A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

Research output: Contribution to journalArticlepeer-review


  • Paul T Seed
  • Abey Eapen
  • Rachel Small
  • Siobhan Quenby
  • Pratima Gupta
  • Feroza Dawood
  • Yvonne Koot
  • Ruth Bender Atik
  • KWM Bloemenkamp
  • Rebecca Brady
  • Annette Briley
  • Rebecca Cavallaro
  • Ying Cheong
  • Ayman Ewies
  • A Hoek
  • EM Kaaijk
  • CAM Koks
  • TC Li
  • M. Maclean
  • BW Mol
  • J Moore
  • JA Ross
  • Lisa Sharpe
  • Jane Stewart
  • Nirmala Vaithilingam
  • RG Farquharson
  • Y Khalaf
  • M Goddijn
  • Lesley Regan
  • Raj Rai

External organisations

  • Heart of England NHS Foundation Trust
  • King’s College London and King’s Health Partners at St. Thomas’ Hospital
  • Women’s Health Research Center, Imperial College at St. Mary’s Hospital Campus
  • King's College Hospital NHS Foundation Trust
  • Guy's and St Thomas' NHS Foundation Trust
  • University of Warwick
  • Liverpool Women’s NHS Foundation Trust
  • The Miscarriage Association, Wakefield
  • Southampton Faculty of Medicine, Princess Anne Hospital, Southampton
  • Royal Hallamshire Hospital, Sheffield
  • Ayrshire Maternity Unit, University Hospital of Crosshouse, Kilmarnock
  • Nottingham University Hospitals NHS Trust
  • Newcastle Hospitals NHS Foundation Trust
  • Portsmouth Hospitals NHS Trust
  • University Medical Center Utrecht
  • Department of Obstetrics, Leiden University Medical Center, Leiden
  • University of Groningen
  • Department of Obstetrics and Gynecology, Onze Lieve Vrouwe Gasthuis
  • Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Academic Medical Center
  • Department of Obstetrics and Gynecology, Maxima Medical Center Veldhoven
  • University of Adelaide


Progesterone is essential for the maintenance of pregnancy. However, whether progesterone supplementation in the first trimester of pregnancy would increase the rate of live births among women with a history of unexplained recurrent miscarriages is uncertain.
We conducted a multicenter, double-blind, placebo-controlled, randomized trial to investigate whether treatment with progesterone would increase the rates of live births and newborn survival among women with unexplained recurrent miscarriage. We randomly assigned women with recurrent miscarriages to receive twice daily vaginal suppositories containing either 400 mg of micronized progesterone or matched placebo from a time soon after a positive urinary pregnancy test (and no later than 6 weeks of gestation) through 12 weeks of gestation. The primary outcome was live birth after 24 weeks of gestation.
A total of 1568 women were assessed for eligibility, and 836 of these women who conceived naturally within 1 year and remained willing to participate in the trial were randomly assigned to receive either progesterone (404 women) or placebo (432 women). The follow-up rate for the primary outcome was 98.8% (826 of 836 women). In an intention-to-treat analysis, the rate of live births was 65.8% (262 of 398 women) in the progesterone group and 63.3% (271 of 428 women) in the placebo group (relative rate, 1.04; 95% confidence interval [CI], 0.94 to 1.15; rate difference, 2.5 percentage points; 95% CI, −4.0 to 9.0). There were no significant between-group differences in the rate of adverse events.
Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with a history of unexplained recurrent miscarriages. (Funded by the United Kingdom National Institute of Health Research; PROMISE Current Controlled Trials number, ISRCTN92644181.)


Original languageEnglish
Pages (from-to)2141-2148
JournalThe New England Journal of Medicine
Issue number22
Publication statusPublished - 26 Nov 2015


  • Progesterone, Miscarriage