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

ABSTRACT

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 11 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.