Research led by the University of Birmingham suggests that giving progesterone to pregnant women with early pregnancy bleeding and a history of miscarriage could increase their chances of having a baby.

The PRISM trial, funded by the National Institute for Health Research (NIHR) and co-ordinated by Birmingham Clinical Trials Unit in collaboration with Tommy’s National Centre for Miscarriage Research, is the largest ever trial of its kind and involved 4,153 pregnant women who presented with early pregnancy bleeding.

The women, being treated at 48 hospitals across the UK and with the average age of 31, were randomly assigned by computer into one of two groups – one group of 2,079 women were given progesterone, while the other group of 2,074 women were given a placebo.

Dr Adam Devall, Senior Clinical Trial Fellow at the University of Birmingham and Manager of Tommy’s National Centre for Miscarriage Research, explained: “Miscarriage is a common complication of pregnancy, affecting one in five women, and vaginal bleeding in early pregnancy is associated with a one in three risk of miscarriage.

“Several small studies have suggested that administering progesterone, a hormone essential for maintaining a pregnancy, may reduce the risk of miscarriage in women presenting with early pregnancy bleeding.

“The PRISM trial was undertaken to answer a very important research question; whether progesterone given to pregnant women with threatened miscarriage would increase the number of babies born after at least 34 weeks of gestation when compared with a placebo.”

While the research did not show statistically strong enough evidence to suggest that progesterone could help all women who are suffering early pregnancy bleeding to go on to have a baby, importantly the results did show the hormone benefitted those who had early pregnancy bleeding and had previously suffered a miscarriage.

The researchers found that there was a 4% increase in the number of babies born to the women in the study who were given progesterone and had previously had one or two miscarriages compared to those given a placebo. (Of the 777 women given progesterone who had previously had one or two miscarriages, 591 (76%) went on to have a live birth, compared with 534 women out of 738 in the placebo group (72%).)

The benefit was even greater for the women who had previous ‘recurrent miscarriages’ (i.e., three or more miscarriages) – with a 15% increase in the live birth rate in the progesterone group compared to the placebo group. (Of the 137 women taking part in the trial who had previously had three or more miscarriages, 98 (72%) went on to have a live birth, compared to 57% (85 out of 148) women in the placebo group who went on to have a baby).

The ground-breaking research was published today in the New England Journal of Medicine.

Arri Coomarasamy, Professor of Gynaecology at the University of Birmingham and Director of Tommy’s National Centre for Miscarriage Research, said: “The role of progesterone in women with early pregnancy bleeding has been studied and debated for about 60 years, however what we have previously lacked is high quality evidence.

“The largest study before the PRISM trial had less than 200 participants; whereas our study had more than 4,000 participants and was of very high quality, which means we can be confident in our findings.

“Our finding that women who are at risk of a miscarriage because of current pregnancy bleeding and a history of a previous miscarriage could benefit from progesterone treatment has huge implications for practice. This treatment could save thousands of babies who may have otherwise been lost to a miscarriage.

“We hope that this evidence will be considered by the National Institute for Health and Care Excellence (NICE) and that it will be used to update national guidelines for women at risk of miscarriage.”

Jane Brewin, Chief Executive of Tommy’s, said: “The results from this study are important for parents who have experienced miscarriage; they now have a robust and effective treatment option which will save many lives and prevent much heartache.

“It gives us confidence to believe that further research will yield more treatments and ultimately make many more miscarriages preventable.”

Samantha Allen, aged 31, of Bradford, is married to 36-year-old Stephen. Samantha, who suffered a miscarriage in December 2015, was recruited to the PRISM trial in June 2017 when she was nine weeks pregnant and she was in the group of participants that were given progesterone. The couple’s son, Noah, was born in February 2018 weighing 9lbs 6oz.

She said: “It was on my birthday in November 2015 when I found out that I was pregnant; it was the best birthday gift I could have hoped for.

“However, my joy soon started to turn to concern when I began having some bleeding when I was around seven weeks pregnant and I ended up in A&E. I had a scan and was told to come back on Christmas Eve for another scan.

“But then on December 23rd I started bleeding quite heavily and had to call an ambulance. I was taken to A&E where I was told the baby had died when I was eight weeks pregnant and I was miscarrying. The following day, on Christmas Eve, I had to also go through the trauma of miscarriage surgery.

“Words can’t describe our devastation. I think people can often be dismissive of miscarriage when it happens in early pregnancy, you are treated as a statistic and told it’s common. But I am not a statistic, we lost our child and it is a loss we will always grieve.

“Around 15 months after I miscarried I found out I was pregnant again and I was delighted. However, when I was around seven weeks pregnant I started having spotting and, given my previous loss, I decided to go to the early pregnancy unit.

“I had a scan and they said they thought they could detect a heartbeat but weren’t certain, so booked me in for another scan two weeks later.

“The spotting continued during those two weeks, so I was relieved when the second scan showed I was pregnant.

“That’s when they told me about the PRISM trial and I decided to take part.

“I was prescribed progesterone pessaries which I self-administered until I was 16 weeks pregnant.

“The bleeding stopped within a week of starting the trial, and apart from having some issues with a condition called symphysis pubis dysfunction, which causes pelvic pain in pregnancy, my pregnancy went really well.

“I opted for a water birth and Noah was born weighing a very healthy 9lbs 6oz in February last year. He’s now 14 months old and he’s such a lively and incredibly bright little boy who brings us so much joy, I can’t imagine life without him.

“Of course, we’ll never know whether or not I would have miscarried if I had not taken part in the trial, or if I had been part of the group that received the placebo, either way I feel fortunate and happy that I did participate. I hope the results of the trial will make a difference to the way women receive treatment moving forwards, and that I had a small part to play in that.”

For more information please contact Emma McKinney, Communications Manager (Health Sciences), University of Birmingham, tel: +44 (0) 121 414 6681, or contact the press office out of hours on +44 (0) 7789 921 165.

• The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 6,500 international students from over 150 countries.
• Coomarasamy et al (2019). ‘A Randomized Trial of Progesterone in Women with Early Pregnancy Bleeding’. New England Journal of Medicine.
• The research was supported by the United Kingdom NIHR Health Technology Assessment Programme (project number HTA 12/167/26).
• The women in the group who received progesterone were given 400mg twice daily as vaginal pessaries. The women in the placebo group received a placebo with an identical appearance. They were given the progesterone or placebo from presentation with bleeding and confirmation of a pregnancy seen on ultrasound scan no later than 12 weeks of gestation, until 16 completed weeks of gestation or earlier if the pregnancy ended before 16 weeks. Recruitment to the trial took place from May 19, 2015, through to July 27, 2017. Follow-up of patients was completed by June 2018.
• The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR:

1. Funds, supports and delivers high quality research that benefits the NHS, public health and social care
2. Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
3. Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
4. Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
5. Partners with other public funders, charities and industry to maximise the value of research to patients and the economy

• NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR commissions applied health research to benefit the poorest people in low- and middle-income countries, using Official Development Assistance funding.
• The research was carried out by:

1. University of Birmingham: Arri Coomarasamy, Adam Devall, Versha Cheed, Hoda Harb, Lee Middleton, Ioannis Gallos, Helen Williams, Tracy Roberts, Chidubem Ogwulu, Andrew Ewer
2. University of Iowa: Abey Eapen
3. University of Melbourne: Ilias Goranitis
4. University of Nottingham: Jane Daniels
5. Sunderland Royal Hospital: Amna Ahmed, Kim Hinshaw
6. The Miscarriage Association: Ruth Bender Atik
7. East Lancashire Hospitals NHS Trust: Kaslang Bhatia
8. University College London Hospitals NHS Foundation Trust: Cecilia Bottomley, Kathiuska Kriedt, Davor Jurkovic
9. Tommy’s: Jane Brewin
10. Newcastle Upon Tyne Hospitals NHS Foundation Trust: Meenakshi Choudhary
11. Lancashire Teaching Hospitals NHS Foundation Trust: Fiona Crosfill
12. Nottingham University Hospitals NHS Trust: Shilpa Deb
13. University of Edinburgh: Colin Duncan
14. Guy's and Saint Thomas' NHS Foundation Trust: Tom Holland
15. University Hospital Coventry: Feras Izzat
16. King's College Hospital NHS Foundation Trust: Jemma Johns, Jackie Ross
17. University of Glasgow: Mary-Ann Lumsden
18. James Cook University Hospital: Padma Manda
19. University of Edinburgh: Jane Norman, Andrew Horne
20. Chelsea and Westminster Hospital NHS Foundation Trust: Natalie Nunes
21. St Michael's University Hospital: Caroline Overton
22. University of Warwick: Siobhan Quenby
23. St Helens and Knowsley Teaching Hospitals NHS Trust: Sandhya Rao
24. Barts Health NHS Trust: Anupama Shahid
25. Shrewsbury and Telford Hospital NHS Trust: Martyn Underwood
26. Portsmouth Hospitals NHS Trust: Nirmala Vaithilingam
27. Liverpool Womens NHS Foundation Trust: Linda Watkins
28. Surrey and Sussex Healthcare NHS Trust: Catherine Wykes