Medical researchers from the University of Birmingham and Tommy’s National Centre for Miscarriage
Research have discovered that giving progesterone
to women with early pregnancy bleeding and a history of miscarriage
could lead to prevention of more than half a million global miscarriages
The research team has published two new studies evidencing both the scientific and economic advantages of giving a course of self-administered twice daily progesterone
pessaries to women from when they first present with early pregnancy bleeding up until 16 weeks of pregnancy to prevent miscarriage
is a hormone that is naturally secreted by the ovaries and placenta in early pregnancy and is vital to the attainment and maintenance of healthy pregnancies.
experts are calling for progesterone
to be offered as standard in the NHS for women with early pregnancy bleeding and a history of miscarriage after their growing body of research has found it is both cost-effective and can increase women’s chances of having a baby.
The initial of the new studies, published in the American Journal of Obstetrics and Gynecology
(i) examines the findings of two major clinical trials: PROMISE (ii) and PRISM (iii), led by the University of Birmingham and Tommy’s National Centre for Miscarriage
Research and funded by the National Institute for Health Research (NIHR).
The PROMISE clinical trial studied 836 women with unexplained recurrent miscarriages
at 45 hospitals in the UK and the Netherlands, and found a 3% higher live birth rate with progesterone
, but with substantial statistical uncertainty. PRISM studied 4,153 women with early pregnancy bleeding at 48 hospitals in the UK and found there was a 5% increase in the number of babies born to those who were given progesterone
who had previously had one or more miscarriages
compared to those given a placebo. 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.
The subsequent study was published in BJOG: an international Journal of Obstetrics & Gynaecology
(iv), and evaluates the economics of the PRISM trial and, importantly, concludes that progesterone
is cost-effective, costing on average £204 per pregnancy.
In an unpublished survey by the University of Birmingham of 130 healthcare practitioners in the UK found that prior to the results of the PRISM study just 13% offered women at threat of miscarriage progesterone
, while post publication of the results in the New England Journal of Medicine in May 2019, 75% now offer the treatment.
“About 20 and 25 percent of pregnanc
ies end in a miscarriage
, which has a major clinical and psychological impact on women and their families. The role of first trimester progesterone
supplementation in the treatment of pregnancies at high risk of miscarriage
is a long-standing research question that has been debated in the medical literature for over 60 years. Thus far, policymakers have been unable to make evidence-based recommendations on the use of progesterone
supplementation to improve outcomes. The PRISM and PROMISE Trials found a small but positive treatment effect, dependent on the number of previous miscarriages
. We believe that the dual risk factors of early pregnancy bleeding and a history of one or more previous miscarriages
identify high-risk women in whom progesterone
is of benefit. The question is, how should this affect clinical practice?” commented Dr. Adam Devall, Senior Clinical Trial Fellow at the University of Birmingham and Manager of Tommy’s National Centre for Miscarriage Research.
Dr Arri Coomarasamy, Professor of Gynaecology at the University of Birmingham and Director of Tommy’s National Centre for Miscarriage Research told Thailand Medical
News, “Our suggestion is to consider offering to women with early pregnancy bleeding and a history of one or more previous miscarriages
a course of treatment of progesterone
400mg twice daily, started at the time of presentation with vaginal bleeding and continued to 16 completed weeks of gestation. In the United Kingdom, we estimate that implementing this treatment strategy would result in an additional 8,450 live births per year.”
He further added, “We believe that women at high risk of having a miscarriage
may not need absolute scientific certainty to choose to have a treatment. We recommend that they are informed about the uncertainty around treatment effects, so they can then decide for themselves the right course of action. We now urge policymakers and guideline developers to consider the evidence carefully to make a balanced recommendation.”
Dr Jane Brewin, CEO ,Tommy’s National Centre for Miscarriage Research said: “Tommy’s continues to hear from women who are being denied treatment and clinicians who seem unsure about the evidence. These thorough studies now provide women and their clinicians with an effective treatment option which women should be routinely offered. I’d like to call on NICE to amend the guidelines with this new information and for NHSE to encourage take up of this treatment across the country, preventing avoidable deaths.”
can be a devastating loss for women, their partners, and families. We, therefore, welcome the findings from this well-researched trial which supports the use of progesterone
among women with early pregnancy bleeding and a history of miscarriage
. This treatment offers an increased chance of a successful birth and appears to be cost effective for the NHS, so we hope NICE will consider this important research in their next update of the guidance. For women with no prior history of miscarriage
, there does not appear to be any benefit of the treatment, and women with concerns about their pregnancy should contact their midwife or early pregnancy unit for care and support. Reassuringly, most women who have had a miscarriage
will have a successful pregnancy and birth in the future.” commented Dr. Pat O’Brien, Consultant and Vice President of The Royal College of Obstetricians and Gynaecologists
(i) Coomarasamy et al (2020). 'Micronized vaginal progesterone to prevent miscarriage: a critical evaluation of randomized evidence'. American Journal of Obstetrics and Gynecology
. DOI: 10.1016/j.ajog.2019.12.006. Copies of this paper are available to credentialed journalists upon request; please contact Elsevier's Newsroom at email@example.com
or +31 20 485 2719.
(ii) Coomarasamy et al (2015). 'A Randomized Trial of Progesterone in Women with Recurrent Miscarriages'. New England Journal of Medicine
. DOI: 10.1056/NEJMoa1504927
(iii) Coomarasamy et al (2019). 'A Randomized Trial of Progesterone in Women with Early Pregnancy Bleeding'. New England Journal of Medicine
. DOI: 10.1056/NEJMoa1813730
(iv) Okeke Ogwulu et al (2020). 'The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM Trial'. BJOG: an international Journal of Obstetrics & Gynaecology
. DOI: 10.1111/1471-0528.16068