Ulipristal-misoprostol regimen ‘viable alternative’ for early medication abortion

Key takeaways:

• A ulipristal-misoprostol medication regimen successfully terminated pregnancies in 97% of women.
• The findings suggest ulipristal-misoprostol could serve as an alternative to mifepristone.

Ulipristal acetate followed by misoprostol was effective and acceptable for medication abortion up to 63 days’ gestation with no serious adverse events, but more studies are needed, data from a proof-of-concept study show.

Ulipristal acetate (Ella, HRA Pharma) is a selective progesterone receptor modulator option available by prescription or over the counter as emergency contraception that may be effective for medication abortion considering the limited accessibility and legal turmoil of mifepristone, Manuel Bousiéguez, MBA, consulting associate at Gynuity Health Projects, and colleagues wrote in NEJM Evidence.

“This study provides strong initial evidence that ulipristal acetate combined with misoprostol is a highly effective and well-accepted regimen for early medication abortion up to 63 days’ gestation,” Bousiéguez told Healio. “With a 97% success rate, no reported serious adverse events and a high acceptability among participants, these findings suggest that ulipristal acetate could serve as a viable alternative to mifepristone, particularly in settings where access to mifepristone is limited.”

Ulipristal-misoprostol regimen

Bousiéguez and colleagues conducted a two-stage, clinical proof-of-concept study with 66 pregnant women seeking medication abortion up to 63 days’ gestation from July to September 2023. All women were randomly assigned to oral ulipristal acetate at 60 mg (n = 33) or 90 mg (n = 33) followed by buccal misoprostol 800 μg after 24 hours. Researchers then conducted an open-label study assessing the safety and efficacy of the 60 mg regimen with 100 additional women. At final follow-up, all women answered a questionnaire asking about adverse effects, overall experience and acceptability.

The primary outcome was the safety and efficacy of a combined ulipristal-misoprostol medication abortion regimen.

Overall, 97% of women who received the 60 mg ulipristal-misoprostol regimen achieved pregnancy termination.

Of those who did not have a terminated pregnancy, one woman had a complete termination with sharp curettage, two women received manual vacuum aspiration and one woman underwent repeat medication abortion with misoprostol only.

The most commonly reported adverse effects after ulipristal-misoprostol use were chills (77.4%), diarrhea (66.9%) and nausea (48.1%). Researchers observed no serious adverse events.

Overall, 97.7% of women deemed the ulipristal-misoprostol regimen as “acceptable” or “highly acceptable.”

According to Bousiéguez, research efforts should focus on dose optimization, including evaluating a lower ulipristal acetate dose, randomized controlled trials to compare ulipristal-misoprostol with mifepristone-misoprostol, assessing effectiveness beyond 63 days’ gestation, implementation research to explore integration into clinical practice and policy and pharmacoeconomic studies to evaluate affordability and cost-effectiveness vs. mifepristone.

“The study suggests that ulipristal acetate may be a safe and effective alternative to mifepristone for medication abortion, which could significantly impact clinical practice [by] expanding options for early medication abortion, particularly in settings where mifepristone is unavailable, restricted or costly,” Bousiéguez told Healio. “High success and acceptability rates indicate that ulipristal acetate has the potential to be integrated into existing medication abortion protocols. The findings support the need for further clinical trials to refine dosing, explore use beyond 63 days’ gestation, and compare ulipristal-misoprostol regimens with standard protocols.”

Reacting to the study findings, ACOG released a statement highlighting that ulipristal acetate on its own does not induce an abortion.

“Although the findings of this study are clear, ACOG expects that the conclusion will be misinterpreted and misrepresented by those who intentionally use it to advance an antiabortion agenda,” Stella Dantas, MD, FACOG, president of ACOG, said in the release. “This study does not in any way, shape or form suggest that Ella, an important option for patients seeing emergency contraception, causes abortion. Emergency contraception does not end a pregnancy; it prevents it.

“Abortion is an essential part of reproductive health care and so is emergency contraception,” Dantas said in the release. “Critically, this study does not conclude — and should not be misrepresented as concluding — that emergency contraception causes abortion.”

Larger trials needed

In an accompanying editorial, Daniel Grossman, MD, professor in the department of obstetrics, gynecology and reproductive sciences and director of Advancing New Standards in Reproductive Health within the University of California, San Francisco, Bixby Center for Global Reproductive Health, wrote that innovation in medication abortion treatment is welcome, especially if ulipristal acetate was equally effective and more accessible and cost-effective for patients vs. the standard of care. However, a larger trial is needed comparing the effectiveness of ulipristal acetate with the mifepristone-misoprostol or misoprostol-only regimens.

“Having an alternative to mifepristone could be advantageous if access to this drug were to become more restricted due to legal rulings or administrative action,” Grossman wrote. “However, in the current political environment in the U.S., if efforts to restrict mifepristone were successful, there may be little that could be done to stop similar efforts aimed at a pharmaceutical alternative.”

For more information:

Manuel Bousiéguez, MBA, can be reached at mbousieguez@gynuity.org; X (Twitter): @Gynuity.

References:

• ACOG responds to new study on ulipristal acetate. Published Jan 23, 2025. Accessed Jan 28, 2025. www.acog.org/news/news-releases/2025/01/acog-responds-to-new-study-on-ulipristal-acetate.
• Grossman D. NEJM Evid. 2025;doi:10.1056/EVIDe2400460.