A randomized trial of progesterone in women with recurrent miscarriages

BACKGROUNDProgesterone is essential for the maintenance of pregnancy. However, whetherprogesterone supplementation in the first trimester of pregnancy would increasethe rate of live births among women with a history of unexplained recurrent miscarriages is uncertain.METHODSWe conducted a multicenter, double-blind, placebo-controlled, randomized trial toinvestigate whether treatment with progesterone would increase the rates of livebirths and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice daily vaginal suppositories containing either 400 mg of micronized progesteroneor matched placebo from a time soon after a positive urinary pregnancy test (andno later than 6 weeks of gestation) through 12 weeks of gestation. The primaryoutcome was live birth after 24 weeks of gestation.RESULTSA total of 1568 women were assessed for eligibility, and 836 of these women whoconceived naturally within 1 year and remained willing to participate in the trialwere randomly assigned to receive either progesterone (404 women) or placebo(432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of398 women) in the progesterone group and 63.3% (271 of 428 women) in theplacebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; ratedifference, 2.5 percentage points; 95% CI, −4.0 to 9.0). There were no significantbetween-group differences in the rate of adverse events.CONCLUSIONSProgesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplainedrecurrent miscarriages. (Funded by the United Kingdom National Institute ofHealth Research; PROMISE Current Controlled Trials number, ISRCTN92644181.