机构地区:[1]Guangdong Provincial Key Laboratory of Reproductive Medicine,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510000,China [2]Reproductive Medicine Center,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510000,China [3]Reproductive Medicine Center,Huizhou Municipal Central Hospital,Huizhou 516001,China [4]Research School for Developmental Biology(GROW),Maastricht University,Maastricht,The Netherlands [5]Division of Obstetrics and Gynecology,Department of Clinical Science,Intervention and Technology(CLINTEC),Karolinska Institute,Stockholm,Sweden
出 处:《南方医科大学学报》2025年第2期213-222,共10页Journal of Southern Medical University
基 金:国家自然科学基金(82001551)。
摘 要:Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.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,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the 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 those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.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体外授精胚胎移植中心进行的这项遗传关联研究中,共有361名年龄≤40岁、基础卵泡刺激素≤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13~24,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差异没有统计学意义。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:androgen receptor GGN polymorphism ovarian reserve ovarian stimulation
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