Effect of progesterone on cervical shortening in women at risk for preterm birth: secondary analysis from a multinational, randomized, double-blind, placebo-controlled trial

Objectives To determine whether progesterone supplementation alters cervical shortening in women at increased risk for preterm birth. Methods We performed a planned secondary analysis from a large, multinational preterm birth prevention trial of daily intravaginal progesterone gel, 90 mg, compared with placebo in women with a history of spontaneous preterm birth or premature cervical shortening. Transvaginal cervical length measurements were obtained in all randomized patients at baseline (18 + 0 to 22 + 6 weeks' gestation) and at 28 weeks' gestation. For this secondary analysis, the difference in cervical length between these time points was compared for the study population with a history of spontaneous preterm birth and for a population with premature cervical shortening (<= 30 mm) at randomization. Differences between groups in cervical length for the 28-week examination were analyzed using ANCOVA, including adjustment for relevant clinical parameters and maternal characteristics. Results Data were analyzed from 547 randomized patients with a history of preterm birth. The progesterone-treated patients had significantly less cervical shortening than the placebo group (difference 1.6 (95% CI, 0.3-3.0) mm; P = 0.02, ANCOVA). In the population of 104 subjects with premature cervical shortening at randomization, the cervical length also differed significantly on multivariable analysis, with the treatment group preserving more cervical length than the placebo group (difference 3.3 (95% CI, 0.3-6.2) mm; P = 0.03, ANCOVA), with adjustment for differences in cervical length at screening. A significant difference was also observed between groups for categorical outcomes including the frequency of cervical length progression to <= 25 mm and a >= 50%, reduction in cervical length from baseline in this subpopulation. Conclusions Intravaginal progesterone enhances preservation of cervical length in women at high risk for preterm birth. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.