Progesterone Reduces The Rate Of Cervical Shortening In Women At Risk For Preterm Birth: Secondary Analysis From A Randomized, Doubleblind, Placebo-Controlled Trial

To determine whether progesterone supplementation alters the rate of cervical shortening in a cohort of women at increased risk for preterm birth. A secondary analysis was performed of women enrolled into a preterm prevention trial utilizing 90mg intravaginal, daily progesterone gel, Procheive®. Participants in this trial had a singleton and a history of spontaneous preterm birth between 20-35 weeks gestation or a history of midtrimester cervical shortening. Patients were randomized 1:1 drug versus placebo. Transvaginal cervical length measures were obtained at randomization (18+0-22+6 weeks’ gestation) and at 28 weeks’ gestation. The difference in cervical length between these time points was compared. In a subpopulation identified as having a treatment effect by prior secondary analysis, those subjects with a cervical length 30mm at randomization, the rate of cervical change was also assessed. 668 women were enrolled with data available for 611 participants (309 progesterone, 302 placebo). Demographic characteristics were similar between groups. Initial mean baseline cervical length was 3.7 ± 0.7 cm for both groups, P=.97. At the 28 week exam, the mean cervical length had decreased significantly in both groups, progesterone 3.3 ± 0.9 cm, P<.001, and placebo 3.1 ± 0.9, P<.001. The progesterone group had significantly less cervical shortening than the placebo group during this interval (−0.2 cm; 95% CI of the difference −0.31 to −0.01; P=.038). In the 116 subjects with cervical shortening at randomization, the difference in cervical length over time was also significant with the treatment group preserving 0.33 cm more cervical length compared to the placebo group (95% CI 0.62 to 0.03), adjusted for the covariate of cervical length at screening. Progesterone supplementation reduces the rate of cervical change when given as a prophylactic therapy in women at higher risk for preterm birth. Whether this effect is a mechanism that contributes to progesterone′s efficacy to prevent preterm birth requires further study.