Summary: Women who use mifepristone for a medical abortion are at risk of severe hemorrhage if they do not complete the procedure with misoprostol, a new study reports.
Source: UC Davis Health
Women who initiate medical abortion but opt to stop in the middle of treatment may be at risk for serious blood loss, a UC Davis Health study finds. Researchers found this is true even for women who use an experimental treatment that claims to “reverse” the effects of the abortion pill. The study, published today in Obstetrics and Gynecology, provides important insights into the safety of using high doses of progesterone during early pregnancy to try to stop a medical abortion.
Medical abortion involves using two medicines in sequence: mifepristone and misoprostol. This combination is approved by the Food and Drug Administration (FDA) for medical abortion during the first 70 days of pregnancy. When mifepristone is followed in 24-48 hours by misoprostol, the abortion regimen is highly effective and safe.
The first randomized clinical study on medical abortion “reversal”
Anti-abortion activists claim that women who take mifepristone for abortion and change their mind before using misoprostol can take progesterone to stop the abortion process. The UC Davis Health study is the first rigorous clinical study to test the efficacy of progesterone after mifepristone. The process of reversing mifepristone’s binding to progesterone receptors is referred to medically as mifepristone antagonization.
Before this study, the medical literature on mifepristone reversal consisted of case reports and series, which do not provide evidence on whether progesterone treatment is effective or safe. None of the case reports describe safety or the outcomes of women who did not have the pregnancy continue.
The UC Davis Health study sought to determine whether a woman who has taken 200 milligrams of mifepristone – the first medicine in the medical abortion process – will be less likely to expel the pregnancy if she receives high-dose progesterone as compared to placebo treatment. The study enrolled women planning a surgical abortion who were willing to delay the procedure for two weeks. Women were followed for up to two weeks after taking mifepristone to identify if the pregnancy continued to develop. Those with continuing pregnancies had a surgical abortion as scheduled.
“We planned to enroll 40 women, but stopped the study due to safety concerns,” said Mitchell Creinin, leading author, professor of obstetrics and gynecology and director of Family Planning at UC Davis Health.
After enrolling 12 women, three participants experienced severe bleeding, requiring ambulance transport to an emergency department. One of the women had received progesterone and two had received placebo. Because of these safety issues, Creinin and his co-investigators stopped the study early.
Since the study was cut short, researchers could not quantify the full extent of the hemorrhage risk. Still, the study provides important insight into the safety of using progesterone and not using both drugs during medical abortion.
“Women who use mifepristone for a medical abortion should be advised that not following up with misoprostol could result in severe hemorrhage, even with progesterone treatment,” Creinin said.
Overall, four of the six women in the progesterone group and two of the six women in the placebo group had a continuing pregnancy at two weeks and had surgical abortions as planned. The authors say these numbers are too small to make conclusions about comparing the outcomes, which could be attributed to random chance.
Policy implications of the study
Some states in the U.S. require physicians who provide medical abortion to inform women that if they change their mind after taking mifepristone, a treatment (progesterone) is available to ensure the pregnancy will continue. There is no scientific consensus that supports this claim.
“For now, the level of evidence is still inadequate to support or refute the benefits and risks of progesterone treatment to stop a medical abortion after taking mifepristone,” Creinin said. “Laws should not mandate counseling or provision of any treatment that claims to reverse abortion when both its efficacy and safety are unclear.”
The researchers propose that progesterone treatment to reverse the mifepristone pill is human experimentation and should only be offered in Institutional Review Board-approved clinical trials to ensure proper design, reporting and oversight.
Other researchers on this study include Melody Hou, Laura Dalton, Rachel Steward and Melissa Chen.
UC Davis Health
Tricia Tomiyoshi – UC Davis Health
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Original Research: Closed access
“Mifepristone Antagonization With Progesterone to Prevent Medical Abortion: A Randomized Controlled Trial”. Creinin, Mitchell D.; Hou, Melody Y.; Dalton, Laura; Steward, Rachel; Chen, Melissa J.
Obstetrics & Gynecology doi:10.1097/AOG.0000000000003620.
Mifepristone Antagonization With Progesterone to Prevent Medical Abortion: A Randomized Controlled Trial
OBJECTIVE: To estimate the efficacy and safety of mifepristone antagonization with high-dose oral progesterone.
METHODS: We planned to enroll 40 patients in a double-blind, placebo-controlled, randomized trial. We enrolled patients at 44–63 days of gestation with ultrasound-confirmed gestational cardiac activity who were planning surgical abortion. Participants ingested mifepristone 200 mg and initiated oral progesterone 400 mg or placebo 24 hours later twice daily for 3 days, then once daily until their planned surgical abortion 14–16 days after enrollment. Follow-up visits were scheduled 3±1, 7±1, and 15±1 days after mifepristone intake with ultrasonography and blood testing for human chorionic gonadotropin and progesterone. Participants exited from the study when they had their surgical abortion or earlier for gestational cardiac activity absence, gestational sac expulsion, or medically indicated suction aspiration. We assessed the primary outcome of continued gestational cardiac activity at approximately 2 weeks (15±1 day), side effects after drug ingestion, and safety outcomes including hemorrhage and emergent treatment.
RESULTS: We enrolled participants from February to July 2019 and stopped enrollment after 12 patients for safety concerns. Mean gestational age was 52.5 days. Two (one per group) voluntarily discontinued 3 days after mifepristone ingestion for subjective symptoms (nausea and vomiting, bleeding). Among the remaining 10 patients (five per group), gestational cardiac activity continued for 2 weeks in four in the progesterone group and two in the placebo group. One patient in the placebo group had no gestational cardiac activity 3 days after mifepristone use. Severe hemorrhage requiring ambulance transport to hospital occurred in three patients; one received progesterone (complete expulsion, no aspiration) and two received placebo (aspiration for both, one required transfusion). We halted enrollment after the third hemorrhage. No other significant side effects were reported.
CONCLUSION: We could not estimate the efficacy of progesterone for mifepristone antagonization due to safety concerns when mifepristone is administered without subsequent prostaglandin analogue treatment. Patients in early pregnancy who use only mifepristone may be at high risk of significant hemorrhage.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03774745.