Progesterone and preterm birth

Progestogens (vaginal progesterone and intramuscular 17‐hydroxyprogesterone acetate) are widely recommended for women at high risk of preterm birth. Typical regimens include 17‐hydroxyprogesterone caproate (250 mg intramuscularly weekly), starting at 16–20 gestational weeks until 36 weeks or delivery for women with a singleton gestation and a history of spontaneous preterm birth, or vaginal progesterone (90‐mg vaginal gel or 200‐mg micronized vaginal soft capsules) for women with a short cervix (typically ≤25 mm). Although some randomized trials support this approach, neither of the largest trials (PROLONG for 17‐hydroxyprogesterone acetate or OPPTIMUM for vaginal progesterone) demonstrated efficacy. There are almost no data on long‐term effects, and none that shows benefit beyond the neonatal period. Although some analyses suggest the cost‐effectiveness of the approach, a cervical length screening program followed by progesterone for those with a short cervix will reduce preterm birth rates by less than 0.5%. The present review assesses evidence on the efficacy, likely impact, and long‐term effects of implementing the recommendations for progestogens in full. Clinicians and pregnant women can look forward to resolution of the conflicting views on efficacy once the Patient‐Centered Outcomes Research Initiative (PCORI)‐funded individual patient data meta‐analysis is published.