Mifepristone-Misoprostol Combo Boosts Care for Late Trimester Pregnancy Loss

Administering mifepristone before misoprostol for late trimester pregnancy loss shortened induction-to-delivery time, according to results of a systematic review.

The median time from induction to delivery was 10 hours after administration of both mifepristone and misoprostol, significantly lower than the 17 hours after administration of misoprostol alone, reported Kaitlyn Mayer, MD, of Virginia Commonwealth University Medical Center in Richmond, and colleagues.

Overall, there was a trend of increased success after 24 hours of induction with the mifepristone and misoprostol combination, Mayer said in a presentation at the American College for Obstetricians and Gynecologists (ACOG) virtual meeting.

“Although there was heterogeneity among the nine studies we included, meta-analysis of five similar trials did find a statistically significant decrease in the time from induction of labor to delivery with the combination therapy,” Mayer told MedPage Today. She added that the majority of patients were able to deliver within 24 hours, and that shortening the duration of medical management for late trimester loss is critical to try to decrease trauma for these patients.

“For any woman who is diagnosed with a fetal demise, or a stillbirth, tenets of care include safety and efficacy, but also being respectful of the patient experience,” Mayer said. “Anything that we can do to increase the safety and efficacy of an induction for these patients, but also have respect for their experience, is really important.”

As mifepristone is a medication that is regulated under the FDA’s risk evaluation and mitigation strategies (REMS) protocol, Mayer hopes that more data about its benefits will support greater access and deregulation. She added that future studies need to explore the optimal dosing of misoprostol when used in combination with mifepristone for third trimester pregnancy loss.

Generally, the management of intrauterine fetal demise has been extrapolated from trials of second trimester induced abortion, due to a “paucity of quality studies that have investigated its use for the management of pregnancy loss in the third trimester,” Mayer said. In this study, Mayer and colleagues conducted a systematic review to compare the efficacy of mifepristone and misoprostol with misoprostol alone for induction of labor due to intrauterine fetal demise during the third trimester.

The researchers identified nine articles that met the inclusion criteria, including three retrospective cohorts, two prospective cohorts, and four randomized controlled trials. They included nearly 700 patients, who had an average gestational age of 32.6 weeks.

Among five trials using similar doses of misoprostol, the mean induction-to-delivery time was significantly shorter with mifepristone and misoprostol combination therapy compared to misoprostol alone (10.2 v.s. 16.9 hours, 95% CI -12.3 to -1.2).

There was heterogeneity in misoprostol dosing among the included studies, which Mayer recognized as a limitation of their work.