Double-blind randomized trial of progesterone to prevent preterm birth in second-trimester bleeding

Introduction: Second-trimester vaginal bleeding increases the risk of spontaneous preterm birth. We aimed to examine the efficacy of vaginal progesterone to reduce preterm birth rate in women with second-trimester vaginal bleeding. Material and methods: Two-center, double-blind, placebo-controlled trial involving pregnant women with second-trimester vaginal bleeding. Women with documented uterine bleeding were randomly assigned in a 1:1 ratio to receive 200 mg of micronized vaginal progesterone or placebo once daily at 16-26 weeks until 36 weeks of gestation. Women who had prior preterm birth or short cervix diagnosed before recruitment were not eligible. The primary outcome was spontaneous delivery <37 weeks. Clinical Trial Registration: clinicaltrials.gov Identifier: NCT01269450. Results: Between March 2011 and January 2017, 128 women gave consent and were randomized; 16 withdrew consent and 3 had a second-trimester termination of pregnancy. The final analysis included 109 women: 60 in the progesterone group and 49 in the placebo group. Demographic and obstetric characteristics did not differ between the groups. Primary outcome occurred in 19 (31.7%) and 12 (24.5%) in the progesterone and placebo groups, respectively (odds ratio [OR] 1.32; 95% confidence interval [CI] 0.55-3.16; P = 0.53). The proportion of births <34 weeks was similar between the groups (OR 1.19; 95% CI 0.47-3.02; P = 0.72), as were the survival curves from randomization to delivery (hazard ratio, 1.24; 95% CI, 0.60-2.56; P = 0.57). There were no significant differences in neonatal morbidities between the groups. The study was ended prematurely because of slow recruitment. Conclusions: Antepartum vaginal progesterone does not seem to reduce the incidence of preterm birth in women with second-trimester bleeding.