BACKGROUND AND PURPOSE:

• Weekly 17-OHPC injections can be used to reduce the risk of recurrent preterm birth
• Evidence is limited to the efficacy of oral natural micronized progesterone  
• Boelig et al. (AJOG MFM, 2019) sought to determine if oral progesterone is an option for prevention of preterm birth in singleton pregnancies with history of previous spontaneous preterm birth

METHODS:

• Systematic review and meta-analysis
• Inclusion criteria
  • Randomized trials of asymptomatic singleton gestations
  • Previous spontaneous singleton preterm birth
  • Participants were randomized to prophylactic treatment with oral progesterone vs
    • Placebo
    • No treatment
    • Other preterm birth intervention
• Exclusion criteria
  • Quasi-randomized trials
  • Trials that involved women with preterm labor/membrane rupture at the time of randomization
  • Trials with multiple gestations
• Data analysis
  • Risk of bias and quality of evidence were assessed for each study
  • Analyses were done with an intention-to-treat approach
  • Summary measures were reported as relative risk or mean difference
• Primary outcome
  • Incidence of preterm birth at <37 weeks gestation
• Secondary outcomes
  • Preterm birth at <34 and <28 weeks gestation
  • Maternal adverse events
  • Maternal serum progesterone level
  • Neonatal morbidity and death

RESULTS:

• 3 out of 79 identified studies met inclusion criteria
  • 386 patients | 196 in oral progesterone | 190 in placebo
  • No studies on oral progesterone vs other interventions met inclusion criteria
• Dosage regimens in these 3 studies were as follows
  • 100 mg every 6 hrs until 37 wks gestation
  • 400 mg twice daily until 34 wks gestation
  • 100 mg twice daily until 36 wks gestation
• Use of oral progesterone vs placebo, resulted in  
  • Decreased risk of preterm birth at <37 weeks gestation (P=.0005)
    • Oral progesterone: 42%
    • Placebo: 63%
    • Relative Risk (RR): 0.68 (95% CI, 0.55–0.84)
  • Decreased risk of preterm birth at <34 weeks gestation (P<.00001)
    • Oral progesterone: 29%
    • Placebo: 53%; P<.00001
    • RR: 0.55 (95% CI, 0.43–0.71)
  • Increased gestational age of delivery
    • Mean difference: 1.71 weeks (95% CI), 1.11–2.30
  • Lower rate of perinatal death (P=.001)
    • Oral progesterone: 5%
    • Placebo: 17%
    • RR: 0.32 (95% CI, 0.16–0.63)
  • Lower rate of NICU admission
    • RR: 0.39 (95% CI, 0.25–0.61)
  • Lower rate of respiratory distress syndrome
    • RR: 0.21 (95% CI, 0.05–0.93)
  • Higher birthweight
    • mean difference: 435.06 g (95% CI, 324.59–545.52)
• Oral progesterone resulted in more adverse maternal events (not considered serious) such as dizziness, somnolence and vaginal dryness

CONCLUSION:

• In singleton pregnancies with a prior history of preterm birth, oral progesterone appears to
  • Be effective for preterm labor prevention
  • Reduces perinatal morbidity and mortality rates
• Oral progesterone was associated with increased, non-serious, adverse effects
• ‘N’ too small to determine optimal dose
• The authors conclude

Head-to-head comparisons of oral progesterone against other formulations of progesterone in asymptomatic singleton pregnancies with previous spontaneous preterm birth are warranted

Learn More – Primary Sources:

Oral progesterone for the prevention of recurrent preterm birth: systematic review and metaanalysis

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