Progesterone Dosing for Pregnancy Maintenance
For women with a history of spontaneous preterm birth, 17-alpha-hydroxyprogesterone caproate (17P) 250 mg intramuscularly weekly from 16-20 weeks until 36 weeks gestation is the recommended progesterone regimen to maintain pregnancy. 1
Recommended Progesterone Regimens Based on Risk Factors
The appropriate progesterone dosing depends on the specific clinical scenario:
For Women with Prior Spontaneous Preterm Birth (SPTB)
- Regimen: 17P 250 mg IM weekly
- Timing: Start at 16-20 weeks gestation
- Duration: Continue until 36 weeks gestation
- Evidence level: High-quality evidence showing reduction in preterm birth rates 1
For Women with Short Cervix but No Prior Preterm Birth
- Regimen: Vaginal progesterone 90 mg gel or 200 mg suppository daily
- Timing: Start when short cervical length (≤20 mm) is diagnosed on transvaginal ultrasound at around 24 weeks
- Duration: Continue until 36 weeks gestation
- Evidence level: High-quality evidence showing reduction in preterm birth and perinatal morbidity/mortality 1
For Women with Threatened Miscarriage and Prior Miscarriage(s)
- Regimen: Vaginal micronized progesterone 400 mg twice daily
- Timing: Start at diagnosis of threatened miscarriage in first trimester
- Duration: Until 16 weeks gestation (though evidence suggests benefit may be complete by 12 weeks) 2, 3
- Evidence level: High-quality evidence from PRISM trial showing 5% increase in live birth rates for women with history of miscarriage and current pregnancy bleeding 2
Clinical Considerations and Caveats
Ineffective Scenarios
Progesterone supplementation has not been shown effective for:
- Multiple gestations (twins, triplets) without other risk factors
- Preterm labor
- Preterm premature rupture of membranes (PPROM)
- Singleton pregnancies without prior SPTB or short cervix 1
Route of Administration Considerations
- Intramuscular 17P: Preferred for prior SPTB history
- Vaginal progesterone: Preferred for short cervix
- Oral vs. Vaginal for threatened miscarriage: Some evidence suggests oral micronized progesterone (200 mg twice daily) may be more effective than vaginal progesterone for threatened miscarriage (91.8% vs 73.5% prevention of miscarriage) 4
Special Populations
For women with recurrent miscarriage and current bleeding, the benefit of progesterone increases with the number of previous miscarriages:
- With 1+ previous miscarriages: 5% absolute increase in live birth rate
- With 3+ previous miscarriages: 15% absolute increase in live birth rate 2
Duration Considerations
While some guidelines recommend continuing progesterone until 16 weeks for threatened miscarriage, recent evidence suggests the full effect may be present by 12 weeks when placental production of progesterone becomes sufficient 3. This is an important consideration given theoretical concerns about prolonged exogenous progesterone exposure.
Algorithm for Progesterone Selection
Assess risk factors:
- History of spontaneous preterm birth?
- Short cervical length on ultrasound?
- Current threatened miscarriage with bleeding?
- History of previous miscarriages?
Select appropriate regimen based on primary risk factor:
- Prior SPTB → 17P 250 mg IM weekly (16-36 weeks)
- Short cervix without prior SPTB → Vaginal progesterone 90 mg gel or 200 mg suppository daily
- Threatened miscarriage with prior miscarriage(s) → Vaginal micronized progesterone 400 mg twice daily
Monitor response:
- For threatened miscarriage: Continue until bleeding stops plus one week, or until 12-16 weeks
- For preterm birth prevention: Continue until 36 weeks
Consider discontinuation:
Remember that progesterone supplementation is not a universal solution for all pregnancy complications, and its effectiveness is specific to certain clinical scenarios with strong supporting evidence.