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Endometrial Immune Profiling: An Emerging Paradigm for Reproductive Disorders

  • Nathalie LéDée
Chapter

Abstract

A unique immune reaction occurs during the implantation window within the endometrium which is essential (1) to promote the embryo adhesion and (2) regulate the invasion phase. Disequilibrium of such a vital reaction may impede implantation. Documenting the immune environment before conception allows deciphering the immune mechanism able to generate or at least participate in the observed recurrent embryo implantation failures (RIF) and/or unexplained recurrent miscarriages (RM). To draw the most suitable personalized care, we hence propose to document the pre-conception endometrial immune environment. The objective is to identify the deregulations which can be corrected to enhance the chance of pregnancy following embryo transfer on the identified mechanism.

The immune profiling is a diagnostic method detailing from an endometrial biopsy collected in the mid-luteal phase, the uterine natural killer cell (uNK) mobilization/activation/maturation state, as well as the local immunoregulatory equilibrium between the Th-1 (cytotoxic) and the Th-2 (angiogenic/immunotropic) cytokines. The biomarkers such as IL-15/Fn-14 (maturation and hyper-activation state of uNK) and IL-18/TWEAK (Th-1/Th-2 equilibrium) mRNA ratios were determined by quantitative RT-PCR and CD56 mobilization by immunohistochemistry. An equilibrated endometrial environment at the time of uterine receptivity should be theoretically Th-2 dominant with an active mobilization of mature but not cytotoxic uterine NK cells. The objective is to understand if RIF and/or RM are the consequence of an over-immune activation (embryo rejection, apoptosis of the endometrium) or, the contrary, of an under-immune activation (no adhesion, low local angiogenesis, and immunotropic) or both (a Th-1 deviation of the endometrial environment with immature NK cells). In function of the immune profile, personalized care is suggested to counteract the identified mechanisms. The primary outcome evaluating the effectiveness of the diagnostic method is the live birth rate (LBR) at the first embryo transfer (fresh or freeze-thawed) following the immune evaluation.

In the chapter, we present the results in large longitudinal cohort studies and controlled cohort studies including RIF patients (after IVF/ICSI or oocyte donation) and unexplained RM. 70–80% of RIF and RM patients show an immune disequilibrium during the implantation window. These results suggest that personalization in function of the immune profile significantly increases the LBR while decreasing the miscarriage rate. We also detail the particularities of the immune profile in case of endometriosis. We also show how immunotherapy (corticoids and slow perfusion of diluted intralipids) in case of over-immune activation may impact adequately or not the immune profile.

Uterine immune profiling enables an integrated approach of infertility that includes endometrial immunity as a key factor in planning personalized IVF/ICSI treatments. Understanding the rationale leading to RIF/RM may be used as a guide to personalizing reproductive treatments accordingly. A randomized prospective cohort study is ongoing.

Keywords

Endometrium Immune profile Implantation failures Recurrent miscarriages Personalized care 

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Nathalie LéDée
    • 1
  1. 1.MatriceLab Innove, Pepinière Paris Santé Cochin, Hospital CochinParisFrance

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