Mifepristone
Mifepristone is also known as RU-486, the abortion pill, medical abortion, or chemical abortion
Short-Term Adverse Outcomes After Mifepristone-Misoprostol Versus Procedural Induced Abortion : A Population-Based Propensity-Weighted Study. Liu, N., & Ray, J. G. (2023). Annals of Internal Medicine, 176(2). https://doi.org/10.7326/M22-2568
Background: Prior studies comparing first-trimester pharmaceutical induced abortion (IA) with procedural IA were prone to selection bias, were underpowered to assess serious adverse events (SAEs), and did not account for confounding by indication. Starting in 2017, mifepristone-misoprostol was dispensed at no cost in outpatient pharmacies across Ontario, Canada.
Objective: To compare short-term risk for adverse outcomes after early IA by mifepristone-misoprostol versus by procedural IA.
Design: Population-based cohort study.
Setting: Ontario, Canada.
Patients: All women who had first-trimester IA.
Measurements: A total of 39 856 women dispensed mifepristone-misoprostol as outpatients were compared with 65 176 women undergoing procedural IA at 14 weeks' gestation or earlier within nonhospital outpatient clinics (comparison 1). A total of 39 856 women prescribed mifepristone-misoprostol were compared with 8861 women undergoing ambulatory hospital-based procedural IA at an estimated 9 weeks' gestation or less (comparison 2). The primary composite outcome was any SAE within 42 days after IA, including severe maternal morbidity, end-organ damage, intensive care unit admission, or death. A coprimary broader outcome comprised any SAE, hemorrhage, retained products of conception, infection, or transfusion. Stabilized inverse probability of treatment weighting accounted for confounding between exposure groups.
Results: Mean age at IA was about 29 years (SD, 7); 33% were primigravidae. Six percent resided in rural areas, and 25% resided in low-income neighborhoods. In comparison 1, SAEs occurred among 133 women after mifepristone-misoprostol IA (3.3 per 1000) versus 114 after procedural IA (1.8 per 1000) (relative risk [RR], 1.87 [95% CI, 1.44 to 2.43]; absolute risk difference [ARD], 1.5 per 1000 [CI, 0.9 to 2.2]). The respective rates of any adverse event were 28.9 versus 12.4 per 1000 (RR, 2.33 [CI, 2.11 to 2.57]; ARD, 16.5 per 1000 [CI, 14.5 to 18.4]). In comparison 2, SAEs occurred among 133 (3.4 per 1000) and 27 (3.3 per 1000) women, respectively (RR, 1.04 [CI, 0.61 to 1.78]). The respective rates of any adverse event were 31.2 versus 24.9 per 1000 (RR, 1.25 [CI, 1.04 to 1.51]).
Limitation: A woman prescribed mifepristone-misoprostol may not have taken the medication, and the exact gestational age at IA was not always known.
Conclusion: Although rare, short-term adverse events are more likely after mifepristone-misoprostol IA than procedural IA, especially for less serious adverse outcomes.
Mifepristone in South Australia Mulligan E, Messenger H. Australian Family Physician. MAY 2011.
- The study found 3.3% of the women who used RU-486 in the first trimester of pregnancy reported to an emergency room compared with 2.2% who used a surgical method and •5.7% of the women who used RU-486 had to be re-admitted to hospitals compared with 0.4% of surgical abortion patients.
Overlooked Dangers of Mifepristone, the FDA’s Reduced REMS, and Self-Managed Abortion Policies: Unwanted Abortions, Unnecessary Abortions, Unsafe Abortions. Reardon, David C., et al. American Report Series 20 (2021).
- It has been argued that abortions induced with mifepristone and misoprostol (or even misoprostol alone) are so safe and efficacious that they can be self-prescribed and self-managed, As a step toward this goal, some have advocated for elimination of the FDA requirements which limit the ability to prescribe mifepristone to any healthcare provider prepared to: (a) accurately assess the gestational age of the pregnancy, (b) diagnose ectopic pregnancies, and (c) provide referrals for surgical intervention in cases of severe bleeding or incomplete abortion. These arguments for reducing or eliminating physician oversight of chemical abortions are based on four premises. First, abortion is a human right that advances the equality, wellbeing, and self-determination of women. Second, the risks of mifepristone/misoprostol abortions are negligible. Third, self-managed abortions are an effective means by which women can control their reproductive lives and achieve their goals. Fourth, physician oversight is unnecessary and counterproductive. If these four premises are true, they present a strong basis for allowing the purchase of mifepristone/misoprostol as an over-the-counter drug. In the discussion which follows, we will show that the four premises above are, in fact, contradicted by real world experience and the best available medical evidence. The first premise is ideological and not supported by data. As a counterargument, we will show that that chemical abortion is often used contrary to women’s self-determination and best interests. The second premise is based primarily on research performed by authors with significant ideological and financial conflicts of interest and entanglement with the manufacturer of mifepristone. Moreover, the FDA has failed to require any systematic investigation of complications associated with mifepristone. Our counterargument will summarize a substantial body of studies documenting detailed evidence of physical and psychological complications associated with chemical abortions, which have simply been ignored, not disproven, by mifepristone advocates. The third premise, that chemical abortions are efficacious, is also ideological and unsupported by any meaningful data. Our counterargument will demonstrate that the actual objectives of women undergoing abortions are not being met, much less reliably quantified. The fourth premise, asserting that physician oversight of chemical abortions is unnecessary is also ideologically driven and unsupported by reliable evidence. Our counterargument will demonstrate that the role of physicians in pre-abortion screening, medical administration, and follow-up should be increased, not eliminated. We conclude with recommendations for modifying FDA’s current Risk Evaluation and Mitigation Strategy [REMS] applicable to mifepristone in order to provide better data.
Medication and procedural abortions before 13 weeks gestation and risk of psychiatric disorders. Steinberg, J. R., Laursen, T. M., Lidegaard, Ø., & Munk-Olsen, T. (2024).American Journal of Obstetrics and Gynecology, 231(4), 437.e1-437.e18. https://doi.org/10.1016/J.AJOG.2024.05.025
Background: The proportion of abortions provided by medication in the United States and worldwide has increased greatly since the U.S. Food and Drug Administration approved mifepristone in 2000. While existing research has shown that abortion does not increase risk of mental health problems, no population-based study has examined specifically whether a procedural or medication abortion increases risk of mental health disorders.
Objective: This study examined whether mental health disorders increased in the shorter and longer-term after a medication or procedural abortion.
Study design: Using Danish population registers' data, we conducted a prospective cohort study in which we included 72,424 females born in Denmark between 1980 and 2006, who were ages 12 to 38 during the study period and had a first first-trimester abortion before 13 weeks gestation in 2000 to 2018. Females with no previous psychiatric diagnoses were followed from 1 year before their abortion until their first psychiatric diagnosis, December 31, 2018, emigration from Demark, or death, whichever came first. Risk of any first psychiatric disorder was defined as a recorded psychiatric diagnosis at an in- or out-patient facility from the 1 year after to more than 5 years after a medication or procedural abortion relative to the year beforehand. Results were adjusted for calendar year, age, gestational age, partner status, prior mental and physical health, childbirth history, childhood environment, and parental mental health history.
Results: Females having medication (n=37,155) and procedural abortions (n=35,269) had the same risk of any first psychiatric diagnosis in the year after their abortion relative to the year before their abortion (medication abortion adjusted incidence rate ratio [MaIRR]=1.02, 95% confidence interval [CI]: 0.93-1.12; procedural abortion adjusted incidence rate ratio [PaIRR]=0.94, 95% CI: 0.86-1.02). Moreover, as more time from the abortion passed, the risk of a psychiatric diagnoses decreased relative to the year before their abortion for each abortion method (MaIRR 1-2 years after=0.89, 95% CI: 0.80-0.98; PaIRR 1-2 years after=0.81, 95% CI: 0.88-1.05; MaIRR 2-5 years after=0.77, 95% CI: 0.71-0.84; PaIRR 2-5 years after=0.72, 95% CI: 0.67-0.78; MaIRR 5+ years after=0.58, 95% CI: 0.53-0.63; PaIRR 5+ years after=0.54, 95% CI: 0.50-0.58).
Conclusion: Because the risk of psychiatric diagnoses was the same in the year after relative to the year before a medication and procedural abortion and the risk did not increase as more time after the abortion increased, neither abortion method increased risk of mental health disorders in the shorter or longer-term.
A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999-2015. Health Serv Res Manag Epidemiol. 2021 Nov 9;8:23333928211053965. doi: 10.1177/23333928211053965.
Introduction: Existing research on postabortion emergency room visits is sparse and limited by methods which underestimate the incidence of adverse events following abortion. Postabortion emergency room (ER) use since Food and Drug Administration approval of chemical abortion in 2000 can identify trends in the relative morbidity burden of chemical versus surgical procedures.
Objective: To complete the first longitudinal cohort study of postabortion emergency room use following chemical and surgical abortions.
Methods: A population-based longitudinal cohort study of 423 000 confirmed induced abortions and 121,283 subsequent ER visits occurring within 30 days of the procedure, in the years 1999-2015, to Medicaid-eligible women over 13 years of age with at least one pregnancy outcome, in the 17 states which provided public funding for abortion.
Results: ER visits are at greater risk to occur following a chemical rather than a surgical abortion: all ER visits (OR 1.22, CL 1.19-1.24); miscoded spontaneous (OR 1.88, CL 1.81-1.96); and abortion-related (OR 1.53, CL 1.49-1.58). ER visit rates per 1000 abortions grew faster for chemical abortions, and by 2015, chemical versus surgical rates were 354.8 versus 357.9 for all ER visits; 31.5 versus 8.6 for miscoded spontaneous abortion visits; and 51.7 versus 22.0 for abortion-related visits. Abortion-related visits as a percent of total visits are twice as high for chemical abortions, reaching 14.6% by 2015. Miscoded spontaneous abortion visits as a percent of total visits are nearly 4 times as high for chemical abortions, reaching 8.9% of total visits and 60.9% of abortion-related visits by 2015.
Conclusion: The incidence and per-abortion rate of ER visits following any induced abortion are growing, but chemical abortion is consistently and progressively associated with more postabortion ER visit morbidity than surgical abortion. There is also a distinct trend of a growing number of women miscoded as receiving treatment for spontaneous abortion in the ER following a chemical abortion.
A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization. Studnicki J, Longbons T, Harrison DJ, Skop I, Cirucci C, Reardon DC, Craver C, Fisher JW, Tsulukidze M. Health Serv Res Manag Epidemiol. 2022 May 20;9:23333928221103107. doi: 10.1177/23333928221103107.
Introduction: Previous research indicates that an increasing number of women who go to an emergency room for complications following an induced abortion are treated for a miscarriage, meaning their abortion is miscoded or concealed.
Objective: To determine if the failure to identify a prior induced abortion during an ER visit is a risk factor for higher rates of subsequent hospitalization.
Methods: Post hoc analysis of hospital admissions following an induced abortion and ER visit within 30 days: 4273 following surgical abortion and 408 following chemical abortion; abortion not miscoded versus miscoded or concealed at prior ER visit.
Results: Chemical abortion patients whose abortions are misclassified as miscarriages during an ER visit subsequently experience on average 3.2 hospital admissions within 30 days. 86% of the patients ultimately have surgical removal of retained products of conception (RPOC). Chemical abortions are more likely than surgical abortions (OR 1.80, CL 1.38-2.35) to result in an RPOC admission, and chemical abortions concealed are more likely to result (OR 2.18, CL 1.65-2.88) in a subsequent RPOC admission than abortions without miscoding. Surgical abortions miscoded/concealed are similarly twice as likely to result in hospital admission than those without miscoding.
Conclusion: Patient concealment and/or physician failure to identify a prior abortion during an ER visit is a significant risk factor for a subsequent hospital admission. Patients and ER personnel should be made aware of this risk.
Extending outpatient medical abortion services through 70 days of gestational age. Winikoff B, Dzuba IG, Chong E, Goldberg AB, Lichtenberg ES, Ball C, Dean G, Sacks D, Crowden WA, Swica Y. Obstet Gynecol. 2012 Nov;120(5):1070-6. doi: 10.1097/aog.0b013e31826c315f. PMID: 23090524.
Objective: To estimate the efficacy and acceptability of medical abortion at 64-70 days from last menstrual period (LMP) and to compare it with the already proven 57-63 days from LMP gestational age range.
Methods: This prospective, comparative, open-label trial enrolled 729 women with pregnancies 57-70 days from LMP requesting abortion at six U.S. clinics. Medical abortions were managed with 200 mg mifepristone and 800 micrograms buccal misoprostol and sites' service delivery protocols. Follow-up visits occurred 7-14 days after mifepristone, with an abortion considered complete if surgical intervention was not performed. Success, ongoing pregnancy, and acceptability rates were compared.
Results: A total of 629 cases were analyzable for efficacy. Success rates were similar in the two groups (57-63 days group: 93.5%, 95% confidence interval [CI] 90-96; 64-70 days group: 92.8%, 95% CI 89-95). Ongoing pregnancy rates also did not differ significantly (57-63 days: 3.1%, 95% CI 1.6-5.8; 64-70 days: 3.0%, 95% CI 1.5-5.7). Acceptability was high and similar in both arms, with most women (57-63 days: 87.4%; 64-70 days: 88.3%) reporting that their experience was either very satisfactory or satisfactory.
Conclusion: Medical abortion with mifepristone and misoprostol in current outpatient settings is an efficacious and acceptable method of ending pregnancies 64-70 days from LMP and can be offered without alteration of existing services.
Risk factors of surgical evacuation following second-trimester medical termination of pregnancy. Mentula M, Heikinheimo O. Contraception. 2012 Aug;86(2):141-6. doi: 10.1016/j.contraception.2011.11.070. Epub 2012 Jan 10. PMID: 22240172.
Background: Second-trimester medical termination of pregnancy (TOP) is associated with a higher risk of surgical evacuation than earlier medical TOP. Little is known about risk factors of surgical evacuation. Therefore, we assessed these risk factors among women undergoing second-trimester medical TOP.
Study design: Data on 227 women were derived from a prospective randomized trial comparing 1- and 2-day mifepristone-misoprostol intervals in second-trimester medical TOP between 2008 and 2010.
Results: The rate of surgical evacuation was 30.8%. The risk of surgical evacuation was increased by a history of curettage [odds ratio (OR) 4.4; 95% confidence interval (CI) 1.7-11.7], fetal indications for TOP (OR 6.1; 95% CI 1.1-34.4), age above 24 years (OR 2.4; 95% CI 1.1-5.3) and a 2-day interval (OR 2.2; 95% CI 1.1-4.1).
Conclusions: History of curettage, fetal indication, increasing age and 2-day interval between mifepristone and misoprostol increase the risk of surgical evacuation in cases of second-trimester medical TOP. These findings are important when optimizing clinical service in second-trimester TOP.
Immediate adverse events after second trimester medical termination of pregnancy: results of a nationwide registry study. Mentula MJ, Niinimäki M, Suhonen S, Hemminki E, Gissler M, Heikinheimo O. Hum Reprod. 2011 Apr;26(4):927-32. doi: 10.1093/humrep/der016. Epub 2011 Feb 11. PMID: 21317416.
BACKGROUND Increasing gestational age is associated with an increased risk of complications in studies assessing surgical termination of pregnancy (TOP). Medical TOP is widely used during the second trimester and little is known about the frequency of complications. This epidemiological study was undertaken to assess the frequency of adverse events following the second trimester medical TOP and to compare it with that after first trimester medical TOP.
METHODS This register-based cohort study covered 18 248 women who underwent medical TOP in Finland between 1 January 2003 and 31 December 2006. The women were identified from the Abortion Registry. Adverse events related to medical TOP within 6 weeks were obtained from the Hospital Discharge Registry.
RESULTS When compared with first trimester medical TOP, second trimester medical TOP increased the risk of surgical evacuation [Adj. odds ratio (OR) 7.8; 95% confidence interval (CI) 6.8-8.9], especially immediately after fetal expulsion (Adj. OR 15.2; 95% CI 12.8-18.0). The risk of infection was also elevated (Adj. OR 2.1; 95% CI 1.5-2.9). Within the second trimester, increased length of gestation did not influence the risk of surgical evacuation or infection after medical TOP.
CONCLUSIONS Medical TOP during the second trimester is generally safe. Surgical evacuation of the uterus is avoided in about two-thirds of cases, though it is much more common than after first trimester medical TOP. The risks of surgical evacuation and infection do not increase with gestational weeks in the second trimester TOP.
Immediate complications after medical compared with surgical termination of pregnancy. Niinimäki M, Pouta A, Bloigu A, Gissler M, Hemminki E, Suhonen S, Heikinheimo O. Obstet Gynecol. 2009 Oct;114(4):795-804. doi: 10.1097/AOG.0b013e3181b5ccf9. PMID: 19888037.
Objective: To estimate the immediate adverse events and safety of medical compared with surgical abortion using high-quality registry data.
Methods: All women in Finland undergoing induced abortion from 2000-2006 with a gestational duration of 63 days or less (n=42,619) were followed up until 42 days postabortion using national health registries. The incidence and risk factors of adverse events after medical (n=22,368) and surgical (n=20,251) abortion were compared. Univariable and multivariable association models were used to analyze the risk of the three main complications (hemorrhage, infection, and incomplete abortion) and surgical (re)evacuation.
Results: The overall incidence of adverse events was fourfold higher in the medical compared with surgical abortion cohort (20.0% compared with 5.6%, P<.001). Hemorrhage (15.6% compared with 2.1%, P<.001) and incomplete abortion (6.7% compared with 1.6%, P<.001) were more common after medical abortion. The rate of surgical (re)evacuation was 5.9% after medical abortion and 1.8% after surgical abortion (P<.001). Although rare, injuries requiring operative treatment or operative complications occurred more often with surgical termination of pregnancy (0.6% compared with 0.03%, P<.001). No differences were noted in the incidence of infections (1.7% compared with 1.7%, P=.85), thromboembolic disease, psychiatric morbidity, or death.
Conclusion: Both methods of abortion are generally safe, but medical termination is associated with a higher incidence of adverse events. These observations are relevant when counseling women seeking early abortion.
" Pain control in medical abortion", E Wiebe, Int'l J Gynecology & Obstetrics 74:275-280,2001
- A Canadian study of abortion procedures using methotrexate and misoprostol reported that the mean pain
Score was 6.2 on a scale from 1-10. Severe pain (scores of 9 or 10) was reported by 23.4% of the women. Women experiencing severe pain were more likely to have a lower maternal age, lower parity, higher anxiety and depression, and less satisfaction with the procedure. The authors reported that pain medication given before the onset of the procedure did not reduce the amount of severe pain.
Mifepristone in South Australia Mulligan E, Messenger H. Australian Family Physician. MAY 2011.
- The study found 3.3% of the women who used RU-486 in the first trimester of pregnancy reported to an emergency room compared with 2.2% who used a surgical method and •5.7% of the women who used RU-486 had to be re-admitted to hospitals compared with 0.4% of surgical abortion patients.
Psychological distress symptoms in women undergoing medical vs. surgical termination of pregnancy. Lowenstein L, Deutcsh M, Gruberg R, Solt I, Yagil Y, Nevo O, et al. (2006), General Hospital Psychiatry, 28(1):43–47.
- Compared to women choosing surgical abortion, those choosing chemical abortion had higher obsessive-compulsive symptoms, higher levels of guilt, higher interpersonal sensitivity scores, more paranoid ideation, and more general psychiatric symptoms.
A comparison of medical and surgical methods of termination of pregnancy: Choice, psychological consequences, and satisfaction with care. Slade, P., Heke, S., Fletcher, J., & Stewart, P. (1998). British Journal of Obstetrics and Gynecology, 105, 1288-1295.
- Those who had a medical abortion rated it as more stressful and experienced more disruption in their lives. “One of the main differences between these two methods of termination is the consciousness and participation of the patient in the medical procedure in a process that involves blood, pain, and death.”
Patient preference in a randomized study comparing medical and surgical abortion at 10-13 weeks gestation. Ashok P.W., Hamoda, H., Flett, G. M. M., Kidd, A., Fitzmaurice, A., Templeton, A. (2005). Contraception, 71, 143-148.
- 46.8% of women undergoing a medical abortion experienced a significant decline in self-esteem 2-3 weeks following the abortion. This was a higher percentage than among those who had a surgical abortion (39.5%).
Comparing medical versus surgical termination of pregnancy at 13-20 weeks of gestation: a randomized controlled trial, Kelly, T., Suddes, J., Howel, D., Hewison, J., & Robson, S. (2010). BJOG, 117, 1512-20.
- Women who had chemical abortions had higher PTSD intrusion scores, such as nightmares, than women who had surgical abortions
Posttraumatic Stress Disorder and psychological distress following medical and surgical abortion. C. Rousset, C. Brulfert, N. Séjourné, N. Goutaudier & H. Chabrol Journal of Reproductive and Infant Psychology, (2011) Volume 29(5), 506-517.
- Method: Eighty-six women were approached a few hours after the abortion and then 6 weeks later. Several questionnaires were completed: the Impact of Event Scale Revised (IES-R), the Multidimensional Scale of Social Support (MSPSS), the Peritraumatic Dissociative Experience Questionnaire (PDEQ), the Peritraumatic Emotions List (PEL), the Hospital Anxiety and Depression Scale (HADS), the Perinatal Grief Scale (PGS) and the Texas Grief Inventory (TGI). Results: Six weeks after the abortion, 38% of women reported a potential PTSD and a significant decrease of the anxious symptomatology was also highlighted. Peritraumatic dissociation and peritraumatic emotions were the main predictors of the intensity of post-abortum PTSD symptoms. Compared to surgical abortion, medical abortion was associated with increasing the risk of developing a possible PTSD. Conclusion: By providing evidence on some of the main risk factors, this study highlights the need for psychological support for women and strategies of prevention to be developed.
Abortion Pill Reversal can be successful
- Article regarding a medical protocol for women who change their minds to stop the RU-486 induced abortion.
Fatal Clostridium sordellii Infections after Medical Abortions N Engl J Med 2010; 363:1382-1383September 30, 2010
- Clostridial toxic shock is a rare and largely fatal syndrome among reproductive-age women. Eight cases were reported after medical abortions using mifepristone and misoprostol between 2000 and 2009 bringing the risk of clostridial toxic shock to 0.58 per 100,000 medical abortions.
Abortion Pill Reversal can be successful
- Article regarding a medical protocol for women who change their minds to stop the RU-486 induced abortion.
" Pain control in medical abortion", E Wiebe, Int'l J Gynecology & Obstetrics 74:275-280,2001
A Canadian study of abortion procedures using methotrexate and misoprostol reported that the mean pain Score was 6.2 on a scale from 1-10. Severe pain (scores of 9 or 10) was reported by 23.4% of the women. Women experiencing severe pain were more likely to have a lower maternal age, lower parity, higher anxiety and depression, and less satisfaction with the procedure. The authors reported that pain medication given before the onset of the procedure did not reduce the amount of severe pain.