Vaginal progesterone for prevention of preterm birth in women with a history of preterm birth regardless of cervical length: an argument against use.

Preterm birth, defined as birth before 37 weeks of gestation, has a significant public health impact as the most frequent cause of neonatal death, and second most frequent cause of infant death at age <5 years. Given the unclear and likely multifactorial etiologic nature of preterm birth, interventions to address this condition have been elusive. Progesterone supplementation was once thought to be a promising strategy to reduce preterm birth among patients with a history of prior preterm birth. However, more recent data suggesting limited efficacy led the US Food and Drug Administration to revoke approval of 17-alpha hydroxyprogesterone caproate (17-OHPC). Vaginal progesterone supplementation remains controversial. Recently published meta-analyses evaluating large, pre-registered randomized controlled trials at low risk of bias and selective outcome reporting, have found recurrent preterm birth rates are not significantly reduced by vaginal progesterone supplementation in patients with a singleton gestation and prior history of spontaneous preterm delivery. Furthermore, studies reporting any benefit from vaginal progesterone in this patient population are noted to have smaller sample sizes, higher risk of bias and selective outcome reporting, and low external validity. As such, we argue against the universal use of vaginal progesterone supplementation for the prevention of recurrent preterm birth. VIDEO ABSTRACT.