This trial is now complete.
The PROMISE trial was the largest yet trial into treating unexplained recurrent miscarriage with progesterone. It was led by Professor Arri Coomarasamy, Director of the Tommy’s National Centre for Miscarriage Research.
Recurrent miscarriage, the loss of 3 or more pregnancies in a row, affects around 1% of couples. Even after investigations, most do not get a cause for their losses. Alongside the physical trauma of repeated miscarriages, this can have severe consequences for mental health and relationships.
The role of progesterone in early pregnancy
Progesterone is a hormone that is released naturally by the female body in the the second half of the menstrual cycle in early pregnancy. Progesterone prepares the lining of the womb for implantation of the embryo.
If implantation happens, progesterone continues to be produced, and at between 8 and 12 weeks of gestation, the placenta takes over the role of producing progesterone and maintains the pregnancy from there on.
Previous research into progesterone supplementation in early pregnancy
The clear importance of progesterone in early pregnancy has prompted a number of research trials to evaluate the effect of progesterone supplementation in the first trimester of pregnancy among women with a history of recurrent miscarriages.
A Cochrane review of four small trials showed a significantly lower risk of miscarriages among women who received progesterone than among those who received placebo or no treatment. The results were exciting but unfortunately the quality of the four trials was considered to be poor.
The PROMISE trial design
In response Professor Coomarasamy designed PROMISE, very high quality a multi-centre, randomised, placebo-controlled trial to see if he could replicate these findings.
- Women had to have had 3 or more unexplained miscarriages.
- Those who took part were randomly given vaginal suppositories twice daily containing either 400 mg of micronized progesterone (Utrogestan, Besins Healthcare) or a similar-looking placebo.
- They started taking them from a time soon after getting a positive pregnancy test (and no later than 6 weeks of pregnancy) through 12 weeks.
- 836 women who had signed up to the trial and conceived naturally within a year took part in the PROMISE trial.
Results of PROMISE
A successful outcome was considered to be a live birth after 24 weeks of gestation.
- For those who received progesterone, it was was 65.8% (262 of 398 pregnancies) in the progesterone group
- For those got the placebo, it was 63.3% (271 of 428 pregnancies).
The difference between the groups was not statistically significant and these results did NOT support the earlier smaller trials. Progesterone was not shown to reduce the risk of another miscarriage in those who have suffered recurrent losses.
Although the results are disappointing, it is helpful after many years of uncertainty, for health professionals to know that progesterone treatment in early pregnancy isn’t the answer for women with unexplained recurrent losses.
The trial did not show that supplementing with progesterone was in any way harmful in pregnancy.
The clear results also mean that researchers can focus on looking at new reasons and treatments.
Professor Coomarasamy and his team have started another trial called PRISM, investigating the role of progesterone in a new group, those who have vaginal bleeding in early pregnancy. This trial is due to report in 2019.
More miscarriage research projects
Craig, 36, lives in North Wales with his fiancée Kerry and her 6-year-old son Jacob. His job as a radio presenter and station director was difficult after the loss of their baby boy Ellis, having to entertain listeners while battling grief, but he’s now using his talent for public speaking to break the silence on miscarriage by sharing their family’s story.
Priyah and Markus from North London started trying for a baby in 2018. Sadly, in the past 2 years, they have experienced 2 miscarriages. In this blog, Markus reflects on what it feels like to lose a baby from a partner’s perspective.
Nicola sadly experienced a miscarriage just before her 12-week scan. As a doctor, she was not used to being in hospital as a patient - but has been inspired to share her story by the support she received.
Jag and her husband coped with the loss of their son in very different ways. In this blog, she reflects on the grieving process and the support that has helped her to manage the pain of her ‘favourite what if’.
A recently published article, co-authored by Professor Catherine Williamson from Tommy’s Research Centre at King’s College London, suggests that certain pregnancy complications can indicate future health issues for women.
Tommy’s has received a grant from the UK Government’s Department for Health and Social Care to support the costs of its PregnancyHub information and support services throughout the summer, due to rising demand in the wake of coronavirus.
Although recruitment to some clinical trials had to be paused when coronavirus hit the UK, scientists at Tommy’s Research Centres across the UK are still hard at work, supporting women and families in our specialist clinics and sharing their latest studies with academic journals.
The day before Mother’s Day, and two days before the UK officially went into coronavirus lockdown, Zara Dawson found out she was having a miscarriage. Her third consecutive miscarriage in less than a year, and fourth consecutive loss, after losing her second son Jesse in 2018 to termination for medical reasons.