Vaginal progesterone for prevention of preterm birth in asymptomatic high-risk women with a normal cervical length: a systematic review and meta-analysis.

Objective: To determine whether vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy and normal mid-gestation cervical length.Study design: Databases were searched (from inception to December 2020) with the search terms "progesterone" and "premature birth" or "preterm birth". Studies were screened and included if they assessed vaginal progesterone compared to placebo in women with normal cervical length. Data were pooled and synthesized in a meta-analysis using a random effects model.Data sources: MEDLINE and Embase databases.Study synthesis: Following PRISMA screening guidelines, data from 1127 women across three studies were available for synthesis. All studies had low risk of bias and were of high quality. The primary outcome was sPTB <37 weeks, with secondary outcomes of sPTB <34 weeks. Vaginal progesterone did not significantly reduce sPTB before 37 weeks, or before 34 weeks with a relative risk (RR) of 0.76 (95% CI 0.37-1.55, p = .45) and 0.51 (95% CI 0.12-2.13, p = .35), respectively.Conclusions: Vaginal progesterone does not decrease the risk of sPTB in high-risk singleton pregnancies with a normal mid-gestation cervical length.