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

Coomarasamy, Arri; Devall, Adam J.; Cheed, Versha; Harb, Hoda; Middleton, Lee J.; Gallos, Ioannis D.; Eapen, Abey K.; Roberts, Tracy; Ogwulu, Chriscasimir C.; Goranitis, Ilias; Daniels, Jane P.; Ahmed, Amna; Bender-Atik, Ruth; Bhatia, Kalsang; Bottomley, Cecilia; Brewin, Jane; Choudhary, Meenakshi; Crosfill, Fiona; Deb, Shilpa; Duncan, W. Colin; Ewer, Andrew; Hinshaw, Kim; Holland, Tom; Izzat, Feras; Johns, Jemma; Kriedt, Kathiuska; Lumsden, Mary-Ann; Manda, Padma; Norman, Jane E.; Nunes, Natalie; Overton, Caroline E.; Quenby, Siobhan; Rao, Sandhya; Ross, Jackie; Shahid, Anupama; Underwood, Martyn; Vaithilingam, Nirmala; Watkins, Linda; Wykes, Catherine; Horne, Andrew; Jurkovic, Davor

Abstract

© 2019 Massachusetts Medical Society.
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.

Citation

Coomarasamy, A., Devall, A. J., Cheed, V., Harb, H., Middleton, L. J., Gallos, I. D., Eapen, A. K., Roberts, T., Ogwulu, C. C., Goranitis, I., Daniels, J. P., Ahmed, A., Bender-Atik, R., Bhatia, K., Bottomley, C., Brewin, J., Choudhary, M., Crosfill, F., Deb, S., Duncan, W. C., …Jurkovic, D. (2019). A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. New England Journal of Medicine, 380(19), 1815-1824. https://doi.org/10.1056/NEJMoa1813730

• Journal Article Type: Article
• Acceptance Date: Feb 27, 2019
• Online Publication Date: May 9, 2019
• Publication Date: May 9, 2019
• Deposit Date: May 21, 2019
• Publicly Available Date: Nov 10, 2019
• Journal: New England Journal of Medicine
• Print ISSN: 0028-4793
• Electronic ISSN: 1533-4406
• Publisher: Massachusetts Medical Society
• Peer Reviewed: Peer Reviewed
• Volume: 380
• Issue: 19
• Pages: 1815-1824
• DOI: https://doi.org/10.1056/NEJMoa1813730
• Keywords: General Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/2077376
• Publisher URL: https://www.nejm.org/doi/10.1056/NEJMoa1813730
• Additional Information: From New England Journal of Medicine, Arri Coomarasamy, M.B., Ch.B., M.D., F.R.C.O.G., Adam J. Devall, B.Med.Sci., Ph.D., Versha Cheed, M.Sc., Hoda Harb, M.B., Ch.B., Ph.D., Lee J. Middleton, B.Sc., Ioannis D. Gallos, D.M.S., M.D., Helen Williams, B.Sc., Abey K. Eapen, M.D., Ph.D., Tracy Roberts, Ph.D., R.G.N., Chriscasimir C. Ogwulu, Ph.D., Ilias Goranitis, Ph.D., Jane P. Daniels, M.Med.Sci., Ph.D., Amna Ahmed, M.B., B.S., M.R.C.O.G., Ruth Bender-Atik, B.A., Kalsang Bhatia, M.B., B.S., F.R.C.O.G., Cecilia Bottomley, DM.B.B.Chir., M.R.C.O.G., M.D., Jane Brewin, B.A., Meenakshi Choudhary, M.B., B.S., M.D., M.R.C.O.G., Ph.D., Fiona Crosfill, M.B., B.S., M.R.C.O.G., Dip.Med.Ed., Shilpa Deb, M.B., B.S., M.R.C.O.G., D.G.O., Ph.D., W. Colin Duncan, M.B., Ch.B., M.D., F.R.C.O.G., Andrew Ewer, M.B., Ch.B., M.D., M.R.C.P., F.R.C.P.C.H., Kim Hinshaw, M.B., B.S., F.R.C.O.G., Tom Holland, M.B., B.S., M.R.C.O.G., M.D., Feras Izzat, M.B., Ch.B., M.R.C.O.G., Jemma Johns, M.B., B.S., M.R.C.O.G., M.D., Kathiuska Kriedt, M.B., B.S., Mary-Ann Lumsden, M.B., B.S., M.D., F.R.C.O.G., Padma Manda, M.B., B.S., D.G.O., D.F.F.P., F.R.C.O.G., Jane E. Norman, M.B., Ch.B., M.D., F.R.C.O.G., F. Med.Sci., F.R.C.P. Edin., Natalie Nunes, M.B., B.S., M.R.C.O.G., M.D. (Res.), Caroline E. Overton, M.B., B.S., M.D., M.R.C.O.G., F.H.E.A., F.R.C.O.G., Siobhan Quenby, B.Sc., M.B., B.S., M.R.C.O.G., C.C.S.T., M.D., F.R.C.O.G., Sandhya Rao, M.B., B.S., M.D., M.R.C.O.G., Jackie Ross, M.B., B.S., F.R.C.O.G., C.C.S.T., Anupama Shahid, M.B., B.S., D.F.S.R.H., M.R.C.O.G., Martyn Underwood, M.B., Ch.B., M.R.C.O.G., Nirmala Vaithilingam, M.D., Linda Watkins, M.B., Ch.B., M.R.C.O.G., D.F.F.P., Catherine Wykes, M.B., B.S., M.R.C.O.G., M.A., Andrew Horne, M.B., Ch.B., M.R.C.O.G., Ph.D., F.R.C.O.G., and Davor Jurkovic, M.B., B.S., M.D., M.R.C.O.G., A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy, 380, 1815-1824 Copyright © 2019 Massachusetts Medical Society. Reprinted with permission.
• Contract Date: Jun 14, 2019