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黄体酮治疗反复自然流产的随机试验
A Randomized Trial of Progesterone in Women with Recurrent Miscarriages


Arri Coomarasamy ... 妇产科和儿科 • 2015.11.26

摘要


背景

黄体酮是维持妊娠的关键因素。但对于有不明原因反复自然流产史的女性而言,目前仍不明确能否通过在妊娠期前3个月补充黄体酮来提高活产率。

 

方法

我们开展了一项多中心、双盲、安慰剂对照随机试验,旨在评估有不明原因反复自然流产的女性能否通过黄体酮治疗来提高活产率和新生儿生存率。试验将反复自然流产女性随机分配至微粉黄体酮阴道栓剂组(每次400 mg)或安慰剂阴道栓剂组,每日给药2次,在尿检妊娠测试阳性后迅速开始给药(不晚于妊娠6周),直至妊娠12周结束。主要结局是妊娠24周后活产。

 

结果

共1,568例女性在评估中符合入组标准,其中836例在1年内自然受孕并愿意参与试验。参与者被随机分配至黄体酮组(404例)或安慰剂组(432例)。主要结局的随访率为98.8%(826/836)。意向性治疗分析表明黄体酮组的活产率为65.8%(262/398),安慰剂组为63.3%(271/428)(相对比率[RR],1.04;95%置信区间[CI],0.94~1.15;率差,2.5个百分点;95% CI,-4.0~9.0)。两组的不良事件发生率无显著差异。

 

结论

在有不明原因反复自然流产史的女性中,妊娠期前3个月的黄体酮治疗未能显著提高活产率(由英国国家卫生研究院[United Kingdom National Institute of Health Research]资助,PROMISE在Current Controlled Trials注册号为ISRCTN92644181)。





作者信息

Arri Coomarasamy, M.B., Ch.B., M.D., Helen Williams, B.Sc., Ewa Truchanowicz, Ph.D., Paul T. Seed, M.Sc., Rachel Small, R.G.N., R.M., Siobhan Quenby, M.D., Pratima Gupta, M.D., Feroza Dawood, M.B., Ch.B., M.D., Yvonne E.M. Koot, M.D., Ruth Bender Atik, B.A., Kitty W.M. Bloemenkamp, M.D., Ph.D., Rebecca Brady, R.N.Dip., M.Sc., T.N.Dip., Annette L. Briley, Ph.D., Rebecca Cavallaro, R.M., R.N., M.Mid., Ying C. Cheong, M.B., Ch.B., M.D., Justin J. Chu, M.D., Abey Eapen, M.D., Ayman Ewies, M.B., Ch.B., M.D., Annemieke Hoek, M.D., Ph.D., Eugenie M. Kaaijk, M.D., Carolien A.M. Koks, M.D., Tin-Chiu Li, M.D., Marjory MacLean, M.D., Ben W. Mol, M.D., Ph.D., Judith Moore, M.R.C.O.G., Jackie A. Ross, M.B., B.S., Lisa Sharpe, R.M.Dip., Jane Stewart, M.B., Ch.B., M.D., Nirmala Vaithilingam, M.D., Roy G. Farquharson, M.D., Mark D. Kilby, M.B., B.S., M.D., Yacoub Khalaf, M.B., B.Ch., M.D., Mariette Goddijn, M.D., Ph.D., Lesley Regan, M.D., and Rajendra Rai, M.D.
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, Adelaide, SA, Australia (B.W.M.). Address reprint requests to Dr. Coomarasamy at a.coomarasamy@bham.ac.uk.

 

参考文献

1. Rai R, Regan L. Recurrent miscarriage. Lancet 2006;368:601-611

2. Practice Committee of the American Society for Reproductive Medicine.. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril 2012;98:1103-1111

3. Malassiné A, Frendo JL, Evain-Brion D. A comparison of placental development and endocrine functions between the human and mouse model. Hum Reprod Update 2003;9:531-539

4. Haas DM, Ramsey PS. Progestogen for preventing miscarriage. Cochrane Database Syst Rev 2013;10:CD003511

5. Stephenson MD, Awartani KA, Robinson WP. Cytogenetic analysis of miscarriages from couples with recurrent miscarriage: a case-control study. Hum Reprod 2002;17:446-451

6. Carmichael SL, Shaw GM, Laurent C, Croughan MS, Olney RS, Lammer EJ. Maternal progestin intake and risk of hypospadias. Arch Pediatr Adolesc Med 2005;159:957-962

7. Peto R, Pike MC, Armitage P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I: introduction and design. Br J Cancer 1976;34:585-612

8. Swyer GI, Daley D. Progesterone implantation in habitual abortion. Br Med J 1953;1:1073-1077

9. Levine L. Habitual abortion: a controlled study of progestational therapy. West J Surg Obs Gynecol 1964;72:30-36

10. Goldzieher JW. Double-blind trial of a progestin in habitual abortion. JAMA 1964;188:651-654

11. El-Zibdeh MY. Dydrogesterone in the reduction of recurrent spontaneous abortion. J Steroid Biochem Mol Biol 2005;97:431-434

12. Kumar A, Begum N, Prasad S, Aggarwal S, Sharma S. Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial. Fertil Steril 2014;102:1357.e3-1363.e3

13. Bulletti C, de Ziegler D, Flamigni C, et al. Targeted drug delivery in gynaecology: the first uterine pass effect. Hum Reprod 1997;12:1073-1079

14. Cicinelli E, Cignarelli M, Sabatelli S, et al. Plasma concentrations of progesterone are higher in the uterine artery than in the radial artery after vaginal administration of micronized progesterone in an oil-based solution to postmenopausal women. Fertil Steril 1998;69:471-473

15. Nosarka S, Kruger T, Siebert I, Grove D. Luteal phase support in in vitro fertilization: meta-analysis of randomized trials. Gynecol Obs Invest 2005;60:67-74

16. Coomarasamy A, Truchanowicz EG, Rai R. Does first trimester progesterone prophylaxis increase the live birth rate in women with unexplained recurrent miscarriages? BMJ 2011;342:d1914-d1914

17. Da Fonseca EB, Bittar RE, Carvalho MH, Zugaib M. Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study. Am J Obstet Gynecol 2003;188:419-424

18. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH. Progesterone and the risk of preterm birth among women with a short cervix. N Engl J Med 2007;357:462-469

19. Daya S. Efficacy of progesterone support for pregnancy in women with recurrent miscarriage: a meta-analysis of controlled trials. Br J Obstet Gynaecol 1989;96:275-280

20. Ozlü T, Güngör AC, Dönmez ME, Duran B. Use of progestogens in pregnant and infertile patients. Arch Gynecol Obstet 2012;286:495-503

21. Sonntag B, Ludwig M. An integrated view on the luteal phase: diagnosis and treatment in subfertility. Clin Endocrinol (Oxf) 2012;77:500-507

22. Shah D, Nagarajan N. Luteal insufficiency in first trimester. Indian J Endocrinol Metab 2013;17:44-49

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