Can progesterone really prevent miscarriage?

There has been a lot of debate around whether progesterone supplementation in early pregnancy can help to prevent miscarriage. By carrying out a complex analysis of all the previous research, our team have shown for certain that progesterone treatment should be recommended for the treatment of women with early pregnancy bleeding who have previously had a miscarriage.
  • Authors list

    Professor Arri Coomarasamy, Dr Ioannis Gallos, Professor Siobhan Quenby, Professor Jan Brosens, Professor Phillip Bennett, Professor Tom Bourne, Dr Adam Devall, Dr Rima Dhillon-Smith, Dr Maya Al-Memar, Rajinder Kaur and external collaborators 

    Start date: 2016
    End date: 2021

Why do we need this research?

Miscarriage is far too common – around 1 in 5 women will experience this devastating loss at some point in their lifetime. We urgently need new treatments that can stop this from happening.

Over the last few years, there has been a lot of debate around whether the hormone progesterone can be used to prevent miscarriage. Progesterone is naturally released by the female body and is essential to maintain a healthy pregnancy. The clear importance of this hormone led researchers to investigate whether progesterone supplementation in the first trimester of pregnancy can help to prevent miscarriage. Trials were carried out in women with a history of recurrent miscarriage – three or more miscarriages in a row – and in women with no history of miscarriage who were​​​​​​​ bleeding in early pregnancy. By combining the results of these trials, it was initially thought that progesterone did prevent miscarriage. However, some of these trials were of poor quality, with different types of progesterone being used, and more research was needed to confirm these results. 

The PRISM and PROMISE studies

More recently, researchers funded by Tommy’s have taken part in two large clinical trials to find out whether treatment with progesterone in the first few weeks of pregnancy really does help to prevent miscarriage. The first of these –​​​​​​​ the PRISM study – included over 4,000 women who had bleeding in early pregnancy. This study found that progesterone did reduce the number of miscarriages, but only in those who had experienced a previous miscarriage. The effect was greatest in women with a history of three or more miscarriages.

The second study – called PROMISE – looked at whether progesterone prevented miscarriage in over 800 women who had experienced three or more previous miscarriages. The women in this study had no symptoms of miscarriage when they were treated with progesterone. Unfortunately, progesterone did not reduce the risk of another miscarriage in these women.

What happened in this project?

Researchers at the Tommy’s National Centre for Miscarriage Research have been working with other scientists to conduct a network meta-analysis into the effect of progesterone treatment in early pregnancy. A network meta-analysis is a complex analysis that combines the results of all relevant trials into a single, clear result. The results of this analysis were consistent with the PRISM study – based on data from two studies, progesterone was shown to increase the chances of women with early pregnancy bleeding having a live birth, but only in those women who had already experienced one or more previous miscarriage. The team also looked for studies into progesterone use in women who had experienced recurrent miscarriage but who had no symptoms of miscarriage and found that the PROMISE study was the only relevant study in this group of women.

What difference will this project make?

This network meta-analysis, along with the PRISM and PROMISE studies, has finally answered the question of whether progesterone should be given to women who are at high risk of having a miscarriage. As a result, NICE treatment guidelines were updated in November 2021 to recommend that progesterone should be given to women with early pregnancy bleeding who have previously had a miscarriage. Our research will therefore have a direct impact on clinical practice and should enable more parents to get the treatment they need to prevent miscarriage.