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子宫内膜免疫分析可能对复发性流产的管理产生积极影响。

The Endometrial Immune Profiling May Positively Affect the Management of Recurrent Pregnancy Loss.

作者信息

Cheloufi Meryam, Kazhalawi Alaa, Pinton Anne, Rahmati Mona, Chevrier Lucie, Prat-Ellenberg Laura, Michel Anne-Sophie, Dray Geraldine, Mekinian Arsène, Kayem Gilles, Lédée Nathalie

机构信息

Department of Obstetrics and Gynecology, Trousseau Hospital, APHP, Sorbonne Université, FHU PREMA, Paris, France.

MatriceLAB Innove SARL, Pépinière Paris Santé Cochin, Paris, France.

出版信息

Front Immunol. 2021 Mar 24;12:656701. doi: 10.3389/fimmu.2021.656701. eCollection 2021.

Abstract

INTRODUCTION

The endometrial immune profiling is an innovative approach based on the analysis of the local immune reaction occurring in the endometrium at the time of the embryo implantation. By documenting the local immune activation during the period of uterine receptivity, we aim to detect and correct potential imbalances before and at the very beginning of placentation. The main objective of the study was to analyze in women with a history of repeated pregnancy loss (RPL) the association of personalized strategies based on immune dysregulations with live birth rates. The secondary objective was to highlight the main prognostic factors for live births.

METHODS

This is an observational retrospective analysis of 104 patients with RPL, included between January 2012 and December 2019. Inclusion criteria included a spontaneous fertility with at least three miscarriages, an assessment including a three-dimension ultrasound scan, an endometrial biopsy for uterine immune profiling and a follow-up over at least 6 months with personalized care if indicated after the complete assessment. We defined as a success if the patients had a live birth after the suggested plan, as a failure if the patient either did not get pregnant or experienced a new miscarriage after the targeted therapies.

RESULTS

Uterine immune profiling was the only exploration to be significantly associated with a higher live birth rate (LBR) if a dysregulation was identified and treated accordingly (55% vs 45%, p=0.01). On the contrary, an absence of local dysregulation (resulting in an apparently balanced immune environment) was associated with a higher risk of a new miscarriage, suggesting that the cause inducing RPL still needed to be identified. Independently of age and AMH level, dysregulated immune profile is significatively associated with 3 times higher LBR than a non-deregulated profile (OR=3.4 CI 95%1.27-9.84) or five times in case of an overactive profile treated by immunotherapy (OR=5 CI 95% 1.65-16.5). The usage of ART was significantly associated with lower LBR regardless of the presence of a subfertility factor (p=0.012). Personalization of medical care using natural cycle or simple hormonal stimulation is associated with a significantly higher LBR than personalization including ART treatments regardless of maternal age and AMH level (OR= 2.9 CI 95% 1.03-8.88).

CONCLUSION

Our study suggests that some endometrial immune profiles with targeted management of RPL are associated with a higher rate of LBR. ART may be negatively associated with LBR.

摘要

引言

子宫内膜免疫分析是一种创新方法,基于对胚胎着床时子宫内膜局部免疫反应的分析。通过记录子宫接受期的局部免疫激活情况,我们旨在在胎盘形成之前及刚开始时检测并纠正潜在的失衡。本研究的主要目的是分析在有复发性流产(RPL)病史的女性中,基于免疫失调的个性化策略与活产率之间的关联。次要目的是突出活产的主要预后因素。

方法

这是一项对104例RPL患者的观察性回顾性分析,纳入时间为2012年1月至2019年12月。纳入标准包括自然受孕且至少有三次流产经历,评估包括三维超声扫描、用于子宫免疫分析的子宫内膜活检,以及在完成评估后如有指征则进行至少6个月的个性化护理随访。如果患者在建议方案后活产,我们定义为成功;如果患者在靶向治疗后未怀孕或经历新的流产,则定义为失败。

结果

如果识别出子宫免疫失调并相应进行治疗,子宫免疫分析是唯一与较高活产率(LBR)显著相关的检查(55%对45%,p = 0.01)。相反,局部无失调(导致明显平衡的免疫环境)与新流产的较高风险相关,这表明导致RPL的原因仍需确定。独立于年龄和抗缪勒管激素(AMH)水平,失调的免疫分析与非失调分析相比,活产率显著高出3倍(OR = 3.4,95%置信区间1.27 - 9.84),如果通过免疫疗法治疗过度活跃的分析情况,则高出5倍(OR = 5,95%置信区间1.65 - 16.5)。无论是否存在生育力低下因素,辅助生殖技术(ART)的使用与较低的活产率显著相关(p = 0.012)。使用自然周期或简单激素刺激进行医疗护理个性化与显著高于包括ART治疗的个性化护理的活产率相关,无论产妇年龄和AMH水平如何(OR = 2.9,95%置信区间1.03 - 8.88)。

结论

我们的研究表明,对一些子宫内膜免疫分析进行RPL的靶向管理与较高的活产率相关。ART可能与活产率呈负相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/631b/8024694/3444a45e1387/fimmu-12-656701-g001.jpg

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