PDF(942 KB)
PCOS患者IVF/ICSI时应用GnRH-a长方案与拮抗剂方案累积活产率的比较
郭希,陈明晖,乌日汗,沈晓婷,刘洋,钟依平
新医学 ›› 2019, Vol. 50 ›› Issue (5) : 341-346.
PDF(942 KB)
PDF(942 KB)
PCOS患者IVF/ICSI时应用GnRH-a长方案与拮抗剂方案累积活产率的比较
Comparison of cumulative live birth rates between GnRH antagonist and long GnRH agonist protocols in patients with PCOS undergoing IVF/ICSI
目的 比较进行体外受精或卵胞浆内单精子注射（IVF/ICSI）助孕治疗的多囊卵巢综合征（PCOS）患者应用促性腺激素释放激素激动剂（GnRH-a）长方案和拮抗剂（GnRH-ant）方案累积活产率的差异。 方法 收集行IVF/ICSI助孕治疗的PCOS患者临床资料,根据控制性促排卵（COH）方案分为GnRH-a长方案组（281例）和GnRH-ant方案组（249例）,比较2组患者的一般资料、COH情况、实验室指标及临床结局。应用多因素Logistic回归分析COH方案与累积活产率的关系。结果 与GnRH-a长方案组相比,GnRH-ant方案组女方年龄较小、基础窦卵泡数较多、基础睾酮水平较低、基础雌二醇值较高、促性腺激素（Gn）用量较少、Gn刺激时间较短、人绒毛膜促性腺激素注射日黄体生成素水平及孕酮水平较高（P均< 0.05）。2组患者的累积活产率及其他指标比较差异均无统计学意义（P均> 0.05）。经校正女方年龄、可利用胚胎数等混杂因素后,COH方案与累积活产率无关（P > 0.05）。结论 PCOS不孕患者行IVF/ICSI应用GnRH-ant方案可获得与GnRH-a长方案相近的累积活产率,而Gn用药量较少、用药时间较短。
Objective To compare the cumulative live birth rates between gonadotropin-releasing hormone （GnRH） antagonist and long GnRH agonist protocols in patients with polycystic ovary syndrome （PCOS） undergoing in vitro fertilization/intracytoplasmic sperm injection （IVF/ICSI）. Methods Clinical data of PCOS patients who underwent IVF/ICSI were collected. All patients were assigned into the long GnRH-a （n = 281） and GnRH-ant groups （n =249） according to the controlled ovarian hyperstimulation （COH） protocol. Baseline data, COH status, laboratory parameters and clinical outcomes were statistically compared between two groups. The association between COH protocol and the cumulative live birth rate was analyzed by using multivariate logistic regression analysis. Results Patients treated with GnRH antagonist protocol were significantly younger with higher antral follicle count （AFC）, higher basal estradiol level, lower basal testosterone level, lower dose of Gn, shorter duration of Gn stimulation, higher levels of luteinizing hormone and progesterone upon the day of HCG injection compared with their counterparts in the long GnRH agonist group （all P < 0.05）. The cumulative live birth rate and other parameters did not significantly differ between two groups （all P > 0.05）. Multivariate logistic regression analysis demonstrated that COH protocol was not significantly correlated with the cumulative live birth rate （P > 0.05） after adjusting the potential confounding factors, such as age of the female patient and the number of qualified embryo, etc. Conclusion Compared with the long GnRH agonist protocol, GnRH antagonist protocol yields comparable cumulative live birth rate, lower dose of Gn and shorter duration of Gn stimulation in patients with PCOS undergoing IVF/ICSI.
多囊卵巢综合征 / 促性腺激素释放激素激动剂 / 促性腺激素释放激素拮抗剂 / 累积活产率 {{custom_keyword}} /
Polycystic ovary syndrome / Gonadotropin-releasing hormone agonist / Gonadotropin-releasing hormone antagonist / Cumulative live birth rate {{custom_keyword}} /
表1 GnRH-a长方案组和GnRH-ant方案组患者的一般资料比较 |
| 项 目 | GnRH-a长方案组（281例） | GnRH-ant方案组（249例） | Z/ | P值 |
|---|---|---|---|---|
| 女方年龄（岁） | 30（28,33） | 29（27,32） | -2.018 | 0.044 |
| 男方年龄（岁） | 34（31,36） | 33（30,36） | -1.939 | 0.053 |
| 周期数（个） | 1（1,1） | 1（1,1） | -1.007 | 0.314 |
| BMI（kg/m2） | 22.2（20.1,24.6 ） | 22.6（20.3,25.4） | -1.415 | 0.157 |
| 不孕年限（年） | 4（2,6） | 4（2,6） | -0.156 | 0.876 |
| 不孕类型[例（%）] | 2.478 | 0.115 | ||
| 原发性 | 177（63） | 173（70） | ||
| 继发性 | 104（37） | 76（31） | ||
| 受精方式[例（%）] | 4.013 | 0.129 | ||
| IVF | 209（74） | 170（68） | ||
| ICSI | 54（19） | 66（27） | ||
| IVF+ICSI | 18（6） | 13（5） | ||
| 基础窦卵泡数（个） | 17（12,20） | 18.5（14,23） | -2.762 | 0.006 |
| 基础FSH（U/L） | 4.9（4.2,5.7） | 4.9（4.2,5.8） | -0.097 | 0.922 |
| 基础LH（U/L） | 5.3（3.5,8.3） | 6.1（3.7,9.3） | -1.594 | 0.111 |
| 基础雌二醇（pg/ml） | 34（26,46） | 38（28,50） | -2.220 | 0.026 |
| 基础睾酮（ng/ml） | 0.6（0.4,0.8） | 0.5（0.4,0.7） | -3.234 | 0.001 |
表2 GnRH-a长方案组和GnRH-ant方案组患者的促排卵周期基本特征比较 |
| 项 目 | GnRH-a长方案组（281例） | GnRH-ant方案组（249例） | Z值 | P值 |
|---|---|---|---|---|
| Gn刺激时间（d） | 10（9,12） | 9（8,10） | -7.867 | <0.001 |
| Gn 用量（U） | 1 575（1 263,2 100） | 1 262（1 025,1 650） | -6.351 | <0.001 |
| HCG日LH（IU/L） | 0.7（0.5,1.1） | 1.9（1.0,3.2） | -12.231 | <0.001 |
| HCG日雌二醇（pg/ml） | 3 186（2 044,5 000） | 3 309（1 987,4 872） | -0.288 | 0.773 |
| HCG日孕酮（ng/ml） | 0.5（0.3,0.7） | 0.6（0.4,0.8） | -4.628 | <0.001 |
| HCG日卵泡总数（个） | 11（5,15） | 11（8,15） | -1.520 | 0.129 |
| HCG日内膜厚度（mm） | 10.0（9,12） | 10.2（9,12） | -0.991 | 0.322 |
| 新鲜移植周期[例（%）] | 169 | 131 | ||
| 无OHSS | 168（99） | 127（97） | -1.640 | 0.101 |
| 轻度OHSS | 0（0） | 1（0.8） | ||
| 中度OHSS | 0（0） | 2（1.5） | ||
| 重度OHSS | 1（1） | 1（0.8） | ||
| 全胚冷冻周期[例（%）] | 112 | 118 | ||
| 无OHSS | 112（100） | 115（98） | -1.695 | 0.090 |
| 轻度OHSS | 0（0） | 3（3） | ||
| 中度OHSS | 0（0） | 0（0） | ||
| 重度OHSS | 0（0） | 0（0） |
表3 GnRH-a长方案组和GnRH-ant方案组患者的实验室及临床结局比较 |
| 项 目 | GnRH-a长方案组（281例） | GnRH-ant方案组（249例） | Z/ | P值 |
|---|---|---|---|---|
| 获卵数（个） | 15（9,23） | 15（9,22） | -0.023 | 0.982 |
| 成熟卵子数（个） | 13（8,21） | 13（8,20） | -0.258 | 0.796 |
| 正常受精数（个） | 10（6,15） | 10（5,15） | -0.851 | 0.395 |
| 可利用胚胎数（个） | 5（3,8） | 6（3,8） | -0.057 | 0.955 |
| 优质胚胎数（个） | 4（2,8） | 4（2,8） | -0.175 | 0.861 |
| 累积活产率[例（%）] | 196（69.8） | 179（71.9） | 0.291 | 0.589 |
表4 累积活产率的多因素Logistic回归分析 |
| 项 目 | B | Wald | OR值 | 95%CI | P值 |
|---|---|---|---|---|---|
| 女方年龄（岁） | -0.052 | 1.890 | 0.950 | 0.882 ~ 1.022 | 0.169 |
| 不孕年限（年） | -0.068 | 1.829 | 0.934 | 0.847 ~ 1.031 | 0.176 |
| BMI（kg/m2） | -0.050 | 1.807 | 0.951 | 0.884 ~ 1.023 | 0.179 |
| 窦卵泡数（个） | 0.023 | 1.838 | 1.023 | 0.990 ~ 1.057 | 0.175 |
| Gn用量（U） | 0.000 | 0.469 | 1.000 | 0.999 ~ 1.000 | 0.494 |
| HCG日雌二醇（pg/ml） | 0.000 | 0.329 | 1.000 | 1.000 ~ 1.000 | 0.566 |
| HCG日孕酮（ng/ml） | 0.529 | 1.141 | 1.697 | 0.643 ~ 4.479 | 0.285 |
| HCG日卵泡数（个） | 0.010 | 0.189 | 1.010 | 0.965 ~ 1.057 | 0.664 |
| 获卵数（个） | -0.070 | 1.978 | 0.932 | 0.846 ~ 1.028 | 0.160 |
| 成熟卵子数（个） | 0.096 | 1.880 | 1.100 | 0.960 ~ 1.261 | 0.170 |
| 正常受精数（个） | -0.002 | 0.001 | 0.998 | 0.889 ~ 1.120 | 0.971 |
| 可利用胚胎数（个） | 0.552 | 42.947 | 1.736 | 1.472 ~ 2.048 | < 0.001 |
| 优质胚胎数（个） | 0.027 | 0.122 | 1.027 | 0.884 ~ 1.194 | 0.727 |
| 用药方案 | |||||
| GnRH-a长方案 | 参照组 | - | - | - | - |
| GnRH-ant方案 | 0.085 | 0.103 | 1.089 | 0.647 ~ 1.833 | 0.748 |
| [1] |
Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [2] |
熊冬梅, 李蓉, 许良智 . 多囊卵巢综合征胰岛素抵抗的发生机制研究进展. 新医学, 2006,37(6):413-414.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [3] |
梁海英, 黄晓晖, 丁勇利, 宋绿茵 . 青春期和成年期多囊卵巢综合征胰岛素抵抗情况分析. 新医学, 2009,40(6):376-378.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [4] |
To examine the outcome of IVF in women who have normal ovaries, ovulatory PCO or PCOS.Study designAnalysis of a prospectively collected database in an assisted conception unit in a university teaching hospital including 290 women ResultsSevere OHSS rates were significantly higher in women with PCO (12.6%) and PCOS (15.4%) compared to those with normal ovaries (2.7%). Coasting was used significantly more often. Live birth rates per cycle started are similar among women with PCO (38%), PCOS (37%) and normal ovaries (40%).ConclusionWomen with ovaries of polycystic morphology are at increased risk of developing severe OHSS and of requiring avoidance techniques such as coasting, regardless of ovulatory status. However, live birth rates per cycle are similar to women with normal ovaries.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [5] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [6] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [7] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [8] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [9] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [10] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [11] |
Abstract OBJECTIVE: To compare self-reported quality of life, psychosocial well-being, and physical well-being during assisted reproductive technology (ART) treatment in 1,023 women allocated to either a short GnRH antagonist or long GnRH agonist protocol. DESIGN: Secondary outcome of a prospective phase 4, open-label, randomized controlled trial. Four times during treatment a questionnaire on self-reported physical well-being was completed. Further, a questionnaire on self-reported quality of life and psychosocial well-being was completed at the day of hCG testing. SETTING: Fertility clinics at university hospitals. PATIENT(S): Women referred for their first ART treatment were randomized in a 1:1 ratio and started standardized ART protocols. INTERVENTION(S): Gonadotropin-releasing hormone analogue; 528 women allocated to a short GnRH antagonist protocol and 495 women allocated to a long GnRH agonist protocol. MAIN OUTCOME MEASURE(S): Self-reported quality of life, psychosocial well-being, and physical well-being based on questionnaires developed for women receiving ART treatment. RESULT(S): Baseline characteristics were similar, and response rates were 79.4% and 74.3% in the GnRH antagonist and GnRH agonist groups, respectively. Self-reported quality of life during ART treatment was rated similar and slightly below normal in both groups. However, women in the GnRH antagonist group felt less emotional (adjusted odds ratio [AOR] 0.69), less limited in their everyday life (AOR 0.74), experienced less unexpected crying (AOR 0.71), and rated quality of sleep better (AOR 1.55). Further, women receiving GnRH agonist treatment felt worse physically. CONCLUSION(S): Women in a short GnRH antagonist protocol rated psychosocial and physical well-being during first ART treatment better than did women in a long GnRH agonist protocol. However, the one item on self-reported general quality of life was rated similarly. CLINICAL TRIAL REGISTRATION NUMBER: NCT00756028 . Copyright 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [12] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [13] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [14] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [15] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [16] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [17] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [18] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [19] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [20] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [21] |
吴春香, 张婷, 舒黎, 黄洁, 刁飞扬, 丁卫, 高彦, 王炜, 冒韵东, 崔毓桂, 刘嘉茵 . 每取卵周期的累积活产率在IVF/ICSI妊娠结局评估中的价值. 中华妇产科杂志, 2018,53(3):160-166.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [22] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [23] |
To compare the use of GnRH agonist (GnRHa) or hCG trigger in potential OHSS patients undergoing freeze-all programs. We also compared the clinical outcomes when fresh versus freeze-thawed embryo transfers were performed in cycles with a high number of retrieved oocytes. The study included potential OHSS patients who received GnRHa (n=74) or hCG (n=49) trigger. The protocols were compared with respect to the clinical outcomes. We also compared the clinical outcomes of cycles in which hCG trigger was used and more than 20 MII oocytes were retrieved when: fresh embryo transfer protocol (n=153) or freeze-all protocol (n=123) were performed. A decreased serum estradiol level, a decreased number of retrieved oocytes, an increased MII retrieved rate, and decreased fertilization rate was observed in the hCG when compared with the GnRHa group. No significant differences were noted concerning clinical outcomes. When fresh cycles were compared with frozen-thawed cycles, the estradiol serum level and the number of cryopreserved embryos were higher in the frozen-thawed cycles. The clinical pregnancy rate was higher among freeze-all cycles, as well as the implantation and cumulative pregnancy rates, when compared with fresh embryo transfer cycles. The use of GnRHa trigger may be a good alternative to prevent the OHSS in patients presenting an extreme ovarian response to COS, leading to similar clinical outcomes, when compared with the traditional hCG trigger. Moreover, our findings demonstrated that the strategy of freezing-all embryos not only decreases the risk of OHSS but also leads to a better pregnancy rate.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [24] |
杨硕, 何艺磊, 梁靓, 李蓉, 陈新娜, 甄秀梅, 王丽娜, 王海燕, 马彩虹, 刘平, 乔杰 . 促性腺激素释放激素激动剂联合低剂量人绒毛膜促性腺激素扳机在高反应患者体外受精治疗中的应用. 中华生殖与避孕杂志, 2018,38(3):181-185.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [25] |
李赛姣, 周丹妮, 尹太郎, 徐望明, 谢青贞, 程丹, 杨菁 . GnRH激动剂联合小剂量HCG双扳机对PCOS患者IVF-ET临床结局的影响. 生殖医学杂志, 2017,26(10):978-982.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| {{custom_ref.label}} |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
The authors have declared that no competing interests exist.
作者已声明无竞争性利益关系。
PDF(942 KB)
表1 GnRH-a长方案组和GnRH-ant方案组患者的一般资料比较表2 GnRH-a长方案组和GnRH-ant方案组患者的促排卵周期基本特征比较表3 GnRH-a长方案组和GnRH-ant方案组患者的实验室及临床结局比较表4 累积活产率的多因素Logistic回归分析/
| 〈 |
|
〉 |
