Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence.
Level 5 - mechanism / opinion, no new human data
Narrative review and critical evaluation summarizing findings from two specific randomized controlled trials.
PubMed 32008730 · doi:10.1016/j.ajog.2019.12.006
What was done
This paper critically evaluated randomized evidence on first-trimester vaginal micronized progesterone (400 mg twice daily) to prevent miscarriage. It synthesized data from two large multicenter, placebo-controlled trials: the PROMISE trial (836 women with unexplained recurrent miscarriages across 45 hospitals in the UK and the Netherlands) and the PRISM trial (4,153 women with early pregnancy bleeding across 48 hospitals in the UK).
What was found
Overall, progesterone was associated with a 3% greater live birth rate in PROMISE (with substantial statistical uncertainty) and a 3% greater live birth rate in PRISM (P = .08). In a prespecified PRISM subgroup of women presenting with early pregnancy bleeding and a history of 1 or more previous miscarriages, progesterone increased live births: 75% (689/914) vs 70% (619/886) with placebo (rate difference 5%; RR 1.09, 95% CI 1.03–1.15; P = .003). For women with bleeding and 3 or more previous miscarriages, live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; RR 1.28, 95% CI 1.08–1.51; P = .004). No short-term safety concerns were identified.
Why it matters
These findings identify a clear, actionable subgroup—women with early pregnancy bleeding and a history of previous miscarriage—who derive meaningful benefit from vaginal micronized progesterone to increase live birth rates.
Limits
The overall main effects in both trials showed statistical uncertainty or borderline significance (P = .08 in PRISM), with clear benefit emerging primarily in subgroup analyses. Long-term developmental outcomes and populations outside the UK and Netherlands were not evaluated in the abstract.
Cited by
- context Low progesterone levels are a primary cause of miscarriage.