There is increasing evidence that many in the elite of the “reproductive rights” movement are pro-abortion rather than pro-choice. These elite advocates attempt to influence public opinion and public policy through the mouthpiece of organizations such as Planned Parenthood and NARAL. However, they are also embedded in, ostensibly, apolitical medical organizations such as the American College of Obstetrics and Gynecology (ACOG), the American Medical Association (AMA), and the New England Journal of Medicine (NEJM).
Perhaps the best illustration of this unfolding reality is the attempt to scuttle any progress on medication abortion “reversal” bills in state legislatures across the country. If Planned Parenthood, NARAL, ACOG, and the AMA were truly interested in providing women with choice, they would do everything to support women who choose to parent/adopt, as well as though who chose abortion. They would not preference one choice over another. However, in the instance when a woman has a wrenching change of heart during the two day medication abortion process, they are decidedly against choice. They are unwilling to contemplate any therapy to reduce the chance of a completed abortion. This is consistent with a pro-abortion rather than a pro-choice orientation.
During a medication abortion, a woman takes the first abortion pill, mifepristone, on day 1, and then the second abortion pill, misoprostol, 24-48 hours later. Many women have changed their mind about abortion after taking the first pill, but before taking the second. Reproductive rights activists refuse to believe these women exist, much less explore the possibility of mitigating the effects of the first of two abortion pills. Fortunately, prolife researchers in several countries have tried to address the plight of these women by devising protocols to inhibit the effects of mifepristone and increase the likelihood that a pregnancy will continue.
In 2019, North Dakota passed an “abortion reversal bill” (HB 1336) that is similar to bills introduced in other state legislatures (including Colorado’s).(1) The bill asks physicians, as part of the informed consent process, to let patients know “that it may be possible to reverse the effects of an abortion-inducing drug, if she changes her mind, but time is of the essence”. At the behest of the American Medical Association (and others), a federal district court has recently issued a preliminary injunction to block enforcement of the law.(2) AMA President Patricia Harris stated that “with this ruling, physicians in North Dakota will not be forced by law to provide patients with false, misleading, nonmedical information about reproductive health that contradicts reality and science.” Planned Parenthood, NARAL, and ACOG, along with numerous media outlets denounced the law as propaganda that had no scientific basis. They have testified in legislatures across the country against abortion informed consent legislation. NEJM previously had published an editorial “Abortion ‘Reversal’ – Legislating without Evidence” deploring the efforts by state legislatures across the country to facilitate a dialogue on mitigating the effect of abortion drugs in informed consent legislation.(3)
So how strong is the evidence that medication abortion could be “reversed”? Are the protocols used to moderate the impact of mifepristone “quackery” as critics suggest? To answer those questions we need to wade into the scientific process and how physicians weigh evidence when providing advice to patients.
The fact is that most of what physicians recommend to patients reflects expert opinion which is the lowest level of clinical evidence. The highest level of evidence is derived from “randomized, double-blind, placebo-controlled trials”. Unfortunately, only a small fraction of any physician’s practice is governed by this level of evidence. The remainder of a physician’s practice is informed by lesser degrees of clinical evidence including from a contemporary series of cases compared to historical controls or lesser quality clinical trials. The evidence for abortion “reversal” falls into this latter category.
Every good science-based medical therapy starts with a plausible scientific justification. Progesterone is the hormone that stimulates the lining of the uterus to grow and support the developing pregnancy. Mifepristone avidly attaches to progesterone receptors in the lining of the uterus and thereby interferes with the action of progesterone to maintain the pregnancy.(4) The abortion “reversal” process involves flooding the body with additional progesterone to dislodge mifepristone from progesterone receptors and allow progesterone to exert its beneficial effects on the uterus.5 The “reversal” protocols administer abundant progesterone in either an oral or injectable form.
Ideally, before pursuing a trial of a new therapy in humans, it is best to look at animal models to find evidence to support the approach. In 1989, a Japanese researcher demonstrated that giving progesterone to pregnant rats treated with mifepristone allowed 100% of the fetal rats to survive compared to only 33% survival in rats given mifepristone alone.(6) This would suggest that at least in one animal model, progesterone can antagonize the effect of mifepristone.
There has also been at least one study published in the contraceptive literature which may have some bearing on the effects of supplemental progesterone administration to interfere with the efficacy of medication abortions in humans. In a multinational randomized trial, women who received depot progesterone (as a long term contraceptive) at the time of mifepristone administration during a medication abortion were 4 times more likely to have a continued pregnancy compared to the women who did not.(7)
The use of progesterone in early pregnancy has a long and safe history. It has been used for decades early in pregnancy in women with a history of recurrent miscarriage.8 Only recently was it determined that progesterone is largely ineffective to prevent miscarriages, except in women with a history of multiple miscarriages.(9-10) Nonetheless, the use of progesterone for threatened abortion is not a new concept in humans.
Based on the scientific plausibility and known safety of progesterone administration in early pregnancy, Dr. George Delgado began offering women, who had changed their mind after taking mifepristone, high dose progesterone. In 2018, Dr. Delgado published his case series which included 547 women.(5) He found that 64-68% of women who took high dose oral/injectable progesterone had a continued pregnancy. This was much higher than historical controls of approximately 25%. Others have published small case reports supporting the conclusion that high dose progesterone might be an effective therapy to preserve a pregnancy after the administration of mifepristone.(11)
Critics have pounced on this data in efforts to discredit its conclusions. They point out that the efficacy of mifepristone as a single agent abortifacient drug depends on the gestational age of the embryo/fetus. Dr. Delgado’s protocol clearly was less successful very early in pregnancy and more successful later. Therefore, giving progesterone may be no better than placebo. However, when you adjust Dr. Delgado’s experience for gestational age, a continued pregnancy is still nearly twice as likely after progesterone.(3) The kicker - because of the small sample size of the historical controls used by critics –is that the results are not “statistically significant”. By low balling (5,12) the success of mifepristone historically, critics attempt to completely dismiss any potential therapeutic value of progesterone administration.
The bottom line is that there is a scientifically plausible rationale to administer progesterone to “reverse” the effects of mifepristone. There is animal data supporting this approach. There is data in the contraceptive literature demonstrating that progesterone interferes with medication abortions. And now there is a large case series suggesting that progesterone administration after mifepristone leads to a higher percentage of continued pregnancies compared to historic controls. While this is not high level evidence, clearly, this is not “no evidence” as NARAL, Planned Parenthood, ACOG, AMA, and NEJM would have you believe. To say otherwise betrays an intellectual dishonesty that is unbecoming these professional organizations.
The next step is to gather randomized trial data to lend further support to the use of progesterone to “reverse” the effects of mifepristone in a medical abortion. Dr. Mitchell Creinin from the University of California, Davis, is an abortion rights advocate. He has begun a trial in which 40 women will be randomized to be given oral progesterone or placebo after mifepristone administration to assess the efficacy of the “reversal” protocol.(13) Typically, you would design the study protocol to maximize the chance to demonstrate efficacy of progesterone as a mifepristone antagonist. Unfortunately, the trial protocol begins the progesterone the day after mifepristone which might diminish its effectiveness and lead to inconclusive results. Furthermore, the small sample size will make it hard to demonstrate the statistical significance of any benefit. Nonetheless, he should be applauded for at least attempting to address the clinical question.
Having demonstrated that there is indeed low to moderate level evidence to support giving progesterone to antagonize the effects of mifepristone, it is perfectly reasonable that states include this tentative information in their abortion informed consent laws – otherwise abortion providers would likely ignore it. When making policy that can potentially save the life of another human being, the medical community and legislators should not require high level evidence before they act. During testimony on Colorado’s “Abortion Pill Reversal Information Act” in 2017, three women tearfully recalled their own change of heart midway through their medication abortions. They were extremely grateful that all three delivered healthy babies after utilizing the progesterone “reversal” protocol. They passionately made the case that this information should be available to other women contemplating medical abortions so that they indeed can make informed choices.
The reproductive rights elite including NARAL, Planned Parenthood, ACOG, AMA, and NEJM show little interest, much less compassion, for women who choose life during a medical abortion. It is time the American public recognizes that they are nominally pro-choice, but in practice, firmly pro-abortion.
References:
1) “North Dakota House Bill 1336”. 2019. Retrieved 9/17/2019 from https://www.legis.nd.gov/…/66-2…/documents/19-0517-03000.pdf.
2) “Court blocks law that would force physicians to mislead patients”. September 10, 2019. Retrieved September 17, 2019 from https://www.ama-assn.org/…/court-blocks-law-would-force-phy….
3) Grossman D, and White K, Abortion “Reversal” – Legislating without Evidence”. New England Journal of Medicine 2018; 379(16): 1491-1493.
4) Soon JA, et.al., Medications used in evidence-based regimens for medical abortion: An Overview. J Obset Gynaecol Can 2016: 38(7): 636-645.
5) Delgado G, et.al., A case series detailing the successful reversal of the effects of mifepristone using progesterone. Issues in Law & Medicine 33(1): 21-31.
6) Yamabe S, et.al., The effect of RU486 and progesterone on luteal function during pregnancy. Nihon Naibunpi Gakkai Zasshi 1989; 65(5): 497-511.
7) Raymond EG et.al., Effects of depot medroxyprogesterone acetate injection timing on medical abortion efficacy and repeat pregnancy. Obstetrics & Gynecology 128(4): 739-745.
8) Hass DM et.al., Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology. Cochrane Database Syst Rev 2018; Oct 8;10CDC003511.doi: 10.1002/14651858.CD003511.pub4.
9) Coomarasamy A, et.al., A randomized trial of progesterone in women with recurrent miscarriages. NEJM 2015; 373(22): 2141-2148.
10) Coomarasamy A.J., et.al., A randomized trial of progesterone in women with bleeding early in pregnancy. NEJM 380(19): 1815-1824.
11) Garratt D and Turner JV, Progesterone for preventing pregnancy termination after initiation of abortion with mifepristone. European Journal of Contraception and Reproductive Health Care 2017; 22(6): 472-475.
12) Van Look PFA and Bygdeman M, Medical approaches to termination of early pregnancy. Bulletin of the World Health Organization 1989; 67(5): 567-575.
13) “SFP Research Grant Awards”. 2018. Retrieved September 17, 2019 from https://www.societyfp.org/research-and-grants/grants-funded.