Oral misoprostol (PGE1) vs vaginal dinoprostone (PGE2) for labor induction: individual participant data meta-analysis of randomized controlled trials

Objective: To compare the effectiveness and safety of oral misoprostol vs vaginal dinoprostone for the induction of labor (IOL) using an individual participant data (IPD) meta-analysis. Methods: We used a Cochrane review and searched Ovid MEDLINE, Ovid Embase, Ovid Emcare, CINAHL Plus, Scopus and ClinicalTrials.gov to identify randomized controlled trials (RCTs) that compared oral misoprostol with vaginal dinoprostone for IOL in viable singleton pregnancies. We invited the authors of eligible trials to share their anonymized data. Primary outcomes were vaginal delivery, a composite measure of adverse maternal outcomes and a composite measure of adverse perinatal outcomes. IPD meta-analysis was conducted using a two-stage random-effects model. An intention-to-treat approach was used for all analyses. Aggregate-data meta-analysis was undertaken with RCTs stratified by Trustworthiness in RAndomised Clinical Trials (TRACT) score. Results: Of 18 eligible RCTs, eight provided IPD, of which five (1892 participants) met the TRACT criteria. IPD meta-analysis showed similar rates of vaginal delivery after IOL with oral misoprostol or vaginal dinoprostone (odds ratio (OR), 0.99 (95% CI, 0.80–1.22); I² = 0%). The rates of composite adverse perinatal outcome (adjusted odds ratio (aOR), 1.02 (95% CI, 0.61–1.72); I² = 0%) and composite adverse maternal outcome (aOR, 1.39 (95% CI, 0.72–2.69); I² = 0%) were also comparable between the groups. Of 10 RCTs that did not share IPD, seven met the TRACT criteria. Aggregate-data meta-analysis of the 12 RCTs (five with IPD and seven without IPD) meeting the trustworthiness criteria also showed comparable rates of vaginal delivery after oral misoprostol and after vaginal dinoprostone (OR, 1.08 (95% CI, 0.92–1.27)). In contrast, six studies not meeting the trustworthiness criteria (three with and three without IPD) reported a higher rate of vaginal delivery following oral misoprostol (OR, 1.34 (95% CI, 1.22–1.48)), resulting in an inflated overall estimate of the vaginal delivery rate after oral misoprostol based on all data (OR, 1.19 (95% CI, 1.05–1.36)). Conclusion: IOL with oral misoprostol or vaginal dinoprostone results in comparable rates of vaginal delivery and composite perinatal and maternal adverse outcomes.