Arri Coomarasamy1, Adam J Devall1, Versha Cheed1, Hoda Harb1, Lee J Middleton1, Ioannis D Gallos1, Helen Williams1, Abey K Eapen1, Tracy Roberts1, Chriscasimir C Ogwulu1, Ilias Goranitis1, Jane P Daniels1, Amna Ahmed1, Ruth Bender-Atik1, Kalsang Bhatia1, Cecilia Bottomley1, Jane Brewin1, Meenakshi Choudhary1, Fiona Crosfill1, Shilpa Deb1, W Colin Duncan1, Andrew Ewer1, Kim Hinshaw1, Tom Holland1, Feras Izzat1, Jemma Johns1, Kathiuska Kriedt1, Mary-Ann Lumsden1, Padma Manda1, Jane E Norman1, Natalie Nunes1, Caroline E Overton1, Siobhan Quenby1, Sandhya Rao1, Jackie Ross1, Anupama Shahid1, Martyn Underwood1, Nirmala Vaithilingam1, Linda Watkins1, Catherine Wykes1, Andrew Horne1, Davor Jurkovic1. 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) orplacebo (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.).
RCT Entities:
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.).
Authors: Arri Coomarasamy; Hoda M Harb; Adam J Devall; Versha Cheed; Tracy E Roberts; Ilias Goranitis; Chidubem B Ogwulu; Helen M Williams; Ioannis D Gallos; Abey Eapen; Jane P Daniels; Amna Ahmed; Ruth Bender-Atik; Kalsang Bhatia; Cecilia Bottomley; Jane Brewin; Meenakshi Choudhary; Fiona Crosfill; Shilpa Deb; W Colin Duncan; Andrew Ewer; Kim Hinshaw; Thomas Holland; Feras Izzat; Jemma Johns; Mary-Ann Lumsden; Padma Manda; Jane E Norman; Natalie Nunes; Caroline E Overton; Kathiuska Kriedt; Siobhan Quenby; Sandhya Rao; Jackie Ross; Anupama Shahid; Martyn Underwood; Nirmala Vaithilingham; Linda Watkins; Catherine Wykes; Andrew W Horne; Davor Jurkovic; Lee J Middleton Journal: Health Technol Assess Date: 2020-06 Impact factor: 4.014
Authors: C B Okeke Ogwulu; I Goranitis; A J Devall; V Cheed; I D Gallos; L J Middleton; H M Harb; H M Williams; A Eapen; J P Daniels; A Ahmed; R Bender-Atik; K Bhatia; C Bottomley; J Brewin; M Choudhary; S Deb; W C Duncan; A K Ewer; K Hinshaw; T Holland; F Izzat; J Johns; M Lumsden; P Manda; J E Norman; N Nunes; C E Overton; K Kriedt; S Quenby; S Rao; J Ross; A Shahid; M Underwood; N Vaithilingham; L Watkins; C Wykes; A W Horne; D Jurkovic; A Coomarasamy; T E Roberts Journal: BJOG Date: 2020-01-30 Impact factor: 6.531
Authors: Arri Coomarasamy; Adam J Devall; Jan J Brosens; Siobhan Quenby; Mary D Stephenson; Sony Sierra; Ole B Christiansen; Rachel Small; Jane Brewin; Tracy E Roberts; Rima Dhillon-Smith; Hoda Harb; Hannah Noordali; Argyro Papadopoulou; Abey Eapen; Matt Prior; Gian Carlo Di Renzo; Kim Hinshaw; Ben W Mol; Mary Ann Lumsden; Yacoub Khalaf; Andrew Shennan; Mariette Goddijn; Madelon van Wely; Maya Al-Memar; Phil Bennett; Tom Bourne; Raj Rai; Lesley Regan; Ioannis D Gallos Journal: Am J Obstet Gynecol Date: 2020-01-31 Impact factor: 8.661