反复种植失败患者冻胚移植后子宫内膜微环境变化及对妊娠结局的影响

Changes in endometrial microenvironment and its impact on pregnancy outcomes after frozen embryo transfer in patients with recurrent implantation failure

摘要

目的 探讨反复种植失败(recurrent implantation failure, RIF)患者在冻胚移植(frozen embryo transfer, FET)前后子宫内膜微环境的动态变化，并分析其对妊娠结局的影响。方法 本研究为前瞻性研究，选择2022年3月至2024年4月行FET治疗RIF患者80例(RIF组)和首次进行FET的非RIF患者80例(对照组)。通过检测两组患者入院时卵泡刺激素(follicle-stimulating hormone, FSH)、抗苗勒管激素(anti-Müllerian hormone, AMH)及移植前后宫腔液中的血管内皮生长因子(vascular endothelial growth factor, VEGF)、白细胞介素-1β(interleukin-1β, IL-1β)、转化生长因子-β1(transforming growth factor-β1, TGF-β1)和干扰素-γ(interferon-γ, IFN-γ)等细胞因子，评估子宫内膜微环境的变化。比较两组患者的妊娠结局，包括生化妊娠、临床妊娠、流产率和活产率。通过单因素和多因素分析，探讨影响RIF患者临床妊娠的独立危险因素。结果 移植前，RIF组IL-1β、TGF-β1和IFN-γ水平高于对照组(P<0.05)，移植后VEGF和TGF-β1水平均低于对照组(P<0.05)，而IL-1β和IFN-γ水平均升高，差异有统计学意义(P<0.05)。妊娠结局方面，RIF组的临床妊娠率和活产率低于对照组(P<0.05)。单因素分析和多因素回归分析均显示，FSH、AMH、移植后IL-1β和IFN-γ是影响RIF患者临床妊娠的重要独立危险因素(P<0.05)。结论 RIF患者子宫内膜微环境存在免疫炎症失衡，FSH、AMH、移植后IL-1β及IFN-γ水平是预测FET妊娠结局的独立危险因素。

Abstract

Objective To investigate the dynamic changes in the endometrial microenvironment before and after frozen embryo transfer (FET) in patients with recurrent implantation failure (RIF), analyze their impact on pregnancy outcomes. Methods This prospective study enrolled 80 patients with RIF (RIF group) and 80 patients undergoing their first FET without RIF (control group) from March 2022 to April 2024. Serum levels follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) were measured upon admission. Changes in endometrial microenvironment were evaluated by quantifying cytokines, including vascular endothelial growth factor (VEGF), interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), and interferon-γ (IFN-γ), in uterine cavity fluid before and after embryo transfer. Pregnancy outcomes, including biochemical pregnancy, clinical pregnancy, miscarriage rate, and live birth rate, were compared between the two groups. Univariate and multivariate analyses were conducted to identify independent risk factors influencing clinical pregnancy in RIF patients. Results Prior to embryo transfer, levels of IL-1β, TGF-β1, and IFN-γ were significantly higher in the RIF group than in the control group (P<0.05). Post-transfer, VEGF and TGF-β1 levels in the RIF group were significantly lower than those in the control group (P<0.05), whereas IL-1β and IFN-γ levels were significantly elevated (P<0.05). The RIF group also exhibited significantly lower clinical pregnancy and live birth rates compared to the control group (P<0.05). Both univariate and multivariate regression analyses indicated that FSH, AMH, post-transplantation IL-1β, and IFN-γ were significant independent risk factors affecting clinical pregnancy in RIF patients (P<0.05). Conclusion Patients with RIF demonstrate an immune-inflammatory imbalance in the endometrial microenvironment. Serum FSH and AMH levels, as well as post-transfer IL-1β and IFN-γ levels, serve as independent predictors of FET pregnancy outcomes.

关键词

反复种植失败 / 冻胚移植 / 子宫内膜微环境 / 妊娠结局

Key words

Recurrent implantation failure / Frozen embryo transfer / Endometrial microenvironment / Pregnancy outcome

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基金资助

2022年度河北省医学科学研究课题(20221767)