The PRISM trial: Progesterone therapy does not alter birth outcomes in women with early pregnancy bleeding

1. Women with early pregnancy bleeding administered progesterone experienced similar rates of live births occurring after 34 weeks’ gestation as women treated with placebo.

2. Subgroup analysis was generally inconclusive, though many subgroups had risk ratios approaching significance supporting progesterone use.

Evidence Rating Level: 1 (Excellent)  

Study Rundown: Miscarriages are not uncommon in pregnancy and are associated with various adverse outcomes. Progesterone use during pregnancy has been evaluated in various contexts as a possible treatment to support pregnancy viability. The Progesterone in Spontaneous Miscarriage (PRISM) trial evaluated if progesterone treatment for women with early pregnancy bleeding results in a higher incidence of live births than placebo treatment. Women treated with progesterone experienced similar rates of live birth as those treated with placebo. Incidence of adverse events was similar between treatment groups as well.

This large, double-blind study provides further clarity on evidence-based uses for progesterone treatment in pregnancy. Its strengths include its large sample size, randomized design, and extensive subgroup analysis. The study was limited by evaluating a single route and routine of progesterone administration and progesterone was not utilized beyond 16 weeks of gestation.

Click to read the study, published today in NEJM

Click to read an accompanying editorial in NEJM

Relevant Reading: Bleeding in early pregnancy

In-Depth [randomized controlled trial]: This double-blinded, placebo-controlled, randomized controlled trial enrolled women between 2015 and 2017. Eligible participants were between 16 and 39 years old, had completed 12 weeks or less of pregnancy, presented with vaginal bleeding, and had an intrauterine gestational sac visible on ultrasound. Participants were randomized into a progesterone group (n=2025) or a placebo group (n=2013). Both groups were administered treatment vaginally or rectally twice daily from the time of study enrollment through 16 weeks of gestation. The primary outcome of live birth at 34 weeks of gestation or greater occurred in 75% and 72% of progesterone and placebo groups, respectfully (relative rate [RR], 1.03; 95% CI, 1.00 to 1.07; P=0.08). Imputation analysis to correct for missing data also showed no significant difference in treatment outcomes. The incidence of miscarriage was 20% and 22% in the progesterone and placebo groups, respectfully (RR, 0.91; 95% CI, 0.81 to 1.01). The incidence of live births in women who had three or more previous miscarriages was 72% and 57% for the progesterone and placebo groups, respectfully (RR, 1.28; 95% CI, 1.08 to 1.51). Maternal or neonatal adverse events did not significantly differ between treatment groups.

Image: PD

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