Mifepristone and misoprostol versus misoprostol alone for induction of labor in women with intrauterine fetal death: A meta-analysis and systematic review

Background: Misoprostol is largely used in labor induction in cases of intrauterine fetal death. However, recent randomized clinical trials (RCTs) showed that the combination of mifepristone and misoprostol might have better effects than the use of misoprostol alone.

Objectives: To compare mifepristone and misoprostol lines of treatment.

Search strategy: Pubmed, Embase, Cochrane and Web of Science databases were systematically searched until April 9, 2024.

Selection criteria: The eligibility criteria were (1) RCT, (2) comparing misoprostol alone versus the combined treatment, (3) patients undergoing labor induction due to intrauterine fetal death and (4) reporting at least one relevant outcome.

Data collection and analysis: Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed using I² statics. R, version 4.2.3 was used for statistical analysis. The analyzed outcomes were delivery time interval, adverse effects (fever, vomiting, diarrhea and nausea) and the preinduction Bishop score. Other important outcomes, such as uterus rupture, could not be included due to lack of data from the included studies.

Main results: A total of seven RCTs comprising 599 patients with intrauterine fetal death were randomized to misoprostol or combined treatment to induce labor. Compared to the misoprostol only group, combined treatment presented lower delivery time interval (MD -6.86 h; 95% CI: -10.32 to -3.4; P = 0.0001; I² = 87%). However, in terms of adverse effects, the combined treatment group presented lower occurrence of fever (2.25% vs 12.12%; RR 0.26; 95% CI: 0.09-0.74; P = 0.01; I² = 0%) and vomiting (7.64% vs 14.45%; RR 0.54; 95% CI: 0.29-1.01; P = 0.05; I² = 0%). No statistically significant differences were observed when comparing the preinduction Bishop score of the two groups (MD -0.09; 95% CI: -0.28-0.10; P = 0.35; I² = 0%). Additionally, the mean of the preinduction Bishop score of the combined treatment was 2 versus 2.1 of the control group.

Conclusion: In this updated meta-analysis, consistent results suggest that the combined treatment is associated with more beneficial outcomes than the misoprostol alone treatment in patients undergoing labor induction in intrauterine fetal death.