来曲唑联合拮抗剂方案对体外受精-胚胎移植中低反应患者有效性的Meta分析_《中国循证医学杂志》

作者：

孙琴 , 陈莉 , 邵一丹 , 姚兵 ,  梁元姣

南京军区南京总医院生殖医学中心（南京 210000）;

关键词：

来曲唑 GnRHA 卵巢低反应体外受精-胚胎移植系统评价 Meta分析

DOI：

10.7507/1672-2531.20130232

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　系统评价来曲唑+促性腺激素释放激素拮抗剂方案对体外受精-胚胎移植（IVF-ET）中低反应患者促排卵的有效性。
方法　计算机检索VIP、CNKI、PubMed、EMbase和FMJS，收集有关来曲唑+拮抗剂方案对体外受精-胚胎移植低反应患者促排卵有效性的随机对照试验或临床对照试验。由2位评价员根据纳入与排除标准独立进行文献筛选、资料提取和质量评价后，采用RevMan 5.0软件进行Meta分析。
结果　最终纳入6个研究，共977例患者。Meta分析结果显示：对体外受精-胚胎移植中低反应患者，来曲唑+拮抗剂方案与对照组相比，Gn用量［MD= –8.05，95%CI（–13.67，–2.43），P=0.005］、HCG日E2值［MD= –1 026.41，95%CI（–1 949.61，–103.20），P=0.03］均小于对照组；而两组获卵数［MD= –0.61，95%CI（–2.41，–1.19），P=0.51］和临床妊娠率［OR=1.03，95%CI（0.53，2.02），P=0.92］无明显差异。
结论　对IVF-ET低反应患者促排卵治疗的有效性而言，来曲唑+拮抗剂方案较对照组临床结局无明显改善，但能减少Gn用量，降低IVF治疗费用。来曲唑+拮抗剂方案为卵巢低反应患者提供了另一种临床选择。由于纳入文献存在质量和数量不足以及方法学差异，建议本研究结论仅作为临床分析的参考，尚需后效评价和不断更新。

引用本文： 孙琴,陈莉,邵一丹,姚兵,梁元姣. 来曲唑联合拮抗剂方案对体外受精-胚胎移植中低反应患者有效性的Meta分析. 中国循证医学杂志, 2013, 13(11): 1354-1360. doi: 10.7507/1672-2531.20130232 复制

1.	Sunkara SK, Tuthill J, Khairy M, et al. Pituitary suppression regimens in poor responders undergoing IVF treatment: a systematic review and meta-analysis. Reprod Biomed Online, 2007, 150(5): 539-546.
2.	Keay SD, Liversedge NH, Mathur RS, et al. Assisted conception following poor ovarion res-ponse to stimulation for IVF: a systematic review. British J Obestet and Gynecol, 1997, 104(5): 521-528.
3.	Zhen XM, Qiao J, Li R, et al. The clinical analysis of poor ovarian response in vitro fertil-izaliton embryo transfer among Chinese couples. Assist Reprod Genet, 2008, 25(1): 17-22.
4.	Mahutte NG, Arici A. Role of gonadotropin-releasing hormone antagonists in poor responders. Fertil Sterl, 2007, 87(2): 241-249.
5.	肖劲松, 陈双陨, 张春莲, 等. GnRH-拮抗剂对体外受精-胚胎移植中低反应患者有效性的系统性评价. 现代妇产科进展, 2011, 120(14): 300-306.
6.	Ferraretti AP, La Marca A, Fauser BC, et al. ESHRE consensus on the definition of poor response to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod, 2011, 26(7): 1616-1624.
7.	Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. 2011. Available from: www.cochrane-handbook.org.
8.	Davar R, Oskouian H, Ahmadi S, et al. GnRH antagonist/letrozole versus microdose GnRH agonist flare protocol in poor responders undergoing in vitro fertilization. Taiwan J Obstet Gynecol, 2010, 49(3): 297-301.
9.	Garcia-Velasco JA, Moreno L, Pacheco A, et al. The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study. Fertil Steril, 2005, 84(1): 82-87.
10.	Ozmen B, Sonmezer M, Atabekoglu CS, et al. Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols. Reprod Biomed Online, 2009, 19(4): 478-485.
11.	Schoolcraft WB, Surrey ES, Minjarez DA, et al. Management of poor responders: can outcomes be im-proved with a novel gonadotropin-releasing hormone antagonist/letrozole protocol? Fertil Steril, 2008, 89(1): 151-156.
12.	Lee VCY, Chan CC, Ng EHY, et al. Sequential use of letrozole and gonadotrophin in women with poor ovarian reserve: a randomized controlled trial. Reprod Biomed Online, 2011, 23(2): 380-388.
13.	夏欢, 孙丽君, 王兴玲, 等. 来曲唑微刺激促排卵方案在卵巢低反应患者中的应用. 中国妇幼保健, 2011, 26(30): 4725-4728.
14.	叶碧绿, 叶练. 芳香化酶抑制剂在诱导排卵中的应用. 生殖医学杂志, 2005, 14(6): 374-377.
15.	Thiruppathi P, Shatavi S, Dias JA, et al. Gonadotrophin receptor expression on human gran-ulosa cells of low and normal responders to FSH. Mol Hum Reprod, 2001, 7(3): 697-704.
16.	Weil S, Vendola K, Zhou J, et al. Androgen and follicle stimulating hormone interactions in primate ovarian follicle development. Clin Endocr Metab, 1999, 84(8): 2951-2956.
17.	刘芸, 刑福琪, 何凌云, 等. 芳香化酶抑制剂在卵巢低反应者超促排卵中的作用. 南方医科大学学报, 2009, 29(3): 559-561.
18.	Ficicioglu C, Kutlu T, Baglam E, et al. Early follicular and anti-mullerian hormone as an indicator of ovarian reserve. Feritil Steril, 2006, 85(3): 592-596.
19.	Kevenaar ME, Meerasahib MF, Kramer P, et al. Serum anti-mullerian hormone levels reflect the size of the primordial follicle pool in mice. Endocrinology, 2006, 147(7): 3228-3234.
20.	Cortinez A, De Carvalho I, Vantman D, et al. Hormonal profile and endometrial morph-ology in letrozle-controlled ovarian hyper-stimulation in ovulatory infertile patients. Fertil Steril, 2005, 83(1): 110-115.
21.	Sunkara SK, Pundir J, Kalaf Y. Effect of androgen supplementation or modulation on ovarion stimulation outcome in poor responders: a meta-analysis. Reprod Biomed Online, 2011, 22(2): 545-555.
22.	Kupesic S, Kurjak A, Bjelos D, et al. Three-dimensional ultrasonographic ovarian measure-ments and in vitro fertilization outcome are related to age. Fertil Steril, 2003, 79(1): 190-197.

1. Sunkara SK, Tuthill J, Khairy M, et al. Pituitary suppression regimens in poor responders undergoing IVF treatment: a systematic review and meta-analysis. Reprod Biomed Online, 2007, 150(5): 539-546.
2. Keay SD, Liversedge NH, Mathur RS, et al. Assisted conception following poor ovarion res-ponse to stimulation for IVF: a systematic review. British J Obestet and Gynecol, 1997, 104(5): 521-528.
3. Zhen XM, Qiao J, Li R, et al. The clinical analysis of poor ovarian response in vitro fertil-izaliton embryo transfer among Chinese couples. Assist Reprod Genet, 2008, 25(1): 17-22.
4. Mahutte NG, Arici A. Role of gonadotropin-releasing hormone antagonists in poor responders. Fertil Sterl, 2007, 87(2): 241-249.
5. 肖劲松, 陈双陨, 张春莲, 等. GnRH-拮抗剂对体外受精-胚胎移植中低反应患者有效性的系统性评价. 现代妇产科进展, 2011, 120(14): 300-306.
6. Ferraretti AP, La Marca A, Fauser BC, et al. ESHRE consensus on the definition of poor response to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod, 2011, 26(7): 1616-1624.
7. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0. 2011. Available from: www.cochrane-handbook.org.
8. Davar R, Oskouian H, Ahmadi S, et al. GnRH antagonist/letrozole versus microdose GnRH agonist flare protocol in poor responders undergoing in vitro fertilization. Taiwan J Obstet Gynecol, 2010, 49(3): 297-301.
9. Garcia-Velasco JA, Moreno L, Pacheco A, et al. The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study. Fertil Steril, 2005, 84(1): 82-87.
10. Ozmen B, Sonmezer M, Atabekoglu CS, et al. Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols. Reprod Biomed Online, 2009, 19(4): 478-485.
11. Schoolcraft WB, Surrey ES, Minjarez DA, et al. Management of poor responders: can outcomes be im-proved with a novel gonadotropin-releasing hormone antagonist/letrozole protocol? Fertil Steril, 2008, 89(1): 151-156.
12. Lee VCY, Chan CC, Ng EHY, et al. Sequential use of letrozole and gonadotrophin in women with poor ovarian reserve: a randomized controlled trial. Reprod Biomed Online, 2011, 23(2): 380-388.
13. 夏欢, 孙丽君, 王兴玲, 等. 来曲唑微刺激促排卵方案在卵巢低反应患者中的应用. 中国妇幼保健, 2011, 26(30): 4725-4728.
14. 叶碧绿, 叶练. 芳香化酶抑制剂在诱导排卵中的应用. 生殖医学杂志, 2005, 14(6): 374-377.
15. Thiruppathi P, Shatavi S, Dias JA, et al. Gonadotrophin receptor expression on human gran-ulosa cells of low and normal responders to FSH. Mol Hum Reprod, 2001, 7(3): 697-704.
16. Weil S, Vendola K, Zhou J, et al. Androgen and follicle stimulating hormone interactions in primate ovarian follicle development. Clin Endocr Metab, 1999, 84(8): 2951-2956.
17. 刘芸, 刑福琪, 何凌云, 等. 芳香化酶抑制剂在卵巢低反应者超促排卵中的作用. 南方医科大学学报, 2009, 29(3): 559-561.
18. Ficicioglu C, Kutlu T, Baglam E, et al. Early follicular and anti-mullerian hormone as an indicator of ovarian reserve. Feritil Steril, 2006, 85(3): 592-596.
19. Kevenaar ME, Meerasahib MF, Kramer P, et al. Serum anti-mullerian hormone levels reflect the size of the primordial follicle pool in mice. Endocrinology, 2006, 147(7): 3228-3234.
20. Cortinez A, De Carvalho I, Vantman D, et al. Hormonal profile and endometrial morph-ology in letrozle-controlled ovarian hyper-stimulation in ovulatory infertile patients. Fertil Steril, 2005, 83(1): 110-115.
21. Sunkara SK, Pundir J, Kalaf Y. Effect of androgen supplementation or modulation on ovarion stimulation outcome in poor responders: a meta-analysis. Reprod Biomed Online, 2011, 22(2): 545-555.
22. Kupesic S, Kurjak A, Bjelos D, et al. Three-dimensional ultrasonographic ovarian measure-ments and in vitro fertilization outcome are related to age. Fertil Steril, 2003, 79(1): 190-197.

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来曲唑联合拮抗剂方案对体外受精-胚胎移植中低反应患者有效性的Meta分析

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