促性腺激素釋放激素拮抗劑在體外受精-胚胎移植中有效性的系統性評價_《中國循證醫學雜志》

作者：

肖勁松 ¹ , 陳雙隕 ¹ , 張春蓮 ¹ ,  常雙 ²

1. 湖北醫藥大學附屬太和醫院婦產科（湖北十堰 442000）；2. 湖北醫藥大學附屬太和醫院腫瘤科（湖北十堰 442000）;

關鍵詞：

GnRH拮抗劑體外受精-胚胎移植超促排卵有效性系統性評價 Meta分析隨機對照試驗

DOI：

10.7507/1672-2531.20100608

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目的　系統性評價促性腺激素釋放激素（GnRH）拮抗劑在體外受精-胚胎移植治療中的有效性。
方法　計算機檢索中國生物醫學文獻數據庫（1979～2010）、萬方數據庫（1994～2010）、中國學術期刊網專題全文數據庫（1994～2010）、中國生物醫學期刊數據庫（1989～2010）和PubMed（1997～2010）、ProQust Medical Library（1997～2010）、外文生物醫學期刊文獻數據庫（2000～2010），并手檢相關雜志，查找GnRH拮抗劑與GnRH激動劑比較在體外受精-胚胎移植治療中有效性的隨機對照試驗。按照納入與排除標準選擇試驗、評價質量后進行Meta分析。
結果　共納入6個RCT，合計1 208例患者，其方法學質量均為B級。Meta分析結果顯示：與GnRH激動劑組相比，GnRH拮抗組刺激天數［WMD= –1.07，95%CI（–1.38，–0.76）］和獲卵數［WMD= –1.80，95%CI（–2.48，–1.12）］均更低，差異有統計學意義；而在Gn量［WMD= –0.49，95%CI（–1.63，0.66）］、HCG日子宮內膜厚度［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）］和流產率［Peto OR=1.49，95%CI（0.79，2.82）］上，兩組差異均無統計學意義。
結論　GnRH拮抗劑較之GnRH激動劑刺激天數短，所需Gn量少，不明顯影響妊娠率，同時可減少OHSS的發生，臨床上使用相對靈活，具有較好的接受性，為體外受精-胚胎移植超促排卵治療提供了另一種選擇。受納入研究質量和例數限制，上述結論尚需開展更多設計嚴謹的多中心、大樣本隨機對照試驗予以證實和更新。

引用本文： 肖勁松,陳雙隕,張春蓮,常雙. 促性腺激素釋放激素拮抗劑在體外受精-胚胎移植中有效性的系統性評價. 中國循證醫學雜志, 2010, 10(12): 1432-1438. doi: 10.7507/1672-2531.20100608 復制

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用藥方案及其在控制性超促排卵中的應用進展. 國外醫學計劃生育/生殖健康分冊, 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用藥方案及其在控制性超促排卵中的應用進展. 國外醫學計劃生育/生殖健康分冊, 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.

《中國循證醫學雜志》

促性腺激素釋放激素拮抗劑在體外受精-胚胎移植中有效性的系統性評價

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《中國循證醫學雜志》

促性腺激素釋放激素拮抗劑在體外受精-胚胎移植中有效性的系統性評價

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