Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization

作者全名：Ruan, Ling-Ling; Lv, Xing-Yu; Hu, Yu-Lin; Chen, Ming-Xing; Jing-Tang; Zhong, Zhao-Hui; Bao, Mei-Hua; Fu, Li-Juan; Luo, Xin; Yu, Shao-Min; Wan, Qi; Ding, Yu-Bin

作者地址：[Ruan, Ling-Ling; Ding, Yu-Bin] Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, 23 Cent Pk North Rd, Chongqing 401147, Peoples R China; [Ruan, Ling-Ling; Chen, Ming-Xing; Zhong, Zhao-Hui; Fu, Li-Juan; Ding, Yu-Bin] Chongqing Med Univ, Sch Publ Hlth, Joint Int Res Lab Reprod & Dev Minist Educ China, Chongqing 400016, Peoples R China; [Yu, Shao-Min] Peoples Hosp Yubei Dist, Dept Obstet & Gynecol, 23 Cent Pk North Rd, Chongqing 401120, Peoples R China; [Wan, Qi] Sichuan Univ, West China Hosp 2, Dept Obstet & Gynecol, Chengdu 610041, Peoples R China; [Wan, Qi] Sichuan Univ, Key Lab Birth Defects & Related Dis Women & Childr, Minist Educ, Chengdu 610041, Peoples R China; [Lv, Xing-Yu; Hu, Yu-Lin; Wan, Qi] Sichuan Jinxin Xinan Women & Childrens Hosp, Reprod Ctr, Chengdu 610011, Sichuan, Peoples R China; [Bao, Mei-Hua; Fu, Li-Juan] Changsha Med Univ, Dept Pharmacol, Academician Workstn, Changsha 410219, Peoples R China; [Luo, Xin] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China; [Jing-Tang] Chongqing Med Univ, Sch Basic Med, Dept Bioinformat, Chongqing 400016, Peoples R China

通信作者：Ding, YB (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, 23 Cent Pk North Rd, Chongqing 401147, Peoples R China.; Ding, YB (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Joint Int Res Lab Reprod & Dev Minist Educ China, Chongqing 400016, Peoples R China.; Yu, SM (通讯作者)，Peoples Hosp Yubei Dist, Dept Obstet & Gynecol, 23 Cent Pk North Rd, Chongqing 401120, Peoples R China.; Wan, Q (通讯作者)，Sichuan Univ, West China Hosp 2, Dept Obstet & Gynecol, Chengdu 610041, Peoples R China.; Wan, Q (通讯作者)，Sichuan Univ, Key Lab Birth Defects & Related Dis Women & Childr, Minist Educ, Chengdu 610041, Peoples R China.; Wan, Q (通讯作者)，Sichuan Jinxin Xinan Women & Childrens Hosp, Reprod Ctr, Chengdu 610011, Sichuan, Peoples R China.

来源：JOURNAL OF OVARIAN RESEARCH

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001227233200001

JCR分区：Q1

影响因子：3.8

年份：2024

卷号：17

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：High ovarian response; Polycystic ovary syndrome; Serum; Metabolome

摘要：Background In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. Methods We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-M & uuml;llerian Hormone (AMH) levels > 4.5ng/mL. Results The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. Conclusion Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

基金机构：National Natural Science Foundation of China

基金资助正文：We sincerely thank Dr Ting-Li Han and Miss Yang Yang from the Department of Obstetrics at the First Affiliated Hospital of Chongqing Medical University for their invaluable guidance and assistance in establishing the metabolomics methods and analyzing data. Their expertise and support were instrumental in making this work possible. Additionally, we would like to thank all the participants of this study and the medical staff for their valuable contributions.