Progesterone Receptor Antagonists for Labor Induction: A Systematic Review and Meta-analysis

To evaluate mifepristone, a progesterone receptor antagonist, for labor induction and cesarean delivery and related measures of maternal and neonatal safety.

A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) 2020 guidelines and registered in PROSPERO (CRD420251236886). MEDLINE, Embase, ClinicalTrials.gov, and Scopus were searched through October 2025.

Eligible studies included randomized trials evaluating mifepristone for labor induction in singleton pregnancies at 37 weeks or more of gestation. Studies involving pregnancy termination, intrauterine fetal death, preterm induction, or concomitant cervical ripening interventions in which the effects of mifepristone could not be isolated were excluded. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. The primary outcome was cesarean delivery. Secondary outcomes included induction-to-delivery interval, time to labor onset, Bishop score, need for prostaglandin or oxytocin, postpartum hemorrhage, neonatal intensive care unit (NICU) admission, and 5-minute Apgar score less than 7. Data were pooled with a random-effects model.

The primary analysis included all 15 eligible randomized controlled trials across mifepristone dosing regimens (n=1,063) and control conditions (n=811). Mifepristone was associated with 33% reduced odds of cesarean delivery (33.1% vs 41.9%, odds ratio 0.67, 95% CI, 0.54-0.82) compared with the control method of induction. Mifepristone was associated with higher Bishop scores at 24 hours, shorter induction-to-delivery intervals, and less prostaglandin and oxytocin use compared with control methods. Findings were similar in sensitivity analysis limited to placebo-controlled and high-quality trials (cesarean delivery odds ratio 0.58, 95% CI, 0.40-0.83). No differences were observed in postpartum hemorrhage, NICU admission, or low Apgar score, although most studies did not report these outcomes.

Use of mifepristone for labor induction was associated with reduced odds of cesarean delivery, as well as improved cervical ripening and labor induction efficiency. No evidence of short-term maternal or neonatal risk was found, although robust data were limited. Findings support the role of progesterone antagonists for labor induction.

PROSPERO, CRD420251236886.