Vaginal progesterone shows no benefit for preventing unexplained recurrent miscarriages: The PROMISE study

1. Women with a history of unexplained recurrent miscarriages who were treated with vaginal progesterone during the first trimester did not have a significant difference in rate of live births compared to those who received placebo.

2. There were no differences in terms of neonatal outcomes or anomalies between the treatment and placebo groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Recurrent miscarriages affect approximately 1% of couples seeking to have a child. Previous research, including a Cochrane review of four small trials, showed a benefit of progesterone in early pregnancy in lowering the risk of further miscarriages. The Progesterone in Recurrent Miscarriages (PROMISE) trial was a multicenter randomized, placebo-controlled trial specifically designed to assess the potential benefit of progesterone in early pregnancy. The trial involved 836 patients who had been diagnosed with unexplained recurrent miscarriages, defined as 3 or more consecutive or nonconsecutive losses of pregnancy in the first trimester.

In an intention-to-treat analysis, the trial did not show a significant difference in rate of live births in women in their first trimester treated with vaginal progesterone versus those treated with placebo. There were no significant differences in terms of adverse outcomes, such as congenital anomalies. The strengths of this trial are its randomized, placebo-controlled design and the relatively large number of patients involved. Previous trials were often not placebo controlled, and varied greatly in methodology. The findings of this study are in direct contrast with a previous Cochrane review.

Click to read the study, published today in NEJM

Relevant Reading: Progesterone for preventing miscarriage

In-Depth [randomized controlled trial]: The PROMISE trial involved 1568 women with unexplained recurrent miscarriages. After assessing for eligibility, 836 were randomized to receive progesterone (daily vaginal suppositories containing 400mg of micronized progesterone) or placebo suppositories, which were continued from no later than 6 weeks of gestation until 12 weeks of gestation. The rate of live births after 24 weeks of gestation was 65.8% in the treatment group compared with 63.3% in the placebo group (RR, 1.04; 95% [CI], 0.94 to 1.15; absolute rate difference, 2.5%; 95% [CI], -4.0 to 9.0). The hazard ratio for miscarriage in the progesterone group compared to the placebo group was 1.04 (95% [CI], 0.91 to 1.19). Additionally, there were no significant differences in terms of other outcomes including rates of clinical pregnancy at 6 to 8 weeks, ongoing pregnancy at 12 weeks, ectopic pregnancy, miscarriage, stillbirth, or neonatal outcomes.

Image: PD

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