title: A Randomized Trial of Progesterone in Women with Recurrent Miscarriages.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.).
authors.affiliation: From the College of Medical and Dental Sciences, University of Birmingham (A.C., H.W., E.T., J.J.C., A. Eapen, M.D.K.), Heart of England NHS Foundation Trust (R.S., P.G.), and Sandwell and West Birmingham Hospitals NHS Teaching Trust (A. Ewies), Birmingham, King's College London and King's Health Partners at St. Thomas' Hospital (P.T.S.), Women's Health Research Center, Imperial College at St. Mary's Hospital Campus (R.B., R.C., L.S., L.R., R.R.), King's Health Partners at St. Thomas' Hospital (A.L.B.), King's College Hospital NHS Foundation Trust (J.A.R.), and Assisted Conception Unit, Guy's and St. Thomas' Foundation Trust (Y.K.), London, Biomedical Research Unit in Reproductive Health, University of Warwick, Warwick (S.Q.), Liverpool Women's NHS Foundation Trust (F.D., R.G.F.), Liverpool, The Miscarriage Association, Wakefield (R.B.A.), University of Southampton Faculty of Medicine, Princess Anne Hospital, Southampton (Y.C.C.), Royal Hallamshire Hospital, Sheffield (T.-C.L.), Ayrshire Maternity Unit, University Hospital of Crosshouse, Kilmarnock (M.M.), Nottingham University Hospitals NHS Trust, Nottingham (J.M.), Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne (J.S.), and Portsmouth Hospitals NHS Trust, Portsmouth (N.V.) - all in the United Kingdom; the Department of Reproductive Medicine, University Medical Center Utrecht, Utrecht (Y.E.M.K.), the Department of Obstetrics, Leiden University Medical Center, Leiden (K.W.M.B.), the Department of Reproductive Medicine and Gynecology, University of Groningen, Groningen (A.H.), the Department of Obstetrics and Gynecology, Onze Lieve Vrouwe Gasthuis (E.M.K.), and Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Academic Medical Center (M.G.), Amsterdam, and the Department of Obstetrics and Gynecology, Maxima Medical Center Veldhoven, Veldhoven (C.A.M.K.) - all in the Netherlands; and the Robinson Institute, School of Pediatrics and Reproductive Health, University of Adelaide, Ade
authors.forename: Arri
authors.initials: A
authors.lastname: Coomarasamy
authors.forename: Helen
authors.initials: H
authors.lastname: Williams
authors.forename: Ewa
authors.initials: E
authors.lastname: Truchanowicz
authors.forename: Paul T
authors.initials: PT
authors.lastname: Seed
authors.forename: Rachel
authors.initials: R
authors.lastname: Small
authors.forename: Siobhan
authors.initials: S
authors.lastname: Quenby
authors.forename: Pratima
authors.initials: P
authors.lastname: Gupta
authors.forename: Feroza
authors.initials: F
authors.lastname: Dawood
authors.forename: Yvonne E M
authors.initials: YE
authors.lastname: Koot
authors.forename: Ruth
authors.initials: R
authors.lastname: Bender Atik
authors.forename: Kitty W M
authors.initials: KW
authors.lastname: Bloemenkamp
authors.forename: Rebecca
authors.initials: R
authors.lastname: Brady
authors.forename: Annette L
authors.initials: AL
authors.lastname: Briley
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cavallaro
authors.forename: Ying C
authors.initials: YC
authors.lastname: Cheong
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Chu
authors.forename: Abey
authors.initials: A
authors.lastname: Eapen
authors.forename: Ayman
authors.initials: A
authors.lastname: Ewies
authors.forename: Annemieke
authors.initials: A
authors.lastname: Hoek
authors.forename: Eugenie M
authors.initials: EM
authors.lastname: Kaaijk
authors.forename: Carolien A M
authors.initials: CA
authors.lastname: Koks
authors.forename: Tin-Chiu
authors.initials: TC
authors.lastname: Li
authors.forename: Marjory
authors.initials: M
authors.lastname: MacLean
authors.forename: Ben W
authors.initials: BW
authors.lastname: Mol
authors.forename: Judith
authors.initials: J
authors.lastname: Moore
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Ross
authors.forename: Lisa
authors.initials: L
authors.lastname: Sharpe
authors.forename: Jane
authors.initials: J
authors.lastname: Stewart
authors.forename: Nirmala
authors.initials: N
authors.lastname: Vaithilingam
authors.forename: Roy G
authors.initials: RG
authors.lastname: Farquharson
authors.forename: Mark D
authors.initials: MD
authors.lastname: Kilby
authors.forename: Yacoub
authors.initials: Y
authors.lastname: Khalaf
authors.forename: Mariette
authors.initials: M
authors.lastname: Goddijn
authors.forename: Lesley
authors.initials: L
authors.lastname: Regan
authors.forename: Rajendra
authors.initials: R
authors.lastname: Rai
mesh_terms: D000026:Abortion, Habitual / Q000517:prevention & control*; D000282:Administration, Intravaginal; D000328:Adult; D015992:Body Mass Index; D004311:Double-Blind Method; D005260:Female; D005865:Gestational Age; D006801:Humans; D050498:Live Birth; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011374:Progesterone / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D011374:Progesterone