What is the continuing pregnancy rate after APR?

Since 2012, three case series (Delgado 20121; Garratt 20172; Delgado 20183), a randomized controlled trial (Creinin 20204), and a single-arm clinical trial (Turner 20235) have studied Abortion Pill Reversal (APR) in humans. The five studies investigated the continuing pregnancy rate (CPR) for mifepristone followed by progesterone using 12 different progesterone dosing and delivery regimens. The chart on this page presents the results of these studies.

The vertical axis shows the continuing pregnancy rate reported by each study, broken down by dosing and delivery regime. For instance, Delgado 2018e shows the CPR for oral administration of micronized progesterone, whereas Delgado 2018f shows the CPR using intramuscular injection (refer to Dataset 2 for details). The horizontal red line indicates the ā‰¤25% CPR for mifepristone alone for ā‰¤49 days gestation. See ā€œWhat is the continuing pregnancy rate after mifepristone alone?ā€ for an analysis of how we arrived at the ā‰¤25% number.

Animal Studies

Animal studies have also demonstrated the reversibility of mifepristoneā€™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.6 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.7 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.

US FDA Mifepristone Pharmacological Review

The United States Food and Drug Administration (US FDA) Mifepristone Drug Approval Package, dated September 28, 2000, documented the effectiveness of APR in rabbits. Refer to the Mifepristone Pharmacological Review, Part 2, at the top of page 17 (see excerpt below).

Bellagio Italy Studies

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, “Biochemical Profile of RU 486,” 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.8 

The action of mifepristone described in the study is an example of competitive inhibition9 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 binding. Thus the Roussel Uclaf study provides a pharmacological foundation for Abortion Pill Reversal therapy. 

Depot Medroxyprogesterone Study

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).10 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 ā€œPatients 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.ā€11 The ACOG recommendation supports Abortion Pill Reversal therapy.

Randomized Controlled Trials versus Observational Studies

The underlying data for the chart above comes from two types of evidence: randomized controlled trials and observational studies. Many clinicians and researchers consider randomized controlled trials (RCT) the ā€œgold standardā€ for medical evidence. However, Dr. Thomas R. Frieden, former director of the Centers for Disease Control and Prevention, argues that non-RCT data sources, such as observational studies, can be as good, and sometimes better than RCTs for making evidence-based health policy decision making.12

Many systematic reviews have found no difference in treatment effect estimates between RCTs and observational studies, in support of Dr. Frieden’s point of view. For instance, in 2024, Toews et al. compared data from 2869 RCTs (N=3,882,115) and 3924 observational studies (N=19,499,970). The authors found ā€œno difference or a very small difference between effect estimates from RCTs and observational studies.ā€13 In 2014, Anglemyer et al. analyzed the results from over 1000 RCTs and over 1000 observational studies. They concluded, ā€œThere is little evidence for significant effect estimate differences between observational studies and RCTs, regardless of specific observational study design, heterogeneity, or inclusion of studies of pharmacological interventions.ā€14

Well-designed RCTs exhibit internal validity. A study with internal validity has medical evidence that supports a strong claim about cause and effect. RCTs use randomization, which minimizes the risk of bias by confounding.15 RCT results may have limited generalizability if the study sample does not represent the general population.16 RCTs are often expensive to perform, resulting in a small sample size. RCTs may be unethical for questions such as when equipoise does not exist.

There has been an increase in the use of evidence obtained from observational studies.17 Well-designed observational studies can offer superior external validity compared to RCTs. A survey with external validity has medical evidence that applies to the general population.18 However, observational studies do not randomize interventions and may exhibit poor internal validity due to the risk of confounding bias.19 Observational studies are rarely unethical to perform, tend to have larger sample sizes, and are often less costly than RCTs.

NEXT: Refer to the Studies page to view APR research collections.

  1. Delgado, George, and Mary L. Davenport. ā€œProgesterone Use to Reverse the Effects of Mifepristone.ā€ Annals of Pharmacotherapy, vol. 46, no. 12, Dec. 2012, pp. 1723ā€“1723. DOI.org (Crossref), https://doi.org/10.1345/aph.1R252. ā†©ļøŽ
  2. Garratt, Deborah, and Joseph V. Turner. ā€œProgesterone for Preventing Pregnancy Termination after Initiation of Medical Abortion with Mifepristone.ā€ The European Journal of Contraception & Reproductive Health Care, vol. 22, no. 6, Nov. 2017, pp. 472ā€“75. DOI.org (Crossref), https://doi.org/10.1080/13625187.2017.1412424. ā†©ļøŽ
  3. Delgado, George, et al. ā€œA Case Series Detailing the Successful Reversal of the Effects of Mifepristone Using Progesterone.ā€ Issues in Law & Medicine, vol. 33, no. 1, 2018, pp. 21ā€“31. https://pubmed.ncbi.nlm.nih.gov/30831017/ ā†©ļøŽ
  4. Creinin, Mitchell D., et al. ā€œMifepristone Antagonization With Progesterone to Prevent Medical Abortion: A Randomized Controlled Trial.ā€ Obstetrics & Gynecology, vol. 135, no. 1, Jan. 2020, p. 158. journals.lww.com, https://doi.org/10.1097/AOG.0000000000003620. ā†©ļøŽ
  5. Turner, Joseph V., Deborah Garratt, Lucas A. McLindon, Anna Barwick, and M. Joy Spark. 2023. ā€œProgesterone after Mifepristone: A Pilot Prospective Single Arm Clinical Trial for Women Who Have Changed Their Mind after Commencing Medical Abortion.ā€ Journal of Obstetrics and Gynaecology Research, November, jog.15826. https://doi.org/10.1111/jog.15826. ā†©ļøŽ
  6. Camilleri, Christina, and Stephen Sammut. 2023. Progesterone-Mediated Reversal of Mifepristone-Induced Pregnancy Termination in a Rat Model: An Exploratory Investigation. Scientific Reports 13 (1): 10942. https://doi.org/10.1038/s41598-023-38025-9. ā†©ļøŽ
  7. Yamabe S., Katayama K., Mochizuki M. 1989. The Effect of RU486 and Progesterone on Luteal Function During Pregnancy. Nihon Naibunpi Gakkai Zasshi 65 (5): 497ā€511. https://doi.org/10.1507/endocrine1927.65.5_497. ā†©ļøŽ
  8. Moguilewsky, M., and D. Philibert. 1985. ā€œBiochemical Profile of RU 486.ā€ In The Antiprogestin Steroid RU 486 and Human Fertility Control, edited by Etienne-Emile Baulieu and Sheldon J. Segal, 87ā€“97. New York, NY: Springer US. https://doi.org/10.1007/978-1-4684-1242-0_7. ā†©ļøŽ
  9. ā€œCompetitive Inhibition – an Overview | ScienceDirect Topics.ā€ https://www.sciencedirect.com/topics/medicine-and-dentistry/competitive-inhibition. ā†©ļøŽ
  10. Carroll, Anna L., Anna M. Strauss, Nicole M. Philipps, Kyra D. Kaczmarczik, Zahrah Shakur, Gerardo Ramirez, Tenley R. Klc, Katelyn M. Tessier, and Christy M. Boraas. 2024. ā€œEfficacy of Medication Abortion with Concurrent Initiation of Progestin Contraceptives: A Retrospective Cohort Study.ā€ Contraception 140 (December):110536. https://doi.org/10.1016/j.contraception.2024.110536. ā†©ļøŽ
  11. ā€œMedication Abortion Up to 70 Days of Gestation.ā€ https://www.acog.org/clinical/clinical-guidance/practice-bulletin/articles/2020/10/medication-abortion-up-to-70-days-of-gestation. ā†©ļøŽ
  12. Frieden, Thomas R. ā€œEvidence for Health Decision Making ā€” Beyond Randomized, Controlled Trials.ā€ New England Journal of Medicine, edited by Jeffrey M. Drazen et al., vol. 377, no. 5, Aug. 2017, pp. 465ā€“75. DOI.org (Crossref), https://doi.org/10.1056/NEJMra1614394. ā†©ļøŽ
  13. Toews, Ingrid, Andrew Anglemyer, John LZ Nyirenda, Dima Alsaid, Sara Balduzzi, Kathrin Grummich, Lukas Schwingshackl, and Lisa Bero. 2024. Healthcare Outcomes Assessed with Observational Study Designs Compared with Those Assessed in Randomized Trials: A Metaā€epidemiological Study. Cochrane Database of Systematic Reviews, no. 1. https://doi.org/10.1002/14651858.MR000034.pub3 ā†©ļøŽ
  14. Anglemyer, Andrew, Hacsi T. Horvath, and Lisa Bero. 2014. ā€œHealthcare Outcomes Assessed with Observational Study Designs Compared with Those Assessed in Randomized Trials.ā€ Cochrane Database of Systematic Reviews, no. 4. https://doi.org/10.1002/14651858.MR000034.pub2. ā†©ļøŽ
  15. Gaudino, Mario, Emilia Bagiella, Helena L. Chang, and Paul Kurlansky. 2022. Randomized Trials, Observational Studies, and the Illusive Search for the Source of Truth. The Journal of Thoracic and Cardiovascular Surgery 163 (2): 757ā€“62. https://doi.org/10.1016/j.jtcvs.2020.10.120. ā†©ļøŽ
  16. Bosdriesz, Jizzo R., Vianda S. Stel, Merel van Diepen, Yvette Meuleman, Friedo W. Dekker, Carmine Zoccali, and Kitty J. Jager. 2020. Evidenceā€based Medicineā€”When Observational Studies Are Better than Randomized Controlled Trials. Nephrology (Carlton, Vic.) 25 (10): 737ā€“43. https://doi.org/10.1111/nep.13742. ā†©ļøŽ
  17. Hong, Yoon Duk, Jeroen P. Jansen, John Guerino, Marc L. Berger, William Crown, Wim G. Goettsch, C. Daniel Mullins, Richard J. Willke, and Lucinda S. Orsini. 2021. Comparative Effectiveness and Safety of Pharmaceuticals Assessed in Observational Studies Compared with Randomized Controlled Trials. BMC Medicine 19 (1): 307. https://doi.org/10.1186/s12916-021-02176-1. ā†©ļøŽ
  18. Booth, C. M., and I. F. Tannock. 2014. Randomised Controlled Trials and Population-Based Observational Research: Partners in the Evolution of Medical Evidence. British Journal of Cancer 110 (3): 551ā€“55. https://doi.org/10.1038/bjc.2013.725. ā†©ļøŽ
  19. Bosdriesz, Jizzo R., Vianda S. Stel, Merel van Diepen, Yvette Meuleman, Friedo W. Dekker, Carmine Zoccali, and Kitty J. Jager. 2020. Evidenceā€based Medicineā€”When Observational Studies Are Better than Randomized Controlled Trials. Nephrology (Carlton, Vic.) 25 (10): 737ā€“43. https://doi.org/10.1111/nep.13742. ā†©ļøŽ