Vaginal progesterone to prevent preterm birth in multiple pregnancy: a randomized controlled trial

Aim: We sought to assess the effect of progesterone in increasing or decreasing duration of pregnancy for mothers with twins and triplets. Methods: Women with multiple pregnancy were randomized at 16 + 0 to 20 + 6 weeks' gestation to receive daily doses of either 90 mg progesterone vaginal gel or placebo until 35 + 6 weeks or delivery. Primary outcome was gestational age (GA) at delivery. Secondary outcomes included preterm birth, infant morbidity and mortality, and adverse events up to 28 days after delivery. A sample size of 40 per group was required to detect a 2-week difference in GA at delivery. Results: Eighty-four women were randomized (42 to progesterone, 42 to placebo). Median GA at delivery was 36 + 3 and 36 + 2, respectively (difference, 1 day; 95% confidence interval, 4 to -1 days, P = 0.585). There were no clinically or statistically significant differences between groups for risk of delivery before 35 or 37 weeks' GA, rates of infant morbidity and mortality, treatment compliance, or adverse events. Conclusions: Daily treatment with progesterone gel did not prolong multiple pregnancy compared with placebo. Effective prevention strategies are needed to reduce preterm deliveries among women with multiple gestations.