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
I never found out the reason for my miscarriage. Without an explanation, you start to blame yourself
In this piece, one of our supporters shares the traumatic experience of her miscarriage. She speaks of the physical and emotional pain it caused, and how difficult it is to grapple with the feelings of guilt, grief, and future uncertainty.
After giving birth to her son Noah in 2012, Faye and her husband Dean had 3 miscarriages. In 2015, Faye took part in the PRISM trial led by researchers at Tommy’s National Centre for Miscarriage Research. Her daughter Leila was born in 2016.
I was a broken mess and I felt like my grief was wrong because it wasn’t a real baby, like I was being dramatic, over-the-top.
Toni and her husband Matt had a miscarriage in 2015 which left Toni with PTSD. The couple live in Leicester with daughters Phoebe and Willow. This is Toni's story.
Roslyn and Paul from South Ayrshire in Scotland had an early miscarriage before getting pregnant with their first daughter Ava who is now 4 years old. They went on to lose another 3 babies before getting a referral to Tommy’s National Centre for Miscarriage Research at University Hospital in Coventry. Their second daughter, Ciara, was born in April 2019 and is now 7 months old.
We asked our lovely friend and supporter, Jennie Agg, what motherhood and Mother's Day means to her. In this piece, she speaks of her difficult past experiences of Mother's Day, how she has grappled with a sense of being in limbo, and the ultimate purity of her feeling of mother love.
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New research has revealed the benefits of giving progesterone to women with early pregnancy bleeding and a history of miscarriage.
Tommy’s spent yesterday morning at the charming Foundling Museum in London, celebrating the work of Tommy’s National Centre for Maternity Improvement alongside the opening of the museum’s new exhibition, ‘Portraying Pregnancy’.