卵巢高反应危险因素分析及预测模型构建

Analysis of risk factors of ovarian hyperresponse and construction of prediction model

目的探讨辅助生殖中卵巢高反应患者的相关危险因素、筛选卵巢高反应遗传标志物,构建卵巢高反应预测模型。方法回顾性收集2020年1月-2021年12月在中国人民解放军联勤保障部队第九四○医院生殖医学中心选择拮抗剂方案控制性超促排卵治疗的不孕妇女141例。根据获卵数是否大于15个,分为病例组和对照组。分别统计2组患者基本临床特征和控制性超促排卵资料,提取外周血脱氧核糖核酸进行全基因组单核苷酸多态性芯片检测分型,通过全基因组关联分析和多基因风险评分系统筛选单核苷酸多态性位点、构建卵巢高反应风险预测模型。结果窦卵泡计数、多囊卵巢综合征病史及扳机日直径>11 mm卵泡数是卵巢高反应的影响因素。全基因组关联分析及多基因风险评分系统筛选出10个单核苷酸多态性标志物,当多基因风险评分>1时,预测为卵巢高反应病例;当多基因风险评分<1时,预测为卵巢正常反应病例。结论临床指标联合卵巢高反应单核苷酸多态性标志物构建的多基因风险评分系统为卵巢高反应患者的个体化精准治疗提供了新的可能性。

Objective To investigate the risk factors of high ovarian response in assisted reproduction,screen the genetic markers of high ovarian response,and construct a prediction model of high ovarian response.Methods A total of 141 infertile women were enrolled in the Center for Reproductive Medicine of The 940th Hospital of Joint Logistics Support Force of the People's Liberation Army from January 2020 to December 2021 for controlled hyperovulatory treatment with an antagonist regimen.According to whether the number of eggs obtained was more than 15,they were divided into a high ovarian response and a normal ovarian response group.Basic clinical characteristics and controlled hyperovulation data of women in the two groups were analyzed,and DNA from peripheral blood was extracted for genome-wide single nucleotide polymorphism microarray detection and typing.The genome-wide association study and polygenic risk scoring system were used to screen single nucleotide polymorphism loci and construct a prediction model for high ovarian response risks.Results The sinus follicle count,polycystic ovary syndrome history and number of follicles with a trigger day diameter>11 mm were the factors influencing a high ovarian response.Ten single nucleotide polymorphism markers were selected by the genome-wide association study and polygenic risk scoring system.When polygenic risk scoring was greater than 1,the cases with the high ovarian response were predicted,and when polygenic risk scoring less than 1,the cases with the normal ovarian response were predicted.Conclusion The multi-gene risk scoring system constructed by the clinical index combined with single nucleotide polymorphism markers of a high ovarian response provides a new possibility for individualized precision treatment of patients with a high ovarian response.