Role of Exogenous Progesterone in Maintaining Pregnancy
For women with singleton pregnancies and a history of spontaneous preterm birth (SPTB), 17-alpha-hydroxyprogesterone caproate (17P) should be administered at 250 mg IM weekly, starting at 16-20 weeks of gestation and continuing until 36 weeks of gestation or delivery. 1, 2
Indications for Exogenous Progesterone
Singleton Pregnancies with Prior Spontaneous Preterm Birth
- 17P at 250 mg IM weekly is recommended for women with singleton gestations and prior SPTB between 20 and 36 6/7 weeks 1
- Treatment should begin at 16-20 weeks gestation and continue until 36 weeks gestation 1, 3
- This regimen has been shown to reduce the risk of recurrent preterm birth by more than 30% 4, 5
- Specifically, 17P reduces the incidence of delivery at <37 weeks (RR, 0.66; 95% CI, 0.54–0.81), <35 weeks (RR, 0.67; 95% CI, 0.48–0.93), and <32 weeks (RR, 0.58; 95% CI, 0.37–0.91) 3, 4
Singleton Pregnancies with Short Cervical Length but No Prior SPTB
- For women with singleton gestations without prior SPTB but with short cervical length ≤20 mm at ≤24 weeks, vaginal progesterone is recommended 1, 2
- Dosing options include:
- Treatment should begin at diagnosis of short cervical length and continue until 36 weeks gestation 1
Populations Where Progesterone is NOT Effective
- Multiple gestations (twins, triplets) - regardless of prior preterm birth history or cervical length 1, 2
- Primary tocolysis in active preterm labor 1, 2
- Preterm premature rupture of membranes (PPROM) 1, 6
- Singleton pregnancies without prior SPTB and with normal or unknown cervical length 1
Dosing and Administration
17-alpha-hydroxyprogesterone caproate (17P)
- Dose: 250 mg IM weekly 1, 3
- Initiation: Between 16-20 weeks gestation 1, 3
- Duration: Continue until 36 weeks gestation or delivery 3, 4
- Route: Intramuscular injection 3
Vaginal Progesterone (for short cervix)
- Dose options:
- Initiation: At diagnosis of short cervical length ≤20 mm 1
- Duration: Continue until 36 weeks gestation 1
- Route: Vaginal 2
Clinical Efficacy and Outcomes
- In FDA trials, 17P reduced preterm birth rates at <37 weeks from 54.9% to 37.1% in women with prior SPTB 3
- Treatment with 17P also reduced delivery rates at <35 weeks (30.7% to 21.3%) and <32 weeks (19.6% to 11.9%) 3
- Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen 4
- For women with prior SPTB, 17P can prolong pregnancy by approximately 3.7-4.3 weeks compared to previous preterm deliveries 7
Clinical Considerations and Pitfalls
- If a woman with prior SPTB on 17P therapy develops cervical shortening (<25 mm), it is recommended to continue 17P rather than switching to vaginal progesterone 1
- Vaginal progesterone appears most efficacious for moderately short cervical length, while cerclage may be more beneficial for very short cervix (<15 mm) 1
- There is insufficient evidence to recommend a different progesterone therapy if the cervix shortens to ≤25 mm in a woman already receiving 17P 1
- Vaginal progesterone should not be considered a substitute for 17P in women with prior SPTB 1
- Despite some conflicting evidence in recent studies (PROLONG trial), current guidelines still recommend 17P for women with prior SPTB 8
Mechanism of Action
- Progesterone helps maintain pregnancy through multiple mechanisms:
By following these evidence-based recommendations for progesterone therapy, clinicians can significantly reduce the risk of recurrent preterm birth in high-risk women, thereby improving neonatal outcomes and reducing associated morbidity and mortality.