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代谢特征与致病机制:体外受精中卵巢高反应性不孕女性的综合分析

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

机构信息

Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, No. 23 Central Park North Road, Yubei District, Chongqing, 401147, PR China.

Joint International Research Laboratory of Reproduction and Development of the Ministry of Education of China, School of Public Health, Chongqing Medical University, Chongqing, 400016, China.

出版信息

J Ovarian Res. 2024 May 17;17(1):105. doi: 10.1186/s13048-024-01411-6.

DOI:10.1186/s13048-024-01411-6
PMID:38760835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11102248/
Abstract

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-Müllerian 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.

摘要

背景

在辅助生殖领域,一部分不孕患者在控制性卵巢刺激(COS)后表现出高卵巢反应,其中约 29.7%面临卵巢过度刺激综合征(OHSS)的风险。OHSS 风险的管理通常需要取消胚胎移植,导致成功怀孕的前景延迟,并带来显著的心理困扰。遗憾的是,这些患者受到的研究关注有限,特别是关于他们的代谢特征。在这项研究中,我们旨在利用气相色谱-质谱法(GC-MS)揭示这些患者独特的血清代谢特征,并深入了解疾病的发病机制。

方法

我们将 145 名不孕妇女分为两组:来自输卵管不孕患者的对照组(CON 不孕组)和多囊卵巢综合征(PCOS)不孕组。在这些组中,我们进一步将其分为四组:CON 组中卵巢反应正常(CON-NOR 组)、卵巢反应高且有 OHSS 风险(CON-HOR 组)的患者,以及 PCOS 组中卵巢反应正常(PCOS-NOR 组)和卵巢反应高且有 OHSS 风险(PCOS-HOR 组)的患者。使用 GC-MS 分析血清代谢谱。OHSS 的风险标准为:发育卵泡数>20 个,峰值雌二醇(E2)>4000pg/mL,抗苗勒管激素(AMH)水平>4.5ng/mL。

结果

CON 组中有 4 种不同的代谢物,PCOS 组中有 14 种不同的代谢物。值得注意的是,10-十五烯酸是 CON-HOR 的一个明显的风险代谢物,也被发现是 CON-NOR 和 PCOS 组之间的差异代谢物。半胱氨酸和 5-甲氧基色胺也被确定为 PCOS-HOR 的风险代谢物。此外,KEGG 分析揭示了 PCOS-NOR 和 PCOS-HOR 之间差异代谢物所涉及的氨基酸酰基-tRNA 生物合成途径的显著富集。

结论

我们的研究强调了在输卵管不孕对照组和 PCOS 不孕组中,卵巢反应正常和卵巢反应高且有 OHSS 风险的患者之间存在显著的代谢物差异。重要的是,我们观察到 PCOS 患者和卵巢反应高但无 PCOS 患者之间存在代谢相似性,这表明它们的潜在病因可能存在相似之处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/3be28ab10cfc/13048_2024_1411_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/1b106710c8b9/13048_2024_1411_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/526d7dabf319/13048_2024_1411_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/add8c5ed45b2/13048_2024_1411_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/3be28ab10cfc/13048_2024_1411_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/1b106710c8b9/13048_2024_1411_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/49c8a358394b/13048_2024_1411_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/d5a523a1e9cf/13048_2024_1411_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/526d7dabf319/13048_2024_1411_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/add8c5ed45b2/13048_2024_1411_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eefd/11102248/3be28ab10cfc/13048_2024_1411_Fig6_HTML.jpg

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