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目的 评估子宫内膜容受性检测(tER)对原发不孕伴反复种植失败(RIF)且种植窗偏移患者的临床应用效果，并结合全外显子测序(WES)初步探索可能影响种植窗偏移的遗传因素。方法 选取2019年3月至2024年11月在解放军总医院第一医学中心生殖医学中心接受tER的原发不孕伴RIF且种植窗偏移的患者作为研究对象，通过自身对照比较tER前常规移植周期和tER指导的个体化胚胎移植周期的临床结局(临床妊娠率、流产率、活产率)。采集所有研究对象外周血DNA进行WES,采用变异质量控制、频率过滤、功能预测及公共数据库检索，筛选可能与种植窗偏移相关的候选基因。结果 本研究共选取21例原发不孕伴RIF且经tER确诊种植窗偏移的患者，并从中筛选出82个在解放军总医院第一医学中心生殖医学中心接受胚胎移植的周期，其中tER前44个常规移植周期、tER后38个个体化胚胎移植周期。相较于tER前的常规移植周期组，tER指导的个体化胚胎移植周期组临床妊娠率和活产率均显著提高(分别为31.58%vs. 2.27%,P<0.001;23.68%vs. 0.00%,P=0.001)。WES筛选出4个与种植窗偏移相关的候选基因，共鉴定到8个DNA变异[(ANOS1基因：c.1464T>G(p.Ile488Met)和c.764C>T(p.Pro255Leu);ASH1L基因：c.3983A>G(p.Tyr1328Cys)和c.1833G>C(p.Leu611Phe);NPDC1基因：c.857C>T(p.Thr286Met)和c.485＿486del(p.Pro162ArgfsTer50);AHNAK2基因：c.5075T>G(p.Val1692Gly)和c.5074G>A(p.Val1692Met)]。结论 根据tER结果进行个体化胚胎移植可改善原发不孕伴RIF且种植窗偏移患者的妊娠结局；通过WES初步揭示了这类患者可能的遗传背景，对于未来完善相关数据库亦具有积极意义。
Abstract：Objective:To evaluate the clinical application effect of tests for endometrial receptivity(tER) in primary infertile patients with repeated implantation failure(RIF) and a displaced implantation window, and to preliminary explore the possible genetic factors influencing the displaced implantation window through whole exome sequencing(WES).Methods:Patients with primary infertility and RIF who had a displaced implantation window and underwent tER at the Reproductive Medicine Center of the First Medical Center of the Chinese People's Liberation Army General Hospital from March 2019 to November 2024 were selected as the research subjects. The clinical outcomes(clinical pregnancy rate, miscarriage rate, and live birth rate) of the conventional embryo transfer cycles before tER and the individualized embryo transfer cycles guided by tER were compared through self-control. Peripheral blood DNA was collected from all research subjects for WES. Variants were filtered through quality control, frequency filtering, functional prediction, and public database search to screen for candidate genes possibly related to the displaced implantation window.Results:A total of 21 patients with primary infertility and RIF who were diagnosed with a displaced implantation window by tER were selected in this study, and 82 embryo transfer cycles at the Reproductive Medicine Center of the First Medical Center of the Chinese People's Liberation Army General Hospital were screened, including 44 conventional embryo transfer cycles before tER and 38 individualized embryo transfer cycles after tER. Compared with the conventional embryo transfer cycle group before tER,the clinical pregnancy rate and the live birth rate in the individualized embryo transfer cycle group guided by tER were significantly improved(31.58% vs. 2.27%,P<0.001 and 23.68% vs. 0.00%,P=0.001). WES identified 4 candidate genes related to the displaced implantation window, and a total of 8 DNA variations were identified [ANOS1 gene: c.1464T>G(p.Ile488Met) and c.764C>T(p.Pro255Leu),ASH1L gene: c.3983A>G(p.Tyr1328Cys) and c.1833G>C(p.Leu611Phe),NPDC1 gene: c.857C>T(p.Thr286Met) and c.485＿486del(p.Pro162ArgfsTer50),AHNAK2 gene: c.5075T>G(p.Val1692Gly) and c.5074G>A(p.Val1692Met)].Conclusions:Individualized embryo transfer based on tER results can improve the pregnancy outcomes of primary infertile patients with RIF and a displaced implantation window. The possible genetic background of such patients was preliminary revealed through WES,which is of positive significance for the future improvement of related databases.
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基本信息:
中图分类号:R714.8
引用信息:
[1]刘婷婷,董明理,高原,等.子宫内膜容受性检测对原发不孕伴反复种植失败且种植窗偏移患者的有效性研究及种植窗偏移遗传机制探索[J].生殖医学杂志,2025,34(06):757-765.
基金信息:
2021年度军队高层次科技创新人才工程人选自主科研项目(联战[2022]151号)
2025-06-15
2025-06-15