Efficacy and Safety of Mifepristone and Misoprostol Compared to Misoprostol Alone for the Resolution of Miscarriage and Intrauterine Fetal Death: A Systematic Review and Meta-Analysis

Objective: To determine the efficacy and safety of mifepristone and misoprostol together (intervention) compared to misoprostol alone (comparator) for the resolution of miscarriage and intrauterine fetal death. Data Sources: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) methodology through July 2024 that evaluated the efficacy and safety of mifepristone and misoprostol together compared to misoprostol alone for the resolution of miscarriage and intrauterine fetal death through July 2024. Study Selection and Data Extraction: Primary endpoints were overall delivery success, 24-hour delivery success, and incidence of safety outcomes. A P-value of <0.05 was considered statistically significant, and heterogeneity was reported as the I 2 value. Data Synthesis: Twelve randomized controlled trials (RCTs) were included. Overall delivery success was higher in the intervention group (0.73 [CI 0.64-0.82], P < 0.01). Twenty-four-hour delivery rate was higher (1.54 [CI 1.32-1.77], P = 0.06), and a shorter time to delivery interval (9.22-18.78 vs 15.47-37.1 hours) was observed in the intervention group. Gastrointestinal adverse effects were more frequent in the intervention group (0.04 [CI –0.03 to 0.12], P < 0.01). Relevance to Patient Care and Clinical Practice: Mifepristone and misoprostol together demonstrated higher delivery success rates and comparable safety outcomes to misoprostol alone, demonstrating the potential of improving patient care and positively impacting the time to successful delivery for patients at the bedside. Conclusions: The use of mifepristone and misoprostol together for the resolution of miscarriage and intrauterine fetal death is warranted over the use of misoprostol alone.