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多囊卵巢综合征无排卵的胰岛素信号和雄激素合成的新遗传风险和代谢特征 被引量:2
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作者 吴效科 黄志超 +24 位作者 曹义娟 李建 李志强 马红丽 高敬书 常惠 张多加 丛晶 王宇 吴奇 Xiaoxiao Han Pui Wah Jacqueline Chung Yiran Li Xu Zheng Lingxi Chen Lin Zeng Astrid Borchert Hartmut Kuhn Zi-Jiang Chen Ernest Hung Yu Ng Elisabet Stener-Victorin 张和平 Richard S.Legro Ben Willem J.Mol 师咏勇 《Engineering》 SCIE EI CAS CSCD 2023年第4期103-111,M0005,M0006,共11页
促排卵是多囊卵巢综合征(PCOS)不孕症的一线治疗方案。卵巢对促排卵治疗的排卵应答差被认为与胰岛素抵抗和高雄激素血症相关。在一个包含1000名PCOS不孕妇女(PCOSAct)的前瞻性队列中,我们开展了一项全外显子联合靶向单核苷酸多态性(SNP... 促排卵是多囊卵巢综合征(PCOS)不孕症的一线治疗方案。卵巢对促排卵治疗的排卵应答差被认为与胰岛素抵抗和高雄激素血症相关。在一个包含1000名PCOS不孕妇女(PCOSAct)的前瞻性队列中,我们开展了一项全外显子联合靶向单核苷酸多态性(SNP)测序以及代谢组学研究。在全基因组水平找出与无排卵显著相关的常见变异和罕见突变,并通过机器学习算法构建排卵预测模型。研究发现,ZNF438基因中标记为rs2994652(p=2.47×10^(-8))的常见变异和REC114基因中的一个罕见功能突变(rs182542888,p=5.79×10^(-6))与促排卵治疗失败显著相关。携带rs2994652 A等位基因和REC114 p.Val101Leu(rs182542888)的PCOS不孕妇女进行促排卵治疗的总排卵率更低(分别为比值比(OR)=1.96,95%置信区间(CI)[1.55~2.49];OR=11.52,95%CI[3.08~43.05]),出现排卵的间隔时间更长(平均56.7天vs.49.0天,p<0.001;78.1天vs.68.6天,p=0.014)。对于rs2994652突变者,L-苯丙氨酸水平升高并与胰岛素抵抗稳态模型(HOMA-IR)指数(r=0.22,p=0.05)和空腹血糖(r=0.33,p=0.003)呈正相关;对于rs182542888突变者,花生四烯酸代谢产物水平下降并与升高的抗苗勒管激素(r=-0.51,p=0.01)和总睾酮(r=-0.71,p=0.02)呈负相关。整合基因变异位点、代谢产物及临床特征的联合预测模型可提高对排卵的预测能力[曲线下面积(AUC)=76.7%]。ZNF438基因的一个常见变异和REC114基因的一个罕见功能突变,以及与二者相关的苯丙氨酸和花生四烯酸代谢物改变,与PCOS女性不孕症的促排卵治疗失败相关。 展开更多
关键词 Polycystic ovary syndrome INFERTILITY Ovulation responses ZNF438 REC114 Whole-exome sequencing Deep machine learning
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Hospital-Based Phenotypic Features and Treatment Outcomes of Chinese Women with Polycystic Ovary Syndrome: The Effect of Body Mass Index and Geographic Distribution 被引量:3
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作者 Jingshu Gao Hongli Ma +5 位作者 Yu Wang Xinming Yang yijuan cao Bei Zhang Conghui Han Xiaoke Wua 《Engineering》 SCIE EI 2021年第2期170-177,共8页
Genetic,lifestyle,and environmental factors contribute to the etiology of polycystic ovary syndrome(PCOS).Increased body mass index(BMI)exacerbates the reproductive and metabolic parameters and reduces the fecundity o... Genetic,lifestyle,and environmental factors contribute to the etiology of polycystic ovary syndrome(PCOS).Increased body mass index(BMI)exacerbates the reproductive and metabolic parameters and reduces the fecundity of women with PCOS.This is a secondary analysis of a large-sample,multicenter,randomized controlled trial conducted at 21 sites in Chinese mainland.A total of 1000 women diagnosed with PCOS were enrolled in this trial.Of these,998 women with PCOS were included in the analysis.Increased BMI was associated with more severe menstrual irregularities,elevated testosterone level,higher prevalence of metabolic syndrome,and poorer quality of life.The rates of ovulation per woman for the normal,overweight,and obese BMI groups were 83.0%,78.2%,and 63.6%,respectively(P<0.001),and the rates of live birth were 23.6%,18.1%,and 15.3%(P=0.030).Northern PCOS patients showed more severe reproductive,glucose,and lipid profiles;less exercise;and lower total ovulation rates compared with PCOS patients from Southern China(74.8%vs 81.2%,absolute difference 6.4%,95%confidence interval 1.2%–11.5%).The results show the typical phenotypic features of Han women with PCOS in Northern and Southern China.The women living in Northern China showed a higher BMI,more severe glycolipid metabolism profiles,and subsequently worse clinical outcomes by the same interventions than those living in Southern China.The difference in phenotypic features can be explained mostly by differences in BMI and the resulting difference in ovulation. 展开更多
关键词 Polycystic ovary syndrome Body mass index PHENOTYPE Chinese cohort Geographic distribution
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Semen Analysis and Fecundity Association Among Women with Polycystic Ovary Syndrome Experiencing Ovulatory Dysfunction Treated by Ovulation Induction 被引量:1
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作者 Jingshu Gao Yu Wang +7 位作者 Mubai Li Mengyi Zhu Xuekui Liu Hongli Ma yijuan cao Lu Li Xinming Yang Xiaoke Wu 《Engineering》 SCIE EI 2021年第11期1586-1591,共6页
In this study,normal values of semen analysis were set for a general infertile population of couples among which most women had normal ovulation.The predictive capacity values of sperm quality,including concentration,... In this study,normal values of semen analysis were set for a general infertile population of couples among which most women had normal ovulation.The predictive capacity values of sperm quality,including concentration,motile count,progressive motile count,and morphology,are unclear for women with polycystic ovary syndrome(PCOS).A secondary analysis was conducted based on a randomized controlled trial investigating infertility among women with PCOS experiencing ovulatory disorder between 2011 and 2016 in China.A total of 1000 women received ovulation induction(acupuncture and clomiphene).We randomized the women with PCOS in 27 hospitals in China who received one of four interventions(acupuncture plus clomiphene,sham acupuncture plus clomiphene,acupuncture plus placebo,or sham acupuncture plus placebo).Semen analysis was performed for every male partner according to the World Health Organization(WHO)criteria.The outcomes included conception,clinical pregnancy,and live birth.Logistic regression was used to evaluate the predictive value of semen analysis among ovulatory women for conception,clinical pregnancy,and live birth.Among the 1000 couples,the number of couples who attained ovulation,conception,clinical pregnancy,and live birth were 780,320,235,and 205,respectively.Semen volume and motility were applied and used as prediction parameters for conception(area under the curve(AUC)of 0.62(95%confidence interval(CI),0.55–0.69)),clinical pregnancy(AUC of 0.67(95%CI:0.61–0.73)),and live birth(AUC of 0.57(95%CI:0.50–0.64)).No poor calibration was shown for these models in Hosmer–Lemeshow tests.The predictive capacity of semen analysis for treatment outcome in PCOS women with PCOS experiencing with ovulatory dysfunction is limited. 展开更多
关键词 Semen analysis FECUNDITY Ovulatory dysfunction Predictive capacity
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