By Katherine Rivlin, MD, MSc
Associate Professor, Department of Obstetrics and Gynecology, University of Chicago
Colorado’s Senate Bill 190, signed in May 2023, declared the practice of “abortion reversal” to be unprofessional conduct, meaning that healthcare providers providing this treatment could face sanctions to their licensure. In doing so, Colorado became the first state to ban the practice. However, Colorado’s Medical Board subsequently issued a draft rule declaring “abortion reversal” as “generally accepted standard of practice” and, therefore, potentially acceptable.1 This shift prompted the American College of Obstetricians and Gynecologists (ACOG), the Society of Family Planning (SFP), and the Society of Maternal-Fetal Medicine (SMFM) to sign a letter to the Colorado Medical Board, urging them to follow the evidence and to acknowledge that “abortion reversal” is unstudied and potentially dangerous.2
Clearly, confusion exists among state medical boards and legislatures, and, potentially, among healthcare providers. This commentary will review both the medical evidence regarding “abortion reversal” and the legal context so that providers can be better informed and communicate the best evidence to their patients. Although this commentary uses the term “abortion reversal” for clarity, we acknowledge that this term is neither accurate nor evidence-based, and that it holds its roots in the anti-abortion movement.
Medication Abortion
Medication abortion accounts for more than half of all abortions performed in the United States and that number likely is growing since the Supreme Court’s Dobbs decision reduced access to in-person abortion.3 The two medications approved by the U.S. Food and Drug Administration (FDA) more than two decades ago for medication abortion are mifepristone in combination with misoprostol. Mifepristone, taken orally, antagonizes the progesterone receptor. Misoprostol, taken buccally or vaginally, then is administered 24 to 48 hours after mifepristone to induce pregnancy expulsion. This combination, currently FDA-approved up to 10 weeks’ gestation, is both highly safe (with the risk of major adverse events as low as 0.16%) and highly effective (with 95% of abortions completed successfully).4,5 Mifepristone and misoprostol are more effective and safer when taken together. Up to half of the patients who take mifepristone alone continue their pregnancies.6
Individuals who initiate an abortion also are confident in their decision to terminate the pregnancy. Although the anti-abortion movement has built an unfounded narrative around the experience of “abortion regret,” regret is rare. Most patients feel relief following an abortion.7 Clinicians always should offer patients the full range of pregnancy options and should confirm the decision to seek an abortion. But, after an individual who chooses abortion begins the medication abortion process by taking mifepristone, less than 0.005% will change their mind prior to taking misoprostol and wish to continue the pregnancy. In this rare clinical situation, the current best evidence is for expectant management.
However, in 2012, Delgado et al reported a case series of six patients who took mifepristone, but instead of completing the abortion by taking misoprostol, took progesterone to “reverse” the effects of the mifepristone.8 This series, which lacks a control group, oversight by an institutional review board, documentation of informed consent, or information on medication dosing and adverse events, reports that four out of six patients continued their pregnancies. Despite serious limitations, the case series was published in 2012.
In response, Grossman et al conducted a systematic review of the available evidence on the effectiveness of ingesting progesterone after mifepristone to stop an abortion in 2015. They compared this intervention to expectant management with fetal surveillance, or “usual care.” The review found “no credible evidence” that taking progesterone after mifepristone improved the rates of continuing pregnancy compared to expectant management.6
Laws and Lack of Evidence
Despite this lack of evidence, state legislatures in the United States began to propose and pass bills requiring that physicians inform all patients seeking medication abortion that the process is “reversible” with the administration of progesterone. Such laws force physicians to provide information that is both medically inaccurate and irrelevant to the overwhelming majority of individuals seeking abortion, most of whom have no desire to stop the effects of mifepristone. Many such bills were proposed, and many have passed successfully.9
Unfortunately, lawmakers exploited the lack of high-quality evidence around “abortion reversal” to pass such bills. To fill this gap in evidence, Creinin et al began recruiting for a randomized controlled trial to determine the efficacy and safety of taking progesterone after mifepristone to stop the medication abortion process. The study planned to enroll 40 participants already seeking abortion. All participants would take mifepristone and then be randomized to take either progesterone or placebo. Two weeks later, all participants would undergo a procedural abortion. The study’s primary outcome was continued pregnancy after two weeks. Secondarily, the study looked at side effects and safety, particularly hemorrhage and emergency treatment.
The study stopped enrollment after 12 patients because of safety concerns, including three hemorrhages requiring emergency services. Unlike the rare risk profile associated with medication abortion using a combination of mifepristone and misoprostol, three hemorrhages out of 12 enrolled participants is not a rare outcome. In the study’s 2020 publication in Obstetrics and Gynecology, the team concluded that they could not determine the efficacy of progesterone for mifepristone antagonization as a result of safety concerns, in particular a concern of hemorrhage, when mifepristone is given without subsequent misoprostol. The paper concluded, “For now, such a treatment is experimental and should be offered only in institutional review board-approved human clinical trials to ensure proper oversight.”10
The findings from Creinin et al’s study subsequently were cited in litigation intended to block “abortion reversal” laws. Although the study did not stop such legislation
from moving forward entirely, it did slow the progress and played an important role in the Colorado bill intended to ban the practice. The study is a powerful example
of research as advocacy. Immense credit is due to the study’s participants, who took on real personal risk to provide higher-quality evidence around this dangerous practice.
The Role of the Physician
Understanding and communicating the real risks of “abortion reversal” to patients is of utmost importance. Patients place high levels of trust in their providers and are likely to follow provider recommendations. Both the passage of “abortion reversal” laws that require physicians to provide medically inaccurate and potentially dangerous information and a lack of laws banning the “abortion reversal” practice erode the doctor-patient relationship. Laws that perpetuate misinformation in either direction undermine a physician’s ethical duty to provide the best evidence to their patients.
The practicing physician should understand that “abortion reversal” is based on an anti-choice narrative comprised of poor-quality and even unethical evidence. The only high-quality evidence used to assess this practice led to dangerous outcomes for patients, including high rates of hemorrhage and the need for emergency care. Patients deserve to be informed of the lack of evidence and associated risks. Therefore, ACOG, SFP, and SMFM all argue in their letter to the Colorado Medical Board that “abortion reversal” is “misleading and can be dangerous to the physical and mental health of patients.”
REFERENCES
- SB23-190 draft. Rules and regulations regarding generally accepted standards of medical practice regarding pregnancy-related services. https://docs.google.com/document/d/1u7VN_r6mQNB5aVrpApIX8ogOzjLA9yho/edit
- Society of Family Planning. Re: 46 Colo. Reg. 157-58, Proposed rules and regulations regarding generally accepted standards of medical practice regarding pregnancy-related services. Aug. 2, 2023. https://societyfp.org/wp-content/uploads/2023/08/ACOG-SMFM-SFP-Comment-on-46-Colo.-Reg.-157-58-Proposed-Rules-and-Regulations.pdf
- Jones RK, Kirstein M, Philbin J. Abortion incidence and service availability in the United States, 2020. Perspect Sex Reprod Health 2022;54:128-141.
- Cleland K, Creinin MD, Nucatola D, et al. Significant adverse events and outcomes after medical abortion. Obstet Gynecol 2013;121:166-171.
- Chen MJ, Creinin MD. Mifepristone with buccal misoprostol for medical abortion: A systematic review. Obstet Gynecol 2015;126:12-21.
- Grossman D, White K, Harris L, et al. Continuing pregnancy after mifepristone and “reversal” of first-trimester medical abortion: A systematic review. Contraception 2015;92:206-211.
- Rocca CH, Samari G, Foster DG, et al. Emotions and decision rightness over five years following an abortion: An examination of decision difficulty and abortion stigma. Soc Sci Med 2020;248:112704.
- Delgado G, Davenport ML. Progesterone use to reverse the effects of mifepristone. Ann Pharmacother 2012;46:e36.
- Redd SK, AbiSamra R, Blake SC, et al. Medication abortion “reversal” laws: How unsound science paved the way for dangerous abortion policy. Am J Public Health 2023;113:202-212
- Creinin MD, Hou MY, Dalton L, et al. Mifepristone antagonization with progesterone to prevent medical abortion: A randomized controlled trial. Obstet Gynecol 2020;135:158-165.
