南方医科大学学报

南方医科大学学报

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雄激素受体基因的GGN重复长度与接受控制性卵巢刺激的中国女性的窦卵泡计数相关

刘新颜，范 琪，邓明芬，许 言，郭 静，曹 苹，周灿权，徐艳文   

  1. 中山大学附属第一医院广东省生殖医学重点实验室，生殖医学中心，广东 广州 510000；惠州市中心人民医院生殖医学中心，广东 惠州 516001；荷兰马斯特里赫特大学发育生物学研究学院（GROW），荷兰 马斯特里赫特；瑞典斯德哥尔摩卡罗林斯卡学院临床科学、干预和技术系妇产科，瑞典 斯德哥尔摩
  • 出版日期:2024-12-30 发布日期:2024-12-30

GGN repeat length of the androgen receptor gene is associated with the antral follicle count in Chinese women undergoing controlled ovarian stimulation

LIU Xinyan, FAN Qi,DENG Mingfen, XU Yan, GUO Jing, CAO Ping, ZHOU Canquan, XU Yanwen   

  1. Guangdong Provincial Key Laboratory of Reproductive Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China; Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China; Reproductive Medicine Center, Huizhou Municipal Central Hospital, Huizhou 516001, China; Research School for Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands; Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institute, Stockholm, Sweden
  • Online:2024-12-30 Published:2024-12-30

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摘要： 目的 评估雄激素受体（AR）的GGN重复多态性与卵巢储备及在控制性卵巢刺激（COS）中的卵巢反应的关联。方法 在一所大学附属的IVF中心进行的这项遗传关联研究中，共有361名年龄≤40岁、基础FSH≤12 IU/L的女性接受了GnRH激动剂长方案进行COS。对AR基因中的GGN重复进行了Sanger测序分析。主要终点是窦卵泡计数（AFCs），次要终点包括刺激天数、使用的促性腺激素（Gn）总剂量、取卵总数、卵巢敏感性指数（OSI）和卵泡输出率（FORT）。结果 AR基因第1外显子中的GGN重复长度从13到24不等，观察到的中位重复长度为22。考虑基因型（GGN重复<22为S，GGN重复≥22为L）时，所有患者被分为3组：SS、SL和LL。广义回归分析指出，SS组的AFCs数量显著低于SL组（调整后β值1.8；95%CI，0.2-3.4；P＝0.024）或与 LL 组比较（调整后β值1.5；95%CI，0.2-2.7；P＝0.021）。SL组与LL组之间的AFCs数量没有观察到显著差异。此外，广义回归分析还表明，在调整混杂因素前后，3组之间的卵巢刺激参数没有显著差异。结论 AR基因上的GGN重复长度与AFC相关，但与中国女性的卵巢反应无关，表明AR基因的多态性可能影响卵巢储备。

关键词: 雄激素受体, GGN多态性, 卵巢储备, 卵巢刺激

Abstract: Objective To evaluate the associations of GGN repeat polymorphism of androgen receptor (AR) with ovarian reserve and ovarian response in controlled ovarian stimulation (COS). Methods In this genetic association study conducted in a university-affiliated IVF center,a total of 361 women aged ≤40 years with basal FSH≤12 IU/L underwent the GnRH-agonist long protocol for COS. GGN repeat in the AR gene was analyzed with Sanger sequencing. The primary endpoint was the number of antral follicle counts (AFCs), and the secondary endpoints were stimulation days, total dose of gonadotropin (Gn) used, total number of retrieved oocytes, ovarian sensitivity index (OSI), and follicular output rate (FORT). Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24, and the median repeat length was observed to be 22. When considering the genotypes (S for GGN repeats <22, L for GGN repeats ≥22), all patients were divided into 3 groups: SS, SL, and LL. Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than that in group SL (adjusted β 1.8; 95% Cl, 0.2-3.4; P＝0.024) or compared with group LL (adjusted β 1.5; 95% Cl 0.2-2.7; P＝0.021). No significant difference in the number of AFCs was observed between group SL and group LL. In addition, generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups, either before or after adjusting for confounding factors. Conclusions GGN repeat length on the AR gene was associated with AFC but not with ovarian response in Chinese women, indicating that polymorphisms of the AR gene may affect ovarian reserve.

Key words: androgen receptor, GGN polymorphism, ovarian reserve, ovarian stimulation