Abstract

IntroductionThe 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.MethodsThis 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.ResultsUterine 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).ConclusionOur 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.

Highlights

  • 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

  • DNA fragmentation was pathological in 32% of the cases. 30% of patients required an operative hysteroscopy for trophoblast retention, synechia, polyp or fibroid. 31% had a thin endometrium in the mid-luteal phase

  • Treatment for endometrial thickness

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Summary

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. 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. In 2018, the ESHRE guideline reduced to two the number of spontaneous miscarriages required before initiating explorations Documented causes of this multifactorial, heterogeneous disorder include oocyte and sperm parameters, parental chromosomal structure, anatomical structure, immunological and thrombophilia factors (antiphospholipid syndrome, factor V Leiden, factor II homozygous mutation carriers), hormonal conditions and lifestyle, which implies that a multidisciplinary approach is required for the management of RPL [3,4,5,6,7,8,9,10,11,12,13,14,15].

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