied in the first and earlier second trimesters of pregnancy, but its use beyond 24 weeks' gestation is less well described. This document attempts to synthesize the existing evidence for the use of misoprostol with or without mifepristone to induce labor for nonviable pregnancies at gestations of 24–28 weeks. The composite evidence suggests that a regimen combining mifepristone and misoprostol may shorten the time to expulsion, though the overall success rates are similar to those seen with misoprostol-only regimens.
    • p.341
  • The prostaglandin E1 analogues have emerged as essential agents in creating uterine contractility in an effort to cause pregnancy expulsion at almost any gestational age. Misoprostol has several advantages over other prostaglandin analogues. Available in tablet form, it is stable at room temperature (20°C) when packaged properly, is inexpensive and can be administered via several mucosal routes (oral, vaginal, buccal and sublingual).
    A progesterone receptor antagonist, mifepristone, is often used to prime the uterus and cervix prior to the use of a prostaglandin analogue for pregnancy expulsion in the first and second trimester of pregnancy. The addition of mifepristone has been shown to increase the overall success rate of the regimen and may shorten the time to expulsion once uterotonics are initiated. In studies of first- and second-trimester abortion (12–28 weeks), a combination of mifepristone with misoprostol (mifepristone–misoprostol) appears to be the most effective regimen [2–4]. Unfortunately, many of these studies included very few pregnancies with a gestation of more than 20 weeks. Moreover, no standard protocols exist delineating the optimal regimen for inducing labor at 24–28 weeks' gestation.
    • p.341
  • Any review of the evidence on this topic has limitations, as there are very few studies focused specifically on 24–28 weeks of gestational age.
    *Indication and gestational age: Most published studies focused on either medication abortion in the second trimester or labor induction in the third trimester.
    • p.342
  • The heterogeneity of these studies does not allow for a meta-analysis. A summary of the main outcomes is shown in Table 1. These include a mean or median time to expulsion of 10–20 h and a 24-h success rate of 62–100%. All doses of misoprostol were effective; the highest doses did not appear to confer a clear benefit, either in time to expulsion or in success of the regimen at 24 or 48 h.
    The more important factor for expulsion time and success rate was the dosing interval. Longer times to expulsion and lower expulsion rates were associated with the longest misoprostol dosing intervals [6,13–15]. Studies with dosing intervals of every 12 h reported 24-h completion rates of about 70%, and expulsion times of 16–20 h (Table 1). In contrast, misoprostol dosing every 4 h conferred expulsion times of 10–15 h. The type of case may also be important, with data from some studies suggesting more rapid expulsion for demised fetuses.
    Route of dosing may also be important, but conclusions are limited by lack of data, as most studies used vaginal dosing. One study did directly compare oral and vaginal regimens at similar doses and found a slightly longer time to expulsion in women receiving oral misoprostol. No studies utilizing sublingual or buccal administration of misoprostol were found, although at least one study using buccal misoprostol is ongoing.
    Based on the study outcomes summarized in Table 1, a dosing regimen of vaginal misoprostol 100 mcg or 200 mcg given every 4 h is associated with a 24-h expulsion rate of 84–100%, with mean or median expulsion times of 10–14 h. Few study subjects required additional uterotonic agents (addressed later in the review). Higher doses (400 mcg every 4 h) were similarly effective, and thus, a higher dose appears unnecessary. More data are needed to conclusively determine whether a difference in success rate exists between “low” (less than 400 mcg) and “high” (400 mcg or greater) doses.
    • p.342
  • The summarized studies had several limitations. Notably, there was broad heterogeneity in regimens including dosage, route and dosing interval of misoprostol and the use of adjunctive agents like oxytocin. Finally, as discussed earlier, most studies did not limit the gestational age to 24–28 weeks but, instead, incorporated these within a larger gestational age range.
    • p.342
  • Seven studies used a mifepristone–misoprostol regimen and included pregnancies at 24–28 weeks' gestational age. There were no RCTs; three of these studies were prospective, and four were retrospective. The mifepristone dose was either 200 mg or 600 mg. The interval between mifepristone and misoprostol was usually 24 to 48 h with the one exception reporting varying intervals between mifepristone and the first misoprostol dose. The amount of misoprostol was even more varied in these studies than in the misoprostol-only studies with doses as low as 25 mcg. Misoprostol was given orally, vaginally or through both routes. No published studies were found that utilized a sublingual or buccal route of misoprostol administration. With the large variation in misoprostol doses following mifepristone, it is difficult to identify a single optimal misoprostol dosing regimen. Mean or median expulsion times ranged from 7 to 13 h, with 24-h completion rates of N 85% (Table 2). Results appear similar whether 200 mg or 600 mg of mifepristone was used. The highest misoprostol doses did not always correlate with shorter expulsion times. One study that compared different misoprostol doses found similar results with doses of 200 mcg and 400 mcg. Other studies also suggest that misoprostol doses of 200 mcg or 400 mcg every 3 to 4 h are associated with similar expulsion times. Again, dosing interval may be at least as important as dose.
    • p.342, 345
  • Generally, mean and median expulsion times in studies of mifepristone–misoprostol seem shorter than those reported for misoprostol-only regimens. However, only two retrospective studies directly compare these regimens, and they differ in when mifepristone was used. One used mifepristone only for live anomalous fetuses, not for IUFDs, whereas the other reported routine use of mifepristone after 2001, when institutional practice patterns changed. In a letter to the editor, a group of authors recently reported that they often use mifepristone 36 h before misoprostol (200 mcg every 3 or 6 h) to induce expulsion in nonviable pregnancies in the second and third trimester. They found that the time to expulsion with this regimen was significantly shorter (p=.04) than with misoprostol alone. No definitive RCTs exist to guide us in this gestational age range, but data suggest that mifepristone shortens expulsion time and increases success rates for pregnancy interruption at earlier gestational ages.
    • p.345
  • Regimens using misoprostol alone or in combination with mifepristone appear quite safe, with few reported serious complications.
    • p.345
  • Hemorrhage necessitating intervention was rare, but most studies were either underpowered for this outcome or did not report any data. One prospective study reported that about 20% of women who received misoprostol had blood loss N 500 cc, with one woman requiring transfusion. Two mifepristone–misoprostol studies, one of which was retro- spective, reported a hemorrhage (N 1000 cc) rate greater than 10%, though the gestational ages at which these cases occurred were not specified. Other studies reported a much lower incidence or even absence of bleeding complications.
    • p.345
  • Rates of retained placenta were not universally reported but when listed were 0–8%.
    • p.345
  • Combined regimens had rates of side effects fairly similar to those of misoprostol-only regimens:
    *Incidence of nausea and vomiting ranged from 2.5% to 34%.
    *Frequency of diarrhea was 10% or lower, if it occurred. Oral misoprostol regimens at higher doses were associated with higher incidence of diarrhea.
    *Noninfectious fever/hyperthermia was reported at frequencies of 10–30%.
    • p.345
  • Many providers express concern about whether it is safe to provide misoprostol to a woman with a uterine scar. While its use is contraindicated in term labor induction, studies have documented its safe use for first- and second-trimester abortion. In our review, some studies excluded women with prior uterine surgery, while others included women with scarred uteri in proportions of up to 14% of the study population. No cases of uterine rupture in women with prior uterine incision were reported in studies of misoprostol-only regimens. In addition, success of the regimen and overall morbidity were similar for women with and without prior uterine incision.
    • p.345
  • Based on what results are available, use of misoprostol with or without mifepristone for women with prior uterine scar appears to be safe at 24–28 weeks of gestational age. Prior cesarean section or uterine scar need not be a contraindication for interruption of pregnancy at this gestational age.
    • p.346
  • Seven misoprostol-only studies restricted enrollment to cases of IUFD, and an additional four included pregnancies with live anomalous fetuses as well. While mean expulsion times seemed slightly shorter for demised fetuses, the confidence intervals overlapped heavily. Only one study reported group-specific results for demised and live fetuses, but authors did not perform statistical comparisons.
    One prospective mifepristone–misoprostol study included both live anomalous fetuses and IUFD. The authors found that time to expulsion was significantly shorter in the IUFD group (9.6 h vs. 13.6 h, pb.05).
    A review article published in 2007 evaluated the use of misoprostol for IUFD [26]. Authors cited two case series that suggest that expulsion times are shorter and cumulative misoprostol doses lower for IUFD in the second and third trimesters. Currently, there are insufficient data to conclude that IUFD decreases time to expulsion or should be managed with a different misoprostol regimen.
    • p.346
  • Data are too scant to determine whether premature rupture of membranes (PROM) affects the outcome of induction for nonviable pregnancy between 24 and 28 weeks' gestational age. Of the studies we reviewed, four explicitly included women with PROM. Only one misoprostol-only study reported outcomes by group. While the authors found a mean time to expulsion of 14.7 h (intact membranes) versus 8.5 h (PROM), they did not perform a statistical comparison. Other studies grouped intact membranes and PROM when reporting outcomes, as numbers of PROM were too small to report separately.
    • p.346
  • One retrospective study addressed the question of whether the addition of mechanical dilators (laminaria) shortens the time to expulsion when added to a mifepristone–misoprostol regimen. Mean gestational age was 30 weeks, and indications were mostly fetal anomalies or preterm membrane rupture. Women received 600 mg of mifepristone 36 h prior to 400 mcg of misoprostol administered vaginally every 3 h (up to 3 doses). At 24 h following the mifepristone dosing, but before initiation of misoprostol, one group received laminaria, and the other received nothing. Median time to expulsion after the first misoprostol dose was 6.4 h in the laminaria group and 9.0 h in the no-laminaria group (p=.01). Another study found no decrease in time to expulsion when laminaria were added to a misoprostol-only regimen.
    • p.346
  • Successful expulsion was often accomplished without the need for adjunctive medications. However, the use of additional agents was difficult to interpret, since reasons for use were varied or not explained. Oxytocin/ Syntocinon was the most commonly used adjunctive uterotonic (Table 3).
    • p.346
  • Although success rates are extremely high with both misoprostol-only and mifepristone–misoprostol regimens, failures can occur. There are no published studies that address the issue of how long to continue the regimen, but many studies arbitrarily choose a 24- or 48-h end point. These end points were not chosen on the basis of patient safety issues. Unpublished international experience has demonstrated that for the rare refractory cases at 48 h, successful expulsion can be achieved by continuing the regimen up to 72 h (personal communication, Ipas). Anecdotally, some clinicians recommend a medication “holiday,” artificial rupture of membranes or a change in the type of uterotonic being utilized. More important, success rates and time to expulsion appear to be linked to timely dosing of the misoprostol. Thus, if expulsion is not occurring, greater attention should be paid to dosing intervals.
    • pp.346-347
  • No published studies evaluate the impact of placenta previa for indicated inductions at gestational ages of 24–28 weeks, and thus, insufficient evidence exists with which to make a recommendation. At less than 24 weeks of gestational age, Thomas et al. found an increased estimated blood loss but no increase in infection, hysterectomy, requirement of postoperative transfusion or other complications in women undergoing pregnancy termination. Clinical experience suggests that advanced gestational age may be associated with an increased likelihood of bleeding complications.
    • p.347
  • Findings and recommendations are limited by the small numbers of studies, poor study design and small numbers of included pregnancies at 24–28 weeks' gestational age. Further limitations include the heterogeneity of regimens, which are varied by dose, route and timing of administration of both misoprostol and mifepristone. Nonetheless, the studies we identified did offer some consistency. Therefore, given the fact that clinical guidance is needed, we present the following recommendations.
    Level B: Recommendations are based on limited or inconsistent scientific evidence. Indicated interruption of pregnancies at 24–28 weeks' gestational age is safe using either a misoprostol-only or mifepristone–misoprostol regimen. The addition of mifepristone seems to shorten expulsion time.
    • p.347
  • Misoprostol-only regimen: Misoprostol 100 mcg or 200 mcg vaginally every 4 h is associated with 24-h expulsion rates of 84–100%, with mean expulsion times of 10–11 h.
    * Shorter misoprostol dosing intervals (every 4 h) appear to decrease time to expulsion and increase 24-h completion rates.
    * Higher doses of misoprostol (400 mcg) appear safe but do not clearly decrease the time to expulsion and, thus, may not be necessary.
    • p.347
  • Mifepristone–Misoprostol regimens: Mifepristone 200 mg or 600 mg can be followed by misoprostol 36 to 48 h later. Misoprostol 200 mcg or 400 mcg every 4 h is associated with 24-h expulsion rates of 80–97%, with mean expulsion times ranging from 8.5 to 13.6 h.
    *Consideration may be given to a shorter interval between mifepristone and misoprostol, such as 24 h.
    * Higher doses of misoprostol (up to 600 mcg) seem safe but do not confer a clear clinical advantage over lower doses and, thus, appear unnecessary.
    • p.347
  • Prior uterine scar: Consideration may be given to using 200 mcg or less per dose of misoprostol for women with a prior uterine scar. Data are insufficient to advise a change in dosing interval.
    • p.347
  • While experience with misoprostol continues to increase, the evidence to guide clinicians in its use for expulsion of pregnancy beyond 24 weeks is limited. Worldwide experience with mifepristone and misoprostol indicate their overall safety. There is a need for larger, well-designed, prospective studies to determine optimal dosing routes and regimens, and use in special patient populations, such as women with IUFD, PROM, prior uterine scar and placenta previa.
    • p.347

"FDA finalizes rule expanding availability of abortion pills" (Jan. 3, 2023)[edit]

Matthew Perrone, "FDA finalizes rule expanding availability of abortion pills", Los Angeles Times, (Jan. 3, 2023)

  • The Food and Drug Administration on Tuesday finalized a rule change that broadens availability of abortion pills to many more pharmacies, including large chains and mail-order companies.
    The Biden administration partially implemented the change last year, announcing it would no longer enforce a long-standing requirement that women pick up the medicine in person. Tuesday’s action formally updates the drug’s labeling to allow many more retail pharmacies to dispense the pills, so long as they complete a certification process.
  • Still, the rule change’s effect has been blunted by numerous state laws limiting abortion broadly and the pills specifically. Legal experts foresee years of court battles over access to the pills, as abortion rights proponents bring test cases to challenge the state restrictions. The Supreme Court overturned the landmark 1973 Roe vs. Wade decision last year, ruling that states may again outlaw abortion.
  • For more than 20 years, the FDA labeling had limited dispensing to a subset of specialty offices and clinics due to safety concerns. After the onset of the COVID-19 pandemic, the FDA temporarily suspended the in-person requirement. The agency later said a new scientific review by its staff supported easing access, concurring with numerous medical societies that had long said the restriction wasn’t necessary.
    Two drugmakers that make brand-name and generic versions of abortion pills requested the latest FDA label update. Agency rules require a company to file an application before modifying dispensing restrictions on drugs.
    Danco Laboratories, which sells branded Mifeprex, said in a statement that the change “is critically important to expanding access to medication abortion services and will provide healthcare providers” with another option for prescribing the drug.
    The American College of Obstetricians and Gynecologists called the update an “important step” forward.
    “Although the FDA’s announcement today will not solve access issues for every person seeking abortion care, it will allow more patients who need mifepristone for medication abortion additional options to secure this vital drug,” the group said in a statement.
  • The FDA in 2000 approved mifepristone to terminate pregnancies of up to 10 weeks, when used with a second drug, misoprostol. Mifepristone is taken first to dilate the cervix and block the hormone progesterone, which is needed to sustain a pregnancy. Misoprostol is taken 24 to 48 hours later, causing the uterus to contract and expel pregnancy tissue.
    Bleeding is a common side effect, though serious complications are very rare. The FDA says more than 3.7 million U.S. women have used mifepristone since its approval.
    Several FDA-mandated safety requirements remain in effect, including training requirements to certify that prescribers can provide emergency care in the case of excessive bleeding. Pharmacies that dispense the pills also need a certification.

"Abortion drugs closer to being subsidised but some states still lag" (April 29, 2013)[edit]

Kerry Peterson, (April 29, 2013). "Abortion drugs closer to being subsidised but some states still lag". The Conversation Australia. The Conversation Media Group.

  • The drugs mifepristone (RU486) and misoprostol are on the threshold of being listed on the Pharmaceutical Benefits Scheme (PBS) after the body that assesses whether medicines should be subsidised gave it the green light late on Friday. The drugs are used to terminate pregnancy. Listing on the PBS would make them available across the country at an affordable price.
    RU486 has been on the World Health Organization’s list of essential medicines for years and available to women internationally since the 1980s. But it was only placed on the Australian Register of Therapeutic Goods (ARTG) in August 2012, which allowed general practitioners to prescribe the drugs.
  • In 1996, former conservative independent senator Brian Harradine successfully moved an amendment to the Therapeutic Goods Act 1989 (Cwlth) that gave the Minister for Health and Ageing the power to reject applications to import and market mifepristone. At the time, Tony Abbott, who is anti-choice, was health minister.
    No applications were made because it was an expensive process and the possibility of approval was minimal. In 2006, legislation to remove the Harradine restriction was passed after a cross-party vote, but until mifepristone could be registered on the ARTG, the drug wasn’t available.
    Now, the Pharmaceutical Benefits Advisory Committee (PBAC) has recommended the listing of mifepristone and misoprostol on the PBS. If this recommendation is approved by the federal government, or more specifically, the Health Minister Tanya Plibersek, the cost of the drugs will fall dramatically and an early medical abortion will be much cheaper than a surgical abortion.
    Plibersek has said on television that the cost of the drugs would be reduced from between $300 and $800 to $12 (for low income earners with concession cards) or $35. The cost of a surgical abortion is much higher but varies as most abortions are performed in private clinics, which decide how much to charge for procedures individually.
  • In Queensland, a woman who used mifepristone and misoprostol to self-abort and her partner who imported the drugs from overseas via the postal system were prosecuted under the Criminal Code 1899 (Qld) in 2010. The court found that the drugs were not “noxious” as required by the legislation and they were acquitted.

"The Abortion Pill | Get the Facts About Medication Abortion"[edit]

"The Abortion Pill | Get the Facts About Medication Abortion". Planned Parenthood.

  • What is the abortion pill?
    Medication abortion — also called the abortion pill — is a safe and effective way to end an early pregnancy.
  • How does the abortion pill work?
    “Abortion pill” is the common name for using two different medicines to end a pregnancy: mifepristone and misoprostol.
    First, you take a pill called mifepristone. Pregnancy needs a hormone called progesterone to grow normally. Mifepristone blocks your body’s own progesterone, stopping the pregnancy from growing.
    Then you take the second medicine, misoprostol, either right away or up to 48 hours later. This medicine causes cramping and bleeding to empty your uterus. It’s kind of like having a really heavy, crampy period, and the process is very similar to an early miscarriage. If you don’t have any bleeding within 24 hours after taking the second medicine, call your nurse or doctor.
    Your doctor or nurse will give you both medicines at the health center. When and where you’ll take them depends on state laws and your health center's policies. Your doctor or nurse will give you detailed directions about where, when, and how to take the medicines. You may also get some antibiotics to prevent infection.
  • How effective is the abortion pill?
    The abortion pill is very effective. The effectiveness depends on how far along you are in your pregnancy when you take the medicine.
    *For people who are 8 weeks pregnant or less, it works about 94-98 out of 100 times.
    *For people who are 8-9 weeks pregnant, it works about 94-96 out of 100 times.
    *For people who are 9-10 weeks pregnant, it works about 91-93 out of 100 times. If you're given an extra dose of medicine, it works about 99 out of 100 times.
    *For people who are 10-11 weeks pregnant, it works about 87 out of 100 times. If you're given an extra dose of medicine, it works about 98 out of 100 times.
    The abortion pill usually works, but if it doesn’t, you can take more medicine or have an in-clinic abortion to complete the abortion.
  • Why do people choose the abortion pill?
    Which kind of abortion you choose all depends on your personal preference and situation. With medication abortion, some people like that you don’t need to have a procedure in a doctor’s office. You can have your medication abortion at home or in another comfortable place that you choose. You get to decide who you want to be with during your abortion, or you can go it alone. Because medication abortion is similar to a miscarriage, many people feel like it’s more “natural” and less invasive.

"New Multi-State Study Shows Telemedicine Abortion Is as Safe and Effective as In-Person Care" (July 11, 2019)[edit]

"New Multi-State Study Shows Telemedicine Abortion Is as Safe and Effective as In-Person Care". www.plannedparenthood.org. (July 11, 2019)

  • New York, NY — A new study published in Obstetrics & Gynecology shows that medication abortion via telemedicine is just as safe and effective as when the health care provider is in the same health center as the patient. The study was conducted by Planned Parenthood Federation of America — with researchers from Ibis Reproductive Health and University of California San Francisco (UCSF) Advancing New Standards in Reproductive Health (ANSIRH) — and supports existing evidence that outcomes for medication abortion via telemedicine are comparable with medication abortion provided in person.
    The study is the nation's largest multi-state study of medication abortion via telemedicine to date, with researchers analyzing records from nearly 6,000 patients receiving medication abortion either through telemedicine or in person at 26 Planned Parenthood health centers in Alaska, Idaho, Nevada, and Washington.
  • “As access to abortion shrinks across the country, telemedicine is one strategy for expanding patients’ access to safe, legal abortion, including for those living in remote or rural areas. At Planned Parenthood, we conduct research and support innovation so we can find new ways to expand people’s access to services and offer the best health care to our patients,” said Dr. Julia Kohn, national director of research, evaluation, and data analytics for Planned Parenthood Federation of America and lead author of the study. “This study confirms what we know firsthand: Telemedicine can improve health equity by ensuring that more people have access to the care they need — including abortion — in a timely manner by reducing the barriers that make it harder for people to get care, including securing transportation, childcare, and time off work.”
  • Medication abortion has been safe and legal in the U.S. since the FDA approved its use nearly 20 years ago. It has helped ensure that patients are able to make their own private medical decisions, and it has expanded access to reproductive health care.
    In a health-center-to-health center model of providing abortion via telemedicine, a patient has an ultrasound scan, laboratory testing, and counseling with health center staff. Telemedicine patients then meet with a provider in another health center through a secure videoconferencing platform, while standard medication abortion patients meet with a provider in person. During the study period, researchers compared rates of ongoing pregnancy, the need for a subsequent in-clinic abortion, and any significant adverse effects between the two groups. Researchers concluded that medication abortion provided remotely offers patients the same effective, high-quality care that they would receive if they were in the same room with the same trained providers. The study also found that complications are very rare for medication abortion via telemedicine, which is consistent with findings from previously published research.
    Restrictions and political attacks on access to abortion have left entire swaths of the country without access to safe, legal abortion, disproportionately affecting people with low incomes, people of color, and people living in rural communities. Right now, anti-abortion politicians are pushing burdensome and medically unnecessary bans that effectively prohibit access to medication abortion via telemedicine. Leading medical associations, such as the American College of Obstetricians and Gynecologists (ACOG), agree these bans are not based in evidence.
  • "The shortage of providers and clinics makes abortion difficult to access in the United States. Telemedicine extends the reach of providers to increase the availability of services," said Dr. Daniel Grossman, director, Advancing New Standards in Reproductive Health (ANSIRH) at UCSF and a co-author of the study. “Given the wave of abortion bans and restrictions on access to health care across the country, people need more access to safe, legal abortion, not less. While medication abortion via telemedicine is not the solution to these abortion bans, this study shows that it is one way to help more people get the care they need, when they need it.”
  • Planned Parenthood is proud to offer medication abortion via health-center-to-health-center telemedicine in 14 states. As the nation’s leading sexual and reproductive health care provider, Planned Parenthood is committed to making sure all patients receive the high-quality health care they need, when they need it — including safe, legal abortion. By providing medication abortion safely and effectively via telemedicine, we can expand access to abortion for people, no matter where they live.

"Some Women 'Self-Manage' Abortions as Access Recedes - Information and medications needed to end a pregnancy are increasingly available outside the health care system" (August 7, 2022)[edit]

Rabin RC (August 7, 2022). "Some Women 'Self-Manage' Abortions as Access Recedes - Information and medications needed to end a pregnancy are increasingly available outside the health care system". The New York Times.

  • More than half a million women had medication abortions in 2020 in the United States, and fewer than half of 1 percent experience serious complications, studies show. Medical interventions like hospitalizations or blood transfusions were needed by fewer than 0.4 percent of patients, according to a 2013 review of dozens of studies involving tens of thousands of patients.
  • In states that have banned abortion, some women with unwanted pregnancies are pursuing an unconventional workaround: They are “self-managing” their abortions, seeking out the necessary know-how online and obtaining the medications without the supervision of a clinic or a doctor.
    At first glance, the practice may recall the days before Roe v. Wade, when women too often were forced to take risky measures to end an unwanted pregnancy. But the advent of medication abortion — accomplished with drugs, rather than in-office procedures — has transformed reproductive care, posing a significant challenge to anti-abortion legislation.
  • There are no reliable estimates of the number of women who undertake their own medication abortions, according to the Guttmacher Institute, which researches and supports abortion access.
  • Critics of abortion in any form insist that medication abortions are riskier than claimed, and even more so without medical supervision. The procedure should not be undertaken beyond 10 weeks gestation, they note, or performed without a doctor’s visit, because dating a pregnancy accurately is not always possible.
    Other medical complications can be missed, they say — including ectopic pregnancy, in which the fertilized egg implants outside the uterus.
    Claims that medication abortion is safe “are based on flawed and incomplete data, which prioritize convenience and cost over the health and safety of patients,” said Dr. Christina Francis, chair of the American Association of Pro-Life Obstetricians and Gynecologists, which opposes all abortions except to prevent permanent harm or death to the mother.
  • Physicians who support abortion tell a different story: There is plentiful evidence that medication abortion is safe, and women already carry out the procedure almost entirely alone at home, even if they do see a doctor to obtain the drugs. Self-management is not so different, supporters argue.
    “It’s quite safe and effective based on studies we’ve done, national data provided by the states and the Guttmacher Institute, and the experience of other countries,” said Dr. Beverly Winikoff, the founder of Gynuity Health Projects, who performed much of the research on medication abortion that led to its approval in the United States more than 20 years ago.
  • More than half a million women had medication abortions in 2020 in the United States, and fewer than half of 1 percent experience serious complications, studies show. Medical interventions like hospitalizations or blood transfusions were needed by fewer than 0.4 percent of patients, according to a 2013 review of dozens of studies involving tens of thousands of patients.
    A 2018 review by the National Academies of Sciences, Engineering and Medicine found that abortion medication ended pregnancies 96.7 percent of the time in gestations of up to nine weeks. The World Health Organization endorses self-managed abortion and says it can be used up to 12 weeks gestation.
    Medication abortion “is noninvasive, doesn’t cause sepsis and doesn’t cause ruptures of internal organs,” like the illegal abortions of the pre-Roe era, Dr. Winikoff said.
    “It doesn’t mean people can’t have excessive bleeding and need to get care occasionally, but those are not the dire circumstances of people from 50 years ago,” she added.
  • The drugs are regulated by the Food and Drug Administration, however, and are intended to be taken under a doctor’s supervision. The agency discourages internet purchases of mifepristone because patients will be “bypassing important safeguards,” officials said in a statement.
    But the F.D.A. does not advise against online purchases of misoprostol (brand name Cytotec), which is used to treat a number of medical conditions. Misoprostol can terminate pregnancies by itself, recent studies have shown.
  • While no treatment is 100 percent safe, taking the pills “on your own at home does not affect your risk of complications,” said Dr. Carolyn Westhoff, an obstetrician gynecologist and professor at Columbia University and the editor in chief of the journal Contraception.
    But self-management also means a woman does not have a familiar health care professional nearby to call in case of an emergency or complications. Dr. Westhoff and other experts fear that women performing their own abortions may be reluctant to seek medical help in states that have criminalized abortion.
  • A medication abortion cannot be distinguished from a miscarriage, and traces of the pills cannot be discovered if they are taken orally, said Dr. Rebecca Gomperts, a Dutch physician who founded Aid Access.
    If a woman needs care after taking the pills, “we always tell people to say they had a miscarriage,” she said. “It’s exactly the same symptoms, and the treatment is exactly the same.”
    A study of thousands of women in the United States who received abortion pills from a provider without an in-person visit during the pandemic found that the practice was safe.
  • Complications are the rare exception. Another recent study looked at self-managed abortions in Nigeria, where abortion is banned except to save the life of the mother, and in Argentina (which legalized abortion up to 14 weeks in late 2020).
    Twenty percent of the nearly 1,000 women who participated in the study sought care at hospitals after the procedure, but most only wanted to confirm the abortion was complete. About 4 percent reported ongoing pain, fever or bleeding. Seventeen required procedures to complete the abortion, 12 stayed in the hospital overnight, and six needed blood transfusions, according to the study, which was published in The Lancet Global Health in late 2021.
    The surprise finding was that while some of the women took the mifepristone-misoprostol combination, the success rate for those taking misoprostol alone — a widely used drug that can be purchased in countries like Mexico without a prescription and is fairly inexpensive — was higher than that of the two-drug combination.
  • Most state laws that restrict abortion make performing an abortion a crime for doctors, not patients. Only three states — South Carolina, Oklahoma and Nevada — have laws that explicitly make it a crime to end one’s own pregnancy.
    Other states, however, have wielded child endangerment statutes or other laws against women suspected of terminating their pregnancies.
    In Indiana, Purvi Patel was sentenced to 20 years in prison in 2015 for inducing a self-managed abortion; her conviction was overturned in 2016. In Texas, murder charges were brought against Lizelle Herrera earlier this year in relation to a self-managed abortion, but prosecutors said they would not pursue the case.
  • At least 11 states have laws with broad personhood language that applies to fetuses, said Dana Sussman, deputy executive director of National Advocates for Pregnant Women. At least six — Kentucky, Louisiana, Ohio, South Dakota, Texas and Wyoming — define a fetus as a person throughout the criminal code, making it easier to prosecute women who terminate their own pregnancies.
  • Both the American Medical Association and the American College of Obstetricians and Gynecologists, which support abortion as an essential component of health care, oppose criminalizing self-managed abortion, as they say doing so will deter women from seeking medical attention.
    At the moment, health care providers are not legally required by any state to report patients they suspect of self-managing an abortion, according to If/When/How, an abortion-rights advocacy group. But laws are in flux.
    “We’re operating in an area of complete uncertainty,” Ms. Sussman said.

“Abortion Drugs May Be Safe Even After the First Trimester, Study Suggests” (July 6, 2023)[edit]

Roni Caryn Rabin, “Abortion Drugs May Be Safe Even After the First Trimester, Study Suggests”, New York Times, (July 6, 2023)

  • An overwhelming majority of women were able to end unwanted pregnancies with abortion medications on their own and without additional medical procedures, even if they were well beyond the first trimester, according to a report published on Thursday.
    The study was based on the experiences of 264 women who were nine to 16 weeks pregnant in Argentina, Nigeria and an unnamed country in Southeast Asia where abortion is illegal. Almost half of the women took only one drug, misoprostol, instead of the standard two-drug regimen, mifepristone and misoprostol.
    They were nonetheless able to terminate the pregnancies, according to the study, published in the journal Obstetrics & Gynecology. All of the participants received information from an abortion support group.
    The findings align with clinical data showing the efficacy and safety of medication abortions conducted under medical supervision throughout pregnancy, said Ruvani Jayaweera, an epidemiologist and research scientist at Ibis Reproductive Health and one of the study’s authors.
  • “This paper adds to previous research indicating that self-managed abortion with medications is safe and effective, including after 12 weeks of pregnancy,” said Dr. Daniel Grossman, a professor of obstetrics, gynecology and reproductive sciences at the University of California, San Francisco. “As clinic-based abortion care becomes less available in many parts of the country due to state-level bans, self-managed abortion will become more common, as we are already seeing.”
  • The two-drug regimen of mifepristone and misoprostol is approved by the Food and Drug Administration for use through only 10 weeks of pregnancy, under the supervision of a health care provider.
    But the W.H.O., taking into account shortages of health care providers in much of the developing world, endorses self-managed medical abortions in pregnancies of up to 12 weeks without medical supervision.

"Medication Abortion and Telemedicine: Innovations and Barriers During the COVID-19 Emergency" (June 16, 2021)[edit]

Amrutha Ramaswamy, Gabriela Weigel, Laurie Sobel, and Alina Salganicoff (June 16, 2021). "Medication Abortion and Telemedicine: Innovations and Barriers During the COVID-19 Emergency". Kaiser Family Foundation (KFF).

  • State actions in response to the COVID-19 crisis have highlighted their divergent approaches to abortion access. Some states classified abortion as a non-essential service, effectively banning services, while others have clarified that abortion is an essential service. In a handful of states, some clinics have begun to offer medication abortions using telemedicine. This approach maintains access to abortion while social distancing, preserving personal protective equipment (PPE), and limiting in-person health care visits and risk of exposure.
    In 2017, 39% of all abortions in the U.S. were medication abortions (also known as abortions induced by pills). These abortions are provided using two medications, mifepristone and misoprostol. While public knowledge about medication abortion is very low, even fewer people may be aware that telemedicine can aid in the provision of this service. Research shows that providing medication abortion by telemedicine is clinically feasible and safe, but COVID-19 has highlighted the impact of new and existing federal and state restrictions on providing abortions using this approach.
  • In an effort to preserve abortion access and maintain patient and provider safety during the COVID-19 pandemic, reproductive health care researchers and providers from Gynuity Health Projects, Advancing New Standards in Reproductive Health (ANSIRH) at UCSF, and the Society of Family Planning, among others, developed a “Telehealth for Medication Abortion Care” protocol for providing medication abortion building on prior research. This method enables patients to obtain their abortions safely without the traditional need for in-person pregnancy testing, pelvic examination, ultrasound or labs. Clinicians are able to evaluate patients remotely via a telehealth visit (e.g. video or phone) to determine their clinical eligibility for this service based on their health and gestational age. If eligible, patients pick up their abortion medications curbside from the clinic and take these pills after they get home. The follow-up visit with a clinician also happens via telehealth or through a phone call (Figure 1). Through this protocol, clinicians can provide abortion services while protecting patients and providers from SARS-CoV2 exposure. Maine Family Planning has implemented a similar protocol to eliminate the need for in-person testing.
    International data support that telehealth for medication abortion protocols are safe and effective. In the UK, the Royal College of Obstetricians and Gynecologists recently approved a telehealth for medication abortion care protocol, with mifepristone available through a minimal-contact pick-up or by mail.
    While this protocol is an innovative response to the provision of abortion services during the COVID-19 pandemic, using telemedicine to provide medication abortions is not new. In certain states, telemedicine abortions have been available through Planned Parenthood using a “site to site” protocol since 2008, and through the Gynuity Health Projects TelAbortion clinical trial using a “direct to patient” protocol since 2016. Gynuity is working to expand the number of states served by the TelAbortion study in response to the COVID-19 pandemic. This protocol, however, still necessitates some in-person care (e.g. ultrasound, blood tests). The protocol goes a step further in making medication abortions accessible during the COVID-19 emergency.
  • In 19 states, telemedicine abortion has been effectively prohibited; 5 states explicitly ban telemedicine for medication abortion, while 14 states require the prescribing clinician be physically present with the patient. The telehealth protocol is also not an option in the 26 states requiring patients receive an ultrasound before an abortion, and in the 12 states with in-person counseling requirements. This leaves 22 states and DC in which the telehealth protocol could be used to provide medication abortion.
  • Another notable barrier to medication abortion is the Risk Evaluation and Mitigation Strategy (REMS) placed on mifepristone by the FDA, which only permits medical providers who have received special certification from the manufacturer to prescribe and dispense the drug. This requirement not only limits the number of clinicians able to prescribe medication abortions, but also means patients cannot obtain the medication from a retail pharmacy or by mail.
    There have been calls to remove or relax the REMS requirement on mifepristone, but there has not yet been a response from the Trump Administration. Former head of the FDA, Jane Henney, has repeatedly called on the FDA to lift the REMS requirement. In March 2020, a coalition of 21 state attorneys general wrote to the FDA and the Department of Health and Human Services (HHS) asking them to waive mifepristone’s REMS to alleviate access issues related to in-person care. In April 2020, Senators Warren, Murray and Baldwin urged the FDA to “temporarily exercise enforcement discretion on in-person dispensing requirements,” so that people can access abortion services without risk of SARS-CoV-2 exposure.
    In May 2020, the ACLU filed a lawsuit challenging the REMS requirement that mifepristone be dispensed in-person; this was filed on behalf of the American College of Obstetricians and Gynecologists (ACOG), in addition to other organizations. The United States District Court of Maryland ruled in favor of ACOG, preventing the FDA from enforcing the REMS for mifepristone, abortion medication during the COVID-19 pandemic. In August 2020, the FDA petitioned the requested that the Supreme Court for an emergency stay to lift the national injunction preventing the FDA from enforcing the REMS, contending that it is constitutional to impose a regulatory requirement on one method of abortion, even if it creates an undue burden on people seeking this method of abortion when another method is safe. On October 8, 2020, six weeks after the FDA’s request, to obtain a more comprehensive record, the Supreme Court issued an order suspending the case and directing the FDA to request the District Court to lift or modify the preliminary injunction. Justices Alito and Thomas dissented from the Court’s order. This unusual order to not rule on the stay until the FDA requests the District Court to reconsider the scope of the injunction may reflect a compromise because there were only eight justices when the Court issued the suspension.
  • On January 12, 2021, in a 6-3 ruling, the Supreme Court decided in favor of the Trump Administration, blocking the lower court’s ruling which had suspended the FDA REMS in–person dispensing requirements for mifepristone during the COVID-19 emergency. Justice Sotomayor wrote a dissent in which Justice Kagan joined, noting the FDA has made other accommodations in the cases of other medications to reduce the risk of exposure to SARS-Cov2. While the case continues to be litigation, abortion providers may not dispense mifepristone by mail to reduce the risk of exposure to COVID-19. However, this ruling does not prevent the FDA, under the Biden Administration, from suspending the REMS in–person dispensing requirements during the pandemic and thereby making the litigation moot. This ruling, until the FDA announcement in April 2021, prohibited providers from continuing to safely dispense mifepristone without the risk of exposure to the SARS-Cov2 as they have been doing since July 2020.
    On April 12th, 2021, the FDA’s Center for Drug Evaluation and Research (CDER) notified ACOG that they will “exercise enforcement discretion” during the ongoing public health emergency with respect to in-person dispensing requirements of mifepristone based on a safety review. Effectively, this will allow providers in states that do not have laws that would otherwise ban this practice to dispense mifepristone using the telehealth protocol for medication abortion.
    On May 7th, 2021, in response to the ACLU lawsuit, the FDA announced in a court filing that a review of the REMS is currently underway.

"First-trimester medical abortion with mifepristone 200 mg and misoprostol: a systematic review" (January 2013)[edit]

Raymond EG, Shannon C, Weaver MA, Winikoff B (January 2013). "First-trimester medical abortion with mifepristone 200 mg and misoprostol: a systematic review". Contraception. 87 (1): 26–37. doi:10.1016/j.contraception.2012.06.011. PMID 22898359.

  • Background: The dose of mifepristone approved by most government agencies for medical abortion is 600 mg. Our aim was to summarize extant data on the effectiveness and safety of regimens using the widely recommended lower mifepristone dose, 200 mg, followed by misoprostol in early pregnancy and to explore potential correlates of abortion failure.
    • p.26
  • Results: We identified 87 trials that collectively included 120 groups of women treated with a regimen of interest. Of the 47,283 treated subjects in these groups, abortion outcome data were reported for 45,528 (96%). Treatment failure occurred in 2,192 (4.8%) of these evaluable subjects. Ongoing pregnancy was reported in 1.1% (499/45,150) of the evaluable subjects in the 117 trial groups reporting this outcome. The risk of medical abortion failure was higher among trial groups in which at least 25% of subjects had gestational age >8 weeks, the specified interval between mifepristone and misoprostol was less than 24 h, the total misoprostol dose was 400 mcg (rather than higher), or the misoprostol was administered by the oral route (rather than by vaginal, buccal, or sublingual routes). Across all trials, 119 evaluable subjects (0.3%) were hospitalized, and 45 (0.1%) received blood transfusions.
    • p.26
  • Since mifepristone was introduced in France and China more than two decades ago, medical abortion with this antiprogestin has expanded rapidly throughout the world. Mifepristone is now registered in 50 countries (www. gynuity.org, accessed 14 December 2011). In the United States, about one fifth of all outpatient abortions are performed medically, and in several countries in Europe, the proportion exceeds 60%.
    Although medical abortion regimens approved by most government regulatory agencies specify 600 mg mifepristone, in practice, a dose of 200 mg is standard worldwide. A prostaglandin, misoprostol, is administered after the mifepristone to enhance success. The dose, route, and timing of administration of misoprostol are not standardized. In the United States, affiliates of Planned Parenthood Federation of America provide 800 mcg buccally 24–48 h after the mifepristone. The International Federation of Obstetricians and Gynaecologists recommends either vaginal, buccal, or sublingual administration as do the World Health Organization and the United Kingdom Royal College of Obstetricians and Gynaecologists, which also recommend oral dosing at gestational ages up to 49 days. Lower doses, divided doses, oral administration, and a shorter or longer interval between the two drugs also have been used clinically or evaluated in research studies.
    • pp.26-27
  • We found strong evidence of heterogeneity across trial groups in both the proportion of subjects who had medical abortion failure and the proportion who had ongoing pregnancy (pb.001 for both outcomes). Logistic regression models included as independent variables all the characteristics listed in Table 2. These models found few associations that were both substantial and significant. After adjustment for other characteristics included in the model, groups in which at least 25% of the women were in the ninth week of pregnancy had higher medical abortion failure rates than groups in which fewer women were so advanced in gestation (OR 1.5; 95% CI 1.1–2.0). Groups instructed to take the misoprostol b 23 h after the mifepristone also had higher medical abortion failure rates than other groups (OR 2.1; 95% CI 1.4–3.2). At each total misoprostol dose level, oral administration was associated with higher medical abortion failure rates than each of the other three routes, but no substantial differences were noted among the other routes. Similarly, for each route, 400 mcg misoprostol was associated with higher failure rates than higher doses, although not all of these associations were significant.
    • p.28
  • Associations of misoprostol dose and route with ongoing pregnancy were mostly consistent with the associations with failure of all types; that is, both the oral route and the 400 mcg dose of misoprostol were generally associated with higher ongoing pregnancy rates than other doses and other routes. Ongoing pregnancy was twice as common in groups in which ultrasound was not routinely used to confirm success than in groups in which it was used in all women (OR 2.0, 95% CI 1.0–3.9). No notable associations were apparent between ongoing pregnancy rates and of any of the other group characteristics, however.
    • p.28
  • Across all trials, 119 of 45,528 evaluable subjects (0.3%) were hospitalized; of these, 46 hospitalizations (38%) occurred in a single trial which included 4,132 treated women. Most of the hospitalizations were for vaginal bleeding, pelvic pain, or infection; some were for ectopic pregnancy or other conditions unrelated to the abortion. Forty-five women (0.1%) received blood transfusions. Hospitalizations and blood transfusions were less common in trials in which women were permitted to take the misoprostol at home (0.15% and 0.08%, respectively) than in trials in which clinic administration was required (0.45% and 0.14%, respectively).
    • pp.28, 30
  • Medical abortion using mifepristone 200 mg followed by misoprostol in the first 63 days of gestation is remarkably effective and safe. In trials that together included more than 45,000 women conducted in disparate settings over nearly two decades using a variety of regimens and treatment protocols, fewer than 5% of subjects required surgery to complete termination of the pregnancy. The proportion who had ongoing pregnancy at follow-up — the outcome of greatest concern to clinicians — was 1.1%. Serious complications requiring hospitalization or transfusion occurred in less than 0.4% of patients.
    • p.30
  • Some random variability in results is expected in any collection of research studies. However, our analysis found strong evidence of statistical heterogeneity across trials in both medical abortion failure rates and rates of ongoing pregnancy. This finding indicates that the non-uniformity in these outcomes was due to underlying differences among the studies rather than simply to chance. We identified a few practices that were associated with a lower risk of medical abortion failure: an interval of at least 24 h between the mifepristone and misoprostol, use of misoprostol doses higher than 400 mcg and administration of misoprostol by a buccal, vaginal, or sublingual rather than oral route. The last of these is consistent with the conclusions of a recent Cochrane review of first trimester medical abortion, which included only randomized trials. As cited previously, most current guidelines for medical abortion incorporate these practices.
    We also found slightly higher risks of medical abortion failure in groups that had a high proportion (N25%) of women in the 9th week of pregnancy: after adjustment for other factors, these groups overall had a 50% higher odds of medical abortion failure. However, we did not find a higher risk of ongoing pregnancy in these groups. Given the low overall risk of medical abortion failure and the relative ease of treating failure using surgical evacuation (which would have been the treatment for all subjects had medical abortion not been attempted), offering medical abortion to women at this gestational age seems reasonable.
    • pp.30-31
  • We observed no significant association between abortion failure rates and the timing of the follow-up evaluation. The data thus are inconclusive with respect to the theory that high surgical intervention rates are in part attributable to impatience among providers and patients. Moreover, although routine ultrasound evaluation at follow-up was associated with a lower risk of diagnosis of ongoing pregnancy, we found no evidence for or against an effect of this practice on overall medical abortion failure rates —that is, the need for surgical intervention. Prompt confirmation of completeness of the abortion and clinical assessment without routine ultrasound may enhance women's satisfaction with the procedure.
    We found no evidence that allowing women to take the misoprostol at home increased the rates of abortion failure or serious complications. Most women prefer this option, and it is presumably substantially more efficient for the health care system than requiring patients to return to the provider for administration of the prostaglandin. This requirement, which is law in some countries such as the United Kingdom, thus is unjustifiable and should be abandoned.
    • pp.31-32
  • The large quantity of data presented in this review demonstrates that currently used medical abortion regimens are so effective and safe that additional research aimed at further clinical improvement will have little public health benefit. Future investigations should focus on service delivery issues: increasing access, reducing cost, enhancing patient comfort and ensuring availability of ancillary services such as contraception that can aid women in reaching their reproductive goals.
    • p.32

"Efficacy of Misoprostol Alone for First-Trimester Medical Abortion: A Systematic Review" (January 2019)[edit]

Elizabeth G. Raymond, Margo S. Harrison, and Mark A. Weaver (January 2019). "Efficacy of Misoprostol Alone for First-Trimester Medical Abortion: A Systematic Review". Obstetrics and Gynecology. 133 (1): 137–147. doi:10.1097/AOG.0000000000003017. PMC 6309472. PMID 30531568.

  • Tabulation, Integration, and Results: We abstracted data about each trial group, including study characteristics, treatment regimen, clinical protocol, number of women treated and followed, and numbers with outcomes of interest. We used meta-analytic methods and logistic regression to examine factors associated with surgical intervention after treatment. Among all 12,829 evaluable women, 2536 (meta-analytic estimate 22.0%, 95% CI 18.8%, 25.5%) had surgical uterine evacuation. Multiple factors were significantly associated with this proportion, including misoprostol amount per dose and route of administration, loss to follow-up rate, publication date, geographic region, number of misoprostol doses, duration of dosing, and time between dosing and evaluation. Of 6359 evaluable women, 384 (meta-analytic estimate 6.8%, 95% CI 5.3%, 8.5%) had ongoing pregnancy. At most 26 of 12,184 evaluable women (meta-analytic estimate 0.7%, 95% CI 0.4%, 1.0%)were transfused or hospitalized for abortion-related reasons. In trials that provided satisfaction data, most of women were satisfied or very satisfied with the treatment (meta-analytic estimate 78%, 95% CI 71%, 85%).
    Conclusions: Misoprostol alone is effective and safe and is a reasonable option for women seeking abortion in the first trimester. Research is indicated to further refine the regimen and to establish efficacy in the late first trimester. Treatment regimens that contain only misoprostol can be effective and safe for first-trimester medical abortion.
    • pp.137-138
  • For early medical abortion, the primary regimens recommended by current clinical guidelines include two drugs: mifepristone and misoprostol. Because mifepristone potentiates the abortifacient action of misoprostol, the combination is highly effective, resulting in complete abortion in more than 95% of women through 63 days of gestation1,2 and 93% between 64 and 70 days. However, mifepristone is costly and is unavailable in many settings. In the United States, although the drug is approved for marketing, the Food and Drug Administration has imposed restrictions on its distribution that substantially limit

both patients’ and providers’ access to it.4 For women who cannot obtain mifepristone, use of misoprostol alone, which is inexpensive and is widely used for various obstetric and gastrointestinal indications, can serve as an important alternative option. A systematic review published in 2007 found that the efficacy of misoprostol single-agent regimens at gestational ages ≤63 days ranged from 84% to 96%, but since then, additional studies have been published. We performed this systematic review to summarize available data on the effectiveness and safety of medical abortion with misoprostol alone in the first trimester of pregnancy. The primary outcome of our analysis was surgical evacuation of the uterus to complete the abortion; secondary outcomes were viable ongoing pregnancy after taking the prescribed misoprostol regimen, transfusions and hospitalizations.

    • p.138
  • The 53 groups used a multitude of misoprostol regimens. In all groups, women were required to take a specified minimum number (1 to 5) of doses of misoprostol vaginally, buccally, orally, sublingually, or by a combination of routes (Table 1). In all but 4 groups, the initial dose was 800 mcg or was administered vaginally; the combination 800 mcg vaginally was used in 31 groups that collectively included 10,010 (78%) of the evaluable women. Misoprostol was moistened before vaginal insertion in 41% of evaluable women who took the drug by that route. In 39 of the 48 groups in which more than one dose was allowed, subsequent doses used the same amount per dose and route of misoprostol as the first dose. Multiple doses were administered 3–48 hours apart, such that the longest duration of the required treatment was 96 hours. In 35 groups (38% of evaluable women), if complete abortion had not occurred after the required doses, women were instructed to take additional contingent doses up to a specified maximum, after which a decision regarding surgical intervention was made. The maximum total number of allowed doses (required + contingent) in any group was 6, and the maximum duration of dosing if all allowed doses were taken was 14 days. Across all groups, most women were instructed to take no more than 3 doses within a maximum of 48 hours. Nine studies, 7 of which were conducted by the same group of investigators, provided extra misoprostol to some or all women who were determined not to need surgery in order to evacuate “remains” from the uterus or for an unspecified reason, and one study provided a dose of misoprostol to all women who were scheduled for surgery.30 We did not count those extra doses in this analysis because they were given after the outcome had been determined and thus did not contribute to the outcome. In at least 24 groups (83% of evaluable women), women were allowed to take some or all of the misoprostol doses at home.
    • p.142
  • Among all 12,829 evaluable subjects (Table 1), 2,536 (20%) underwent surgical uterine evacuation (meta-analytic estimate 22.0%, 95% CI 18.8%, 25.5%). Across trial groups, the proportion with this outcome ranged from 0 to 77% (Figure 2, Panel A). More than 90% of the evaluable subjects were in trial groups in which the failure proportion was 24% or less.
    • p.142
  • We found strong evidence of heterogeneity across trial groups in the proportion of subjects who ultimately had surgery (p < 0.001, I2 = 94.2%). In unadjusted analyses, this proportion was significantly associated with characteristics of the initial misoprostol dose (Table 2). Among groups treated vaginally, the odds of surgery decreased with the amount of misoprostol in the initial dose (linear trend p<0.001); groups treated with ≥800 mcg had about one quarter the risk of surgery as groups treated with 200 mcg. Among groups treated with 800 mcg in the initial dose, oral administration was associated with nearly a 3-fold higher risk of surgery than vaginal administration, whereas risks were similar in groups who took the drug sublingually, buccally, and vaginally.
    • pp.142-143
  • In the 31 groups treated initially with 800 mcg vaginally, the proportion of women who had surgery was significantly associated with numerous group characteristics (Table 3). Some of these were details of the clinical protocol: the risk of surgery declined with increases in both the allowed number of misoprostol doses and the duration of dosing (linear trend p≤0.01 for both associations). Surgery was less common in groups in which the misoprostol was moistened before vaginal insertion and in groups in which the decision to perform surgery was delayed until 4–7 days after treatment. Surgery was also associated with other characteristics of the studies; for example, the two groups with loss rates >10% had higher surgery rates than groups with no loss, later studies had higher rates than earlier ones, and studies conducted in Asia and Latin America had higher rates than those conducted in North America. Many of the group characteristics were correlated with each other: for example, groups that were given more doses also had longer duration of dosing and were more likely to use moistened tablets if the route of administration was vaginal, and both of the two studies with >10% loss took place in Latin America and did not report using moistened tablets.
    • p.143
  • Data on abortion status after only the required misoprostol doses was available from 42 trial groups (Table 4). In these groups, each woman was evaluated to determine abortion completeness after she took all of the required doses but before any additional doses. Complete abortion was significantly more common after 3 doses than after only one, but no significant linear trend was apparent by number of doses from 1 to 5 (p=0.73).
    In 36 groups, researchers noted the number of surgical interventions performed for ongoing pregnancy. Of the 6359 evaluable women in these groups (50% of the total), 384 (6%) had

ongoing pregnancies (meta-analytic estimate 6.8%, 95% CI 5.3%, 8.5%,heterogeneity: p < 0.001, I2 = 81.7%). The proportion across groups ranged from 0 to 33%; more than 90% of the women were in groups in which no more than 11% of subjects had ongoing pregnancy (Figure 2, Panel B). The 384 ongoing pregnancies constituted 39% of the 989 medical abortion failures in these groups.
Across the 38 papers, 14 women were hospitalized for abortion-related reasons and 12 received transfusions. Excluding the studies in which women were or may have been hospitalized routinely throughout the abortion process, the sum of these numbers (26) constitutes at most 0.2% of the total 12,184 evaluable women (meta-analytic estimate 0.7%, 95% CI 0.4%, 1.0%). No deaths or ectopic pregnancies were reported.
Women in 20 groups provided information about satisfaction about the treatment regimen (Appendix 1, http://links.lww.com/xxx). In these groups, 2549 of 2961 women (86%; meta-analytic estimate 78%, 95% CI 71%, 85%) said that they were satisfied or very satisfied, and 2396 of 2832 (85%; meta-analytic estimate 76%, 95% CI 76%, 82%) said that they would use the method if needed in the future.

    • p.143
  • Data from 42 studies that included nearly 13,000 evaluable women indicate that misoprostol used alone can be effective and safe for inducing abortion in the first trimester. Across all studies, about 78% of women had complete abortions without recourse to surgery, and viable pregnancy was terminated in more than 93%. The reported incidence of serious complications requiring hospitalization or transfusion was at most 0.2%. Most women were satisfied with the treatment.
    Our analysis identified some treatment characteristics that were associated with higher effectiveness. The chance of surgical uterine evacuation decreased significantly as the amount of misoprostol in the initial dose increased and was lower in trial groups that administered this dose vaginally, sublingually, or buccally rather than orally. Among groups in which the dose was 800 mcg vaginally, surgical intervention was substantially less common if women were permitted to take at least four doses, if these doses were taken over an interval of more than 48 hours, and if the tablets were moistened before insertion. Among all 53 groups, 20 were treated with at least three doses, the first of which consisted of at least 800 mcg misoprostol administered vaginally (moistened), sublingually, or buccally; of the 5338 evaluable women in these groups, 87% aborted without surgery.
    The data reviewed here have many strengths: the studies were conducted in numerous diverse settings, the study populations were typical abortion clients unselected except with respect to gestational age, and follow-up rates were high. The variety of regimens and clinical protocols used in the 42 included studies enabled us to examine multiple factors that may contribute to the likelihood of surgical intervention following treatment with misoprostol alone. Our analysis of all of these studies provides insights not available from only the 7 individual studies published to date that directly compared different misoprostol-only regimens or protocols.
    • p.144
  • [M]oistening of vaginally administered tablets was associated with higher numbers of allowed doses, and both were associated with lower surgery rates; our analysis did not establish the extent to which either factor may have been independently responsible for improved regimen effectiveness. Nevertheless, this finding is consistent with other data. In particular, wetting the tablets has been shown to improve vaginal absorption of misoprostol and enhance cervical dilation before surgical abortion, and two randomized trials have suggested that it decreases risk of surgical intervention in first trimester medical abortion. Our finding that surgery was less common in trial groups without loss to follow-up may be explained by the fact that indications for surgery (abortion failure, bleeding) prompt patients to seek care. It suggests that the true risk among all treated patients may be lower than our estimate.
    • pp.144-145
  • Despite these limitations, currently available data suggest that misoprostol as a single agent is a reasonable option for women seeking abortion in the first trimester. This treatment is clearly less effective than standard regimens that also contain mifepristone, and thus enhanced vigilance should be recommended to detect potential failures. Nevertheless, misoprostol alone may be preferred by some women because it may be easier to obtain, less costly, or have other advantages. Further research is indicated to refine the regimen, addressing issues such as the optimal misoprostol amount per dose and dosing intervals if the drug is administered sublingually or buccally, which may be more convenient for women than vaginal insertion, and the efficacy of these regimens in the late first trimester.
    • p.145

"Prosecuting Women for Self-Inducing Abortion: Counterproductive and Lacking Compassion" (2015)[edit]

Andrea Rowan (2015). "Prosecuting Women for Self-Inducing Abortion: Counterproductive and Lacking Compassion". Guttmacher Policy Review. 18 (3): 70–76. First published online: September 22, 2015

  • The advent of medication abortion has further allowed some women to take matters into their own hands; however, doing so has exposed them to the risk of criminal prosecution. Mifepristone, also known as Mifeprex or RU-486, was developed in the early 1980s and is the backbone of the most effective medication abortion regimens available. The American College of Obstetricians and Gynecologists recommends that mifepristone be used in conjunction with another drug called misoprostol (also commonly referred to as Cytotec) for the most effective medication abortion protocol with the fewest side effects. Misoprostol can also be safely used on its own to induce an abortion, although it is less effective than the combination protocol (see box).
  • Mifepristone and Misoprostol
    Medication abortion is widely used in many countries where abortion is legal. In the United States, medication abortion accounted for 23% of all nonhospital abortions in 2011. The evidence-based mifepristone-misoprostol protocol recommended by the American College of Obstetricians and Gynecologists has been found to be safe and effective in multiple trials. For example, the most recent study published in 2015 found that medication abortion using the evidence-based protocol was effective in 97.7% of procedures.
    Overseas, the ability to obtain a medication abortion using the mifepristone-misoprostol combination varies by country. Because the primary use for mifepristone is abortion, it is not approved in many countries with strict abortion laws; however, misoprostol is used to prevent or treat several conditions unrelated to abortion, such as treatment of postpartum hemorrhage, and is available over the counter in many countries. Accordingly, the World Health Organization has developed protocols for the safe use of misoprostol alone for abortion in settings where it is the only drug available.
    As misoprostol is currently licensed in approximately 90 countries across the world, and is temperature-stable and inexpensive, it has become the method of choice for self-induced abortions for women in many countries with no other options. In fact, in Latin American countries where abortion is highly restricted and where almost all abortions are illegal and unsafe, women’s use of misoprostol— as opposed to some traditional means of self-inducing an abortion—may be associated with a possible decline in the severity of complications from self-induced abortion.
    Still, misoprostol-only medication abortion is not as effective as the combination protocol. This means that women using it alone are at higher risk of needing follow-up medical attention. Similarly, women who misdate their pregnancy and are too far along to effectively use misoprostol run the risk of incomplete abortion, which will require additional care.
    Misoprostol is not available over the counter in the United States, but it can be obtained from other countries and over the Internet. As more states erect more barriers to safe abortion care from health care professionals, some U.S. women are effectively finding themselves in the same legal quandary as women living in countries where abortion is illegal and are discovering that self-administering misoprostol is a way to take matters back into their own hands.
  • Compared with the traditional and often extreme methods women have used to terminate unwanted pregnancies themselves, such as inserting sticks or toxic liquids into the vagina, self-induced medication abortion can lower the physical risks that women face. In countries where misoprostol is available over-the-counter, women are able to obtain it with relative ease. In countries where misoprostol is not readily available, women can use the Internet to obtain it (and possibly mifepristone), although sometimes from dubious sources.
  • There have been at least half a dozen U.S. cases where women have been arrested and charged after attempting to self-induce an abortion using illicitly obtained abortifacients.
  • However, the availability of abortifacients does not shield women from prosecution. There have been at least half a dozen U.S. cases where women have been arrested and charged after attempting to self-induce an abortion using illicitly obtained abortifacients. For instance, in 2004, one woman in South Carolina was charged with illegal abortion and failure to report the abortion to the coroner after using an abortifacient. In a 2007 case in Massachusetts, a woman was charged with illegal procurement of a miscarriage; however, because of the state’s inability to assess whether the fetus met its definition of viability at the time of the abortion, she was not charged with murder. In Idaho in 2011, a woman was charged with unlawful abortion and the prosecutor threatened to charge her under the state’s newly enacted 20-week ban on abortion. In a case in Pennsylvania in 2013, a mother who had ordered abortifacients off the Internet for her daughter was reported by hospital staff after they sought medical attention for side effects; she was eventually charged with "providing abortion without a medical license, dispensing drugs without being a pharmacist, assault and endangering the welfare of a child." And in 2015, a Georgia woman was arrested and charged with murder after she gave birth on her way to the hospital after taking abortifacients she ordered off the Internet.
    Conviction and punishments varied in these recorded cases. In the South Carolina and Pennsylvania cases, both women were convicted; the woman in South Carolina was sentenced to jail time and a fine, but was let out on time served, while the Pennsylvania woman began a 9–18-month jail sentence in September 2014. In Massachusetts, the defendant was given probation and ordered to attend counseling. In the Idaho case, the charges were dropped due to lack of evidence. The murder charges were eventually dropped in the Georgia case as well, although the woman is still facing a misdemeanor charge of possession of a dangerous drug.
  • Beyond Abortion
    While it is unknown how many women in the United States have actually been charged for self-inducing using medication abortion, it is likely a small number. However, the mere existence of medication abortion is providing some legal authorities reason to conduct fishing expeditions to go after not only women who have clearly terminated a pregnancy, but also women whom they suspect have done so.
    This phenomenon has been playing out for some time and most starkly in other countries where abortion is illegal altogether. For instance, El Salvador has been one of the most aggressive countries in terms of accusing, prosecuting and imprisoning women believed to have medically self-induced an abortion. An estimated 129 women in El Salvador were charged with self-inducing an abortion between 2000 and mid-2011, and at least 26 were convicted of homicide and imprisoned; however, some of these women emphatically assert that they did not know they were pregnant or that they miscarried without attempting to self-induce.
    For example, in 2012, one Salvadoran woman was sentenced to 40 years in prison for aggravated homicide after suffering a miscarriage and going to the hospital for medical attention; although she did not know she was pregnant at the time, hospital staff still reported her to the authorities. In 2007, a teenager was sentenced to 30 years in prison after seeking medical care for a stillbirth, after medical staff reported her to the authorities on the unsubstantiated suspicion she had attempted to induce an abortion; she was recently pardoned as a result of a sustained campaign brought by Agrupación Ciudadana and other nongovernmental organizations.

"There's no proof "abortion reversals" are real. This study could end the debate" (April 17, 2019)[edit]

Carter Sherman (April 17, 2019). "There's no proof "abortion reversals" are real. This study could end the debate". Vice.

  • In theory, an “abortion reversal” works like this: In a medication abortion, a woman ends her pregnancy by taking two pills, mifepristone and misoprostol, several hours apart. If a woman changes her mind, however, after taking the mifepristone — which works to block progesterone, a hormone that helps sustain pregnancy — proponents of abortion reversal say that she can take repeated doses of progesterone to reverse its effects.
    Such a regimen is probably safe. But critics say it remains unproven, and testing it out on patients just isn’t good medicine. Still, in Arkansas, Idaho, South Dakota, and Virginia, doctors are required by law to advise women that it’s an option if they change their mind about wanting an abortion.
    “The tragedy, in a lot of this, is when legislators get involved in things that aren’t proven and then legislate requirements that impede care or are basically, potentially, lies,” said Mitchell Creinin, a professor at the University of California, Davis. “Without good science, we never know if something’s real or not. I mean, you wouldn’t want your doctor to tell you to take an aspirin to treat your cancer.”
  • The progesterone protocol is not recommended by the American Congress of Obstetricians and Gynecologists, which says any claims about abortion reversal’s effectiveness “are not based on science and do not meet clinical standards.”
    Even Creinin, who plans to spend a year on his study, doesn’t think it’s possible. “It just doesn’t make any physiological sense,” he said.
    Mifepristone helps end pregnancies because it binds tightly to the hormone receptors that also attach to progesterone, he explained, and no amount of progesterone can unwind those bonds. “If you have four bolts on your door, if you think that coming with some extra keys is gonna help you unlock the bolts when none of the keys necessarily work in the lock, it ain’t gonna open the door,” he said.
    But mifepristone doesn’t always work — when taken alone, it’s commonly cited as ending just between 10 and 50 percent of pregnancies. Generally, if a woman changes her mind about having a medication abortion, doctors will advise her to simply not take the second pill.
  • While Delgado agrees that there should be more medical research into what he calls “abortion pill reversal,” he has concerns about Crienin’s approach. “He’s right: None of the studies that we’ve published have been prospective, randomized controlled trials, so that is a weakness, absolutely,” Delgado said.
    But he’s worried that Creinin will use a less-effective progesterone regimen and that his study’s sample size is too small. (Creinin says that if Delgado is right about how effective the progesterone regimen is, Creinin will have enough participants to prove whether it works.)
  • Many researchers remained unconvinced that Delgado’s work was credible. In an article published in the New England Journal of Medicine, researchers pointed out multiple flaws in the second paper, including that some providers had excluded women whose pregnancies had already effectively ended by the time they decided to undergo the progesterone protocol — a move that potentially inflated its success rate.
    “It is poorly designed and falls far short of providing sufficient evidence to recommend this course of treatment,” Hal Lawrence, a doctor and ACOG’s executive vice president and CEO, told VICE News of Delago’s second study soon after its publication.
  • Despite the need for more research into the treatment, Delgado says it’s safe enough to recommend.
    “There’s no reason to withhold the treatment, pending the other studies, because right now all the evidence shows that it is safe and effective,” he said. “And this is how we’ve done any other new treatment throughout the history of medicine.”
  • VICE News reached out to several state legislators who backed abortion reversal bills about Creinin’s study, and its impact on their proposals.
    “If you talk to the doctors who have done this, it’s pretty convincing, and see the babies — and I have seen some of those babies — which are now thriving, growing people, that’s pretty good evidence in my mind,” said North Carolina Sen. Joyce Krawiec, a Republican. “But I would be very anxious to see the results of [Creinin’s] study as well.”
    Kansas Gov. Laura Kelly, a Democrat, has not yet decided whether to sign an abortion reversal bill that recently passed the state legislature, her office said.
  • Creinin knows that legislators don’t have to pay attention to the results of his study, regardless of what he finds. But it’s important to test the treatment anyway, he said, as a doctor who cares for women. While a woman has never told him that she wanted to change her mind after taking mifepristone — and at least one study has indicated that most women are sure of their decision to get abortions — Creinin says it is possible.
    “Rather than people doing shams of treatment and calling it ‘studies,’ the goal is to really find out, ‘Is this real or not?’” Creinin said. “So that if it’s not real, we can stop stupid laws from being passed. And so that, if it is potentially real, then we can at least understand what the right treatment is.”

“What's next for the abortion pill mifepristone?” (April 10, 2023)[edit]

Becky Sullivan, Sarah McCammon; “What's next for the abortion pill mifepristone?”, NPR, (Updated April 10, 2023)

  • Mifepristone is widely used across the U.S. to end pregnancy in the first 10 weeks of gestation. About half of all abortions nationwide are performed using mifepristone as the first of a two-pill regimen. The drug is also commonly used to help manage miscarriages.
    The name-brand drug Mifeprex was first approved by the Food and Drug Administration more than 20 years ago. Since then, it has been used millions of times, and major medical groups say it has a strong safety record. A generic version was approved in 2019.
  • The Texas ruling's quick timeline has left open a number of questions for medical providers and pharmacies regarding access to the widely used drug.
    "For example, if medication is already in pharmacy and has already been prescribed, can those prescriptions be filled?" said David Donatti, an attorney at the ACLU of Texas. "These are questions that the lowest court order just does not answer."
  • On Monday, the DOJ filed a request for an emergency stay of the injunction while the Fifth Circuit considers the appeal, asking the court to decide by noon CT on Thursday, April 13.
    "Plaintiffs lack standing to challenge FDA's approval of a drug they neither take nor prescribe; their challenge to FDA actions dating back to 2000 is manifestly untimely; and they have provided no basis for second-guessing FDA's scientific judgment," the motion reads.

“Outrage at jail sentence for woman who took abortion pills later than UK limit” (12 June 2023)[edit]

Tobi Thomas, “Outrage at jail sentence for woman who took abortion pills later than UK limit”, The Guardian, (12 June 2023)

  • Campaigners and MPs have reacted with outrage to a woman being sentenced to more than two years in prison for procuring drugs to induce an abortion after the legal limit.
    The mother of three received the medication under the “pills by post” scheme, which was introduced during the Covid pandemic for unwanted pregnancies up to 10 weeks, after a remote consultation.
    Prosecutors said the woman had knowingly misled the British Pregnancy Advisory Service (BPAS) by saying she was below the 10-week cut-off, when she believed she was about 28 weeks pregnant.
    Doctors later concluded the foetus was from 32 to 34 weeks’ gestation (between seven and eight months) at the time of termination. In England, Scotland and Wales, abortion is generally legal up to 24 weeks but is carried out in a hospital or clinic after 10 weeks.
  • Justice Pepperall said: “This case concerns one woman’s tragic and unlawful decision to obtain a late-term abortion. In my judgment your culpability was high … because you knew full well your pregnancy was beyond the limit of 24 weeks, and you deliberately lied to gain access to telemedical services.
    “I accept that you feel very deep and genuine remorse for your actions. You are racked by guilt and have suffered depression. I also accept that you had a very deep emotional attachment to your unborn child and that you are plagued by nightmares and flashbacks to seeing your dead child’s face.”
  • The number of women and girls facing police investigations and the threat of life imprisonment under current abortion laws has risen over the past three years, according to BPAS. In 2022, a woman who used abortion medication in a failed attempt to end her own pregnancy was reported to the police by her medical team.
  • A mitigation plea was sent to the judge in April 2023 signed by groups including the Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives. “We plead to Your Honour to consider leniency in this case … we are fearful that if the case before you receives a custodial sentence it may signal to other women who access tele-medical abortion services, or who experience later gestation deliveries, that they risk imprisonment if they seek medical care,” it said.
    The judge said the letter was "inappropriate", adding that he "does not accept that imprisonment in this case is likely to deter women and girls from lawfully seeking abortion care within the 24-week limit”.
    After the sentencing, Clare Murphy, the chief executive of BPAS, said she was "shocked and appalled" by the custodial sentence, adding: “In their sentencing remarks, the judge made it clear that women will only be protected from prosecution if MPs bring forward legal change. There has never been a clearer mandate for parliamentary action, and the need has never been so urgent.
    "Over the last three years, there has been an increase in the numbers of women and girls facing the trauma of lengthy police investigations and threatened with up to life imprisonment under our archaic abortion law."
    Mandu Reid, the leader of the Women's Equality party, said: “I am devastated for the woman at the centre of this case, and for her children, who have been forcibly separated from their mum ...
    “This conviction serves no one, not her, not her children, not the public interest. All it does is punish a woman for seeking healthcare in the middle of a pandemic and risk deterring women who want or need an abortion from seeking that care in future. No one deserves to be criminalised for seeking healthcare, which is a human right.”
    The Labour MP Stella Creasy said: “It is an hangover from another era that our abortion laws are based not on healthcare considerations, but first and foremost criminal sanctions.
    “This case shows that the failure to address this has very real modern-day implications. In the light of repeated attacks on women’s rights and the lack of compassion this case shows, it’s never been more urgent to ensure it is a formal human right of all women in the UK to access a safe, legal and local abortion if she chooses.”
    In his sentencing remarks the judge made reference to Sarah Catt who in 2012 was originally sentenced to eight years’ imprisonment after aborting her unborn baby within a week of a due date, although her sentence was reduced to three and a half years on appeal.

“Safe Abortion: Technical and Policy Guidance for Health Systems” (2003)[edit]

“Safe Abortion: Technical and Policy Guidance for Health Systems”. World Health Organization. (2003).

  • For medical methods of abortion, if abortion is not complete before they leave the health facility, women should return after 10-15 days for confirmation that the abortion has been completed.
    • Follow-up, p.21
  • The preferred methods are manual or electric vacuum aspiration, or medical methods using a combination of mifepristone followed by a prostaglandin. Mifepristone followed by a prostaglandin has been shown safe and effective up to 9 completed weeks of pregnancy, and the safety and effectiveness of the regimen between 9 and 12 completed weeks is under investigation.
    The use of medical methods of abortion requires the back-up of vacuum aspiration on site or through referral in case of failed or incomplete abortion.
    • Methods up to 12 completed weeks since last menstrual period, p.29
  • The preferred medical method for abortions after 12 completed weeks since last menstrual period is mifepristone followed by repeated doses of a prostaglandin such as misoprostol or gemeprost. The preferred surgical method is dilation and evacuation (D&E), using vacuum aspiration and forceps.
    • Methods of abortion continued, p.30
  • Medical methods of abortion have been proved to be safe and effective (Ashok et al. 1998a, Peyron et al. 1993, Schaff et al. 1999, Spitz et al. 1998, Trussel and Ellertson 1999, Urquhart et al. 1997, Winikoff et al. 1997). The most widely used regimens rely on the antiprogestogen, mifepristone, which binds to progesterone receptors, inhibiting the action of progesterone and hence interfering with the continuation of pregnancy. Treatment regimens entail an initial dose of mifepristone followed by administration of a synthetic prostaglandin analogue, which enhances uterine contractions and helps expel the products of conception (Swahn and Bygdeman 1988).
    The effects of medical methods of abortion are similar to those associated with spontaneous abortion adninclude cramping and prolonged menstrual-like bleeding. Bleeding occurs for nine days on average but can last up to 45 days in rare cases (Creinin and Aubeny 19999). Side-effects include nausea, vomiting and diarrhea. Conditions that warrant cuatino with the use of mifepristone and a prostaglandin include chronic or acure adrenal or hepatic failure, bleeding disorders, heavy smoking and allergies to any of the drugs used. Mifepristone is not an effective treatment for ectopic pregnancy, suspicion of ectopic pregnancy demands further investigation and, if confirmed, immediate treatment (see World Health Organization 2000a for specifics on treatment).
    Medical methods of abortion have proved acceptable in several low-resource settings (Elul et al. 1999, Ngoc et al. 1999). However, the drugs mifepristone in particular, are currently available in only a few developing countries. This may change in coming years, and programme managers would be required to introduce medical methods of abortion into health services.
    • 2.4 Medical methods of abortion p.35
  • Commonly used mifepristone plus prostaglandin regimens
    *Up to 9 completed weeks since LMP
    200 mg mifepristoine followed after 36-48 hours by 1.0 mg vaginal gemeprost or 800 ug vaginal misoprostol or 400 ug oral misoprostol up to 7 completed weeks
    After 12 completed weeks since LMP 200 mg mifepristone followed after 36-48 ours by 1 mg vaginal gemeprost (repeated every 6 hours up to maximum of 4 doses, and if necessary every 3 hours up to 4 additional doses) or 400 ug misoprostol orally every 3 hours up to 5 doses or 800 ug vaginal misoprostol followed by 400 ug oral misoprostol every 3 hours up to a maximum of 4 doses.
    • p.36
  • Misepristione with misorprostol or gemeprost as been proved to be highly effective, safe and acceptable for early first trimester abortions (RCOG 2000). Efficacy rates up to 98% are reported (Trussell and Ellerston 1999). Approximately 2 to 5% of women treated with the mifepristone and misoprostol regimen will require surgical intervention to resolve an incomplete abortion, terminate a continuing pregnancy, or control bleeding (World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation 2000).
    The original protocols for the use of mifepristone recommended an oral dose of 600mg mifepristone followed by 1 mg of vaginal gemeprost after 36-48 hours. However, several studies have established that 200 mg of mifepristone is the dosage of choice since it is as effective as 600 mg (McKinley et al. 1993; World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation 1993), and reduces costs.
    • Mifepristone and prostaglandin 2.4.1 2.4.1.1. Up to 9 completed weeks since last menstrual period. p.36
  • Misoprostol, a prostaglandin which has also been shown to be effective (RCOG 2000), is considerably cheapter than gemeprost, and does not require regrigeration. It is therefore the prostaglandin of choice for most countries. An oral dose of 200mg mifepristone followed by 800 uf misprostol administered vaginally is an effective regimen (RCOG 2000). Vaginal misoprostol has been shown to be more ffective and better tolerated than misoprostol given orally (El-Refaey et al. 1995). An oral dose of 400 ug of misoprostol is effective up to 7 completed weeks of pregnancy (World Health Organization Task Force on Post-ovulatory Methods of Fertility Regulation 2000).
    Most protocolsrequire that women takeboth mifepristone and prostaglandin under clinical supervision, involving a second visit to thehealth care facility two days after receiving mifepristone to take the prostaglandin. Women may leave the facility shortly after taking the mifepristone, after being told to expect bleeding and possible expulsion of products of conception, how to recognize complications and whom to contact if they should occur. Staff should be available on a 24-hour basis to respond to such situations.
    Following administration of the prostaglandin at the second visit, the standard observation period is 4-6 hours, during which up to 90% of women will expel the products of conception. Some women may require medication for cramps during this period (see 2.2.1 above). The approximately 10% of women who do not abort during the observation period should return to the healthcare facility about 2 weeks later to confirm that the abortion has been completed.
    Protocols which allow the woman to leave the facility immediately after prostaglandin administration, call for explanation that she is likely to expel the products of conception at home or somewhere else without medical supervision. In this case, women should return to the health care facility about two weeks later to confirm completion of the abortion through a physical examination or laboratory test.
    Some investigators consider that the second visit to the facility for the prostaglandin is unnecessary and suggest that women be allowed to take the prostaglandin at home (Schaff et al. 1997). This approach has recently also been used in communities in Tunisa and Viet Nam and found to be acceptable to many women (Elul et al. 2001). However, the safety and appropriateness of this approach in different settings is still the subject of review.
    In the case of an incomplete or failed abortion, surgical abortion is required. Every facility offering medical methods of abortion must be able to ensure provision of vacuum aspiration in case the need arises. Such provision can be available on site or through an arrangement with another facility that performs vacuum aspiration. In all cases, health care providers must ensure that the woman can reach such services in case of an emergency.
    • p.37
  • Women are more likely to be satisfied with the procedure if they have realistic expectations (Brietbart 2000). Hence, they need complete information about what is to be expected with, and the possible side-effects of, medical methods of abortion Health workers should ensure that women understand the importance of complying with the protocol, especially if any of the drugs are self-administered, and that they know how to recognize, and what to do in case of, complications.
    • Methods of abortion continued, p.38

2.4.1.2 From 9 to 12 completed weeks since last menstrual period
Mifepristone and misprostol are also being investigated between 9 and 12 weeks of pregnancy (Ashok et al. 1998b). Initial positive findings need to be confirmed in order to establish the optimal regimens.
2.4.1.3 After 12 completed weeks since last menstrual period
A regimen of oral mifepristone followed by repeated doses of misorprostol or gemeprost is safe and highly effective (RCOG 2000). An oral dose off 200mf mifepristone followed by 800ug misoprostol administered vaginally 36-48 hours later and further 400ug oral doses of misoprostol every three hours, to a maximum of four doses, has been found to be effective in 97% of cases (El-Refaey and Templeton 1995). An oral dose of 400ug of misoprostol every 3 hours up t 5 doses after 200 mg mifepristone has also been used successfully (Ngai et al. 2000). A vaginally administered dose of 1 mg gemeprost used after 200 mf mifepristone and repeated if necessary every 6 hours up to four doses can also be used effectively (Ho et al. 1996). The treatment with gemeprost could continue with 1mf gemeprost every 3 hours for 4 additional doses if necessary (Gemzell-Danielsson and Ostlund 2000, Tang et al. 2001).

    • p.38
  • 2.4.2 Misoprostol of gemeprost alone 2.4.2.1 Up to 12 cmpleted weeks since last menstrual period
    Misprostol alone has also been studied in terms of effectiveness and safety. Although no comparative studies have been conducted, available data suggest that the effectiveness sof misoprostol alone is lower, the procedure lasts longer and is more painful with greater gastro-intestinal side-effects than the combined regimen with mifepristone (Bugalho et al. 2000).
    Because of the drug’s wide availability and low cost and since in some settings its broader use has been reported to contribute to the derease in the complications from unsafe abortion (Cost and Vessy 1993), the development of an optimal treatment regimen for the delivery of misoprostol is currently under investigation (Blanchard et al. 2000).
    There are concerns about the consequence sof ongoing pregnancies with the use of misprostol alone (Foseca et al. 1991, Gonzalez et al. 1998, Schonhofer 1991, Orioli and Castilla 2000). Further research is needed to evaluate the possible teratogenicity of misoprostol.
    • p.38
  • Misoprostol has been found to be up to 84% effective in inducing abortion within 24 hours with a variety of oses administered orally or vaginally (Dickinson et al. 1998, Wong et al. 1996), although it is not as rapid as when used in combination with mifepristone. Further research is needed to identify the optimal regimen for the use of misoprostol alone for pregnancies of more than 12 weeks.
    Vaginal administration of gemeprost alone is registered for termination of second-trimester pregnancy in several countries. The recommended dose is 1mg which is given every 3 hours up to 5 times during the first day and repeated the next day if necessary. With this treatment, 80% and 95% of women will abort within 24 and 48 hours, respectively (Thong et al. 1992).
    • 2.4.2.2 After 12 completed weeks since last menstrual period p.39
  • Methotrexate, which is a cytotoxic drug used to treat cancer, rheumatoid arthritis, psoriasis and some other conditions, has been used in combination with misoprostol as a medical method for early abortion (up to 7 completed weeks since LMP) in some countries where mifepristone has not been available. A recent randomized controlled trial reported an overall 92%success rate with 50mf of methotrexate followed by 800ug intravaginally administered misoprostol 6 or 7 days later. Success rate at day 15 was 83% (Creinin 2000). However, a WHO Toxicology Panel recommended against the use of methotrexate for inducing abortion, based on concerns about teratogenicity (UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction 1997). Although the actual risks are yet unknown, limb defects and skull and facial abnormalities in pregnancies that continued after failed attempts to induce abortion with methotrexate have been reported (Powell and Ekert 1971, Diniz et al. 1978, Feldkamp and Carey 1993). It is therefore recommended that services that wish to introduce medical methods of abortion use mifepristone and misoprostol, not methotrexate.
    Other agents are used to stimulate uterine contractions and induce abortion from 12 completed weeks since last menstrual period. They include intra-amniotic injection of hypertonic saline or hyperosmolar urea; intra-or extra-amniotic administration of ethacridine; parenteral, intra-amniotic or extra-amniotic administration of prostaglandin analogues; and intravenous or intramuscular administration of oxytocin (World Health Organization 1997). Most of these methods and routes of administration, however, are invasive and less safe than the newer medical methods.
    • 2.4.3 Other medical abortion agents p.39
  • Incomplete abortion is uncommon with vacuum aspiration when the abortion is performed by a skilled provider. It is more common with medical methods of abortion. Signs and symptoms include vaginal bleeding, abdominal pain and signs of infection. It should also be suspected if, upon visual examination, the tissue aspirated during surgical abortion does not conform to estimated duration of pregnancy. Staff at every health care facility should be trained and equipped to treat incomplete abortion by re-evacuating the uterus with vacuum aspiration, paying attention to the possibility of haemorrhage or infection.
    • Incomplete abortion 2.5.2.1, p.42
  • As described earlier, treatment protocols for medical methods of abortion used up to 9 completed weeks of pregnancy generally require women to remain under clinical observation for 4-6 hours after taking the prostaglandin. Providers should inspect all sanitary pads and bed pans used during the period of observation, maximizing the opportunity to confirm an abortion during this time.
    Women for whom complete abortion is not confirmed at that time, those who take the prostaglandin at home or those who leave the facility shortly after prostaglandin administration should be scheduled for a return visit in 10-15 days to confirm that the abortion has been completed, that there is no infection, and that no other complications have occurred. IN most cases, complete abortion will be confirmed at this visit. If not, women may opt to undergo vacuum aspiration, but it is not clinically necessary for them to do so unless the physical examination, the clinical symptoms or a laboratory test suggest that the pregnancy is still growing.
    In view of the greater risk of haemorrhage and of incomplete abortion associated with procedures undertaken after 12 completed weeks of pregnancy, all women in these cases should remain under observation until both fetus and placenta have been expelled.
    • 3.1.2 Medical methods of abortion p.44
  • Medical methods of abortion
    Basic gynaecological and medical instruments and supplies (e.g. open speculum gauze or swabs, menstrual pads, gloves)
    Depending on the protocol used:
    Mifepristone + misoprostol or gemeprost
    Analgesics
    Glass bowl for tissue inspection
    Private area for counselling
    Private area with chairs to wait for expulsion separate from women giving birth
    Adequate toilet facilities
    Capacity to provide or refer for vacuum aspiration.
    • Establishing national norms and standards continued p.64

International Consensus Conference on Non-surgical (Medical) Abortion in Early First Trimester on Issues Related to Regimens and Service Delivery (2006)[edit]

International Consensus Conference on Non-surgical (Medical) Abortion in Early First Trimester on Issues Related to Regimens and Service Delivery (2006). Frequently asked clinical questions about medical abortion (PDF). Geneva: World Health Organization. ISBN 978-92-4-159484-4. Archived from the original (PDF) on January 17, 2009.

  • Provision of safe abortion to the full extent of the law is an important component of reproductive health services. The development of methods of inducing abortion medically (non-surgically) has created alternative options to make abortion available to women in a variety of health-care settings. The topic has been reviewed extensively in the past five years and a number of evidence-based guidelines have been published.
    • p.3
  • Ideally, any method of medical abortion should have an overall efficacy comparable to that of vacuum aspiration, i.e. a rate of complete abortion of more than 95% and an ongoing pregnancy rate of less than 1%.
    • p.3
  • The only regimen that meets the efficacy criteria is a combination of mifepristone and a prostaglandin – either misoprostol or gemeprost. Use of mifepristone or a prostaglandin alone does not meet them. Use of methotrexate in combination with prostaglandin can approach the required efficacy, but is not recommended because it is teratogenic.
    The recommendations on medical abortion given here are restricted to early first trimester (up to 63 days since the first day of the last menstrual period – LMP). Although administration of mifepristone followed by a prostaglandin will terminate pregnancy at any stage (and in some countries is licensed for abortion up to 24 weeks), termination of pregnancy when gestational age is >63 days is less common, requires an inpatient setting, and raises separate medical, legal and service issues.
    • p.3
  • There is little, if any, difference between medical and surgical abortion in terms of safety and efficacy. Thus, both methods are similar from a medical point of view and there are only very few situations where a recommendation for one or the other method for medical reasons can be given.
    Two studies have found that women are more likely to find a method of abortion have found that women are more likely to find a method of abortion acceptable if they have chosen it themselves. Being provided with a choice of methods is seen as extremely important by the majority of women undergoing abortion. Many studies suggest that women who choose medical abortion find it more acceptable at earlier than later gestations.
    • p.8
  • Medical abortion may be preferred:
    * if it is the woman’s preference;
    * in very early gestation; up to 49 days of gestation, medical abortion is considered to be more effective than surgical abortion, especially when clinical practice does not include detailed inspection of aspirated tissue;
    * if the woman is severely obese (body mass index greater than 30) but does not have other cardiovascular risk factors (see question 3), as surgical treatment may be technically more difficult;
    * if the woman has uterine malformations or a fibroid uterus, or has previously had cervical surgery (which may make surgical abortion technically more difficult);
    * if the woman wants to avoid a surgical intervention.
    • p.8
  • 3. What are the contraindications to medical abortion?
    *There are very few absolute contraindications to medical abortion. They include:
    * previous allergic reaction to one of the drugs involved;
    * inherited porphyria;
    * chronic adrenal failure;
    * known or suspected ectopic pregnancy.
    • p.9
  • Caution is required in a range of circumstances including:
    * if the woman is on long-term corticosteroid therapy (including those with severe, uncontrolled asthma);
    * if she has a haemorrhagic disorder;
    * if she has severe anaemia;
    * if she has pre-existing heart disease or cardiovascular risk factors (e.g. hypertension and smoking).
    • p.9
  • 4. Do any other characteristics of the woman need to be taken into account in providing medical abortion?
    Age. Neither adolescence nor older age (e.g. over 35 years) should be regarded as a contraindication to medical abortion.
    Anaemia. This need not be regarded as a contraindication. However, anaemia detected at the time of abortion should be treated. Average blood loss in medical abortion may be more than that in surgical abortion, and the incidence of heavy bleeding may be higher.
    Breastfeeding. It is likely that mifepristone passes into breast milk. Studies investigating the endocrine effects of mifepristone on the fetus have found increased levels of adrenocorticotropic hormone and cortisol. The clinical implications of these changes are unclear.
    Small amounts of misoprostol also enter breast milk soon after administration, but it is not known whether this could have any effect on the infant. As misoprostol levels decline rapidly, it has been recommended that misoprostol should be taken immediately after a feed and the next feed given after four hours in case of oral administration. After vaginal administration, misoprostol levels stay high for longer, and the feed should preferably be given more than six hours later. Unfortunately, the available data do not allow a precise recommendation on optimum timing.
    Insulin-dependent diabetes or thyroid disorder. There is no evidence that medicalInsulin-dependent diabetes or thyroid disorder. There is no evidence that medicalInsulin-dependent diabetes or thyroid disorder abortion causes particular problems in women with these disorders. However, mifepristone has been shown to alter insulin sensitivity in vitro and these effects may or may not be and these effects may or may not be reflected in blood sugar and insulin levels.
    Multiple pregnancy (current gestation). There is no evidence that the failure rate of medical abortion is increased or that a different dosage regimen is required in the case of multiple pregnancy.
    Obesity. There is no evidence that the failure rate of medical abortion is increased or Obesity. There is no evidence that the failure rate of medical abortion is increased or Obesity that a different dosage regimen is required in obese women.
    Previous Caesarean section. There is evidence from one study that the safety and efficacy of early medical abortion are unaffected by previous Caesarean section.
    Smoking. There is no evidence of interaction between the risks of smoking and medical abortion. However, smoking contributes to cardiovascular risk and this factor should be considered when assessing a woman’s overall suitability for medical abortion. Uterine malformations, congenital and acquired; previous cervical surgery. There Uterine malformations, congenital and acquired; previous cervical surgery. There Uterine malformations, congenital and acquired; previous cervical surgery is no evidence that these represent contraindications.
    • p.10
  • 5. How should pregnancy be confirmed and gestation estimated?
    In most cases, pregnancy can be confirmed and its length estimated on the basis of the woman’s history and a physical examination. Occasionally, laboratory tests may be needed when the typical signs of pregnancy are not clearly present and the health-care provider is unsure whether the woman is pregnant.
    Ultrasound scanning is not necessary for the provision of early abortion. Where ultrasound equipment is available, a scan can help identify an intrauterine pregnancy and exclude an ectopic one after about six weeks. It also helps determine gestational age and diagnose pathologies or non-viability of a pregnancy.
    • p.11
  • 6. What clinical assessment and laboratory investigations are required prior to medical abortion?
    As for any method of abortion, clinical history-taking should serve to identify contraindications (see question 3) and to identify risk factors for complications. History-taking should include: personal and family history of relevant diseases; current use of medications and known allergies; obstetric and gynaecological history, including ectopic pregnancies; any bleeding tendencies; and history of sexually transmitted infections (STIs). Social history should include risk assessment for STIs, taking into account local STI prevalence rates. The clinician must be alert to the possibility of violence or coercion in the context of the unwanted pregnancy.
    Basic routine observations (pulse, blood pressure, and temperature) are useful as a baseline.
    There are no laboratory tests that are essential before medical abortion. However, tests such as haemoglobin level, blood group and rhesus (Rh) typing, and screening for hepatitis, human immunodeficiency virus (HIV), and STIs, may be offered on the basis of individual risk factors or available resources. Ideally, services should offer testing for pathogens in the lower genital tract, and treat women found positive.
    Rhesus status. The prevalence of Rh-negative status varies markedly with ethnicity, being highest among Caucasians. For pregnancies up to 63 days gestation, the theoretical risk of maternal Rh sensitization is very low; there is no evidence that sensitization occurs at this stage of pregnancy. Thus, determination of blood group and Rh status and the offer of anti-D prophylaxis to Rh-negative women are not considered prerequisites for early medical abortion. In settings where the prevalence of Rh-negative status is high, and where resources permit, the offer of Rh typing and anti-D prophylaxis could be worthwhile as precautionary components of medical abortion care.
    • p.12
  • 7. What steps are necessary to minimize the risk of undiagnosed ectopic pregnancy?
    Mifepristone and misoprostol are not treatments for ectopic pregnancy, which, if present, will continue to grow. If medical abortion is contemplated very early in gestation, i.e. before an intrauterine pregnancy can be diagnosed with ultrasound, clinicians must be particularly alert to the possibility of ectopic pregnancy. They should check whether the uterus feels smaller than expected according to the date of the woman’s last menstrual period. Women should be told to seek medical advice promptly if they experience symptoms and signs that may indicate ectopic pregnancy, such as abdominal pain on one side. Verification of expulsion in these very early cases can be done only by comparing human chorionic gonadotrophin (hCG) levels prior to the treatment and at follow-up (see question 19).
    Where clinical features (e.g. history of ectopic pregnancy or STI, discrepancy between menstrual dates and ultrasound appearance, vaginal bleeding, or pelvic pain) raise suspicion of an ectopic pregnancy, appropriate tests should be done. If ectopic pregnancy is diagnosed or strongly suspected, the woman should be transferred to an appropriate gynaecology service for continuing care.
    • p.13
  • 8. What is the recommended regimen for medical abortion?
    The recommended regimen for medical abortion is 200 mg of mifepristone given orally, followed 36–48 hours later by a prostaglandin – either 0.8 mg of misoprostol or 1 mg of gemeprost – given vaginally. This combination results in complete abortion in more than 96% of cases; the rate of continuing pregnancies is less than 1% in gestations up to 63 days’ amenorrhoea.
    Misoprostol can also be given orally at a dose of 0.4 mg, but owing to the higher failure rate with dose, it is recommended that oral misoprostol use at this dosage be restricted to

very early pregnancy – i.e. < 50 days.

    • p.17
  • Both mifepristone and prostaglandins, given alone, may lead to abortion; however, they have either a low effectiveness or a high rate of side-effects. In combination, they act synergistically. The challenge, therefore, is to find a regimen combining the lowest doses for both drugs that is highly effective and has few side-effects. In addition, in many parts of the world, cost considerations are important.
    In many countries, mifepristone is licensed for use as a single oral dose of 600 mg. However, there is no evidence that a dose of greater than 200 mg is necessary for optimal effect when followed by a suitable prostaglandin. Some studies have indicated that mifepristone can be given as five or six divided doses of 25 mg over three days, for a total dose of 125–150 mg. This regimen is widely used in China and has been shown to be highly effective up to 49 days of gestation when used in combination with a suitable prostaglandin. However, for service delivery and patient convenience, the single dose of mifepristone is preferred.
    A 50 mg dose of mifepristone has been shown to be less effective than a 200 mg dose, when given in combination with gemeprost vaginally (6). Studies are continuing to investigate the minimum effective dose of mifepristone.
    • p.18
  • 10. Are other doses or routes of administration of the prostaglandin possible?
    Vaginal administration of misoprostol is more effective and associated with fewer side-effects than oral administration of the same dose. However, if the woman prefers to take the drug orally, and the gestational age is less than 50 days LMP, two tablets of 0.2 mg of misoprostol can be taken orally 36–48 hours after the mifepristone dose. If the gestational age is 50 days or more LMP, oral administration of misoprostol is not recommended because of its higher failure rate.
    In some studies, repeated doses of misoprostol have been used, either routinely for all women or in those with evidence of incomplete abortion. Repeated doses are associated with an increased incidence of prostaglandin-related side-effects. There is insufficient evidence at the moment that the overall efficacy is increased by using repeated doses of prostaglandin.
    Lower vaginal doses and different routes of administration, e.g. buccal and sublingual, of misoprostol are currently under investigation.
    • p.19
  • Although not covered in these guidelines, abortion in late first trimester and in the second trimester of pregnancy usually requires repeat administration of prostagla
    • p.19
  • 11. What are the advantages and disadvantages of misoprostol versus gemeprost?
    Misoprostol is cheaper than gemeprost and is stable at room temperature. Gemeprost is formulated for use as 1 mg vaginal pessaries and needs to be kept frozen until about half an hour before use. Some studies report that severe pain is more common after gemeprost compared to misoprostol. Although misoprostol is formulated for oral use, it is more effective if given vaginally or sublingually.
    • p.20
  • 12. Can other prostaglandins be used?
    A number of prostaglandins that were used in the past, such as sulprostone and 15-methyl prostaglandin F2, are no longer used because of their adverse side-effects or relative lack of efficacy.
    • p.20
  • 13. Is the interval between administration of mifepristone and prostaglandin crucial?
    The licensed and most commonly used interval, of 36–48 hours, corresponds to the time when the uterus is most sensitive to prostaglandin after priming with mifepristone; hence the therapeutic dose can be reduced to the minimum. This interval was also found to be the most effective in initial studies when uterine contractility was measured at different times between administration of mifepristone and of prostaglandin. It has been shown recently, however, that the interval can be shortened to 24 hours or lengthened to 72 hours, without loss of efficacy, when mifepristone is used in combination with 0.8 mg of vaginally administered misoprostol. If misoprostol is given as an oral dose of 0.4 mg, the interval of 36–48 hours should be adhered to. Other time intervals are currently being studied.
    • p.21
  • 14. Can abortion be induced using prostaglandin alone?
    It is possible to induce abortion in early pregnancy using prostaglandins alone. However, even the most effective regimens, involving repeated relatively large doses of misoprostol (0.8 mg) or gemeprost (1 mg) vaginally, are less effective and have more side-effects than the combination regimens with mifepristone pretreatment.
    There is insufficient evidence to support recommendations on the dose, route of administration and timing of regimens using prostaglandins alone. Reported case series suggest that repeated administration of 0.8 mg of vaginal misoprostol is needed. The only randomized study (yet unpublished), that compared a short (3-hour) and a long (12-hour) interval between vaginal and sublingual doses, demonstrated that if misoprostol is given sublingually, it has to be administered at the shorter interval to have a similar effectiveness as vaginal administration
    • pp.21-22
  • 15. What pain relief should be available to women during medical abortion?
    Pain is caused both by the abortion process and as a side-effect of the prostaglandin. It is most likely to be felt in the few hours after administration of the prostaglandin, when the gestational sac/embryo is being expelled from the uterus. Studies have shown that women feel less pain if they are older, have been pregnant before or are in the early stages of pregnancy. However, none of these factors is sufficiently predictive to be useful in the management of individual cases.
    The perception of pain and request for relief vary greatly from one individual to another and among cultures. In any case, health-care providers should make adequate analgesia easily available to all women who request it during medical abortion. Examples of commonly used preparations are: paracetamol 500–1000 mg or nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen 200 mg. In cases of severe pain, codeine 30–40 mg may be added to either of the above-mentioned treatments.
    • p.22
  • 16. If a woman has an incomplete abortion, is it necessary to evacuate the uterus surgically?
    On average, vaginal bleeding gradually diminishes over about two weeks after a medical abortion, but in individual cases spotting can last up to 45 days. Generally, bleeding after medical abortion lasts longer than after vacuum aspiration. If the woman is well, neither prolonged bleeding nor the presence of tissue in the uterus (as detected by ultrasound) is an indication for surgical intervention. Remaining products of conception will be expelled during subsequent vaginal bleeding. Surgical evacuation of the uterus may be carried out on the woman’s request or if the bleeding is heavy or prolonged, or causes anaemia, or if there is evidence of infection. In the latter case, antibiotic treatment should be initiated.
    • p.27
  • 17. How should pelvic infection be diagnosed and treated after abortion?
    The genital tract is more susceptible to ascending infection when the cervix is dilated after abortion or childbirth. There are few data on the incidence of clinically significant pelvic infection after medical abortion, but it seems to be rare and probably occurs less often than after vacuum aspiration. Many of the symptoms of pelvic infection, such as pain, are rather nonspecific and hence precise diagnosis is difficult. Women with clinical signs such as pelvic pain, abdominal or adnexal tenderness, vaginal discharge and fever should be treated with broad-spectrum antibiotics.
    Rare cases of anaerobic infection without fever have been reported from Canada (one case) and the USA (four cases) following medical termination of pregnancy. No such cases have been reported from China or from Europe. In the reported cases women had little or no fever; variable nausea, vomiting, weakness and some abdominal pain; rapid deterioration within hours or days; tachycardia and refractory hypotension; multiple effusions; elevated haematocrit and elevated leukocyte count, neutrophilia. All five of the women had Clostridium sordellii-related toxic shock.Clostridium sordellii-related toxic shock.
    • p.27
  • 18. How should the success of medical abortion be confirmed?
    For all women who undergo medical abortion, it is important to confirm that the pregnancy has indeed been terminated. If expulsion of the products of conception was confirmed by a qualified person in the hours after administration of the prostaglandin, further follow-up is not absolutely necessary. Otherwise, a follow-up visit should be arranged about two weeks after the administration of mifepristone, at the convenience of the patient.
    At the follow-up visit, complete abortion should be confirmed clinically, either by bimanual pelvic examination or, if available, pelvic ultrasound. If serial measurements of human chorionic gonadotrophin (hCG) in blood or urine are used, it should be remembered that in some cases low hCG levels can be detectable for up to four weeks after successful expulsion. Women who continue to have symptoms of pregnancy or who have minimal bleeding are most likely to be still pregnant.
    • p.28
  • 19. How should ectopic pregnancy be identified after medical abortion?
    Ectopic pregnancy is a life-threatening condition and a significant cause of maternal mortality. See question 7 for the steps that should be taken before medical abortion to detect ectopic pregnancy.
    Even where these steps have been taken, health-care providers should be aware of the possibility of ectopic pregnancy and of the fact that medical abortion may mask its symptoms. Very occasionally, an ectopic pregnancy may co-exist with an intrauterine pregnancy.
    If an ectopic pregnancy is clinically suspected (e.g. the woman has continuing symptoms of pregnancy or abdominal pain), further investigations, such as pelvic ultrasound and serial measurement of hCG, should be performed. If this is not possible, the woman should be referred to a specialist centre.
    • p.28
  • 20. Is there a risk of fetal abnormality after an unsuccessful medical abortion?
    Only one anomaly has been reported after the use of mifepristone alone. This case, described as a sirenomelia, could not be related to the drug intake. Indeed, this type of anomaly occurs at a very early stage of pregnancy – at about four weeks of embryo development – while the treatment was taken in the fifth week of pregnancy. Thirteen other cases of malformation have been reported: all occurred in pregnancies in which mifepristone was administered at 7–9 weeks of amenorrhoea, followed in eight cases by gemeprost and in five cases by misoprostol. None of the events could be conclusively related to the treatment.
    It is not possible to determine whether the reported anomalies were caused by the treatment, since the incidence of birth defects in a normal population is around 2 per 100 births. Some prostaglandins have been classified as teratogenic, although misoprostol did not induce such effects in embryotoxicology studies. Mifepristone is not a teratogenic agent but, when used in combination with a prostaglandin, may induce uterine contraction, which could account for some of the observed defects. Since the available data are limited and inconclusive, there is no need to insist on termination of an exposed pregnancy if the woman wishes to continue it. Women should, nevertheless, be informed that, because of the unknown risk of abortifacient drugs to the fetus, follow-up is important.
    • p.29
  • 21. Which methods of contraception can a woman use after medical abortion?
    Most women who have an induced abortion for an unwanted pregnancy do not want to get pregnant again immediately. In a few cases, there may be medical reasons for avoiding immediate pregnancy. Postabortion family planning is therefore an integral part of comprehensive abortion care.
    Women who have had an early abortion are almost immediately at risk of becoming pregnant again. Ovulation may occur as early as day 10 (3)3)3 after a first-trimester abortion;) after a first-trimester abortion;) up to 78% of women in one study had ovulated by the time of the six-week follow-up.
    Women who have had a medical abortion can use any modern method of contraception afterwards. When the woman is counselled about the abortion, the opportunity should be taken to review her contraceptive needs. Ideally, she should be provided with an effective contraceptive method immediately after the abortion.
    Combined oral contraceptive pills can be started on the day that misoprostol is administered, when expulsion usually occurs. Two prospective randomized controlled studies evaluated the effects of immediate use of combined oral contraceptive pills versus placebo following medical abortion and found no difference in complete abortion rates, side-effects and duration of bleeding. Progestogen-only methods are commonly associated with breakthrough bleeding, which may be confused with an incomplete abortion.
    Depot-medroxyprogesterone injections and implants are often associated with amenorrhoea, or irregular bleeding, which may make it difficult to determine whether pregnancy has been terminated. It may therefore be preferable to start using these methods only after it has been confirmed that the pregnancy has been terminated. Sterilization and insertion of an intrauterine device should be deferred until confirmation that the abortion is complete.
    Women who choose a contraceptive method that cannot be started immediately should be encouraged to use condoms in the meantime. Other methods, such as caps, sponges, diaphragm, spermicidal foams, jellies and vaginal tablets, can be used as soon as sexual intercourse is resumed, preferably when bleeding has stopped. Methods of natural family planning can be resumed only after the return of regular cycle.
    • p.30
  • ISSUES RELATED TO PROVISION OF MEDICAL ABORTION SERVICES
    Legal and regulatory issues
    The practice of abortion is governed by regulations operating within the legal framework of the specific country and/or locality. In most countries, termination of pregnancy is legally permitted for at least one indication, e.g. after rape or to protect the life of the pregnant woman. Legislation in some countries permits abortion for a broad range of indications. Often, the legal framework was established long before medical abortion became available. The development of methods for medical abortion can raise some uncertainty in the interpretation of existing laws or regulations, as these were generally formulated on the basis of surgical abortion as the prevailing method. For example, in some countries, the law requires that abortions take place in a clinic registered for the purpose. With surgical methods there is no doubt as to where the abortion is performed. But when abortion is induced by medication, is the abortion performed where the drugs are prescribed or where they are administered? Or is it where the products of conception are expelled?
    • p.32
  • Setting up a medical abortion service
    Health-care managers who are contemplating setting up a service to provide medical abortion will first need to find out what is the relevant legal framework in their country with regard to medical abortion. In many countries, there are no specific regulations dealing with medical abortion; in this case, medical abortion is governed by the general abortion regulations. Other countries may have specific regulations relating to the provision of medical abortion.
    There may be regulations governing which facilities can provide abortion services. In some countries, the national government may stipulate standards through legislation or through health system norms and regulations. Elsewhere, such regulations may be drawn up at the province, state or local level.
    Medical abortion may be provided in health-care settings that do not already provide abortion services. Ideally, it should be integrated into broader reproductive health services. This would allow women who have had a medical abortion easy access to other services – such as family planning – as an important element of comprehensive abortion care. Emergency care and facilities for surgical intervention should be available locally or through a referral mechanism with established linkages. Back-up services should include uterine evacuation, fluid replacement and blood transfusion.
    • p.32
  • Obtaining the necessary medicines
    Where mifepristone is already licensed for use in medical abortion, the licence will usually specify that it should be used with a specific prostaglandin (usually misoprostol), or simply that a “suitable prostaglandin” should be used. In countries where medical abortion is

permitted, mifepristone is available from the physician or clinic. However, it is possible that no prostaglandin appropriate for use in early medical abortion is licensed. When no licensed prostaglandin is available, misoprostol is generally used since it is available in many countries, although it is not specifically licensed for use in abortion.
In many places, licensed medicines can be used for clinical indications that are not covered by the original product registration. Often, physicians have the freedom to use medicines for unlicensed purposes when there is medical evidence to support such use. If a physician uses a drug for purposes other than for which the drug is licensed, the physician must inform the patient about this. Managers considering the introduction of medical abortion should check the situation in their country with regard to this issue. In some reimbursement systems, doctors may prescribe off-label use, but patients may not be able to claim reimbursement for the treatment.
According to the United States Food and Drug Administration, “Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment. If physicians use a product for an indication not in the approved labelling, they have the responsibility to be well informed about the product, to base its use on firm scientific rationale and on sound medical evidence, and to maintain records of the product’s use and effects.”

    • p.33

“Health worker roles in providing safe abortion care and post-abortion contraception”[edit]

“Health worker roles in providing safe abortion care and post-abortion contraception”, World Health Organization", (2015)

  • Although in many contexts abortion-related care provision is limited to specialist doctors, many of the evidence-based interventions for safe abortion and post-abortion care, particularly those in early pregnancy, can be provided on an outpatient basis at the primary care level. The emergence of medical abortion (i.e. non-surgical abortion using medications) as a safe and effective option has resulted in the further simplification of the appropriate standards and health worker skills required for safe abortion provision, making it possible to consider expanding the roles of a much wider range of health workers in the provision of safe abortion.
    • p.3
  • Task shifting and task sharing are plausible and feasible options as many of the interventions for safe abortion care, particularly those in early pregnancy, can be provided at the primary care level and on an outpatient basis. While even vacuum aspiration is a primary care procedure, medical abortion (using pills) is non-invasive and simplifies the requirements of place, equipment and health worker skills. It is suggested that the WHO definition of unsafe abortion (an abortion performed by a person lacking the necessary skills or in an environment not in conformity with medical standards, or both) be reinterpreted in light of current technical evidence and to account for the differences in what constitutes a safe environment for these two methods.
    • Effective, safe and simple interventions exist for safe abortion and post- abortion care, p.17
  • Manual or electric vacuum aspiration, as well as medical abortion with mifepristone followed by misoprostol (or misoprostol alone in contexts where mifepristone is not available), are appropriate methods to terminate a pregnancy in the first trimester. Uncomplicated incomplete abortion (both induced and spontaneous) can be managed with manual vacuum aspiration (MVA) or electric vacuum aspiration (EVA), or with oral or sublingual misoprostol.
** Management of abortion and post-abortion care for pregnancies in the first trimester, p.33
  • Medical abortion (MA) refers to the sequential use of mifepristone followed by misoprostol or, in settings where mifepristone is not available, the use of misoprostol alone. The specific dosage, route and regimens are different at differing pregnancy durations and are detailed in the Clinical practice handbook for safe abortion (14).
    MA is a process that takes place over a period of several days rather than being a discrete procedure. The process includes several components or subtasks: *assessing eligibility for MA (diagnosing and dating the pregnancy, ruling out medical contraindications,
    screening for possible ectopic pregnancy); * administering the medications with instructions on their appropriate use and managing the common side-effects;
    * assessing that the abortion process is complete and that no further intervention is required.
    One health worker can provide the entire package, but it is equally possible for the subtasks to be performed by different health workers and at different locations.
    • Medical abortion in the first trimester p.37
  • Specialist doctors, non-specialist doctors
    Recommended
    Within their typical scope of practice. No assessment of the evidence was therefore conducted.
    * Associate and advanced associate clinicians
    Recommended
    There is evidence for the effectiveness of carrying out components of the task, e.g. assessing gestation as part of MVA provision. There is also evidence that health worker types with similar or less comprehensive basic training (e.g. midwives, nurses, auxiliary nurse midwives) can provide MA safely and effectively (moderate certainty). The option is feasible and the potential to expand access to underserved populations is high.
    * Midwives
    Recommended
    There is evidence for the safety and effectiveness of this option (moderate certainty). More women are satisfied with the provider when midwives provide MA (moderate certainty). The option appears feasible and is already being implemented in several countries.
    * Nurses
    Recommended
    There is evidence for the safety and effectiveness, and for women’s satisfaction with abortion services with this option (moderate certainty).
    * Auxiliary nurses and auxiliary nurse midwives
    Recommended
    There is evidence for the safety and effectiveness (moderate certainty) of this option. The option appears feasible and is already being implemented in some low-resource settings.
  • Table 5. The provision of medical abortion (MA) in the first trimester, p.37
  • Doctors of complementary systems of medicine
    Recommended in specific circumstances
    We recommend this option only in contexts with established health system mechanisms for the participation of doctors of complementary systems of medicine in other tasks related to maternal and reproductive health.
    There is evidence for the safety and effectiveness, and for women’s satisfaction with this type of provider and services (low certainty). The benefits outweigh any possible harms, and the potential to reduce inequities in access to safe abortion care in regions where such professionals form a significant proportion of the health workforce is high.
    * Pharmacists
    No recommendation for independent provision of MA; see Table 6 for recommendations made for subtasks.
    Before making a recommendation on full independent provision of MA it is necessary to demonstrate the effectiveness and feasibility of the subtasks.
    * Pharmacy workers
    Recommended against
    There was no evidence for the safety, effectiveness, acceptability or feasibility of this option. However, it is important to note that as with all other drugs and medications, pharmacy workers should dispense mifepristone and misoprostol as indicated by prescription.
    * Lay health workers
    No recommendation for the overall package; see Table 7 for recommendations made for subtasks.
    Before making a recommendation on full independent provision of MA it is necessary to demonstrate the safety and feasibility of carrying out the subtasks.
  • p.38
  • Additional remarks
    Available evidence for the independent provision of MA by non-physicians is for pregnancy durations up to 10 weeks (70 days). Further research is needed on pregnancies of 11–12 weeks.
    It is not essential that the person providing the MA should also be trained and competent in MVA provision. However, in such cases, backup referral access to a provider who can perform MVA if needed should be ensured. Such backup does not necessarily have to be at the same site.
    Implementation considerations
    Restrictions on prescribing authority for some categories of providers may need to be modified or other mechanisms put in place for allowing such providers to administer the MA medications within the regulatory framework of the health system.
    There is a higher chance of ongoing pregnancy when misoprostol alone is used; hence, irrespective of the level of provider, training has to emphasize the ability to detect these cases for further management/ referral.
    • p.38
  • Subtasks for medical abortion
    No recommendations are made regarding the independent provision of MA in the first trimester for pharmacists or lay health workers, but recommendations were made for specific subtasks of MA provision, as presented in Tables 6 and 7.
    • p.39
  • Table 6. The provision of medical abortion subtasks in the first trimester by pharmacists
    * Assessing eligibility for medical abortion
    Recommended within the context of rigorous research
    The approach has the potential to improve the triage of health care by screening and referral to appropriate health-care facilities. Rigorous research on this approach using simple tools and checklists is needed to address the uncertainties and to test the feasibility of the option in a programme setting.
    * Administering the medications an managing the process and common side-effects independently
    Recommended within the context of rigorous research
    Dispensing medications on prescription is within the typical scope of practice of these health worker and should be continued.
    However, well designed research is still needed on the effectiveness and feasibility in a programme setting of the approach of pharmacists independently making clinical judgments related to managing the process and its common side-effects.
    The approach has the potential to improve access as pharmacies are often women’s first point of contact with the health system; however, the feasibility of developing referral linkages with the health system also needs to be studied.
    * Assessing completeness of the procedure and the need for further clinic-based follow-up
    Recommended within the context of rigorous research
    This option has the potential to improve the triage of health care by screening women in need of further care. Research on this approach using simple tools like urine pregnancy tests and checklists is needed, as is research to test the feasibility of the option in a programme setting.
  • p.39
  • Table 7. The provision of medical abortion subtasks in the first trimester by lay health workers
    * Assessing eligibility for medical abortion
    Recommended within the context of rigorous research
    Fewer women may be assessed as eligible when lay health workers assess eligibility for medical abortion using simple checklists (low certainty). However, the option is promising and lay health workers are often involved, either formally or informally, in advising women who are seeking such care (moderate confidence). Well designed research is needed to refine the optimum tools and checklists needed and to test the feasibility in community settings.
    * Administering the medications and managing the process and common side-effects.
    Recommended within the contet of rigorous research
    The option has the potential to expand access to safe care, and well designed research has the potential to address any uncertainties around safety, effectiveness and feasibility.
    * Assessing completeness of the procedure and the need for further clinic-based follow-up
    Recommended within the context of rigorous research
    There is evidence that lay health workers can accurately assess abortion completeness using simple checklists (low certainty). Approaches using a urine pregnancy test as part of the assessment toolkit could yield better results and require further research.
    * Strong referral linkage and backup care to emergency services must always be available as part of the research. Initial research should focus on pregnancy durations of 10 weeks (70 days) or less.
    As with all other drugs and medications, dispensing mifepristone and misoprostol on prescription is within the typical scope of practice of pharmacists and the research recommendation above is not intended to imply any change in that scope of practice.
  • p.40
  • Self-management of the medical abortion process in the first trimester
    Given the nature of the medical abortion (MA) process, it is possible for women to play a role in managing some of the components by themselves outside of a health-care facility. Such self-assessment and self-management approaches can be empowering for women and help to triage care, leading to a more optimal use of health resources. See the recommendations in Table 8.
    • p.41
  • Table 8. Women’s role in managing the process of medical abortion
    * Managing the entire process of medical abortion up to 84 days
    No recommendation for the overall package; recommendations made for subtasks as below.
    Individual components of the self-management of medical abortion have been tested; however, there is as yet insufficient evidence on using all three components together. * Self-assessing eligibility for medical abortion
    Recommended within the context of rigorous research
    Women may be more conservative in assessing eligibility using simple checklists (low certainty). However, the approach is promising and further work is needed on developing appropriate assessment tools.
    * Managing the mifepristone and misoprostol medication without direct supervision of a health-care provider
    Recommended in specific circumstances
    We recommend this option in circumstances where women have a source of accurate information and access to a health-care provider should they need or want it at any stage of the process.
    There is evidence that the option is safe and effective (low-certainty evidence from numerous studies, but using non-randomized designs given the strong preferences of women for one or the other option). More women report the method to be satisfactory when it is self-managed (low certainty). Women find the option acceptable and feasible (high confidence) and providers also find the option feasible (high confidence).
    * Self-assessing completeness of the abortion process using pregnancy tests and checklists
    Recommended in specific circumstances
    We recommend this option in circumstances where both mifepristone and misoprostol are being used and where women have a source of accurate information and access to a health- care provider should they need or want it at any stage of the process.
    There is evidence that the option is safe and effective including in low-literacy, low-resource settings (moderate to high certainty).
  • p.41
  • A follow-up visit after MA using mifepristone–misoprostol is not mandatory (3). The efficacy of MA is lower when misoprostol alone is used; hence the self-assessment of completeness when misoprostol alone is used requires further research.
    Available evidence for managing the medications and process without direct supervision of the provider is for pregnancy durations of nine weeks (63 days) or less.
    Self-management approaches reflect an active extension of health systems and health care. These recommendations are NOT an endorsement of clandestine self-use by women without access to information or a trained health-care provider/health-care facility as a backup. All women should have access to health services should they want or need it.
    Implementation considerations
    Mechanisms to ensure access and linkages to post-abortion contraception services need to be established.
    • p.42
  • Managing uncomplicated incomplete abortion with misoprostol (when uterine size is up to 13 weeks) includes recognizing the condition, assessing uterine size and administering oral or buccal misoprostol in the correct dose. Table 9 gives the recommendations on this.
    • p.43
  • Table 9. Management of uncomplicated incomplete abortion/miscarriage in the first trimester with misoprostol
    * Specialist doctors, non-specialist doctors
    Recommended
    Within their typical scope of practice. No assessment of the evidence was therefore conducted.
    * Associate and advanced associate clinicians
    Recommended
    There is moderate-certainty evidence for the safety and effectiveness of medical management of incomplete abortion by midwives and moderate-certainty evidence for the effectiveness of medical abortion provision by health worker types with similar or less comprehensive

basic training. Additionally, there is direct evidence that these health workers can assess gestational age as part of MVA provision. The option is feasible and the potential to expand access to underserved populations is high.
* Midwives
Recommended
There is evidence from a low-resource setting for the safety and effectiveness (moderate certainty) of this option and for women’s overall satisfaction with the provider (moderate certainty) when midwives manage incomplete abortion. The option appears feasible and has the potential to reduce inequities in access to safe abortion.
* Nurses
Recommended
There is evidence for the safety, effectiveness and satisfaction of providing medical abortion (moderate certainty; see Table 5), and the skills required for managing incomplete abortion with misoprostol are similar. The option appears feasible and has the potential to reduce inequities in access to safe abortion.
* Auxiliary nurses and auxiliary nurse midwives
Recommended
There is evidence for the safety and effectiveness of the provision of medical abortion in the first trimester (moderate certainty; see Table 5), and the skills required for managing incomplete abortion with misoprostol are similar.

  • p.43
  • Doctors of complementary systems of medicine
    Recommended in specific circumstances
    We recommend this option only in contexts with established health system mechanisms for the participation of doctors of complementary systems of medicine in other tasks related to maternal and reproductive health.
    There is evidence for the safety and effectiveness of the provision of medical abortion in the first trimester (low certainty; see Table 5), and the skills required for managing incomplete abortion with misoprostol are similar. *Pharmacists and pharmacy workers
    Recommended against
    There was insufficient evidence for the safety and effectiveness of this option. It is also not within the typical scope of practice of pharmacists or pharmacy workers to conduct a full evaluation to diagnose incomplete abortion or determine uterine size.
    * Lay health workers
    Recommended within the context of rigorous research
    There was no direct evidence for this option, but there is some evidence that lay health workers can use simple tools and checklists to determine gestational age or abortion completeness (low certainty). Such health workers are often involved in advising women seeking such care (moderate confidence). In general, lay health worker interventions are acceptable and have proved feasible in many contexts. The further development of tools and carrying out rigorous research can help to address some of the uncertainties associated with this option.
  • p.44
  • Uncomplicated incomplete abortion can result after an induced or spontaneous abortion (i.e. miscarriage). The management is identical and the above recommendations apply to both situations.
    * Restrictions on prescribing authority for some categories of providers may need to be modified or other mechanisms put in place for making the medications available for these providers within the regulatory framework of the health system
    The evacuation of retained products is a signal function of basic EmOC; thus training and implementation of these tasks can be integrated with EmOC services.
    * Research into lay health worker roles in carrying out this task requires the documentation of safety and effectiveness of their ability to recognize uncomplicated incomplete abortions, to administer the correct dose of misoprostol and to recognize and refer if other complications are present. Strong referral linkage and backup care to emergency services must always be available.
  • p.44
  • Management of abortion and post-abortion care for pregnancies beyond 12 weeks
    Dilatation and evacuation (D&E) and medical abortion with mifepristone followed by misoprostol (or misoprostol alone in contexts where mifepristone is not available) are the recommended options.
    • p.45
  • The provision of medical abortion for pregnancies beyond 12 weeks is a facility-based procedure and women should remain under observation until the process is complete.
    • p.51
  • Table 13. Provision of medical abortion beyond 12 weeks*
    Specialist doctors
    Recommended
    Within their typical scope of practice. No assessment of the evidence was therefore conducted.
    * Non-specialist doctors
    Recommended
    There was insufficient direct evidence for this option; however, non-specialist doctors routinely carry out tasks of similar or greater complexity (e.g. conducting deliveries, manual removal of placenta, vacuum extraction). The potential benefits of this option outweigh the harms and the intervention has proven feasible in several settings. A specialist provider may not always be available on-site and this option may increase the ability of the health system to provide care for women needing it.
    * Associate and advanced associate clinicians
    Recommended in specific circumstances
    We recommend this option in contexts where established and easy access to appropriate surgical backup and proper infrastructure is available to address incomplete abortion or other complications.
    There was insufficient direct evidence for this option; however, such professionals are considered as options for tasks of similar complexity, like vacuum extraction and manual removal of placentas. They are often present at higher-level facilities where second trimester care is provided. A trained specialist provider may not always be present at such a facility and the potential to sustain second trimester services is increased with more than one trained provider on site.
    *Midwives
    Recommended in specific circumstances
    We recommend this option in contexts where established and easy access to appropriate surgical backup and proper infrastructure to address incomplete abortion or other complications is available.
    Although there was insufficient direct evidence for the effectiveness of the intervention as a whole, midwives are often responsible for the monitoring and care of the woman from the time of misoprostol administration to completion of abortion, and women often find care provided by midwives to be more acceptable (moderate confidence).
    • p.51
  • Nurses
    Recommended in specific circumstances
    We recommend this option in contexts where established and easy access to appropriate surgical backup and proper infrastructure is available to address incomplete abortion or other complications.
    Although there was insufficient direct evidence for the effectiveness of the intervention as a whole, nurses are often responsible for the monitoring and care of the woman from the time of misoprostol administration to completion of abortion, and women often find care provided by nurses to be more acceptable (moderate confidence).
    *Auxiliary nurses and auxiliary nurse midwives
    Recommended against
    There was no direct evidence for the effectiveness, safety or acceptability of this option. These health workers are unlikely to be present at the higher-level facilities where such care is provided or be involved in second trimester abortion care.
    * Doctors of complementary systems of medicine
    Recommended against
    There was no direct evidence for the effectiveness, safety or acceptability of this option. These doctors are unlikely to be involved in second trimester abortion care and the procedure is performed at a higher-level facility where specialist/non-specialist doctors are usually present.
    * Pharmacists, pharmacy workers, lay health workers
    Recommend against
    Outside of their typical scope of practice. No assessment of the evidence was therefore conducted.
  • p.52
  • Research priorities
    Further research is needed into the roles of non-physician providers – such as associate and advanced associate clinicians, midwives and nurses – for carrying out second trimester abortions.
    Implementation considerations
    Medical abortions for pregnancies beyond 12 weeks need to take place in health-care facilities with provision for inpatient stay.
    Health workers providing, or caring for women undergoing, abortion in the second trimester may have additional needs for professional and mentoring support.
    • p.52
  • A formal research prioritization exercise was not possible, but priority areas for future research were identified, including documenting the safety, effectiveness and feasibility of approaches to expanding roles of pharmacists and lay health workers in performing components of medical abortion provision. Further research is also needed into the development of simple tools, tests and checklists that can facilitate the assessment of eligibility for early medical abortion or of abortion completeness by women themselves or other community-based health workers.
    Research is also needed into the safety, effectiveness and feasibility of non-specialist providers such as associate and advanced associate clinicians, midwives and nurses in providing abortion care beyond the first trimester.
    Equally critical is implementation research on interventions to expand health worker roles within health systems and at scale, and to identify what works and what does not. Given that task shifting and task sharing already exist in many contexts, more rigorous documentation and evaluation of existing programmes and the roles played by different types of health workers can also provide much-needed feasibility evidence. Programmes, as well as research (including clinical research), should clearly document and make visible the roles of health workers who provide the various interventions.
    • p.67

“Medical management of abortion” (2018)[edit]

“Medical management of abortion”. WHO. 2018. p. 24. ISBN 978-9241550406.

  • Duration of pregnancy (gestation): Size of the uterus, estimated in weeks, based on clinical examination, that corresponds to a pregnant uterus of the same gestational age dated by last menstrual period (LMP). Medical methods of abortion (medical abortion): Use of pharmacological drugs to terminate pregnancy. Sometimes the terms “non-surgical abortion” or “medication abortion” are also used. Routes of misoprostol administration: oral pills are swallowed; buccal pills are placed between the cheek and gums and swallowed after 30 minutes; sublingual pills are placed under the tongue and swallowed after 30 minutes; vaginal pills are placed in the vaginal fornices (deepest portions of the vagina) and the individual is instructed to lie down for 30 minutes. Surgical methods of abortion (surgical abortion): use of transcervical procedures for terminating pregnancy, including vacuum aspiration and dilatation and evacuation (D&E). See Chapter 2, section 2.2.4 in the WHO Safe abortion guideline (2012) 1 for a more detailed description of methods of surgical abortion.
    • v
  • Medical abortion care encompasses the management of various clinical conditions including spontaneous and induced abortion (both viable and non-viable pregnancies), incomplete abortion and intrauterine fetal demise, as well as post-abortion contraception.
    Medical management of abortion generally involves either a combination regimen of mifepristone and misoprostol or a misoprostol-only regimen. Medical abortion care plays a crucial role in providing access to safe, effective and acceptable abortion care. In both high- and low-resource settings, the use of medical methods of abortion have contributed to task shifting and sharing and more efficient use of resources. Moreover, many interventions in medical abortion care, particularly those in early pregnancy, can now be provided at the primary-care level and on an outpatient basis, which further increases access to care. Medical abortion care reduces the need for skilled surgical abortion providers and offers a non-invasive and highly acceptable option to pregnant individuals.
    • vii
  • Recommendations for the use of mifepristone and misoprostol for inducing abortion and for managing incomplete abortion are contained within the 2012 WHO guideline Safe abortion: technical and policy guidance for health systems. Evidence related to home use of medication and self-assessment is included in the 2015 WHO guideline Health worker roles in providing safe abortion and post-abortion contraception. However, a number of new studies have been published in more recent years providing evidence related to the timing, dosage, dosing intervals and routes of administration of medications to manage abortion, and also the timing of contraception initiation following a medical abortion. Hence it was critical for WHO to review the evidence and update its own recommendations.
    • p.viii
  • Mifepristone and misoprostol in combination or misoprostol alone are the medications generally used to induce abortion and to manage incomplete abortion or intrauterine fetal demise (IUFD). These medications are increasingly available globally, and they are on the World Health Organization (WHO) List of Essential Medicines. Mifepristone is an anti-progestin which binds to progesterone receptors, inhibiting the action of progesterone and hence interfering with the continuation of pregnancy. Treatment regimens entail an initial dose of mifepristone followed by administration of a synthetic prostaglandin analogue, misoprostol, which induces cervical softening and dilation and enhances uterine contractions, which aids in expelling the products of conception.
    Misoprostol is a prostaglandin E1 analogue that can be used either in combination with mifepristone or on its own. Misoprostol has a wide range of reproductive health applications, including induction of labour, management of spontaneous and induced abortion, and prevention and treatment of postpartum haemorrhage. Due to the ease of handling and storing it, as well as its non-invasiveness and proven cost-effectiveness, the use of misoprostol within abortion care – either in combination with mifepristone or alone – offers several advantages. It reduces the need for skilled surgical abortion providers, equipment, sterilization and anaesthesia, while offering a non-invasive and highly acceptable option to pregnant individuals. For these reasons, and because it is stable at room temperature within its packaging, misoprostol is particularly useful in low-resource settings.
    • Introduction, 1.1 background, p.1
  • Medical abortion plays a crucial role in providing access to safe, effective and acceptable abortion care. Previous guidance published by WHO, including Safe abortion: technical and policy guidance for health systems (2012), provided recommendations for the use of mifepristone and misoprostol in combination or misoprostol alone for the management of medical abortion. The 2012 guidance stated that many interventions in medical abortion care, particularly those in early pregnancy, can be provided at the primary care level and on an outpatient basis, which further increases access to care. In both high- and low-resource settings, the use of medical methods of abortion have contributed to task shifting and sharing and more efficient use of resources. Given the nature of the medical abortion process, it is also possible for individuals to play a role in managing some of the components by themselves, outside of a health-care facility. Another existing WHO guideline, Health worker roles in providing safe abortion and post-abortion contraception (2015), recommends that in specific circumstances, individuals may self-manage their mifepristone and/or misoprostol medication without direct supervision of a health-care provider, as well as self-assess the success of the abortion process using pregnancy tests and checklists (see Box 1). It should be noted that pregnancy tests used to self-assess the success of the abortion process are low-sensitivity urine pregnancy tests, which are different from those tests commonly used to diagnose pregnancy. Such self-assessment and self-management approaches can be empowering for individuals and help to triage care, leading to a more optimal use of health-care resources.
    • pp.1-2
  • Health-care providers, health managers, policy-makers and other stakeholders need up-to-date, evidence-based recommendations to inform clinical policies and practices, to enable improved health-care outcomes and to provide information that is complete, accurate and easy to understand. Expansion of medical abortion and new studies related to the timing, interval and routes of administration of medical abortion medications, necessitated a review of the evidence and the development of new recommendations as well as updates to the WHO recommendations issued in 2012.
    • p.3
  • While legal, policy and regulatory contexts vary, abortion is legal at least to save the life of the pregnant individual in most countries and more than two thirds of countries have one or more additional grounds for legal abortion (16). The provision of post-abortion care is always legal. These recommendations will be relevant across a diverse range of settings as the need to make care more accessible and rationalize the use of available health resources exists in both high- and low-resource settings.
    • 1.3 Target audience and relevance, p.5
  • The final PICO questions for this guideline represent prioritized thematic areas that needed to be updated most urgently, based on input during the technical consultation and scoping meeting. The finalized priority PICO questions covered the following thematic areas:
    medical management of incomplete abortion at ≥ 13 weeks of gestation;
    medical management of intrauterine fetal demise (IUFD) at ≥ 14 to ≤ 28 weeks of gestation;
    medical management of induced abortion at 9–12 weeks of gestation;
    medical management of induced abortion at ≥ 12 weeks of gestation;
    timing of initiation of contraception after a medical abortion. Several other thematic areas were noted as important, two of which were re-addressed in an effort to provide a more comprehensive set of recommendations: medical management of incomplete abortion at
    < 13 weeks of gestation; and medical management of induced abortion at < 9 weeks of gestation.
    • pp.9-10
  • Information is a necessary component of any medical care and should always be provided to individuals considering abortion. At a minimum, this should include:
    the available options for abortion methods and pain management;
    what will be done before, during and after the procedure, including any tests that may be performed;
    what they are likely to experience (e.g. pain and bleeding) and how long the procedure and the recovery are likely to take (vaginal bleeding for two weeks is normal after medical abortion – such bleeding can last up to 45 days in rare cases);
    how to recognize potential complications, and how and where to seek help, if required (individuals should return to the hospital or clinic if they experience increased intensity of cramping or abdominal pain, heavy vaginal bleeding and/or fever);
    when normal activities can be resumed, including sexual intercourse (the return of fertility can occur within two weeks following abortion);
    where and how to access additional services and follow-up care (see section 3.1.4 on the right).
    • 3.1.1 Provide information, p.14
  • Additional services may need to be provided to individuals seeking medical abortion (19).
    Provide iron tablets for anaemia, if needed.
    Provide any necessary pain medications.
    Provide emotional support, if needed.
    Refer the individual to other services as determined by an assessment of their needs; these services may include: counselling and testing for sexually transmitted infections (STIs, including HIV), abuse support services, psychological or social services, or other specialist health or medical services.
    • 3.1.3 Additional services, p.15
  • Routine follow-up is not necessary following an uncomplicated surgical or medical abortion using mifepristone and misoprostol. However, an optional follow-up visit 7–14 days after their procedure may be offered to provide further contraceptive counselling and services, further emotional support, or to address any medical concerns.
    A routine follow-up visit is recommended only in the case of medical abortion using misoprostol alone, to assess success of the abortion.
    At the follow-up appointment: assess the individual’s recovery and inquire about any signs or symptoms of ongoing pregnancy;
    review any available medical records and referral documents;
    ask about any symptoms experienced since the procedure;
    perform a focused physical examination in response to any complaints; and assess the individual’s fertility goals and need for contraceptive services.
    * If no method was started prior to discharge from the facility, provide information and offer counselling and the appropriate contraceptive method, if desired by the client.
    * If a contraceptive method was already started, assess the method used and note any concerns – where there are no concerns, resupply as needed; where there are concerns, help with selection of another appropriate method.
    • 3.1.4 Follow-up care p.15
  • 3.2.1 Diagnosis of incomplete abortion
    Incomplete abortion is defined by clinical presence of open cervical os and bleeding, whereby all products of conception have not been expelled from the uterus. Common symptoms include vaginal bleeding and abdominal pain. Incomplete abortion should also be suspected if, upon visual examination, the expulsed tissue is not consistent with the estimated duration of pregnancy.
    3.2.2 Medical management of incomplete abortion: Recommendations 1a and 1b Incomplete abortion may be managed expectantly, or treated surgically or medically. The mode of management to be used should be selected based on the individual’s clinical condition and preference for treatment.
    • 3.2 Incomplete abortion p.16
  • A Cochrane review served as the evidence base for the medical management of incomplete abortion; the review assessed the effectiveness, safety and acceptability of various management options. There were 24 studies included in the review that focused on incomplete abortion at < 13 weeks of gestation. Of those 24 studies, 22 compared different doses and routes of misoprostol in misoprostol-only regimens and options of expectant, medical or surgical management.
    Effects (benefits and harms) Two studies focused on misoprostol dosage regimens; these studies found higher rates of successful abortion and fewer unplanned surgical interventions with 600 μg repeat oral dosing. In the studies that compared misoprostol routes, there was no clear evidence of one route being superior to another. In the studies that compared medical management with surgical or expectant management, the incidence
    There were no studies that focused exclusively on incomplete abortion at ≥ 13 weeks. One study set in Finland evaluated the management of incomplete abortion in pregnancies up to 24 weeks of gestation, but it included only three women whose pregnancies fell within the gestational age between 13 and 24 weeks by menstrual dating. Of these three women, one received medical treatment and the other two received surgical intervention.
    • 3.2.3 Evidence summary and rationale for Recommendations 1a and 1b pp.17-18
  • Recommendation 1B, “Medical management of incomplete abortion at ≥ 13 weeks of gestation”
    For the treatment of incomplete abortion at ≥ 13 weeks uterine size, we suggest the use of repeat doses of 400 μg misoprostol administered sublingually, vaginally or buccally every 3 hours.
    • p.17
  • Repeat doses of misoprostol can be considered when needed to achieve success of the abortion process. In this guideline we do not provide a maximum number of doses of misoprostol. Health-care providers should use caution and clinical judgement to decide the maximum number of doses of misoprostol in pregnant individuals with prior uterine incision. Uterine rupture is a rare complication; clinical judgement and health system preparedness for emergency management of uterine rupture must be considered with advanced gestational age.
    • p.17
  • There was no evidence identified in the Cochrane review that looked directly at how women value medical abortion procedures. However, generally, women describe avoidance of surgery as a positive feature of medical management, while some women value the shorter abortion process and minimal bleeding associated with surgical management (22,23). Some women dislike the side-effects associated with medical management, including bleeding, fevers and chills.
    Equity We were unable to identify research on aspects of equity relating to the relative effectiveness of the intervention in different subgroups; no assumptions were made.
    Resources We attempted to collect programmatic data from organizations involved in service delivery in order to inform the decision on how resources factor into the recommendation. However, we were only able to collect limited information, and the available data varied considerably in its reporting (e.g. definition of terms), thus these data were not used in the decision-making. In cases where additional hospital resources are required, such as blood transfusion, inpatient management or analgesic measures, we assume that the costs associated with this care will be higher.
    Acceptability Women generally find medical management of incomplete abortion with misoprostol alone acceptable and would recommend the procedure to a friend.
    Feasibility We were unable to identify research on the feasibility of implementing the use of misoprostol alone or in combination with mifepristone for the management of incomplete abortion. However, the Cochrane review included 22 studies conducted across 24 countries, providing information related to the varying country contexts in which such services may be provided. Of these 24 countries, seven were in low-income economies, seven were in lower-middle-income economies, four were in upper-middle-income economies and six were in high-income economies.
    • p.18
  • Rationale for Recommendation 1a (on incomplete abortion at < 13 weeks): Women treated with 600 μg oral misoprostol had higher rates of successful abortion and lower occurrence of additional surgical interventions; this is based on low-certainty evidence. Low-certainty evidence also suggests that the use of 400 μg sublingual misoprostol leads to high rates of successful abortion. Acceptability of these regimens also appears high. Rationale for Recommendation 1b (on incomplete abortion at ≥ 13 weeks): Due to the lack of direct evidence on medical management of incomplete abortion at ≥ 13 weeks of gestation, this recommendation is based on information extrapolated from data related to the medical management of abortion at > 12 weeks using misoprostol alone. Individuals presenting with incomplete abortion at ≥ 13 weeks may present with varying amounts of residual tissue or products of conception. Thus, the GDG members took the view that since the regimen utilized for medical abortion at > 12 weeks is safe, effective and acceptable, then this regimen can also be applied to those being treated for incomplete abortion where expulsion of uterine contents has begun, as evidenced by bleeding, cramping or contractions.
    • p.19
  • 3.2.4 Additional considerations
    Ultrasound scanning is not routinely required for the provision of abortion. Ultrasound is useful to detect ongoing pregnancy; measuring endometrial thickness, however, is not generally useful for diagnosing incomplete abortion and may lead to inappropriate surgical interventions.
    The following health worker cadres can provide medical management of uncomplicated incomplete abortion, given task-specific training and functioning systems for monitoring and supportive supervision: auxiliary nurses, auxiliary nurse midwives, nurses, midwives, associate/advanced associate clinicians, and non-specialist and specialist doctors.
    3.2.5 Research gaps
    General: Identification of the most effective medical abortion regimen for incomplete abortion at ≥ 13 weeks of gestation (including the use of mifepristone in combination with misoprostol versus misoprostol alone) is still needed. Recommendations have been made for this regimen using indirect evidence. Results from the survey on research gaps (completed by GDG members) noted the lack of evidence for effective regimens in this clinical scenario and, therefore, further research on this topic should be pursued.
    • p.19
  • 3.3.1 Diagnosis of intrauterine fetal demise (IUFD) Fetal demise refers to situations in which the fetus is no longer alive, but the uterus has not yet started to expel its contents and the cervical os remains closed. The diagnosis is made by ultrasound scan following the clinical findings, which can include vaginal bleeding, absent fetal heart sounds on electronic auscultation, a failure to feel fetal movements or a uterus that is significantly smaller than the expected size.
    3.3.2 Medical management of IUFD at ≥ 14 to ≤ 28 weeks of gestation: Recommendation 2
    IUFD may be managed expectantly, or treated surgically or medically. The decision about the mode of management of IUFD should be based upon the individual’s clinical condition and preference for treatment. Medical management of IUFD includes the use of mifepristone in combination with misoprostol (recommended) or misoprostol alone (alternate).
    3.3.3 Evidence summary and rationale for Recommendation 2 A systematic review assessed the effectiveness, safety and acceptability of misoprostol treatment of IUFD at ≥ 14 to ≤ 28 weeks of gestation (32). A total of 16 RCTs were identified for inclusion in the review. Studies were included in the review if they included cases of IUFD at ≥ 14 to ≤ 28 weeks and if these cases were evenly distributed between the study arms. Studies that included IUFD at < 14 weeks or > 28 weeks of gestation were considered only if the mean gestational age of participants was within the range of ≥ 14 to ≤ 28 weeks.
    The review included studies that compared regimens of mifepristone used in combination with misoprostol versus misoprostol alone, as well as those that compared different doses of misoprostol after administration of mifepristone, different doses of misoprostol with or without a loading dose, different routes of administration of misoprostol and different preparations of misoprostol (i.e. moistened or dry).
  • 3.3 Intrauterine fetal demise, p.20
  • Medical management for intrauterine fetal demise at ≥ 14 to ≤ 28 weeks of gestation
    We suggest the use of 200 mg mifepristone administered orally, followed 1–2 days later by repeat doses of 400 μg misoprostol administered sublingually or vaginally every 4–6 hours. b The minimum recommended interval between use of mifepristone and misoprostol is 24 hours.
    For the misoprostol-only regimen, we suggest the use of repeat doses of 400 μg misoprostol administered sublingually every 4–6 hours.b
    Where sublingual misoprostol is not used, we suggest the use of repeat doses of 400 μg misoprostol administered vaginally every 4–6 hours.b
    Notes:
    *Data related to gestational ages over 24 weeks of gestation were more limited.
    *The use of a loading dose of misoprostol is not necessary. There is no advantage to the use of moistened over dry misoprostol.
    • p.21
  • a Combination regimen is recommended because it is more effective.
    b Repeat doses of misoprostol can be considered when needed to achieve success of the abortion process. In this guideline we do not provide a maximum number of doses of misoprostol. Health-care providers should use caution and clinical judgement to decide the maximum number of doses of misoprostol in pregnant individuals with prior uterine incision. Uterine rupture is a rare complication; clinical judgement and health system preparedness for emergency management of uterine rupture must be considered with advanced gestational age.
    • p.21
  • Effects (benefits and harms) The reviewed studies showed that women treated with a combination of mifepristone and misoprostol had higher rates of complete abortion within 24 hours and a shorter expulsion time than those treated with misoprostol alone. For both combination regimens and misoprostol-only regimens, women treated with 400 μg misoprostol had higher rates of complete abortion within 24 hours and lower rates of serious adverse events than women treated with alternative dosages of misoprostol. In the studies that compared routes of administration for misoprostol, there was no strong evidence of one route being superior to another.
    • pp.20-21
  • Values We were not able to identify research addressing the value placed on management of IUFD. Generally, we made the assumption that individuals would value shorter induction to expulsion times, and would value avoiding additional surgical intervention, serious adverse events and minor side-effects. However, there may be important variability in how much individuals value these outcomes, particularly in relation to each other. For example, a person may choose a longer induction to expulsion time if it is associated with a lower risk of serious adverse events and minor side-effects.
    • p.21
  • Equity We were unable to identify research on aspects of equity related to the relative effectiveness of the intervention in different subgroups; no assumptions were made.
    Resources We were unable to identify research that explored the costs involved or the cost-effectiveness of the intervention among the studies included in the systematic review. However, serious adverse events related to medical management of IUFD are rare. In cases where additional hospital resources are required, such as blood transfusion, inpatient management or analgesic measures, we assume that the costs associated with this care will be higher. We were unable to determine the impact that the use of mifepristone has on costs. While there may be an increased upfront cost in the delivery of a combination regimen (mifepristone and misoprostol), the overall resource use (and cost) may be decreased due to a shorter abortion process and higher success rates.
    Acceptability Several factors impacting acceptability were considered in the development of this recommendation, including tolerability of medication. Overall, women were satisfied with their treatment and found the pain associated with the induction less than or the same as they expected.
    Feasibility We were unable to identify research on the feasibility of implementing the use of misoprostol alone or in combination with mifepristone for the management of IUFD at ≥ 14 to ≤ 28 weeks specifically. However, the 16 studies were conducted across 17 countries (one study was conducted across sites in two countries) providing information on the varying country contexts in which such services may be provided. Of these 17 countries, six were lower-middle-income economies, seven were upper-middle-income economies and four were high-income economies.
    • p.22
  • Rationale for Recommendation 2: Women treated with a combination of mifepristone and misoprostol had higher rates of successful abortion within 24 hours and a shorter expulsion time than those treated with misoprostol alone. The certainty of the evidence ranged from low to very low. Evidence suggests that in both combination regimens and misoprostol-only regimens, the use of 400 μg misoprostol leads to higher rates of successful abortion within 24 hours and lower rates of serious adverse events compared with other doses.
    • p.22
  • 3.3.4 Additional considerations
    For the health-care providers managing IUFD at ≥ 14 to ≤ 28 weeks of gestation, the recommendations for cadres who can manage medical abortion at > 12 weeks can be followed. Alongside non-specialist and specialist doctors, additional cadres – including nurses, midwives and associate/advanced associate clinicians – can provide care where there is access to appropriate surgical backup and the proper infrastructure is available to address incomplete abortion or other complications. Patient preference should be considered when determining the route of misoprostol administration in medical management.
    • pp.22-23
  • 3.3.5 Research gaps General:
    Identification of the most effective medical regimen for IUFD management is needed. In particular, future research can investigate the efficacy of lower doses of misoprostol, such as 200 μg, when used with mifepristone. Misoprostol dosage for management of IUFD at < 20 weeks versus 20–28 weeks of gestation should be investigated.
    • p.23
  • 3.4.1 Indication for induced abortion
    People with an unplanned, mistimed or unwanted pregnancy may choose to have a medical abortion. Medical abortion refers to the sequential use of mifepristone followed by misoprostol or, in settings where mifepristone is not available, the use of misoprostol alone, to induce abortion, as an alternative to surgical management of abortion. An enabling regulatory and policy environment is needed to ensure that every individual who can become pregnant and who is legally eligible has ready access to safe abortion care. Laws and policies on abortion should protect health and human rights.
    • 3.4 Induced abortion p.24
  • Medical management of induced abortion at < 12 weeks of gestation
    We recommend the use of 200 mg mifepristone administered orally, followed 1–2 days later by 800 μg misoprostol administered vaginally, sublingually or buccally. The minimum recommended interval between use of mifepristone and misoprostol is 24 hours.
    For the misoprostol-only regimen, we recommend the use of 800 μg misoprostol administered vaginally, sublingually or buccally.
    Notes:
    * There is limited evidence to suggest that simultaneous dosing of mifepristone and misoprostol is efficacious.
    • p.24
  • Recommendation 3a has been updated from the WHO 2012 Safe abortion guidance. This updated recommendation applies to pregnancies up to 12 weeks of gestation, whereas in the prior guidance, different regimens were recommended for pregnancies up to 7 weeks, 9 weeks and 12 weeks. For the recommended misoprostol-only regimen, buccal route of administration has been added and the maximum number of doses has been removed. Interval dosing has been removed and a note has been added that repeat doses of misoprostol can be considered to achieve success of the abortion process.
    • p.24
  • a Combination regimen is recommended because it is more effective.
    b Consideration for patient and provider preference suggests the inclusion of all routes, including buccal administration.
    • p.24
  • 3.4.2 Medical management of induced abortion: Recommendations 3a and 3b
    The decision about abortion management should be based on the individual’s preference for treatment. The WHO guideline, Safe abortion: technical and policy guidance for health systems (2012), recommends manual or electric vacuum aspiration, dilation and evacuation, or medical management, either using a combination regimen (mifepristone followed by misoprostol) or misoprostol alone. Mifepristone followed by a prostaglandin analogue has been shown to be safe and effective. Limited evidence also suggests that a regimen with repeated doses of misoprostol between 9 and 12 weeks of gestation is safe and effective; however, use of misoprostol alone is less effective than its use in combination with mifepristone.
    • p.25
  • Medical management of induced abortion at ≥ 12 weeks of gestation
    We suggest the use of 200 mg mifepristone administered orally, followed 1–2 days later by repeat doses of 400 μg misoprostol administered vaginally, sublingually or buccally every 3 hours. The minimum recommended interval between use of mifepristone and misoprostol is 24 hours.
    For the misoprostol-only regimen, we suggest the use of repeat doses of 400 μg misoprostol administered vaginally, sublingually or buccally every 3 hours.
    Notes:
    *The use of a loading dose of misoprostol is not necessary. There is no advantage to the use of moistened over dry misoprostol.
    • p.25
  • Recommendation 3b has been updated from the WHO 2012 Safe abortion guidance (6). For this recommendation, the combination regimen (mifepristone and misoprostol) does not have the loading dose of 800 μg misoprostol as in the prior guidance. For both the combination regimen and the misoprostol-only regimen, the buccal route has been added as an option. Maximum number of doses has been removed and the time period between mifepristone and misoprostol dosing is given in days.
    This guideline provides updated information related to specific dosages, routes and regimens for medical abortion, which differ for pregnancies of different gestational ages.
    • pp.25-26
  • a Combination regimen is recommended because it is more effective.
    b Evidence suggests that vaginal route is the most effective. Consideration for patient and provider preference suggests the inclusion of all routes, including buccal administration.
    c Repeat doses of misoprostol can be considered when needed to achieve success of the abortion process. In this guideline we do not provide a maximum number of doses of misoprostol. Health-care providers should use caution and clinical judgement to decide the maximum number of doses of misoprostol in pregnant individuals with prior uterine incision. Uterine rupture is a rare complication; clinical judgement and health system preparedness for emergency management of uterine rupture must be considered with advanced gestational age.
    • p.25
  • Three systematic reviews served as the evidence base for the effectiveness, safety and acceptability of medical management of induced abortion regimens using mifepristone plus misoprostol (the combination regimen) or misoprostol alone: the first was for induced abortions at ≤ 63 days of gestation; the second was for induced abortions at > 63 days and up to 84 days (42); and the third was for induced abortions at ≥ 12 weeks of gestation. In the first systematic review, 41 studies were included towards the development of this recommendation comparing the combination regimen to the use of misoprostol alone, and comparing different routes, doses and dosing intervals for misoprostol after administration of mifepristone, and different doses of misoprostol in misoprostol-only regimens.
    In the second systematic review, five studies were included towards the development of these recommendations comparing different routes of misoprostol administration after use of mifepristone, different doses of misoprostol administration in misoprostol-only regimens, and comparing the management of induced abortion in a health-care facility to self-management by the pregnant individual.
    In the third systematic review, a total of 44 RCTs were identified for inclusion. The review included studies that compared the combination regimen with misoprostol alone. Studies also compared different doses of misoprostol after administration of mifepristone, different doses of misoprostol with or without a loading dose, different routes of administration of misoprostol, and different preparations of misoprostol (i.e. moistened or dry).
    • p.26
  • The first review, on induced abortions at ≤ 63 days of gestation, revealed that the combination regimen had higher rates of successful abortion and lower rates of ongoing pregnancy than the misoprostol-only regimen. In the studies comparing misoprostol doses and interval of misoprostol administration in the combination regimen, there were higher rates of successful abortion and lower rates of ongoing pregnancy with 800 μg of misoprostol and an interval of at least 24 hours between use of mifepristone and misoprostol. Studies comparing the different routes of misoprostol administration revealed the vaginal and sublingual routes to be more effective. In the few studies that compared misoprostol dosages in misoprostol-only regimen, 800 μg of misoprostol had lower rates of ongoing pregnancy and higher rates of successful abortion.
    The second systematic review revealed that medical abortion is effective in the late first trimester (> 63 days and up to 84 days of gestation). A combination regimen is significantly more effective than a misoprostol-only regimen. Success rates were higher with repeat dosing of misoprostol both in combination regimens and when misoprostol was used alone, and they were also higher with vaginal rather than oral administration for repeat dosing. Two studies addressed outpatient medical abortion, showing no significant difference in effectiveness, safety or acceptability between the two groups.
    The third systematic review, on induced abortion at ≥ 12 weeks, showed that combination regimens had lower rates of ongoing pregnancy at 24 and 48 hours when compared with misoprostol-only regimens. Dosing of mifepristone 24 hours before misoprostol had lower rates of ongoing pregnancy when compared to simultaneous dosing of both medications. In misoprostol-only regimens, dosing intervals of 3 hours had lower rates of ongoing pregnancy at 24 and 48 hours compared to other dosing intervals. For both combination and misoprostol-only regimens, sublingual and vaginal misoprostol routes of administration had better efficacy and lower rates of side-effects than the oral route.
    • Effects (benefits and harms), pp.26-27
  • An enabling regulatory and policy environment is needed to ensure that every individual who can become pregnant and who is legally eligible has ready access to abortion care.
    • p.27
  • Values We were unable to identify research on values relating to the management of medical abortion. We made the assumption that individuals value outcomes of effectiveness and safety, but it is unclear how they would value those outcomes when weighed against side-effects and markers of acceptability.
    Women may also strongly value certain interventions over others, with preferences for route and timing of medication administration, and type of intervention (medical or surgical) differing significantly between one woman and another, or one region of the world and another. Consideration should also be given to the value women place on the timing and cost of abortion services as well as opportunities to take part in managing their own abortion care in situations where at-home dosing or abortion self-management are available.
    • p.27
  • Equity
    We were unable to identify research on aspects of equity around relative effectiveness of the interventions in different subgroups. However, in 4 studies, participants ranged in age from 16 to 44 years, demonstrating inclusion of people across age groups. Resources In the studies included in the three systematic reviews, we were unable to identify research that explored the costs involved or the cost-effectiveness. Studies on medical abortion include analgesic options ranging from oral to parenteral administration, including opiates, depending on gestational age. In cases where additional hospital resources are required, such as blood transfusion, inpatient management, analgesic measures or foeticide, we assume that the costs associated with these services will be higher. We were unable to determine the impact that the use of mifepristone has on costs. While there may be an increased upfront cost with the use of a combination regimen, the overall resources used may be decreased due to a shorter abortion process and a higher success rate.
    • pp.27-28
  • Feasibility
    We were unable to identify research on the feasibility of implementing the use of misoprostol alone or in combination with mifepristone for the management of medical abortion. However, four studies conducted in women with pregnancies 9–12 weeks of gestation reported that the medical abortion service was provided as outpatient care indicating feasibility of offering the service through outpatient health-care facilities. Additionally, studies related to management of medical abortion at < 12 weeks of gestation were conducted across 10 countries: two high-income, three upper-middle-income, four lower-middle-income and one low-income economy. Studies related to management of medical abortion at ≥ 12 weeks of gestation were conducted across 23 countries (four studies were conducted across sites in multiple countries): one was a low-income economy, six were lower-middle-income economies, five were upper- middle-income economies, and 11 were high-income economies.
    Acceptability
    Generally, women find various routes of misoprostol administration acceptable (48,49,54–59). Additionally, women found the side-effects to be acceptable. Women receiving care for management of medical abortion at < 12 weeks of gestation reported that the ability to predict timing of the bleeding was the best feature of taking the medicines at home. Home use of medical abortion at < 12 weeks gestation following an interaction with a health-care provider enabled women to keep working or reduced opportunity costs.
    • p.28
  • Women receiving care for management of medical abortion at < 12 weeks of gestation reported that the ability to predict timing of the bleeding was the best feature of taking the medicines at home.
    • p.28
  • Rationale for Recommendation 3a (on medical abortion at < 12 weeks of gestation): The combination mifepristone and misoprostol regimen is based on moderate certainty of evidence for induced abortion at < 12 weeks. In combination regimens, misoprostol dosage of 800 μg administered vaginally, sublingually or buccally is recommended based on moderate certainty of evidence. Evidence is limited regarding the use of misoprostol-only regimens, especially between 9 and 12 weeks of gestation. Thus, the GDG members took the view that when using misoprostol-only regimens, the dose of 800 μg administered vaginally, sublingually or buccally is safe, effective and acceptable.
    • p.28
  • Rationale for Recommendation 3b (on medical abortion at ≥ 12 weeks of gestation): The combination mifepristone and misoprostol regimen is based on moderate certainty of evidence for induced abortion at ≥ 12 weeks. Mifepristone 200 mg is suggested based on success, women’s values and cost (given the higher price of 600 mg of mifepristone) based on low to very low certainty of evidence. Misoprostol dosage of 400 μg administered every 3 hours is suggested based on overall very low certainty of evidence and is conditional upon resources available in different settings. Evidence on use of the buccal route was inconclusive, but it should be considered as an acceptable option if an individual prefers this route of administration. This is based on low to very low certainty of evidence.
    • pp.28-29
  • Given the nature of the medical abortion process when using the combination regimen, it is possible for individuals to play a role in managing some of the components by themselves outside of a health-care facility. Where there is access to a source of accurate information and to a health-care provider (should one be needed or wanted at any stage of the process), the abortion process can be self-managed with pregnancies < 12 weeks of gestation without the direct supervision of a health-care provider (10) (evidence is limited for pregnancies > 10 weeks).
    For provision of medical abortion of pregnancies < 12 weeks, the following cadres have been recommended: auxiliary nurses, auxiliary nurse midwives, nurses, midwives, associate/advanced associate clinicians, and non-specialist and specialist doctors. Doctors of complementary systems of medicine can be providers of this service in health system contexts with an established mechanism for the participation of such doctors in other tasks related to maternal and reproductive health.
    Alongside non-specialist and specialist doctors, the following cadres can provide medical abortion for pregnancies ≥ 12 weeks in contexts where appropriate surgical backup and proper infrastructure is established and easily accessible to address incomplete abortion or other complications: nurses, midwives, associate/advanced associate clinicians.
    • 3.4.4 Additional considerations, p.29
  • 3.4.5 Research gaps
    General:
    The various next steps that individuals can take, if needed, after medical abortion should be further evaluated. This includes self-assessment of the success of medical abortion, in particular for misoprostol-only regimens, which tend to be used in more restrictive settings and which are less effective.
    For those with uterine scars, the safety and efficacy of medical abortion regimens is an area requiring more research. In particular, the misoprostol dosage when used in combination with mifepristone and when used in misoprostol-only regimens for pregnancies 13–20 weeks versus 20–28 weeks of gestation can be investigated.
    Additional evidence is needed on the cost-effectiveness of all medical abortion interventions.
    Qualitative research is needed on individuals’ values and preferences relating to all medical abortion interventions.
    Medical abortion at < 12 weeks of gestation:
    Studies are needed on the efficacy, safety and acceptability of medical abortion (combination mifepristone and misoprostol regimens and misoprostol-only regimens) in the outpatient setting for pregnancies 9–12 weeks of gestation. This includes the follow-up care for medical abortion when self-assessment is used to determine eligibility for and success of the medical abortion.
    Medical abortion at ≥ 12 weeks of gestation: Studies are needed to determine the gestational age limit within which it is safe to carry out medical abortion without hospital admission.
    In connection to the research gap noted above, qualitative research will also be needed on the acceptability of outpatient medical abortion.
    • pp.29-30
  • 3.5.1 Provision of post-abortion contraception
    Contraception can be initiated at the time of administration of the first pill of the medical abortion regimen or after assessment of successful medical abortion. All contraceptive options may be used. Criteria laid out in the WHO publications Medical eligibility criteria for contraceptive use and Ensuring human rights in the provision of contraceptive information and services should be adhered to.
    • 3.5 Post-abortion contraception, p.31
  • 3.5.3 Evidence summary and rationale for Recommendations 4a and 4b
    Three systematic reviews served as the evidence base for the timing of post-abortion contraception. The first systematic review assessed the efficacy and safety of non-IUD hormonal contraception initiation after abortion (including medical abortion). Three RCTs and one cohort study compared immediate versus delayed initiation of implants or DMPA after medical abortion with mifepristone and misoprostol. No studies assessed hormonal contraception initiation after medical abortion with a misoprostol-only regimen.
    The second systematic review assessed contraceptive continuation at six months (implants, DMPA and IUD) and unintended pregnancies after the index abortion. This review included the same three RCTs and one cohort study that were included in the first review.
    The third systematic review assessed the effectiveness and safety of initiation of IUD after abortion. In this review, three studies compared immediate versus delayed IUD insertion after medical abortion with mifepristone and misoprostol. The included studies assessed copper-bearing and levonorgestrel-releasing IUDs. No studies assessed IUD initiation after medical abortion with a misoprostol-only regimen.
    • pp.32-33
  • For individuals undergoing medical abortion with the combination mifepristone and misoprostol regimen or the misoprostol-only regimen who desire hormonal contraception (oral contraceptive pills, contraceptive patch, contraceptive ring, contraceptive implant or contraceptive injections), we suggest that they be given the option of starting hormonal contraception immediately after the first pill of the medical abortion regimen.
    Notes:
    *All individuals who can become pregnant should be provided with all of the necessary information to make an informed decision regarding the use of contraception. Immediate initiation of intramuscular (IM) depot medroxyprogesterone acetate (DMPA) is associated with a slight decrease in the effectiveness of medical abortion regimens. However, immediate initiation of DMPA should still be offered as an available contraceptive method after an abortion.
    *Indirect evidence was used as a basis for decision-making on initiation of hormonal contraception as an option for individuals undergoing medical abortion with misoprostol alone.
    *No data were available on the use of combined hormonal contraception (pills or injections) by those undergoing medical abortion.
    • Timing of post-abortion hormonal contraception initiation, except for intrauterine device (IUD), p.32
  • For individuals undergoing medical abortion with the combination mifepristone and misoprostol regimen or the misoprostol-only regimen who wish to have an IUD inserted, we suggest IUD placement at the time that success of the abortion procedure is determined. The use of clinical signs with bimanual examination, serum human chorionic gonadotrophin (hCG) levels or ultrasonography (if available), and an assessment of the individual’s current symptoms can be used to determine whether or not there is an ongoing pregnancy.
    • p.33
  • The findings of the three RCTs and one cohort study in the first systematic review showed that there was little difference in the rates of successful abortion between the two groups (immediate versus delayed initiation of implants or DMPA after medical abortion) and satisfaction regarding the timing of their contraception initiation was high. Findings from the same studies, which were also reviewed in the second systematic review, showed that continuation rates at six months were higher for the women in the immediate initiation group. Contraceptive failure rates were lower among women who initiated the implant, DMPA or the IUD immediately. The studies on immediate versus delayed IUD insertion after medical abortion in the third systematic review showed that there was no difference between the immediate and delayed insertion groups with regard to adverse events or the need for further intervention after IUD placement. There were fewer expulsions of the IUD at 12 months among women who had undergone immediate IUD placement.
    • Effects (benefits and harms), pp.33-34
  • Values
    Women placed high value on accepting a contraceptive method to prevent a future pregnancy. Two studies looking at DMPA and implants reported that women undergoing an abortion placed high importance on preventing a pregnancy in the next six months.
    Resources
    In regard to resource requirements and cost-effectiveness, there was no direct research evidence that explored these domains. The cost of the IUD and implant versus pills and injections in various country contexts could not be determined. While there may be increased upfront costs of the IUD and implant, related to the cost of the devices, provider training and additional placement and removal visits, costs may decrease over time compared with the repeated need for pills and injections.
    Equity
    There was no research evidence identified on aspects of equity around the relative effectiveness of the intervention in different subgroups. However, three studies included adolescents and three studies included nulliparous women.
    • p.34
  • Acceptability
    Women reported high satisfaction with immediate initiation of their implant or DMPA administration. Acceptability and satisfaction were also reported by women in the immediate-start group based on fewer visits made to the health-care provider compared with the delayed-start group. Immediate initiators of implants had higher attendance at follow-up appointments.
    For the IUD studies, similar considerations were taken into account. None of the included studies specifically addressed acceptability of the service to women. However, timing of insertion can be used as a proxy indicator for acceptability; more women had the IUD placed at the time that successful abortion was determined compared with the number of women who opted for delayed insertion. The rate of loss to follow-up at six months was reportedly lower for the early-insertion group as compared with the delayed insertion group.
    Feasibility
    Initiation of post-abortion contraception appears feasible to implement. The included studies for both IUD and hormonal contraception were conducted through outpatient clinics, indicating feasibility of offering the service through outpatient health-care facilities.
    • p.34
  • Rationale for Recommendation 4a (on post-abortion hormonal contraception initiation, except for IUD): There was little difference in the successful abortion rates between women who started non-IUD hormonal contraception after receiving mifepristone versus those who started after receiving both mifepristone and misoprostol. This difference was based on low certainty of evidence. Women placed value on accepting a contraceptive method and they placed value on preventing future pregnancies. Satisfaction with and acceptability of immediate initiation of a contraceptive method was high. Continuation rates for the implant at six months were higher for the women in the immediate-initiation group. The certainty of the evidence was very low.
    Rationale for Recommendation 4b (on post-abortion IUD placement): Placement of an IUD at the time the abortion process has been deemed successful leads to lower rates of contraceptive failure and higher continuation rates at 6 and 12 months. The 6-month continuation rates are based on moderate certainty of evidence while the contraceptive failure rates are based on low certainty of evidence and the continuation rates at 12 months are based on very low certainty of evidence. There is no difference in the number of women requiring further intervention post-IUD placement due to retained tissue or bleeding, but the certainty of the evidence was low. There is no difference in the side-effect of pain at IUD insertion between the two groups, based on moderate certainty of evidence. Serious adverse events are rare and there was no difference between the two groups for uterine perforation or death, but this was based on very low certainty of evidence. Acceptability and feasibility of immediate placement of the IUD was high.
    • p.35
  • 3.5.5 Research gaps General:
    Studies are needed on the efficacy, safety and acceptability of immediate initiation of contraception with misoprostol-only regimens.
    Studies on the efficacy, safety and acceptability of the initiation of combined hormonal contraception at the time of mifepristone administration are also lacking.
    Recommendations on the timing of post-abortion contraception are inclusive of combined hormonal contraception and misoprostol-only regimens, based on indirect evidence. Results from the survey on research gaps (completed by GDG members) noted the lack of direct evidence for these clinical scenarios and, therefore, further research on this topic should be pursued.
    • p.37
  • IMPORTANT NOTE: The quality of medicines used is an important factor that can influence the process and overall success of a medical abortion. Substandard mifepristone and/or misoprostol products that do not contain the right active ingredients in the right dosages, and those that are not manufactured, transported or stored under the specified conditions, can affect the outcomes of a medical abortion. It is critical that mifepristone and misoprostol used for medical abortion are properly manufactured in line with specifications and are handled appropriately through the supply chain until use at the point of care. Ensuring use of quality-assured mifepristone and misoprostol that has been transported and stored correctly according to the specified conditions can contribute to the overall quality of a medical abortion process.
    • 4. General implementation considerations, p.39
  • Q: Where should medical abortion services be available?
    A: Services should be available at the primary-care level, with referral systems in place for all required higher-level care.
    Q: Who can provide these medical abortion services?
    A: In addition to non-specialist doctors and specialist doctors, with task-specific training and functioning systems for monitoring and supportive supervision, a wide range of health worker cadres – such as auxiliary nurses, auxiliary nurse midwives, nurses, midwives, associate/advanced associate clinicians, pharmacists and doctors of complementary medicine – can provide various aspects of medical abortion services. In addition, indirect evidence from a qualitative systematic review on factors affecting implementation of task sharing in abortion identified that some providers in a middle-income setting where abortion is legal saw medical abortion as having a number of benefits for health services. These reported benefits included that it was safe and effective; it would reduce the burden on health services; and it may make it easier for people involved to act in accordance with their conscience. A discussion of general considerations for task shifting in maternal health and family planning can be found in the 2012 OptimizeMNH guideline: WHO recommendations: optimizing health worker roles to improve access to key maternal and newborn health interventions through task shifting.
    The specific cadres able to provide medical abortion services have been outlined in the additional considerations section for each recommendation.
    • pp.39-40
  • Q: Can medical abortion processes be self-managed?
    A: When using the combination mifepristone and misoprostol regimen, the medical abortion process can be self-managed for pregnancies up to 12 weeks of gestation, including the ability to take the medications at home, without direct supervision of a health-care provider; it should be noted that there was limited evidence for pregnancies beyond 10 weeks. This is an option in circumstances where individuals have a source of accurate information and access to a health-care provider should they need or want it at any stage during the process (10).
    Q: What general considerations should be taken into account when providing care to adolescents/youth?
    A: Ensure that you are fully aware of the national and local laws and policies. In your work with adolescents, you may find that in some situations, prevailing laws and policies may not permit you to do what is in the best interests of your adolescent patient (e.g. in some places, the provision of contraceptives to unmarried adolescents is illegal). In such situations, you may need to draw upon your experience and the support of caring and knowledgeable people to find the best way to balance your legal obligations with your ethical obligations (13). Provide information on the implications of each treatment option and help the adolescent choose the one best suited to his/her needs. While doing this:
    present all the relevant information;
    respond to questions as fully and honestly as you can;
    help them choose;
    and respect their choice, even if it is not the one you would have wanted them to make.
    • pp.40-41
  • Q: How can success of the medical abortion be determined?
    A: Success of medical abortion is determined by signs and symptoms as experienced by the individual. These may include heavy bleeding with clots, passage of the products of conception, and pain that may be significantly stronger than normal menstrual cramps. If ongoing symptoms of pregnancy are reported and/or there has only been minimal or no bleeding after taking the medications as directed, ongoing pregnancy should be suspected and further evaluation could include pelvic examination (demonstrating a growing uterus) or an ultrasound scan (demonstrating an ongoing pregnancy)
    • p.42
  • IUDs can be inserted whenever the medical abortion has been deemed successful (19).
    • p.42
  • Q: Is there a maximum number of doses of misoprostol that can be used in the medical management of abortion?
    A: Repeat doses of misoprostol can be considered when needed to achieve success of the abortion process. In this guideline we do not provide a maximum number of doses of misoprostol. Health-care providers should use caution and clinical judgement to decide the maximum number of doses of misoprostol in pregnant individuals with prior uterine incision. Uterine rupture is a rare complication; clinical judgement and health system preparedness for emergency management of uterine rupture must be considered

with advanced gestational age.

  • pp.42-43
  • Q: What is the best way to store misoprostol?
    A: Aluminium blister packs are the best way to store misoprostol. Cutting the blister pack and storing misoprostol outside the aluminium blister may increase the risk of damage to the packaging (i.e. the inner seal), leading to exposure to environmental conditions.
    Store misoprostol in dry conditions at temperatures at or below 25 °C (77 °F).
    Exposure to heat and humidity during manufacturing, packaging and storage may compromise the quality of misoprostol (81).
    Q: What is the best way to store mifepristone?
    A: Store at 25 °C (77 °F); excursions permitted between 15 ° and 30 °C (59 ° and 86 °F) (82).
    Q: When does return to ovulation occur after a medical abortion?
    A: Ovulation can occur as few as eight days after a medical abortion.
  • p.43

"Self-management Recommendation 50: Self-management of medical abortion in whole or in part at gestational ages < 12 weeks (3.6.2) - Abortion care guideline" (November 19, 2021)[edit]

"Self-management Recommendation 50: Self-management of medical abortion in whole or in part at gestational ages < 12 weeks (3.6.2) - Abortion care guideline". WHO Department of Sexual and Reproductive Health and Research. (November 19, 2021).

  • Self-care, as defined the in Glossary, is a broad-based concept and can encompass numerous actions that are intended to empower the individual to enhance their own health. Self-management approaches are one component of self-care. Given the nature of the medical abortion process, it is possible for women to manage the process by themselves in whole or part. While individuals may conduct some or all elements related to the abortion process (self-assessment of eligibility, self-administration of medicines and self-assessment of the success of the abortion) entirely on their own, more typically, self-management co-exists with interactions with trained health workers or with a health-care facility and in conjunction with service-delivery approaches described in section 3.6.1. It is the individual (i.e. the “self”) who drives the process of deciding which aspects of the abortion care will be self-managed and which aspects will be supported or provided by trained health workers or in a health-care facility.
    Women may self-manage parts or all of the abortion process for a variety of reasons related to individual circumstances and preferences. For some women, this may be the only feasible option within their context and for others it may represent an active choice. However, from the perspective of the health system, self-management should not be considered a “last resort” option or a substitute for a non-functioning health system. Self-management must be recognized as a potentially empowering and active extension of the health system and task-sharing approaches. A supportive enabling environment as described in Chapter 1, section 1.3, is equally applicable to self-management approaches as it is to other elements of care provision.
  • For medical abortion at < 12 weeks (using the combination of mifepristone plus misoprostol or using misoprostol alone): Recommend the option of self-management of the medical abortion process in whole or any of the three component parts of the process:
    *self-assessment of eligibility (determining pregnancy duration; ruling out contraindications)
    *self-administration of abortion medicines outside of a health-care facility and without the direct supervision of a trained health worker, and management of the abortion process
    *self-assessment of the success of the abortion.
  • Remarks:
    *There was more evidence for self-management of medical abortion (with either of the regimens) for pregnancies before 10 weeks of gestation.
    *This recommendation applies to the combination regimen of mifepristone plus misoprostol, and the use of misoprostol alone. The included studies informing these recommendations did not assess the letrozole plus misoprostol regimen.
    *All individuals engaging in self-management of medical abortion must also have access to accurate information, quality-assured medicines including for pain management, the support of trained health workers and access to a health-care facility and to referral services if they need or desire it.
    *Restrictions on prescribing and dispensing authority for abortion medicines may need to be modified or other mechanisms put in place for self-management within the regulatory framework of the health system.
  • Self-assessment of eligibility: There is low-certainty evidence on the safety, effectiveness and acceptability of self-assessment of eligibility for a medical abortion, using the start date of last menstrual period (LMP) alone or in combination with other tools (e.g. checklists). The expert panel discussed the feasibility of this intervention in certain scenarios such as the woman having regular menses, a known LMP and the availability of validated tools. When they have the necessary information, women are able to determine their eligibility for medical abortion. Given this and taking into account the values and preferences and high acceptability of this approach, the panel determined that the intervention was favoured.
  • Self-administration of medicines: There is evidence that the option of self-administering medicines for medical abortion is effective (moderate certainty) and safe (low certainty). Women reported high satisfaction with taking their own medicines for the abortion (very low-certainty evidence). There was high adherence to the medical abortion regimen (low-certainty evidence). The high acceptability and feasibility favoured this intervention.
  • Self-assessment of success: There is high-certainty evidence that self-assessment of abortion outcome/success (using tools such as a low-sensitivity pregnant test or multi-level pregnancy test) is as effective as assessment by a trained health worker. Low-certainty evidence indicated that more women in the self-assessment group expressed satisfaction with the process.

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