Biomolecular Markers of Recurrent Implantation Failure-A Review

Abstract

Currently, infertility affects 8-12% of reproductive age couples worldwide, a problem that also affects women suffering from recurrent implantation failure (RIF). RIF is a complex condition resulting from many physiological and molecular mechanisms involving dynamic endometrium-blastocyst interaction. The most important are the endometrial receptivity process, decidualization, trophoblast invasion, and blastocyst nesting. Although the exact multifactorial pathogenesis of RIF remains unclear, many studies have suggested the association between hormone level imbalance, disturbances of angiogenic and immunomodulatory factors, certain genetic polymorphisms, and occurrence of RIF. These studies were performed in quite small groups. Additionally, the results are inconsistent between ethnicities. The present review briefly summarizes the importance of factors involved in RIF development that could also serve as diagnostic determinants. Moreover, our review could constitute part of a new platform for discovery of novel diagnostic and therapeutic solutions for RIF.

Keywords: endometrial receptivity; recurrent implantation failure; risk factors; vaginal microbiota.

Figure 1

Creation of utero environment for appropriate endometrium receptivity, trophoblast proliferation, and embryo nesting. COX-2, cyclooxygenase-2; ECM, extracellular matrix; ER, estrogen receptors; GP130, glycoprotein 130; IL-1β, interleukin-1β; IL-6, interleukin-6; JAK-2, Janus kinase 2; LIF, leukemia inhibitor factor; LIFR, membrane LIF receptor; MMP-3, metalloproteinase-3; NK, natural killer; p53, tumor protein p53; PlGF, placental growth factor; PR-A/PR-B, progesterone receptors; STAT-3, signal transducer and activator of transcription 3; Th1/Th2, T cells involved in inflammatory response; Treg, T-regulatory cell profile; WOI, window of implantation; VEGF, vascular endothelial growth factor.