Live birth rates were no higher after progesterone therapy, as compared with placebo, during the first trimester of pregnancy in women with a history of unexplained recurrent miscarriages, according to data published in the New England Journal of Medicine.
“The physiological importance of progesterone in early pregnancy has prompted the performance of several trials to evaluate the effect of progesterone supplementation in the first trimester of pregnancy among women with a history of recurrent miscarriages,” researchers wrote in the study. They noted, however, that the studies were of low quality.
In the multicenter, double-blind, placebo-controlled PROMISE (Progesterone in Recurrent Miscarriages) trial, researchers sought to assess outcomes among women with a history of unexplained recurrent miscarriages who were randomly assigned to placebo or twice daily vaginal suppositories containing 400 mg of micronized progesterone.
Treatment was initiated from a time soon after a positive pregnancy test through 12 weeks of gestation. Women were excluded if they were unable to conceive within 1 year of recruitment.
The primary outcome was live birth after 24 weeks of gestation.
A total of 836 women were assigned progesterone (n=404) or placebo (n=432), with a follow-up rate of 98.8% for the primary outcome (n=826).
Results from an intention-to-treat analysis revealed no significant difference in the live birth rates between the progesterone group (65.8%; 262 of 398 women) and the placebo group (63.3%; 271 of 428 women). The relative rate was 1.04 (95% CI, 0.94-1.15), with a rate difference of 2.5 percentage points (95% CI, -4.0 to 9.0).
“We had hoped, like many people, that this research would confirm progesterone as an effective treatment,” study researcher Arri Coomarasamy, MBChB, MD, of the University of Birmingham in the United Kingdom, said in a press release.
“Though disappointing, it does address a question that has remained unanswered since progesterone was first proposed as a treatment back in 1953. Fortunately, there are a number of other positives that we can take from the trial as a whole.”
The researchers observed no significant differences in neonatal or obstetrical adverse outcomes between groups, which may also help add to the knowledge base regarding progesterone therapy, according to Dr Coomarasamy.
“It may well be that progesterone supplements have other uses, such as preventing miscarriage in women with early pregnancy bleeding, so it’s not the end of the road,” Dr Coomarasamy noted.
“Furthermore, the PROMISE trial created a solid network of doctors, nurses, and midwives across the U.K. and beyond, all committed to miscarriage research. That wealth of expertise and information will be invaluable as we continue to explore and test other treatments that really can reduce the risk of miscarriage,” added Dr Coomarasamy.