The PRISM trial - bleeding in early pregnancy and miscarriage

UPDATED 08/05/2019. This trial is now completed

The PRISM trial is an important trial into a potential treatment for bleeding in early pregnancy, led by Professor Arri Coomarasamy, Director of the Tommy’s National Centre for Miscarriage Research.

When a woman has bleeding in early pregnancy her risk of miscarriage increases:

• 1 in 3 women have a miscarriage
• 2 in 3 women go on to carry the baby to full term.

This research trial looked at whether progesterone can prevent miscarriage in women with early pregnancy bleeding.

How was the trial carried out?

4153 women took part in the trial in 48 hospitals across the UK.

Of those who were pregnant and experienced vaginal bleeding, around half were given progesterone pessaries (400mg) to take twice a day, and the other half were given dummy tablets.

A pessary is a tablet that you insert into your vagina (similar to inserting a tampon). Women were asked to do this twice a day until 16 weeks of pregnancy.

What is progesterone?

Progesterone is a hormone that is produced before and during pregnancy to thicken the uterine lining (endometrium) and to help the mother’s body accept the growing baby. It is used during fertility treatment to prepare the lining of the uterus for the implantation of the embryo.

What did the results show?

The results showed that although the treatment did not reduce the rate of miscarriage for those with no previous miscarriages, there was a small reduction in miscarriage for those with 1-2 previous miscarriages and a big reduction in miscarriage for those with 3 or more previous miscarriages.

The overall live birth rate was 75% (1513/2025) in the progesterone group and 72% (1459/2013) in the placebo group. That 3% difference in live birth was not ‘statistically significant’ – meaning that the difference could have been due to chance.

However, when the results were split by the number of previous miscarriages that the participants had suffered, the analysis showed that:

• No previous miscarriages: the live birth rate was 74% (824/1111) in the progesterone group and 75% (840/1127) in the placebo group, ie no benefit
• 1-2 previous miscarriages: the live birth rate was 76% (591/777) in the progesterone group and 72% (534/738) in the placebo group, ie some benefit
• 3 or more previous miscarriages: the live birth rate was 72% (98/137) in the progesterone group and 57% (85/148) in the placebo group, ie substantial benefit

How do we know the results of PRISM are reliable?

PRISM is a randomised, double-blind, placebo-controlled trial. This is the gold standard for a research trials. It was carried out with more than 4,000 women, which is the number needed to be certain that the results are reliable.

Together, these two factors mean the results can be trusted and we can be confident in recommending progesterone for women who have early pregnancy bleeding and 1 or more previous miscarriages.

What is a randomised, double blind, placebo-controlled trial?

Randomised: A computer made the selection completely randomly on which women were given the treatment drug (progesterone) or a placebo – a dummy drug that has no active ingredients.

Double-blind: The women in the study weren’t told whether they were taking the active medicine or the placebo – and neither were their doctors.

Placebo-controlled: Half the women in the study had the active medicine and the other 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.

What does this mean for women who have bleeding in pregnancy

If you have bleeding in your current pregnancy and you have had 1 or more previous miscarriages, we recommend that you ask your doctor for the progesterone treatment.

As this research is new your doctor may not be aware of it yet, and to help you we have prepared this document that explains the background and research to them. Print this out and take it with you, or, if you don’t have a printer, show it to them on your phone. 

If you have any type of bleeding in pregnancy you need to see your midwife of doctor. Find out more about the causes and treatment here.

High quality evidence

Professor Arri Coomarasamy said: “The role of progesterone in women with early pregnancy bleeding has been studied and debated for about 60 years. But what we lacked was high quality evidence. The largest study before ours had less than 200 participants; our study had more than 4000 participants and was of very high quality.

This meant we could be confident about our findings. The 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.”

Information for clinicians

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