Preterm birth prevention in twin pregnancies with progesterone, pessary, or cerclage: a systematic review and meta-analysis

Background About half of twin pregnancies deliver preterm, and it is unclear whether any intervention reduces this risk. Objectives To assess the evidence for the effectiveness of progesterone, cerclage, and pessary in twin pregnancies. Search strategy We searched Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and ISI Web of Science, without language restrictions, up to 25 January 2016. Selection criteria Randomised controlled trials of progesterone, cerclage, or pessary for preventing preterm birth in women with twin pregnancies, without symptoms of threatened preterm labour. Data collection and analysis Two independent reviewers extracted data using a piloted form. Study quality was appraised with the Cochrane Risk of Bias tool. We performed pairwise inverse variance random-effects meta-analyses. Main results We included 23 trials (all but three were considered to have a low risk of bias) comprising 6626 women with twin pregnancies. None of the interventions significantly reduced the risk of preterm birth overall at <34 or <37 weeks of gestation, or neonatal death, our primary outcomes, compared to a control group. In women receiving vaginal progesterone, the relative risk (RR) of preterm birth <34 weeks of gestation was 0.82 (95% CI 0.64–1.05, seven studies, I2 36%), with a significant reduction in some key secondary outcomes, including very low birthweight (<1500 g, RR 0.71, 95% CI 0.52–0.98, four studies, I2 46%) and mechanical ventilation (RR 0.61, 95% CI 0.45–0.82, four studies, I2 22%). Conclusion In twin gestations, although no overarching intervention was beneficial for the prevention of preterm birth and its sequelae, vaginal progesterone improved some important secondary outcomes. Tweetable abstract Vaginal progesterone may be beneficial in twin pregnancies, but not 17-OHPC, cerclage, or pessary.