[Post-publication update, 4/23/23 – (1) I clarified the results of the 2018 Delgado study. Previously I had stated the study found up to 68% success rate for APR. The average rate was 48%, with different methods of progesterone administration having different success rates up to 68%. (2) I added a note about method limitations in the Delgado study regarding which women were included in APR success calculations.]
How do abortion pills and abortion pill reversal work?
The abortion pill regimen commonly involves a woman (1) taking mifepristone, which blocks progesterone and breaks down the uterine lining, (2) waiting about 48 hours, and then (3) taking misoprostol, which causes contractions. In this way, abortion pills disconnect embryos from their source of oxygen and nutrients, and then expel them from women’s bodies.
Abortion Pill Reversal (APR) is the process of giving supplemental progesterone to women who have taken mifepristone but haven’t yet taken misoprostol, and have decided they don’t want to go through with the abortion. The theory is that if there’s enough supplemental progesterone, it will outcompete mifepristone to bind to the relevant receptors, thus keeping the uterine lining and the embryo’s connection to it intact.
[Read more – How abortion pill reversal works scientifically]
In mid-April, Colorado attempted to implement SB 23-190, a bill that conditionally prohibits healthcare providers from offering APR unless and until the Colorado medical board, state board of nursing, and state board of pharmacy each separately find that APR is a generally accepted standard of practice. (I say “attempted to implement” because, as of my drafting this post, a federal judge had issued a temporary restraining order.)
Why would pro-choice groups oppose APR?
Pro-choice groups and abortion advocates argue that APR is scientifically unproven and potentially dangerous. Here are some example quotes:
Claims regarding abortion “reversal” treatment are not based on science and do not meet clinical standards. … So-called abortion “reversal” procedures are unproven and unethical.ACOG Bulletin “Facts Are Important: Medication Abortion “Reversal” Is Not Supported By Science
The anti-abortion movement’s push for abortion reversal to be tested on pregnant people is clearly disregarding human dignity and using these individuals as test subjects to further their agenda.Planned Parenthood Action, “The Myth of Abortion ‘Reversal'”
Even if the concept of “reversal” is biologically plausible, rigorous testing of the protocol should be required in order to determine whether it is effective and safe.ANSIRH, “Medication abortion ‘reversal’
Is there evidence that APR works?
There have been animal studies finding progesterone counteracts mifepristone. For example, this experiment on rats concluded “progesterone can spare the effect of RU [mifepristone] on the corpus luteum during pregnancy.” But of course rats aren’t humans.
In humans specifically, supplemental progesterone has long been used to decrease incidence of miscarriage. However in the case of miscarriage, there’s no mifepristone present to counteract.
The real question is how supplemental progesterone may work when competing with mifepristone in the same (human) system.
There is an observational study: “A case series detailing the successful reversal of the effects of mifepristone using progesterone,” George Delgado et al, 2018. The case series found that, of the women who first took mifepristone and then took supplemental progesterone, 48% “reversed” their abortions, meaning they went on to have live births instead. (This statistic incorporates different methods of taking progesterone, which ranged from 32% live birth rate when women received progesterone via vaginal suppository to 68% live birth rate when they received a high dosage of progesterone orally.) By comparison, when embryos are exposed to mifepristone only, and no supplemental progesterone, only between 10-23% survive.
The pro-choice side counters that this study is poor quality for a couple reasons. One reason is that the study doesn’t include a control group. The study’s authors instead compared reversal rates to the survival rates of embryos exposed to mifepristone documented in other literature.
The lead researcher, Dr. George Delgado, touched on this point in his interview with Rewire News Group:
Rewire.News: I just want to push back a minute though, because it hasn’t been proven. I mean it was a case series. So it suggests that yes, there is this thing that’s happening, but you know with research you can’t prove …
Dr. Delgado: What does it take to prove then?
Rewire.News: Well it would probably take a study or at least several studies of the kind that you said that you don’t want to do, where when people come into this, they either are going to have a placebo or the treatment. And that way you could compare groups …
Dr. Delgado: …So let’s say.
Rewire.News: But even that wouldn’t be proof…
Dr. Delgado: … Let’s say you had a heart attack, right. Yes. If you had a heart attack and the people in this room went to do CPR on you. What if I told him, “Stop, don’t do CPR. There is no randomized controlled placebo trial proving that CPR works.” Would you want me to do that? I don’t think so. You would want me to do CPR right away because you know that there’s no better treatment when somebody has a heart attack outside of a hospital and their heart stops. And that’s the best way to start it. Wouldn’t it be unethical to put you in a placebo controlled trial to mark you and say, “You’re the one who did not get CPR.” We would just put our hands on your chest and not push in. Wouldn’t that be unethical, to let you die?
Same thing with these women who want reversal .… It would be unethical and unfair to those women who were assigned to the placebo group. And just because we don’t yet have a randomized controlled trial doesn’t mean that the study we’ve done now is valueless. It has a lot of value. The next study of course will be more powerful and we’re planning that, but until we get to there, since we don’t have another alternative treatment, then for sure we should go with this trial, which shows safety and effectiveness.Rewire News Group, “Abortion Pill ‘Reversal’ Doctor: I See It Becoming the ‘Standard of Care’”
In other words, Dr. Delgado argues that, while a case series isn’t the most rigorous form of evidence, it still is a form of evidence. It’s incorrect to suggest there is “no evidence” that APR works. And if a woman takes mifepristone and then decides she wants to keep her child, it would be unethical to deny her the option to try.
Pro-choice groups have also argued the study is poor quality because it included women who initiated supplemental progesterone only after ultrasound confirmation of an ongoing pregnancy; this selection could artificially inflate the success rate of APR because women who have ongoing pregnancies 2-3 days after taking mifepristone are more likely to have had mifepristone failure regardless of whether they also take supplemental progesterone. On the other hand, the study also included women who took progesterone without confirming ongoing pregnancy first, meaning some women would have already experienced intrauterine death before they attempted APR. This inclusion would artificially deflate the success rate of APR. Both of these inclusions lend to the uncertainty of the results.
Is there evidence that APR is dangerous?
For quite a while the argument that APR could be dangerous was based on the idea that it is unproven and not rigorously tested. In other words, claims of danger weren’t based on evidence of danger, but rather on alleged absence of evidence of safety.
However, in 2020 researchers out of UC Davis attempted to test APR in a randomized controlled study. They planned to enroll 40 patients between 6-9 weeks gestation who wanted to abort. They would give enrollees mifepristone, and then one group would take progesterone and the other would take a placebo. Participants were automatically scheduled for surgical abortions approximately 2 weeks after initiating the study, in case the mifepristone failed and/or the APR was successful.
After enrolling only 12 patients, the study was cancelled due to safety concerns: three patients experienced severe hemorrhaging. Abortion rights organizations point to this result as evidence that APR is dangerous.
Pro-life groups have been quick to point out that more patients in the placebo group (2 women) than the progesterone group (1 woman) experienced severe hemorrhaging, and only in the placebo group did a patient require a transfusion. They also point out that women who took progesterone were twice as likely to have continuing pregnancies as women who took only the placebo (4 women vs 2 women). Pro-lifers argue this study suggests that APR works, and that abortion pills, not APR, are dangerous – specifically it is dangerous to take mifepristone and not follow up with misoprostol.
[Read a more detailed breakdown of the study in this Twitter thread by Dr. Calum Miller]
If this is true, APR is dangerous in the narrower sense that it involves women choosing not to finish the abortion pill regimen, and abortion pills taken incompletely are dangerous. This is an interesting conclusion, given abortion proponents’ insistence that the pills are so safe they should be available not only via telemedicine, but also via advance provision (prescribed before a patient is even pregnant) and, ultimately, available over the counter. Those promoting abortion pills are apparently unconcerned about the pills falling into the wrong hands (abusers, women with contraindications) and/or being used without medical supervision.
[Read more – The risks of telemedicine abortion]
If APR is dangerous, should women be prohibited from attempting it?
Women are not required to abort even for high-risk pregnancies. Even under the premise that APR is dangerous, it’s difficult to see the argument that women can’t opt to try APR anyway, provided they have properly informed consent. If a woman can opt to continue a pregnancy even when it is a serious threat to her health, why wouldn’t she likewise be able to opt to “reverse” an abortion with similar or less risk?
So now what?
Until Colorado’s SB 23-190, no state has attempted to ban APR. But as the post-Roe legal and social landscapes around abortion keep shifting, it’s anyone’s guess how each state will handle the option of supplemental progesterone.