来曲唑联合高纯度尿促性素治疗克罗米芬耐药的多囊卵巢综合征不孕患者的临床研究

doi:10.3969/j.issn.1006-7795.2016.04.004

首都医科大学学报 ›› 2016, Vol. 37 ›› Issue (4): 431-436.doi: 10.3969/j.issn.1006-7795.2016.04.004

来曲唑联合高纯度尿促性素治疗克罗米芬耐药的多囊卵巢综合征不孕患者的临床研究

赵越¹, 阮祥燕^1,2, 李扬璐¹, 杜娟¹, Alfred O. Mueck^1,2

1. 首都医科大学附属北京妇产医院内分泌科, 北京 100026;
2. 德国图宾根大学妇产医院绝经内分泌中心, 图宾根 D-72076, 德国

收稿日期:2016-06-15 出版日期:2016-08-21 发布日期:2016-07-18
通讯作者: 阮祥燕 E-mail:ruanxiangyan@163.com
基金资助:
北京市自然科学基金（Y161011），北京市卫生系统高层次卫生技术人才（学科带头人）（2014-2-016），首都医科大学附属北京妇产医院，北京妇幼保健院学科带头人项目（2013-1）。

Letrozole combined with low dose highly purified human menopausal gonadotropin for ovulation induction in clomiphene citrate-resistant infertile women with polycystic ovary syndrome: a prospective study

Zhao Yue¹, Ruan Xiangyan^1,2, Li Yanglu¹, Du Juan¹, Alfred O. Mueck^1,2

1. Department of Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China;
2. Section of Endocrinology and Menopause, Department of Women's Health, University of Tubingen, Tubingen D-72076, Germany

Received:2016-06-15 Online:2016-08-21 Published:2016-07-18
Supported by:
This study was supported by Natural Science Foundation of Beijing(Y161011),Beijing Municipality Health Technology High-level Talent(2014-2-016);Project of Discipline Leader,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing Maternal and Child Health Care Hospital(2013-1).

摘要/Abstract

摘要： 目的评估来曲唑（letrozole，LTZ）联合高纯度尿促性素（highly purified human menopausal gonadotropin，Hp-HMG）低剂量方案治疗多囊卵巢综合征（polycystic ovary syndrome，PCOS）耐克罗米芬（clomiphene citrate，CC）无排卵不孕患者的有效性和安全性。方法选取2015年1月至2015年6月在首都医科大学附属北京妇产医院内分泌科就诊的耐CC的PCOS不孕症患者120例，进行237个周期LTZ联合Hp-HMG低剂量方案促排卵治疗。观察主要研究终点：临床妊娠率、排卵率、单卵泡发生率。次要研究终点：排卵率、注射促性腺激素释放激素激动剂（gonadotropin-releasing hormone agonist，GnRH-a）日血清雌二醇（estradiol，E2）、促黄体生成素（luteinizing hormone，LH）浓度、注射GnRH-a日子宫内膜厚度；主要安全性评价指标：不良事件发生率包括早期流产率、卵巢过度刺激综合征（ovarian hyper-stimulation syndrome，OHSS）发生率、多胎妊娠率。结果周期排卵率96.2%（228/237），单卵泡发育率为70%（166/237），周期取消率为1.3%（3/237），无排卵周期为9个（3.8%）。237个周期中，单胎妊娠率为32.9%（75/228），早期流产率为5.3%（12/228）。120例患者中，3个周期累计临床妊娠率65%（78/120），有2例双胎妊娠，1例输卵管妊娠，无重度OHSS，无多胎妊娠发生，无局部及全身不良反应。结论 LTZ联合低剂量Hp-HMG促排卵方案可以降低卵巢过度刺激发生率、增加临床妊娠率，对于耐CC的PCOS无排卵不孕患者是有效而安全的选择。

关键词: 多囊卵巢综合征, 高纯度尿促性素, 来曲唑, 克罗米芬抵抗, 临床妊娠率

Abstract: Objective To evaluate the efficacy, safety and feasibility of letrozole (LTZ) combined with low dose highly purified human menopausal gonadotropin (Hp-HMG) in clomiphene citrate (CC)-resistant infertile women with polycystic ovary syndrome (PCOS). Methods Totally 120 infertile women with PCOS with CC resistance were enrolled for ovulation induction by LTZ combined with low dose Hp-HMG, together with 237 cycles. The primary study endpoints were the clinical pregnancy rate, the ovulation rate and the percentage of monofollicular development. The secondary efficacy endpoints included the number of ovulated follicles, serum level of estradiol and luteinizing hormone (LH) and endometrial thickness on the day of gonadotropin releasing hormone agonist (GnRH-a) triggering. The main safety parameters were the incidence of adverse events, including the early abortion, ovarian hyperstimulation syndrome (OHSS), and multiple pregnancy. Results The rate of cycle ovulation was 96.2% (228/237), the percentage of monofollicular development was 70% (166/237), cycle cancellation rate was 1.3% (3/237) and anovulation rate was 3.8% (9/237); 237 cycles achieved the periodic single pregnancy rate was 32.9% (75/228), the early abortion rate was 5.3% (12/228). Two twin gestation and 1 ectopic pregnancy; In 120 patients, the rate of cumulative clinical pregnancy was 65% (78/120). No severe OHSS, multiple pregnancy, local or systemic side effects were seen. Conclusion Letrozole combined with low dose Hp-HMG maybe an effective and safe choice for reducing hyperstimulation and increasing pregnancy rate for ovulation induction in CC-resistant women with PCOS.

Key words: polycystic ovary syndrome, highly purified human menopausal gonadotropin, letrozole, clomiphene citrate resistance, clinical pregnancy rate

中图分类号:

R711.75

赵越, 阮祥燕, 李扬璐, 杜娟, Alfred O. Mueck. 来曲唑联合高纯度尿促性素治疗克罗米芬耐药的多囊卵巢综合征不孕患者的临床研究[J]. 首都医科大学学报, 2016, 37(4): 431-436.

Zhao Yue, Ruan Xiangyan, Li Yanglu, Du Juan, Alfred O. Mueck. Letrozole combined with low dose highly purified human menopausal gonadotropin for ovulation induction in clomiphene citrate-resistant infertile women with polycystic ovary syndrome: a prospective study[J]. Journal of Capital Medical University, 2016, 37(4): 431-436.

参考文献

[1] 赵越, 阮祥燕, 崔亚美, 等.不同亚型的多囊卵巢综合征患者临床及实验室指标特征的研究[J]. 首都医科大学学报, 2015, 36(4): 567-572.
[2] Mitwally F M, Casper R F. Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate[J]. Fertile Steril, 2001, 75(2): 305-309.
[3] Homburg R, Hendriks M L, König T E, et al. Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study[J]. Human Reprod, 2012, 27(2): 468-473.
[4] Elnashar A, Fouad H, Eldosoky M, et al. Letrozole induction of ovualtion in women with clomiphene citrate-resistant polycystic ovary syndrome may not depend on the period of infertility, the body mass index, or the luteinizing hormone/follicle-stimulating hormone ratio[J]. Fertil Steril, 2006, 85(2): 511-513.
[5] Andersen Nyboe A N, Devroey P, Arce J C. Clinical outcome following stimulation with highly purified hMG or recombinant FSH in patients undergoing IVF: a randomized assessor-blind controlled trial[J]. Human Reprod, 2006, 21(12): 3217-3227.
[6] The Rotterdam ESHER/ASRM-sponseored PCOS Consensus Workshop Group. Revised 2003 consensus of diagnostic criteria and long-term health risks related to polycystic ovary syndrome(PCOS)[J]. Hum Reprod, 2004, 19(1): 41-47.
[7] Xi W, Liu S, Mao H, et al. Use of letrozole and clomiphene citrate combined with gonadotropins in clomiphene-resistant infertile women with polycystic ovary syndrome: a prospective study[J]. Drug Des Devel Ther, 2015, 11(9): 6001-6008.
[8] Boothroyd C, Karia S, Andreadis N, et al. Consensus statement on prevention and detection of ovarian hyperstimulationsyndrome[J].Aust N J Obstet Gynaecol, 2015, 55(6): 523-534.
[9] De Ziegler D, Fraisse T, de Candonlle G, et al. Outlook: Roles of FSH and LH during the follicular phase: insight into natural cycle IVF[J]. Rprod Biomed Online, 2007, 15(5): 507-513.
[10] Zhao Y, Du B, Jiang X, et al.Effects of combining low-dose aspirin with a Chinese patent medicine on follicular blood flow and pregnancy outcome[J]. Mol Med Rep, 2014,10(5): 2372-2376.
[11] Balasch J, Fabregues F. Is luteinizing hormone needed for optimal ovulation induction?[J]. Curr Opin Obstet Hynecol, 2002, 14(3): 265-274.
[12] O'Dea L, O'Brien F, Currie K, et al. Follicular development induced by recombinant luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in anovulatory women with LH and FSH deficiency: evidence of a threshold effect[J]. Curr Med Res Opinm, 2008, 24(10): 2785-2793.
[13] Ziebe S, Lundin K, Janssens R, et al. Influence of ovarian stimulation with HP-hMG or recombinant FSH on embryo quality parameters in patients undergoing IVF[J]. Hum Reprod, 2007, 22(9): 2404-2413.
[14] Moro F, Scarinci E, Palla C, et al. Highly purified hMG versus recombinant FSH plus recombinant LH in intrauterine insemination cycles in women≥35 years: a RCT[J]. Hum Reprod, 2015, 30(1): 179-185.
[15] Foutouch L A, Khattab S, Mohesn L A, et al. Clinical outcome following stimulation with HMG versus highly purified HMG in patients undergong ICSI[J]. Reprod Biomed Online, 2007, 14(2): 145-147.
[16] Weiss NS, Nahuis M, Bayram N, et al. Gonadotrophins for ovulation in women with polycystic ovarian syndrome[J]. Cochrane Database Syst Rev, 2015,9(9):CD010290.
[17] Bu Z, Sun Y. The impact of endometrial thickness on the day of human chrionic gonadotrophin (hCG) administration on ongoing pregnancy rate in patients with different ovarian response[J]. PLoS One, 2015,10(12): e0145703.
[18] Platteau P, Andersen AN, Balen A, et al. Similar ovulation rates, but different follicular development with highly purified menotrophin compared with recombinant FSH in WHO Group Ⅱ anovulatory infertility: a randomized controlled study[J]. Hum Rerpod, 2006, 21(7): 1798-1804.
[19] 刘宝莲,韩宝生,邱忠君,等. 克罗米芬、来曲唑联合醋酸曲普瑞林促排卵在宫腔内人工授精助孕中的效果分析[J]. 中国煤炭工业医学杂志,2015,18(10):1645-1647.
[20] 杨颖,王金敏,彭书苹,等. 多囊卵巢综合征与不孕的诊治进展及个体化治疗疗效的临床研究[J]. 中国煤炭工业医学杂志, 2014,17(10) :1568-1570.

来曲唑联合高纯度尿促性素治疗克罗米芬耐药的多囊卵巢综合征不孕患者的临床研究

Letrozole combined with low dose highly purified human menopausal gonadotropin for ovulation induction in clomiphene citrate-resistant infertile women with polycystic ovary syndrome: a prospective study

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