BACKGROUND AND PURPOSE:

• Devall et al. (Cochrane Reviews, 2021) assessed the relative effectiveness and safety profiles for different progestogen treatments for threatened and recurrent miscarriage

METHODS:

• Systematic review and meta-analysis
• Study inclusion criteria
  • Randomized and cluster-randomized controlled trials
  • Studies that assessed the effectiveness or safety of progestogen treatment for the prevention of miscarriage
• Study design
  • The relative effects for the primary and secondary outcomes were estimated
  • Relative effects were reported by the type of miscarriage
    • Threatened: Bleeding in early pregnancy
    • Recurrent: ≥3 losses
  • GRADE criteria were used to assess the certainty of evidence
• Primary outcome
  • Live birth
• Secondary outcomes
  • Miscarriage (< 24 weeks of gestation)
  • Preterm birth (< 37 weeks of gestation)
  • Stillbirth
  • Ectopic pregnancy
  • Congenital abnormalities
  • Adverse drug events

• 7 randomized trials (total 14 treatment arms) | 5682 women
  • Vaginal micronized progesterone: 21% (3 treatment arms)
  • Dydrogesterone: 21% (3 arms)
  • Oral micronized progesterone: 7% (1 arm)
  • 17-α-hydroxyprogesterone: 7% (1 arm)
  • Placebo: 43% (6 arms)

Women with Threatened Miscarriage

• Compared to placebo, vaginal micronized progesterone and dydrogesterone probably make little or no difference to the live birth rate
  • Vaginal micronized progesterone
    • Relative risk (RR) 1.03 (95% CI, 1.00 to 1.07)
    • 2 trials; 4090 women; high-certainty evidence
  • Dydrogesterone
    • RR 0.98 (95% CI, 0.89 to 1.07)
    • 1 trial; 406 women; moderate-certainty evidence
  • There were no data to assess the effectiveness of 17-α-hydroxyprogesterone on live birth

Subgroup Analysis: Previous Miscarriages

• No previous miscarriages and early pregnancy bleeding
  • Probably little or no improvement in the live birth rate with vaginal micronized progesterone
  • RR 0.99 (95% CI, 0.95 to 1.04); high-certainty evidence
• Subgroup analysis: ≥1 previous miscarriages and early pregnancy bleeding
  • Vaginal micronized progesterone increases the live birth rate
  • RR 1.08 (95% CI, 1.02 to 1.15); high-certainty evidence

Women with Recurrent Miscarriage

• Vaginal micronized progesterone probably makes little or no difference to the live birth rate vs placebo
  • RR 1.04 (95% CI, 0.95 to 1.15); high-certainty evidence
• The effects of dydrogesterone are unclear due to very low-certainty evidence
• No data available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone on live birth

Other Outcomes: Adverse Events and Congenital Anomalies

• There is probably no difference in other outcomes for vaginal micronized progesterone vs placebo (data limited for other progestogens)
  • Threatened miscarriage
    • Congenital abnormalities
      • RR 1.00 (95% CI, 0.68 to 1.46)
      • Moderate-certainty evidence
    • Adverse drug events
      • RR 1.07 (95% CI, 0.81 to 1.39)
      • Moderate-certainty evidence
  • Recurrent miscarriage
    • Congenital abnormalities
      • RR 0.75 (95% CI, 0.31 to 1.85)
      • Low-certainty evidence
    • Adverse drug events
      • RR 1.46 (95% CI 0.93 to 2.29)
      • Moderate-certainty evidence

Note: Data limited and very low‐certainty evidence on congenital abnormalities and adverse drug events for the other progestogens

CONCLUSION:

• Vaginal micronized progesterone increased the rate of live births among women with threatened miscarriage and ≥1 previous miscarriage
• There was no difference in adverse events between treatments and placebo

Learn More – Primary Sources:

Progestogens for preventing miscarriage: a network meta‐analysis

Related ObG Topics:

EPPPIC Meta-analysis Results: Progestogens for Preterm Birth Prevention

PRISM Trial Results: Does Progesterone for Bleeding Early in Pregnancy Prevent Pregnancy Loss?

A New Biomarker for the Detection of Miscarriage?