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 should finally find out whether the use of progesterone should be recommended.
  • Author's 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: 2020

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 has led researchers to investigate whether progesterone supplementation in the first trimester of pregnancy can help to prevent miscarriage. Trials have been 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 so 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 in these women, 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, in this study, progesterone did not reduce the risk of another miscarriage in women who have suffered recurrent losses.

What’s happening in this project?

Now, researchers at the Tommy’s National Centre for Miscarriage Research are 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 enables the researchers to combine the results of lots of relevant trials into a single, clear result. The team are looking at any relevant trial that used progesterone to treat women with bleeding in early pregnancy, or women who had experienced recurrent miscarriage. They want to find out whether progesterone treatment reduced the number of women who had a miscarriage and increased the number of women who had a live birth. They will also look at the safety of progesterone treatment and will check what effect it had on other pregnancy complications, such as premature birth, stillbirth and ectopic pregnancy.

What difference will this project make?

This network meta-analysis is essential to finally answer the question of whether progesterone should be given to women who are at high risk of having a miscarriage. Along with the results of the PRISM and PROMISE studies, the results of this analysis will be used to update treatment guidelines in the UK, and so will have a direct impact on clinical practice.