Prevention of Preterm Birth with Progesterone

Benefits of Progesterone Supplementation

The American College of Obstetricians and Gynecologists recommends progesterone supplementation for women with prior spontaneous preterm birth, as 17-alpha-hydroxyprogesterone caproate (17P) 250 mg IM weekly from 16-20 weeks until 36 weeks reduces preterm birth <37 weeks (RR 0.66; 95% CI 0.54-0.81) and neonatal complications, including intraventricular hemorrhage 1, 2.
For women without prior preterm birth but with short cervix ≤20 mm on transvaginal ultrasound, vaginal progesterone (90-mg gel or 200-mg suppository daily) from diagnosis until 36 weeks significantly reduces preterm birth <33 weeks (RR 0.54; 95% CI 0.30-0.98) and composite neonatal morbidity/mortality (RR 0.41; 95% CI 0.17-0.98) 1, 3, 4.

The Society for Maternal-Fetal Medicine states that progesterone has no evidence of effectiveness for symptomatic preterm labor 1, 3, 5, 6.
Progesterone works as prevention when started early in pregnancy (16-24 weeks), not as treatment for active labor at 32 weeks 1, 2.

For women at risk for preterm birth, assess cervical length by transvaginal ultrasound immediately, and if cervical length <25 mm and she has prior spontaneous preterm birth, continue or start 17P 250 mg IM weekly 1, 3, 4.
If cervical length ≤20 mm and no prior preterm birth, start vaginal progesterone 90-mg gel or 200-mg suppository daily 1, 3.

Do not confuse prevention with treatment: progesterone prevents preterm birth when started early in at-risk women, but does not treat active preterm labor 1, 5, 6.
Do not use progesterone in multiple gestations, as multiple RCTs show no benefit of progesterone (17P or vaginal) in twin or triplet pregnancies 5, 6.
Do not switch progesterone formulations mid-pregnancy, as there is no evidence that switching provides additional benefit 7, 8.