A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.
Level 2 - randomized trial
Multicenter, double-blind, placebo-controlled randomized trial
PubMed 31067371 · doi:10.1056/NEJMoa1813730
What was done
A multicenter, randomized, double-blind, placebo-controlled trial across 48 hospitals in the United Kingdom evaluated progesterone therapy in women with vaginal bleeding in early pregnancy. A total of 4,153 women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone (2,079 women) or matching placebo (2,074 women) twice daily from presentation with bleeding through 16 weeks of gestation. The primary outcome was live birth after at least 34 weeks of gestation, evaluated among participants with available outcome data (97%, 4,038 of 4,153) and with multiple imputation sensitivity analysis.
What was found
The incidence of live births after at least 34 weeks of gestation was 75% (1,513 of 2,025 women) in the progesterone group versus 72% (1,459 of 2,013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis using multiple imputation yielded an identical estimate (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between groups.
Why it matters
This large trial indicates that routine first-trimester vaginal progesterone supplementation does not significantly improve live birth rates in the broad population of women presenting with early pregnancy bleeding.
Limits
The abstract does not report subgroup analyses (such as history of recurrent pregnancy loss), reports only a single administration route and dose (400 mg vaginally twice daily through 16 weeks), and is limited to women recruited within UK hospitals.
Cited by
- context Low progesterone levels are a primary cause of miscarriage.