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既往整倍体囊胚移植失败患者的子宫内膜免疫评估

Endometrial immune assessment in patients with a history of previous euploid blastocyst failure.

作者信息

Garratt Jemma, Mohammadi Baharak, Al-Hashimi Balsam, Linara-Demakakou Elena, Bhattacharya Rukma, Ahuja Kamal K, Macklon Nick, Rahmati Mona

机构信息

Department of Reproductive Medicine, London Women's Clinic, London, United Kingdom.

School of Biosciences, University of Kent, Canterbury, United Kingdom.

出版信息

Front Immunol. 2025 Apr 7;16:1547159. doi: 10.3389/fimmu.2025.1547159. eCollection 2025.

DOI:10.3389/fimmu.2025.1547159
PMID:40260249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12009886/
Abstract

BACKGROUND

Influx and establishment of key endometrial immune factors in the mid-luteal phase of the menstrual cycle is paramount for successful embryo implantation. Endometrial immune dysregulation is associated with repeated embryo implantation failure and miscarriage. In fertilisation cycles, approximately 30% of embryos diagnosed as chromosomally normal will still fail to produce a viable live birth, yet factors such as the endometrium are rarely clinically explored.

METHODS

In this retrospective analysis, clinical outcomes were compared between patients undergoing their first euploid transfer in a conventional substituted cycle (n=612), patients undergoing a euploid transfer in a similar cycle after previous euploid failure (n=149) and the study group of patients with previous euploid transfer failure who received a modified endometrial preparatory regimen following endometrial immune profiling targeting uterine natural killer cell recruitment, maturity and activity as well as their key regulatory counterparts (n=37).

RESULTS

Significant differences were found between first euploid attempt outcomes and patients with previous failures who didn't use endometrial testing (implantation rate 63% vs 51, =0.02; clinical pregnancy rates 55% vs 40%, =0.002; live birth rates 50% vs 38%, =0.02). Patients with previous failures who underwent endometrial immune profiling and a subsequent personalised plan exhibited a trend towards improved clinical outcomes than those with previous failures and no testing (implantation rate 65% vs 51%; clinical pregnancy rate 57% vs 40%; live birth rate 54% vs 38%, respectively) although statistical significance was not demonstrated. Clinical outcomes were comparable between the endometrial immune profiling group and those undergoing a first euploid attempt (implantation rate 65% vs 63%; clinical pregnancy rate 57% vs 55%; live birth rate 54% vs 50%, respectively).

CONCLUSIONS

Patients who had a failed attempt when using a euploid embryo had lower chances of pregnancy when repeating their treatment, unless they received a personalised endometrial preparation regimen derived from the results of endometrial immune profiling. These preliminary findings indicate the potential value of guiding management based on immune endometrial testing.

摘要

背景

月经周期黄体中期关键子宫内膜免疫因子的流入和建立对于胚胎成功着床至关重要。子宫内膜免疫失调与反复胚胎着床失败和流产有关。在体外受精周期中,约30%被诊断为染色体正常的胚胎仍无法实现活产,然而诸如子宫内膜等因素在临床上很少被探究。

方法

在这项回顾性分析中,比较了在传统替代周期中首次进行整倍体移植的患者(n = 612)、之前整倍体移植失败后在类似周期中进行整倍体移植的患者(n = 149)以及之前整倍体移植失败且在针对子宫自然杀伤细胞募集、成熟度和活性及其关键调节对应物进行子宫内膜免疫分析后接受改良子宫内膜准备方案的患者研究组(n = 37)的临床结局。

结果

首次整倍体移植尝试的结局与之前失败且未进行子宫内膜检测的患者之间存在显著差异(着床率63%对51%,P = 0.02;临床妊娠率55%对40%,P = 0.002;活产率50%对38%,P = 0.02)。与之前失败且未检测的患者相比,之前失败且进行了子宫内膜免疫分析及后续个性化方案的患者临床结局有改善趋势(着床率分别为65%对51%;临床妊娠率57%对40%;活产率54%对38%),尽管未显示出统计学显著性。子宫内膜免疫分析组与首次进行整倍体移植尝试的患者的临床结局相当(着床率分别为65%对63%;临床妊娠率57%对55%;活产率54%对50%)。

结论

使用整倍体胚胎尝试失败的患者在重复治疗时怀孕几率较低,除非他们接受基于子宫内膜免疫分析结果的个性化子宫内膜准备方案。这些初步发现表明了基于子宫内膜免疫检测指导治疗管理的潜在价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0604/12009886/bbe0299387a9/fimmu-16-1547159-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0604/12009886/bbe0299387a9/fimmu-16-1547159-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0604/12009886/bbe0299387a9/fimmu-16-1547159-g001.jpg

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本文引用的文献

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Hum Reprod. 2024 May 2;39(5):974-980. doi: 10.1093/humrep/deae040.
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The Next Frontier in ART: Harnessing the Uterine Immune Profile for Improved Performance.ART 的下一个前沿:利用子宫免疫特征提高性能。
Int J Mol Sci. 2023 Jul 11;24(14):11322. doi: 10.3390/ijms241411322.
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Endometrial immune cell ratios and implantation success in patients with recurrent implantation failure.
反复着床失败患者的子宫内膜免疫细胞比值与着床成功的关系。
J Reprod Immunol. 2023 Mar;156:103816. doi: 10.1016/j.jri.2023.103816. Epub 2023 Jan 24.
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Transcriptomic analysis of mid-secretory endometrium reveals essential immune factors associated with pregnancy after single euploid blastocyst transfer.中分泌期子宫内膜转录组分析揭示了与单囊胚移植后妊娠相关的重要免疫因子。
Am J Reprod Immunol. 2023 Mar;89(3):e13672. doi: 10.1111/aji.13672. Epub 2022 Dec 28.
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On the reproductive capabilities of aneuploid human preimplantation embryos.人类胚胎植入前非整倍体的生殖能力。
Am J Hum Genet. 2022 Sep 1;109(9):1572-1581. doi: 10.1016/j.ajhg.2022.07.009.
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IVF outcomes of embryos with abnormal PGT-A biopsy previously refused transfer: a prospective cohort study.PGT-A 活检异常的胚胎 IVF 结局:一项前瞻性队列研究。
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Number and function of uterine natural killer cells in recurrent miscarriage and implantation failure: a systematic review and meta-analysis.复发性流产和着床失败中子宫自然杀伤细胞的数量和功能:系统评价和荟萃分析。
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