Progesterone Therapy in Pregnancy

Clinical Evidence and Recommendations

Vaginal progesterone (400 mg daily) has been shown to increase latency until delivery and reduce respiratory distress syndrome in women with singleton gestation after successful tocolysis for preterm labor 1
For singleton pregnancies with prior spontaneous preterm birth, 17-alpha-hydroxy-progesterone caproate (17P) 250 mg IM weekly from 16-20 weeks until 36 weeks is recommended by the American College of Obstetricians and Gynecologists 1
In singleton pregnancies without prior preterm birth but with short cervical length (≤20 mm) at ≤24 weeks, vaginal progesterone 90-mg gel or 200-mg suppository daily until 36 weeks is recommended by the American College of Obstetricians and Gynecologists 1
In women with singleton gestation still pregnant after successful tocolysis for preterm labor, 17P 341 mg twice weekly was associated with significant reduction in preterm birth <37 weeks 1
Natural micronized progesterone is often preferred for hormone replacement therapy due to its favorable cardiovascular and thrombotic risk profile compared to synthetic progestogens, as suggested by clinical guidelines 2

Despite its widespread use, progesterone has not shown effectiveness in multiple gestations, active preterm labor, or preterm premature rupture of membranes, as reported by the American College of Obstetricians and Gynecologists 1
For women with preterm premature rupture of membranes (PPROM), there is insufficient evidence to recommend progesterone supplementation, according to the American College of Obstetricians and Gynecologists 1
In multiple gestations (twins, triplets), progesterone supplementation has not shown effectiveness in preventing preterm birth, as stated by the American College of Obstetricians and Gynecologists 1