Can intravaginal progesterone help in preterm labor?

Intravaginal Progesterone for Prevention of Preterm Birth

Vaginal progesterone is effective for preventing preterm birth in specific high-risk populations, but is not recommended for women with active preterm labor or preterm premature rupture of membranes. 1

Effectiveness Based on Risk Factors

Women with Prior Spontaneous Preterm Birth

• For women with singleton pregnancies and history of spontaneous preterm birth (SPTB) at 20-36 6/7 weeks, 17-alpha-hydroxy-progesterone caproate (17P) 250 mg intramuscularly weekly starting at 16-20 weeks until 36 weeks is the first-line recommendation 1
• If 17P is unavailable, vaginal progesterone may be considered as an alternative 1
• Vaginal progesterone (100 mg nightly from 24-34 weeks) has been shown to significantly reduce preterm birth before 37 weeks (RR 0.48) and 34 weeks in women with prior preterm birth 1

Women with Short Cervical Length

• In women with singleton gestations, no prior preterm birth, and short cervical length ≤20 mm at ≤24 weeks, vaginal progesterone (either 90-mg gel or 200-mg suppository) is recommended as it reduces preterm birth and perinatal morbidity/mortality 1
• In women with prior preterm birth who develop short cervical length (<25 mm) despite 17P treatment, cervical cerclage may be offered 1
• Vaginal progesterone appears most effective for moderately short cervical lengths, while cerclage may be more beneficial for very short cervical lengths (<15 mm) 1

Dosing and Administration

• Vaginal progesterone options:
  • 90-mg gel daily 1
  • 200-mg suppository daily 1
  • 100-mg suppositories nightly 1
• Treatment should typically begin between 16-24 weeks gestation and continue until 36-37 weeks 1

Ineffective Uses of Progesterone

• Progesterone (vaginal or intramuscular) is not recommended for:
  • Women with multiple gestations 1
  • Women with active preterm labor 1
  • Women with preterm premature rupture of membranes (PPROM) 1

Recent Conflicting Evidence

• While the 2012 guidelines strongly support progesterone use in specific populations, more recent research has shown conflicting results:
  • A 2022 randomized controlled trial found that vaginal progesterone (400 mg daily) significantly increased the interval to delivery and reduced neonatal morbidities in women with arrested preterm labor 2
  • However, a 2017 meta-analysis of high-quality trials found no significant benefit of progesterone for preventing preterm birth following arrested preterm labor 3

Route of Administration Considerations

• Vaginal progesterone appears to be nearly as effective as intramuscular progesterone for prevention of preterm birth in high-risk women 4
• Vaginal administration is associated with fewer adverse events compared to intramuscular administration 4

Clinical Algorithm for Progesterone Use

1. For women with singleton pregnancy and prior spontaneous preterm birth (20-36 6/7 weeks):

   • First choice: 17P 250 mg IM weekly from 16-20 weeks until 36 weeks 1
   • If 17P unavailable: Consider vaginal progesterone 1
   • Monitor cervical length; if <25 mm, consider adding cervical cerclage 1

2. For women with singleton pregnancy, no prior preterm birth, but short cervical length ≤20 mm at ≤24 weeks:

   • Vaginal progesterone (90-mg gel or 200-mg suppository) daily until 36-37 weeks 1

3. For women with multiple gestations, active preterm labor, or PPROM:

   • Progesterone is not recommended 1

Caveats and Pitfalls

• Universal cervical length screening in women without prior preterm birth remains controversial and cannot be universally mandated 1
• The long-term effects of progesterone therapy on child development are not well-established, though limited follow-up studies have not shown adverse effects 1
• Progesterone therapy should be started early (ideally 16-20 weeks) for maximum effectiveness in prevention 1
• Progesterone is not effective as a rescue therapy once active preterm labor has begun 1