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N Engl J Med. 2019 May 9;380(19):1815-1824. doi: 10.1056/NEJMoa1813730.

A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy.

Author information

1
From Tommy's National Centre for Miscarriage Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham (A.C., A.J.D., V.C., H.H., L.J.M., I.D.G., H.W., A.K.E., T.R., C.C.O.), the Faculty of Medicine and Health Sciences, University of Nottingham (J.P.D.), and Nottingham University Hospitals NHS Trust (S.D.), Nottingham, City Hospitals Sunderland NHS Foundation Trust, Sunderland (A.A., K.H.), the Miscarriage Association, Wakefield (R.B.A.), East Lancashire Hospitals NHS Trust, Burnley (K.B.), Tommy's Charity (J.B.), Guy's and St. Thomas' NHS Foundation Trust (T.H.), King's College Hospital NHS Foundation Trust (J.J., J.R.), University College London Hospitals NHS Foundation Trust (K.K., D.J.), West Middlesex Hospital, Chelsea and Westminster NHS Foundation Trust (N.N., C.B.), and Barts and the London NHS Trust (A.S.), London, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle (M.C.), Lancashire Teaching Hospitals NHS Foundation Trust, Preston (F.C.), the MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh (W.C.D., J.E.N., A.W.H.), Liverpool Women's NHS Foundation Trust (L.W.) and St. Helens and Knowsley NHS Trust (S.R.), Liverpool, University Hospitals Coventry and Warwickshire NHS Trust, Coventry (F.I.), the Department of Medicine, University of Glasgow, Glasgow (M.-A.L.), South Tees Hospitals NHS Foundation Trust, Middlesbrough (P.M.), University Hospitals Bristol NHS Foundation Trust, Bristol (C.E.O.), the Biomedical Research Unit in Reproductive Health, University of Warwick, Warwick (S.Q.), Shrewsbury and Telford NHS Trust, Telford (M.U.), Portsmouth Hospitals NHS Trust, Portsmouth (N.V.), and Surrey and Sussex Healthcare NHS Trust, Redhill (C.W.) - all in the United Kingdom; the Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia (I.G.); and the Carver College of Medicine, University of Iowa Health Care, Iowa City (A.E.).

Abstract

BACKGROUND:

Bleeding in early pregnancy is strongly associated with pregnancy loss. Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone therapy may improve pregnancy outcomes in women who have bleeding in early pregnancy.

METHODS:

We conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate progesterone, as compared with placebo, in women with vaginal bleeding in early pregnancy. Women were randomly assigned to receive vaginal suppositories containing either 400 mg of progesterone or matching placebo twice daily, from the time at which they presented with bleeding through 16 weeks of gestation. The primary outcome was the birth of a live-born baby after at least 34 weeks of gestation. The primary analysis was performed in all participants for whom data on the primary outcome were available. A sensitivity analysis of the primary outcome that included all the participants was performed with the use of multiple imputation to account for missing data.

RESULTS:

A total of 4153 women, recruited at 48 hospitals in the United Kingdom, were randomly assigned to receive progesterone (2079 women) or placebo (2074 women). The percentage of women with available data for the primary outcome was 97% (4038 of 4153 women). The incidence of live births after at least 34 weeks of gestation was 75% (1513 of 2025 women) in the progesterone group and 72% (1459 of 2013 women) in the placebo group (relative rate, 1.03; 95% confidence interval [CI], 1.00 to 1.07; P = 0.08). The sensitivity analysis, in which missing primary outcome data were imputed, resulted in a similar finding (relative rate, 1.03; 95% CI, 1.00 to 1.07; P = 0.08). The incidence of adverse events did not differ significantly between the groups.

CONCLUSIONS:

Among women with bleeding in early pregnancy, progesterone therapy administered during the first trimester did not result in a significantly higher incidence of live births than placebo. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment program; PRISM Current Controlled Trials number, ISRCTN14163439.).

Comment in

PMID:
31067371
DOI:
10.1056/NEJMoa1813730
[Indexed for MEDLINE]

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