BACKGROUND AND PURPOSE:

• Evidence is limited as to whether progesterone supplementation early in pregnancy may be beneficial to prevent miscarriage for those with bleeding in pregnancy
• Coomarasamy et al. (NEJM, 2019), examined whether progesterone administered to women who are bleeding early in pregnancy results in a higher incidence of live birth ≥34 weeks

METHODS:

• Multicenter, randomized, double-blind, placebo-controlled trial
• Participants
  • 16 to 39 years of age
  • <12 weeks of pregnancy
  • Vaginal bleeding,
  • Gestational sac on ultrasound (intrauterine)
• Randomized to
  • Progesterone arm: 400 mg vaginal suppositories twice a day from time of bleeding to 16 weeks
  • Control: Matching placebo
• Primary outcome: Incidence of live-born ≥34 weeks
• Multiple secondary outcomes including ongoing pregnancy beyond 12 weeks, miscarriage, live birth <34 weeks etc.
• Statistical analysis
  • Power calculation: 90% power to detect a minimally important absolute difference of 5 percentage points between groups
  • 1,972 women required in each arm with plan to include 4150 to account for loss to follow-up

RESULTS:

• 4,153 women | 48 UK hospitals
  • Progesterone: 2079 women | Placebo 2074 women
  • 97% of women available for analysis (primary outcome)
• Incidence of live births ≥34 weeks was similar in the two groups (P=0.08)
  • Progesterone: 75%
  • Control: 72%
  • Relative rate 1.03 (95% CI, 1.00 to 1.07
  • When accounting for missing data, there was still no significant difference between groups
• Secondary outcomes
  • Overall, there were no significant differences found for either maternal or fetal outcomes
  • The only finding was a small increase in ongoing pregnancy beyond 12 weeks (83% vs 80%; 95% CI, 1.04 (95% CI, 1.01 – 1.07)
• Only one subgroup, women with ≥3 previous losses, showed a statistical difference for primary outcome (P=0.007)
  • Progesterone: 72%
  • Control: 57%
  • RR 1.28 (95% CI, 1.08 to 1.51)

CONCLUSION:

• Progesterone therapy did not impact outcomes in women with bleeding early in pregnancy
• Progesterone therapy for women with bleeding in pregnancy did not result in more live births ≥34 nor most clinically relevant secondary maternal or fetal outcomes
• Authors caution that in the case of multiple miscarriages and subgroup analysis of pregnancy lasting beyond 12 weeks
  • Confirmation of results is required as there was no adjustment for multiple comparisons  

Learn More – Primary Sources:

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy

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