The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature

Abstract

Recurrent implantation failure (RIF) is a multifactorial condition affecting 10–15% of in vitro fertilization (IVF) couples. Data suggest that functional dysregulation of the endometrial immune system constitutes one of the main pathophysiological mechanisms leading to RIF. The aim of this article is to provide a thorough presentation and evaluation of the role of interleukins (ILs) in the pathogenesis of RIF. A comprehensive literature screening was performed summarizing current evidence. During implantation, several classes of ILs are secreted by epithelial and stromal endometrial cells, including IL-6, IL-10, IL-12, IL-15, IL-18, and the leukemia inhibitory factor. These ILs create a perplexing network that orchestrates both proliferation and maturation of uterine natural killer cells, controls the function of regulatory T and B cells inhibiting the secretion of antifetal antibodies, and supports trophoblast invasion and decidua formation. The existing data indicate associations between ILs and RIF. The extensive analysis performed herein concludes that the dysregulation of the ILs network indeed jeopardizes implantation leading to RIF. This review further proposes a mapping of future research on how to move forward from mere associations to robust molecular data that will allow an accurate profiling of ILs in turn enabling evidence-based consultancy and decision making when addressing RIF patients.

Commercially Available Molecular Approaches to Evaluate Endometrial Receptivity: A Systematic Review and Critical Analysis of the Literature

“…Recurrent implantation failure (RIF) constitutes one of the most challenging pathologies encountered in the field of human reproduction, raising concerns among researchers and clinicians alike. There is a lack of consensus regarding the exact definition of RIF; nonetheless, the most widely accepted definition refers to RIF as the failure to achieve a clinical pregnancy following at least three or more consecutive transfers of good-quality embryos in fresh or frozen cycles for woman younger than 40 years of age [ 18 ]. Hysteroscopy and the treatment of hydrosalpinxes have been proven to be effective tools for the management of RIF cases [ 19 , 20 ].…”

Deciphering the endometrial immune landscape of RIF during the window of implantation from cellular senescence by integrated bioinformatics analysis and machine learning

“…Despite tremendous advances in reproductive medicine, it remains an ongoing conundrum. About 15% of patients seeking IVF treatment are reported to be afflicted by RIF, which is a huge distress and frustration for both patients and clinicians ( 3 ). Statistics have shown that approximately 40% of euploid blastocysts fail to implant in transfers, which suggests the desynchronization between the embryo and the endometrium in the window of implantation (WOI) as a potential cause of RIF ( 4 , 5 ).…”

FHL1 mediates HOXA10 deacetylation via SIRT2 to enhance blastocyst-epithelial adhesion

“…In fact, the majority of these patients do not achieve a successful pregnancy despite the transfer of normally developing highquality embryos. Impaired maternal endometrial receptivity is the key reason for the failure of embryo implantation in these patients [4][5][6]. Endometrial epithelial cells, which are under the control of oestrogen and progesterone, play a key role in the establishment of endometrial receptivity in the mid-secretory phase and mediate the first contact between the blastocyst and the maternal uterus [7].…”