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.