促性腺激素释放激素拮抗剂在体外受精-胚胎移植中有效性的系统性评价_《中国循证医学杂志》

作者：

肖劲松 ¹ , 陈双陨 ¹ , 张春莲 ¹ ,  常双 ²

1. 湖北医药大学附属太和医院妇产科（湖北十堰 442000）；2. 湖北医药大学附属太和医院肿瘤科（湖北十堰 442000）;

关键词：

GnRH拮抗剂体外受精-胚胎移植超促排卵有效性系统性评价 Meta分析随机对照试验

DOI：

10.7507/1672-2531.20100608

视频：

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摘要 全文 图表 视频 参考文献 施引文献 补充材料

目的　系统性评价促性腺激素释放激素（GnRH）拮抗剂在体外受精-胚胎移植治疗中的有效性。
方法　计算机检索中国生物医学文献数据库（1979～2010）、万方数据库（1994～2010）、中国学术期刊网专题全文数据库（1994～2010）、中国生物医学期刊数据库（1989～2010）和PubMed（1997～2010）、ProQust Medical Library（1997～2010）、外文生物医学期刊文献数据库（2000～2010），并手检相关杂志，查找GnRH拮抗剂与GnRH激动剂比较在体外受精-胚胎移植治疗中有效性的随机对照试验。按照纳入与排除标准选择试验、评价质量后进行Meta分析。
结果　共纳入6个RCT，合计1 208例患者，其方法学质量均为B级。Meta分析结果显示：与GnRH激动剂组相比，GnRH拮抗组刺激天数［WMD= –1.07，95%CI（–1.38，–0.76）］和获卵数［WMD= –1.80，95%CI（–2.48，–1.12）］均更低，差异有统计学意义；而在Gn量［WMD= –0.49，95%CI（–1.63，0.66）］、HCG日子宫内膜厚度［WMD= –0.09，95%CI（–0.42，0.24）］、妊娠率［Peto OR=0.83，95%CI（0.65，1.05）］、OHSS率［Peto OR=0.77，95%CI（0.35，1.72）］和流产率［Peto OR=1.49，95%CI（0.79，2.82）］上，两组差异均无统计学意义。
结论　GnRH拮抗剂较之GnRH激动剂刺激天数短，所需Gn量少，不明显影响妊娠率，同时可减少OHSS的发生，临床上使用相对灵活，具有较好的接受性，为体外受精-胚胎移植超促排卵治疗提供了另一种选择。受纳入研究质量和例数限制，上述结论尚需开展更多设计严谨的多中心、大样本随机对照试验予以证实和更新。

引用本文： 肖劲松,陈双陨,张春莲,常双. 促性腺激素释放激素拮抗剂在体外受精-胚胎移植中有效性的系统性评价. 中国循证医学杂志, 2010, 10(12): 1432-1438. doi: 10.7507/1672-2531.20100608 复制

1.	Xavier P, Gamboa C, Calejo L. A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy. Eur J Obstet Gynecol Reprod Biol, 2005, 120(1): 185-189.
2.	Albano C, Felberbaum RE, Smitzl J, et al. Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. Hum Reprod, 2000, 15(3): 2421-2425.
3.	The North American Ganirelix Study Group: M Fluker, W Schoolcraft, R T Scott, et al．Efficacy and safety of ganirelix acetate versus leuprolide acetate in womenundergoing controlled ovarian hyperstimulation. Fertil Steril, 2001, 75(1): 38-45.
4.	Roulier R, Chabert-Orsini V, Sitri MC, et al. Depot GnRH agonist versus the single dose GnRH antagonist regimen (cetrorelix, 3mg) in patients undergoing assisted reproduction treatment. Repred Biomed Online, 2003, 7(2): 185-189.
5.	Ye H, Huang GN, Zeng PH, et al. IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study. J Assist Reprod Genet, 2009, 26: 105-111.
6.	Juni P, Altman DG, Egger M. Assessing the quality of controlled clinical trials. BMJ, 2001, 323: 42-46.
7.	Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observa¬tional studies epidemiology: a proposal for reporting. JAMA, 2000, 283(15): 2008-2012.
8.	European and Middle East Orgalutran Study Group. Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation. Hum Reprod, 2001, 16(4): 644-651.
9.	Olivennes F, Belaisch-Allart J, Emperaire JC. Prospective, randomized controlled study of in vitro fertilization-embryo transfer witha single dose of a luteinizing hormone releasing hormone (LH-RH) antagonist(cetrorelix) or a depot formula of anLH-RH agonist (triptorelin). Fertil Steril, 2000, 73(2): 314-320.
10.	Cochrane Reviewer’ Handbook 4.1. The Cochrane Collaboration, 2000.
11.	Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias. JAMA, 1995, 273: 408-421.
12.	Stadtmauer L, Dit koff EC, Session D, et al. High dosages of gonadotropins are associated with poor pregnancy outcomes after in vitro fertilization - embryo transfer. Fertil Steril, 1994, 61(6): 1058-1064.
13.	Al-Inany HG, Abou-Setta AM, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review. Reprod Biomed Online, 2007, 14(5): 640-649.
14.	Ragni G, VegettiW, Riccaboni A, et al. Comparison of GnRH agonists and antagonists in assisted rep roduction cycles of patients at high risk of ovarian hyperstimulation syndrome. Hum Reprod, 2005, 20(9): 2421-2425.
15.	Ludwig M, Katalanic A, Diedrich K. Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to the long protocol. Arch Gynecol Obstect, 2001, 265(4): 175-182.
16.	朱亮, 邢福祺. GnRHA用药方案及其在控制性超促排卵中的应用进展. 国外医学计划生育/生殖健康分册, 2007, 26(4): 183-186.
17.	Kolibianakis EM, Bourgain C, Platteau P, et al. Abnormal endometrial development occurs during the luteal phase of nonsupplemented donor cycles treated with recombinant follicle - stimulating hormone and gonadotrop in - releasing hormone antagonists. Fertil Steril, 2003, 80(2): 464-466.
18.	Bodri D, Vernaeve V, Guillén JJ, et al. Comparison between a GnRH antagonist and a GnRH agonist flare - up protocol in oocyte donors: a randomized clinical trial. Hum Reprod, 2006, 21(9): 2246-2251.
19.	Orvieto R, Meltcer S, Rabinson J, et al. GnRH agonist versus GnRH antagonist in ovarian stimulation: the role of endometrial receptivity. Fertil Steril. In press.
20.	Bahceci M, Ulug U, Sismanoglu A, et al. Early pregnancy loss rates were different among singleton gestations conceived by ICSI using GnRH agonist and antagonist. J Assist Reprod Genet, 2009, 26(4): 227-229.

1. Xavier P, Gamboa C, Calejo L. A randomised study of GnRH antagonist (cetrorelix) versus agonist (busereline) for controlled ovarian stimulation: effect on safety and efficacy. Eur J Obstet Gynecol Reprod Biol, 2005, 120(1): 185-189.
2. Albano C, Felberbaum RE, Smitzl J, et al. Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin. Hum Reprod, 2000, 15(3): 2421-2425.
3. The North American Ganirelix Study Group: M Fluker, W Schoolcraft, R T Scott, et al．Efficacy and safety of ganirelix acetate versus leuprolide acetate in womenundergoing controlled ovarian hyperstimulation. Fertil Steril, 2001, 75(1): 38-45.
4. Roulier R, Chabert-Orsini V, Sitri MC, et al. Depot GnRH agonist versus the single dose GnRH antagonist regimen (cetrorelix, 3mg) in patients undergoing assisted reproduction treatment. Repred Biomed Online, 2003, 7(2): 185-189.
5. Ye H, Huang GN, Zeng PH, et al. IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study. J Assist Reprod Genet, 2009, 26: 105-111.
6. Juni P, Altman DG, Egger M. Assessing the quality of controlled clinical trials. BMJ, 2001, 323: 42-46.
7. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observa¬tional studies epidemiology: a proposal for reporting. JAMA, 2000, 283(15): 2008-2012.
8. European and Middle East Orgalutran Study Group. Comparable clinical outcome using the GnRH antagonist ganirelix or a long protocol of the GnRH agonist triptorelin for the prevention of premature LH surges in women undergoing ovarian stimulation. Hum Reprod, 2001, 16(4): 644-651.
9. Olivennes F, Belaisch-Allart J, Emperaire JC. Prospective, randomized controlled study of in vitro fertilization-embryo transfer witha single dose of a luteinizing hormone releasing hormone (LH-RH) antagonist(cetrorelix) or a depot formula of anLH-RH agonist (triptorelin). Fertil Steril, 2000, 73(2): 314-320.
10. Cochrane Reviewer’ Handbook 4.1. The Cochrane Collaboration, 2000.
11. Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias. JAMA, 1995, 273: 408-421.
12. Stadtmauer L, Dit koff EC, Session D, et al. High dosages of gonadotropins are associated with poor pregnancy outcomes after in vitro fertilization - embryo transfer. Fertil Steril, 1994, 61(6): 1058-1064.
13. Al-Inany HG, Abou-Setta AM, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception: a Cochrane review. Reprod Biomed Online, 2007, 14(5): 640-649.
14. Ragni G, VegettiW, Riccaboni A, et al. Comparison of GnRH agonists and antagonists in assisted rep roduction cycles of patients at high risk of ovarian hyperstimulation syndrome. Hum Reprod, 2005, 20(9): 2421-2425.
15. Ludwig M, Katalanic A, Diedrich K. Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to the long protocol. Arch Gynecol Obstect, 2001, 265(4): 175-182.
16. 朱亮, 邢福祺. GnRHA用药方案及其在控制性超促排卵中的应用进展. 国外医学计划生育/生殖健康分册, 2007, 26(4): 183-186.
17. Kolibianakis EM, Bourgain C, Platteau P, et al. Abnormal endometrial development occurs during the luteal phase of nonsupplemented donor cycles treated with recombinant follicle - stimulating hormone and gonadotrop in - releasing hormone antagonists. Fertil Steril, 2003, 80(2): 464-466.
18. Bodri D, Vernaeve V, Guillén JJ, et al. Comparison between a GnRH antagonist and a GnRH agonist flare - up protocol in oocyte donors: a randomized clinical trial. Hum Reprod, 2006, 21(9): 2246-2251.
19. Orvieto R, Meltcer S, Rabinson J, et al. GnRH agonist versus GnRH antagonist in ovarian stimulation: the role of endometrial receptivity. Fertil Steril. In press.
20. Bahceci M, Ulug U, Sismanoglu A, et al. Early pregnancy loss rates were different among singleton gestations conceived by ICSI using GnRH agonist and antagonist. J Assist Reprod Genet, 2009, 26(4): 227-229.

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促性腺激素释放激素拮抗剂在体外受精-胚胎移植中有效性的系统性评价

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《中国循证医学杂志》

促性腺激素释放激素拮抗剂在体外受精-胚胎移植中有效性的系统性评价

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