Progesterone supplementation in the first trimester of pregnancy does not improve outcomes for women with unexplained recurrent miscarriages, according to a large clinical trial.
The PROMISE trial conducted in the UK and Netherlands included 826 women aged between 18–39 years with a history of recurrent miscarriages. Participants received either twice-daily vaginal preparations of 400 mg progesterone or placebo from shortly after conception up to the 12th week of pregnancy. Neither participants nor doctors knew which they were receiving.
During the study, almost two-thirds of participants gave birth at 24 weeks gestation or later. With a live birth rate of 65.8 percent and 63.3 percent in the progesterone therapy and placebo group, respectively, the researchers concluded that administration of progesterone does not significantly affect the rate of live births. This was true regardless of the women's age, ethnicity, medical history and pregnancy history.
Progesterone is produced naturally in early pregnancy by the corpus luteum in the ovary, and is essential to help achieve and maintain early pregnancy. For this reason, many studies have sought to evaluate the effectiveness of supplementation for reducing the risk of recurrent miscarriages.
After 60 years of uncertainty, the researchers say the PROMISE trial, which is published in the New England Journal of Medicine, should provide a conclusive answer.
Lead author, Professor Arri Coomarasamy, from the University of Birmingham, commented, 'We had hoped, like many people, that this research would confirm progesterone as an effective treatment. Though disappointing, it does address a question that has remained unanswered since progesterone was first proposed as a treatment back in 1953.'
Contrary to the results of this trial, previous findings from a Cochrane analysis of four small studies support the use of first-trimester progesterone therapy. However, these trials had 'substantive methodological limitations', the authors of the current study state.
Professor Coomarasamy said, 'Fortunately, there are a number of other positives that we can take from the trial as a whole.' For example, no statistical difference in adverse outcomes (such as congenital abnormalities) between the groups were reported. This is reassuring for women who take progesterone for fertility treatment purposes or those involved in other trials.
'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,' Professor Coomarasamy added.