The PRISM trial
The results of the PRISM trial (progestersone in early pregnancy bleeding) were published in the New England Journal of Medicine on 9 May 2019.
The results showed that overall, among women with bleeding in early pregnancy, treatment with progesterone during the first trimester did not result in a significantly higher incidence of live births than amongst those who had a placebo (a pessary with no active ingredients).
Further analysis, however, showed that a sub-group of women with a history of recurrent miscarriage (three or more miscarriages before this pregnancy), did show a significant improvement in outcome for those who had the progesterone treatment. There was also a small improved outcome for those who had previously had one or two miscarriages.
November 2021: a new recommendation
On 24 November 2021, NICE, the National Institute of Health and Care Excellence, published new guidance [1] recommending treatment with progesterone for women with early pregnancy bleeding and at least one previous miscarriage.
Based on a systematic review of research studies[2], including the PRISM trial, the guidance includes new recommendations on the use of progesterone for women who have vaginal bleeding in early pregnancy and have had one or more previous miscarriages.
The recommendations are very specific:
- It is for women who have vaginal bleeding and have previously had at least one miscarriage
- They need to have had a scan that shows that here is a pregnancy in the uterus
- The treatment is with micronised progesterone[3], 400 mg, twice a day
- If a fetal (baby’s) heartbeat is seen on scan, treatment is continued until 16 completed weeks of pregnancy.
A bit more information
The NICE guidance does not recommend progesterone treatment for
- Women who have vaginal bleeding in early pregnancy but have not had a previous miscarriage
- Women who have had one or more previous miscarriages but don’t have any vaginal bleeding during early pregnancy.
It does, however, recommend further research into
- The possible benefits of progesterone for women with unexplained recurrent miscarriage
- Research into the effectiveness of other progesterone preparations
If you have any questions or concerns about the research or about possible treatment with progesterone, please do consult your GP or Early Pregnancy Unit.
If it might help just to talk, please do get in touch. You’ll find information about how we can help here.
Notes and references:
[1] www.nice.org.uk/guidance/ng126
[2] A Cochrane’s network meta-analysis – a review that combines data from several different studies
[3] Micronised progesterone is identical in structure to naturally produced progesterone
We provide information about the trial background below, and further down the page you can read comments from two women who took part in the trial.
About the PRISM trial
PRISM was a randomised, double-blind, placebo-controlled trial:
Randomised: The women who take part were given either the treatment drug (progesterone) or a placebo – a dummy drug that has no active ingredients. A computer made the selection so it was completely random.
Double-blind: The women in the study weren’t told whether they are taking the active medicine or the placebo – and neither were their doctors. So both were blinded to this information.
Placebo-controlled: Half the women in the study had the active medicine and half (the controls) had the placebo. The medicine that they received looked exactly the same to them and their doctors, but a completely separate group kept a record of which women had progesterone and which had the placebo.
Other information
Who could take part?
The researchers recruited women who:
- were aged 16 – 39
- were in the first 12 weeks of pregnancy and are having vaginal spotting or bleeding
- a scan showed an ongoing pregnancy
- were willing to be selected at random to have either the treatment or a placebo, without knowing which they are given.
What did participants need to do?
Women who agreed to take part were given a pack of capsules and asked to insert two capsules twice a day (morning and evening) into their vagina until 16 weeks of pregnancy.
The trial team collected most of their study information from hospital notes but may have made individual contact to check some details.
You can read Amanda and Faye’s accounts of taking part in the trial, at the bottom of this page.
Where did it take place?
The trial recruited women from 48 centres across England and Scotland:
- Barnstaple: North Devon District Hospital
- Birmingham: Birmingham Heartlands Hospital
- Birmingham: Birmingham Women’s Hospital
- Bradford: Bradford Royal Infirmary
- Bristol: St Michael’s Hospital
- Burnley: General Hospital
- Burton: Queen’s Hospital
- Carlisle: Cumberland Infirmary
- Chertsey: St Peter’s Hospital
- Coventry: University Hospital Coventry
- Edinburgh: Royal Infirmary of Edinburgh
- Exeter: Royal Devon & Exeter Hospital
- Glasgow: Glasgow Royal Infirmary
- Hull: Hull & E Yorks Women and Children’s Hospital
- Huntingdon: Hinchingbrooke Hospital
- Keighley: Airedale General Hospital
- Leeds: St James’s University Hospital
- Liverpool: Liverpool Women’s Hospital
- London: Chelsea & Westminster Hospital
- London: Kings College Hospital
- London: St Mary’s Hospital
- London: St Thomas’s Hospital
- London: University College London Hospital
- London: West Middlesex University Hospital
- London: Whipps Cross University Hospital
- Manchester: St Mary’s Hospital
- Merseyside: Whiston Hospital
- Middlesborough: James Cook University Hospital
- Newcastle: Royal Victoria Infirmary
- Nottingham: Queen’s Medical Centre
- Oxford: John Radcliffe Hospital
- Plymouth: Derriford Hospital
- Portsmouth: Queen Alexandra Hospital
- Preston: Royal Preston Hospital
- Redhill: East Surrey Hospital
- Scunthorpe: Scunthorpe General Hospital
- Sheffield: Royal Hallamshire Hospital
- Stoke-on-Trent: Royal Stoke University Hospital
- Sunderland: Sunderland Royal Hospital
- Taunton: Musgrove Park Hospital
- Telford: Princess Royal Hospital
- Walsall: Walsall Manor Hospital
- Warrington: Warrington Hospital
- Wolverhampton: New Cross Hospital
- Worcester: Worcester Royal Hospital
Some personal views
Amanda took part in the PRISM trial. She writes:
At 6 weeks pregnant I was bleeding and went to the Early Pregnancy Unit at University College Hospital, London. Here I was offered the chance to take part in the PRISM trial.
With the potential outcome of not miscarrying I was very keen to learn more. I was told about the possible side effects, and also that I might only be taking a placebo. I read up on how successful taking progesterone only has been in other countries. I felt that it was a great opportunity to not only support the trial for women in this country but also giving my fetus an extra chance of not miscarrying. So I agreed to take part.
During the trial I was given fantastic one to one advice from the PRISM research team. It was extremely reassuring knowing that I had a point of contact thought my pregnancy, someone who I could contact any time. She was easy to talk to and answered any of my questions, putting my mind at rest. I also had additional scans, to see the progress of my fetus, which was fantastic.
I was a little uncomfortable about using the (vaginal) pessaries to start with and worried – would I use them properly, would they have side effects. After literally 24 hours I was inserting the pessaries with ease and with no discomfort. I found wearing a pantie liner useful for any discharge that I had.
I travel a lot for work which was another worry but taking the pills didn’t affect my day to day life at all.
I don’t know if I took the progesterone or a placebo, but I am so pleased that I was lucky enough to take part in the trial. I am now 38 weeks pregnant, with a healthy baby girl on her way.
Faye also took part in the PRISM trial, and writes:
I was signed up to the PRISM trial after having bleeding in early pregnancy. After experiencing three miscarriages since the birth of my son it was a relief to feel like we were doing something proactive in this pregnancy.
I obviously don’t know whether the trial made a difference to this pregnancy’s outcome, but I was absolutely delighted when our baby daughter was born. We’ve waited two years for her arrival and experienced a lot of heartache along the way so I just wanted to say thank you for offering hope to more parents through these trials.