Prior Cesarean Birth and Risk of Uterine Rupture in Second-Trimester Medication Abortions Using Mifepristone and Misoprostol: A Systematic Review and Meta-analysis

Abstract

Objective: To assess the risk difference of uterine rupture when using current mifepristone and misoprostol regimens for second-trimester abortion among individuals with prior cesarean birth compared with those without prior cesarean birth.

Data sources: We searched the terms second trimester, induction, mifepristone, and abortion in PubMed, EMBASE, POPLINE, ClinicalTrials.gov , and Cochrane Library from inception until December 2022.

Methods of study selection: We included randomized trials and observational studies including a mixed cohort, with and without uterine scar, of individuals at 14-28 weeks of gestation who used mifepristone and misoprostol to end a pregnancy or to manage a fetal death. We excluded case reports, narrative reviews, and studies not published in English. Two reviewers independently screened studies.

Tabulation, integration, and results: Absolute risks with binomial CIs were calculated from pooled data. Using R software, we estimated total risk difference by the Mantel-Haenszel random-effects method without continuity correction. For studies with zero events, a continuity correction of 0.5 was applied for individual risk differences and plotted graphically with forest plots. Statistical heterogeneity was assessed with Higgins I2 statistics. Funnel plot assessed for publication bias. Of 198 articles identified, 22 met the inclusion criteria: seven randomized trials (n=923) and 15 observational studies (n=6,195). Uterine rupture risk with prior cesarean birth was 1.1% (10/874) (95% CI 0.6-2.1) and without prior cesarean birth was 0.01% (2/6,244) (95% CI 0.0-0.12). The risk difference was 1.23% (95% CI 0.46-2.00, I2 =0%). Of the 12 reported uterine ruptures, three resulted in hysterectomy.

Conclusion: Uterine rupture with mifepristone and misoprostol use during second-trimester induction abortion is rare, with the risk increased to 1% in individuals with prior cesarean birth.

Systematic review registration: PROSPERO, CRD42022302626.