The Morning After Pill ella® is NOT an Abortifacient

And why you should care

Credit: ellaone.co.uk

Ulipristal acetate or UPA (trade name ella® or ellaOne®, with a lowercase e) is the “other” morning-after pill or emergency contraceptive, a.k.a post-coital contraceptive. Plan B, or levonorgestrel, is the one most commonly discussed in our lexicon as it was available first, tends to be easier to access, and, let’s be honest, “Plan B” as a name is a stroke of marketing genius.

A reader recently raised concerns that the new Trump administration might falsely claim that ulipristal acetate or UPA is an abortifacient and have it recategorized. This is a realistic concern and could affect people everywhere in America, not just in the states where abortion is banned. This is because the Trump administration can effectively ban most abortions without changing a single law; the playbook here involves enforcing the Comstock Act, a set of two laws, both more than one hundred years old, that ban the use of US mail or non-US mail couriers for abortion-related materials.

If this route for banning abortion has always been available, why be worried now? While it’s true that the Comstock Act has been previously considered unenforceable, on January 20, 2025, right-wing extremists will control all branches of the government, and so the unenforceable can easily move from a wish list to reality. And while someone might say, “Well, I’ll go pick up my UPA from the pharmacy; I don’t need it mailed,” pharmacies get their products by mail or courier. According to the Center for American Progress, the Department of Justice (DOJ) “has the authority to decide what punishment can be attached to a Comstock violation, including potential felony charges, severe monetary fees, loss of professional license, and prison time. Cumulatively, a far-right DOJ can destroy—from start to finish—the entire system of medication abortion via mail.” That the Comstock Act is on the table as an easier path to banning abortion without changing any laws isn’t any secret; in February of 2024, the New York Times reported that Jonathan F. Mitchell, one of the forces behind Project 2025, said, “We don’t need a federal ban when we have Comstock on the books.”

By the way, enforcing Comstock could also affect the ability of hospitals and clinics to get disposable instruments, like cervical dilators and suction catheters, that are used in many surgical abortions.

What is UPA?

It is a selective progesterone receptor modulator or SPRM, which means it can either stimulate and/or block progesterone receptors. Several compounds in this class are being studied for many conditions, such as uterine fibroids, endometriosis, breast cancer, and even menopause hormone therapy. If UPA is falsely labeled as an abortifacient, all research here will likely stop. Right-wing forced birth legislation can have a devastating ripple effect on medical research that has nothing to do with abortion, or even pregnancy, for that matter.

UPA blocks the LH surge, delaying or preventing ovulation. It is even better at blocking the LH surge than levonorgestrel (Plan B), but unlike Plan B, it also has an impact once the LH surge has started but before ovulation has occurred. While Plan B is considered to have an effect for 72 hours after unprotected intercourse, UPA has an effect for 120 hours or five days after unprotected intercourse. A good way to think about UPA is that it is more effective for longer than Plan B. UPA reduces the chances of getting pregnant after an episode of unprotected intercourse by about 80-85%.

Even when people have emergency contraception pills on hand, they are often underused. In one study, 45% of people who had them at home did not use them when they had unprotected intercourse. I suspect some people truly forget they have them. Look, I have purchased three different bottles of acetaminophen in the past 18 or so months because I keep thinking I don't have any at home, and now I have enough tablets to stock a small pharmacy. But I also suspect some people get the medication and, based on misinformation/propaganda they may have heard, mistakenly think the pills aren’t very effective or worry they may really be abortifacients. People have even told me that when they went to pick up the medication, they were misinformed about the pills being abortifacients by the pharmacist!

What About UPA and Abortion?

Since progesterone is essential for the establishment and maintenance of pregnancy, there have been concerns that as UPA blocks progesterone receptors, it could do more than prevent ovulation and actually interfere with the implantation of an embryo or harm an implanted embryo.

This was not an unreasonable question when UPA was first studied. After all, mifepristone, one of the drugs used for medication abortion, also blocks progesterone. Mifepristone, potency-wise, is approximately comparable mg for mg with UPA, and doses as low as 50 mg of mifepristone have been studied for medication abortion but were not pursued because the failure rate was too high, although it certainly wasn’t zero. If this were 1995 and someone was wondering if 30 mg of UPA could be an abortifacient, I’d probably say, “Hmmm, good question.” But it’s two-thousand and fucking twenty-four. Do you know what else we were doing in 1995? Going to Blockbuster to get fucking Batman Forever on videotape to watch on our VCRs. Just as watching movies at home has evolved a tad, so has the medical research on UPA. Apparently, the Republicans have no difficulty brushing up on applying a hundred-plus-year-old law, but availing themself of research from the past decade or so is just a bridge too far.

We do actually have researchers who have asked good questions and designed elegant studies to look at the potential impact of the dose of UPA used in emergency contraception on an embryo. While forced-birth politicians will undoubtedly ignore these studies, here is a summary of the research that tells us UPA is not an abortifacient:

• Animal studies show no effect of UPA on early embryo development.

• Human studies show no negative effect of UPA in the dose used for emergency contraception on the endometrium (uterine lining), although truthfully, whether this kind of study is valuable has been questioned by newer techniques.

• An elegant study where endometrial tissue from volunteers was sampled four days after the LH surge, and this tissue was then cultured in the lab to create a 3D model of the uterine lining that would be receptive to implantation (pretty cool!). Then, human blastocysts were introduced, and adding a dose of UPA equivalent to that used for emergency contraception had no impact on the blastocysts' ability to implant. Misoprostol did affect implantation (as expected), proving the value of this model. This study also looked at genes involved in the endometrium being receptive to embryo implantation and concluded there was no negative effect of UPA. Expect a ban on research with blastocysts once Trump is in power, stifling the ability to prove medications are not abortifacients and, of course, other very important research.

• In another study that used a different lab model, human endometrial cells cultured with human trophoblastic spheroids (a surrogate for the embryo) found no impact of UPA on the surrogate embryo attaching to the endometrium, but again, as expected, found an effect from mifepristone.

• In a prospective study, women who took UPA were evaluated with hormone levels and ultrasound so the investigators knew who took the medication before ovulation and who took it after ovulation. If UPA had an effect on those who took it after ovulation, then that might support an early abortion as a potential effect. UPA prevented 81% of pregnancies when taken before ovulation but did not have a statistically significant effect on the pregnancy rate when taken after ovulation.

• When ulipristal acetate fails and people get pregnant, there is no increased risk of miscarriage (from post-marketing surveillance).

This data obviously has limitations, not in a gaping-holes-in-the-literature kind of way, but rather, this is the literal best science can do because we are using animal models and indirect evidence. A direct study would involve recruiting a large number of women who want to take post-coital contraception and then randomize them to UPA or placebo, which is unethical, so, you know, that’s kind of a roadblock. There would also have to be enough people enrolled so there would be sufficient numbers of people who had taken the medication when it was too late to have an emergency contraception effect. The enrollees would also need to be tracked with ultrasounds and blood tests to know who took it after ovulation and then followed for 4-6 weeks to determine the pregnancy rates in both groups and the rate of early miscarriage. This would be a large and expensive study, but as it’s not ethical to give someone who wants emergency contraception a placebo, it’s really moot. Sometimes, indirect studies are the best we can do.

It’s also important to point out that no one has provided proof that UPA affects implantation, so it’s not as if we are dealing with major conflicting studies. The three things that often come up supporting UPA as an abortifacient have easy explanations:

• One study of the dose used as post-coital contraception resulted in a delay of development in the endometrium. People have wondered if this delay could affect a pregnancy trying to implant. Except…UPA delays ovulation, so a delay in endometrial development is expected. A later study proved just that, meaning there is no real delay. As mentioned above, whether these kinds of studies are even valuable is questionable.

• Another study suggests that some genes in the endometrium that may not be favorable to implantation could be triggered by UPA. This finding is contradicted by the study I mentioned above, which cultured endometrium and introduced a blastocyst; here, the researchers did not find those changes. How the endometrium might change with UPA when it isn’t exposed to pregnancy could well be different than when it is exposed to a pregnancy, and it’s the latter that actually matters.

• The ella® package insert is offered up as some kind of gotcha. It says, “When taken immediately before ovulation is to occur, ella® postpones follicular rupture. The likely primary mechanism of action of ulipristal acetate for emergency contraception is therefore inhibition or delay of ovulation; however, alterations to the endometrium that may affect implantation may also contribute to efficacy.” Package inserts are legal documents, not up-to-date reviews of the literature, and getting them changed is expensive and almost never worth it to the pharmaceutical company, given the time and effort involved. Also, this package insert was published in 2010, before the studies that show no impact were published.

Trying to get a radical ring-wing extremist to accept the science of how UPA works for post-coital contraception is akin to getting them to believe that dinosaurs and humans did not co-exist. Science cannot undo right-wing extremist dogma, and science can't possibly prevail where there is no reason or where reason is proactively ignored and where the goal is not better health but rather control. If I could shout this with the full force of my being into the face of the forced birthers salivating to gut abortion, I would, but it would be an exercise in futility because they are unmoved by facts. (But it would make me feel better for a few minutes).

I don’t think I’m being paranoid when I say if you live in the United States and you don’t have an IUD, contraceptive implant, or tubal ligation, and you have a uterus and are not in menopause, consider getting a couple of packs of UPA now. And if you have some at home, check the expiration date. Given the superiority of ulipristal acetate for emergency contraception over levonorgestrel, this is the best product to invest in keeping at home or on your person, but if it’s not an option, then go for levonorgestrel. If Plan B is levonorgestrel emergency contraception, think of ulipristal as Plan B+.

Because we have not always been at war with Eastasia (a reference to George Orwell’s novel 1984 and the government propaganda that constantly rewrote history so the government was never wrong), I want you to know the truth before my telling it becomes dangerous. To the best of our scientific ability, UPA is not an abortifacient, but whether that will mean anything after January 20, 2025, remains to be seen.

For more on emergency contraception and weight, check out this post: Should you double dose Plan B if you weigh more than 70 kg? I will be looking for more updates on this as well, as this post is 2 years old.

References

Li HWR, Resche-Rigon M, Bagchi IC, Gemzell-Danielsson K, Glasier A. Does ulipristal acetate emergency contraception (ella®) interfere with implantation? Contraception. 2019 Nov;100(5):386-390. doi: 10.1016/j.contraception.2019.07.140. Epub 2019 Jul 24. PMID: 31351035.

Prasad RN, Choolani M. Termination of early human pregnancy with either 50 mg or 200 mg single oral dose of mifepristone (RU486) in combination with either 0.5 mg or 1.0 mg vaginal gemeprost. Aust N Z J Obstet Gynaecol. 1996 Feb;36(1):20-3. doi: 10.1111/j.1479-828x.1996.tb02915.x. PMID: 8775244.

Li HWR, Li YX, Li TT, Fan H, Ng EH, Yeung WS, Ho PC, Lee KF. Effect of ulipristal acetate and mifepristone at emergency contraception dose on the embryo-endometrial attachment using an in vitro human trophoblastic spheroid and endometrial cell co-culture model. Hum Reprod. 2017 Dec 1;32(12):2414-2422. doi: 10.1093/humrep/dex328. PMID: 29121217.

Islam MS, Afrin S, Jones SI, Segars J. Selective Progesterone Receptor Modulators-Mechanisms and Therapeutic Utility. Endocr Rev. 2020 Oct 1;41(5):bnaa012. doi: 10.1210/endrev/bnaa012. PMID: 32365199; PMCID: PMC8659360.

Levy DP, Jager M, Kapp N, Abitbol JL. Ulipristal acetate for emergency contraception:post-marketing experience after use by more than 1 million women. Contraception2014;89:431–3.

Li HWR, Lo SST, Ng EHY, Ho PC. Efficacy of ulipristal acetate for emergency contraception and its effect on the subsequent bleeding pattern when administered before or after ovulation. Hum Reprod 2016;31(6):1200–7.

Package insert ella® https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022474s000lbl.pdf