Sublingual versus Vaginal Misoprostol for Medical Management of First-Trimester Missed Miscarriage: A Systematic Review and Meta-Analysis

Abstract

Background: The relative effectiveness and tolerability of sublingual and vaginal misoprostol for first-trimester missed miscarriage remain uncertain when treatment regimens and assessment intervals differ.

Objective: To compare complete evacuation, surgical evacuation, time to expulsion, and adverse effects between equal-dose sublingual and vaginal misoprostol regimens.

Methods: This manuscript synthesizes the supplied evidence extraction dated 2 October 2026. Reports were identified through web, registry and citation searching. Eligible studies were randomized trials of misoprostol alone for ultrasound-diagnosed first-trimester missed miscarriage or closely related early pregnancy failure. Only separable first-trimester outcomes were used from mixed gestational age populations. Formal database searches and independent duplicate extraction had not been completed. Study-specific risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were presented without pooling because outcome definitions, assessment intervals, and data reliability differed. Risk of bias and certainty ratings were provisional.

Results: The supplied screening record contained 23 reports: 10 excluded, eight awaiting classification and five provisionally included trials. Four trials provided numerical complete evacuation data for 361 participants. Complete evacuation RRs were 0.95 (95% CI 0.52–1.73), 1.14 (0.87–1.49), 1.37 (1.06–1.77) and 0.05 (0.003–0.80); the last estimate depended on disputed denominators and continuity correction. Two trials reported less surgical evacuation with sublingual treatment, with RRs of 0.67 (0.40–1.12) and 0.62 (0.41–0.92). Time to expulsion findings differed: MD −8.5 hours (−11.5 to −5.5) and +3.6 hours (2.8–4.4). Heavy bleeding was more frequent with sublingual treatment in one trial, RR 4.00 (1.19–13.48). Provisional certainty was low or very low.

Conclusion: The extracted evidence does not establish consistent superiority of either route. A possible reduction in surgical evacuation with sublingual treatment must be weighed against uncertain effectiveness estimates and possible increases in adverse effects. Incomplete evidence identification, unresolved reporting discrepancies and methodological limitations prevent definitive conclusions.