Can a medication abortion be reversed?

Progesterone plays a critical role in the normal functioning of the human female reproductive system. It activates uterine progesterone receptors (see “Activation” figure), promotes placental development, prepares the uterus for embryo implantation,1 and inhibits uterine contractions.2 Mifepristone is a progesterone antagonist. It binds more aggressively to uterine progesterone receptors than progesterone but does not activate the receptor. The primary effect of mifepristone in medication abortion is to cause a separation of the decidua basalis from the trophoblast, which results in the death of the embryo.3 Misoprostol (aka Cytotec) is a prostaglandin E1 analogue that causes cervical softening and uterine contractions, expelling the embryo.4 

In October 1984, scientists working on the chemistry, pharmacology, and clinical applications of mifepristone came together at a conference in Bellagio, Italy, to review their results. Researchers from French pharmaceutical company Roussel Uclaf, inventors of mifepristone, published a study of the biochemical profile of mifepristone at the conference. The study authors, M. Moguilewsky and D. Philibert, stated that mifepristone is a potent progesterone antagonist because it can aggressively inhibit progesterone binding to the uterine progesterone receptors (see Inhibition figure).5 

The action of mifepristone described in the study is an example of competitive inhibition which is the ability of one chemical substance (e.g., mifepristone) to inhibit the effect of another (e.g., progesterone) by competing with it for binding (e.g., uterine progesterone receptor binding). Mifepristone competitive inhibition can be reversed by adding more progesterone, which increases the chances of progesterone and uterine progesterone receptor (PR) binding. Thus the Roussel Uclaf study provides a pharmacological foundation for Abortion Pill Rescue (APR) therapy. 

A 2023 study assessed the ongoing pregnancy rate for medication abortion patients who received depot medroxyprogesterone (DMPA) injection on the same day as mifepristone compared with those who did not. Among 7,296 medication abortion patients, 225 elected to receive DMPA injections concurrently with mifepristone; the mean gestational age was 50 days. The study found that 10.6% of DPMA patients had ongoing pregnancies compared with 3.0% control patients (p<0.001).6 This study supports the contention that progesterone can inhibit mifepristone effectiveness and increase the continuing pregnancy rate.

The American College of Obstetrics and Gynecology (ACOG) Practice Bulletin 225 states that “Patients who select depot medroxyprogesterone acetate (DMPA) for contraception should be counseled that administration of DMPA on day 1 of the medication abortion regimen may increase the risk of ongoing pregnancy.”7 The ACOG recommendation supports Abortion Pill Rescue therapy.

Animal studies have also demonstrated the reversibility of mifepristone’s effect by increasing progesterone concentration. Research published in 2023 by Camilleri and Sammut studied the reversal of mifepristone-induced pregnancy termination in a rat model.8 Researchers divided female Long-Evans rats into three groups: Control group (no mifepristone, no progesterone), termination group (mifepristone only), reverse group (mifepristone followed by progesterone).

The study found that progesterone administration following initiation of mifepristone-induced pregnancy termination inhibited the abortion process in 81% of the female rats in the reverse group. This study improves upon the preclinical research by Yamabe et al.9 because it administered progesterone following mifepristone-induced pregnancy termination (indicated by weight loss and uterine bleeding) instead of simultaneous administration. In addition, this study used ultrasound at the end of gestation (day 21) to confirm pregnancy and measure fetal heart rate.

NEXT: Is APR Therapy Safe for Women?

  1. Coomarasamy, A., H. Williams, E. Truchanowicz, P. T. Seed, R. Small, S. Quenby, P. Gupta, et al. 2015. “A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.” New England Journal of Medicine 373 (22): 2141‐2148. https://doi. org/10.1056/NEJMoa1504927 ↩︎
  2. Scarpin, Katherine M., J. Dinny Graham, Patricia A. Mote, and Christine L. Clarke. 2009. “Progesterone Action in Human Tissues: Regulation by Progesterone Receptor (Pr) Isoform Expression, Nuclear Positioning and Coregulator Expression.” Nuclear Receptor Signaling 7 (December): e009. https://doi.org/10.1621/nrs.07009. ↩︎
  3. AAPLOG. 2022. “The Reversal of the Effects of Mifepristone by Progesterone, Practice Guideline 6.” https://aaplog.org/wp-content/uploads/2023/01/ PG-6-Reversal-of-the-Effects-of-Mifepristone- by-Progesterone.pdf. ↩︎
  4. ACOG. 2020. Medication Abortion Up to 70 Days of Gestation. https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/10/medication-abortion-up-to-70-days-of-gestation. ↩︎
  5. Baulieu E. E., Segal S. J. 1985. The Antiprogestin Steroid RU 486 and Human Fertility Control. Proceedings of a Conference on the Antiprogestational Compound RU486. Oct 23-25. Bellagio, Italy. Reproductive Biology. Published in the series Reproductive Biology. 1984. Sheldon Segal Series Editor. Plenum Press. https://link.springer.com/book/10.1007/978-1-4684-1242-0. ↩︎
  6. Carroll, Al, Am Strauss, Nm Philipps, Kd Kaczmarczik, Z Shakur, G Ramirez, Tr Klc, Km Tessier, and Cm Boraas. 2023. “CONCURRENT ADMINISTRATION OF DEPOT MEDROXYPROGESTERONE ACETATE WITH MIFEPRISTONE MAY DECREASE MEDICATION ABORTION EFFICACY: A RETROSPECTIVE COHORT STUDY.” Contraception 127 (November): 110192. https://doi.org/10.1016/j.contraception.2023.110192. ↩︎
  7. AAPLOG. 2022. “The Reversal of the Effects of Mifepristone by Progesterone, Practice Guideline 6.” https://aaplog.org/wp-content/uploads/2023/01/PG-6-Reversal-of-the-Effects-of-Mifepristone-by-Progesterone.pdf. ↩︎
  8. Camilleri, Christina, and Stephen Sammut. “Progesterone-Mediated Reversal of Mifepristone-Induced Pregnancy Termination in a Rat Model: An Exploratory Investigation.” Scientific Reports, vol. 13, no. 1, July 2023, p. 10942. www.nature.com, https://doi.org/10.1038/s41598-023-38025-9. ↩︎
  9. Yamabe, S., et al. “[The effect of RU486 and progesterone on luteal function during pregnancy].” Nihon Naibunpi Gakkai Zasshi, vol. 65, no. 5, May 1989, pp. 497–511. PubMed, https://doi.org/10.1507/endocrine1927.65.5_497. ↩︎