Immunohistochemical examination of PNAd, α4β1 integrin and MUC-2 expressions in the secretary phase endometrium of women diagnosed with recurrent implantation failure.

Objective: Successful embryo implantation is contingent upon the intricate interaction between the endometrium and the blastocyst. Recurrent implantation failure (RIF) signifies the clinical challenge of failing pregnancy post-transfer of high-quality embryos, fresh or frozen, in at least three in vitro fertilization (IVF) cycles, often in women under 40 years. Recent studies identify impaired blastocyst maternal tissue communication among recurrent implantation failure causes. Despite successful embryo transfer in vitro fertilization cycles, endometrial factors persist in women with recurrent implantation failure history, underscoring implantation's complexity. The implantation window, during which the endometrium becomes receptive to the blastocyst, involves the expression of key molecules that facilitate the implantation process. When the literature was examined, it was observed that comparative immunohistochemical studies on key molecules such as α4β1 integrin, MUC-2 and PNAd, which are thought to play a critical role in the endometrium before and during implantation, were limited. In this study, we aimed to investigate, through immunohistochemical and histological analyses, the roles of adhesion molecules in the secretory phase endometrium of patients diagnosed with RIF.

Design: Twenty-one patients diagnosed with recurrent implantation failure and 21 patients with a history of previous pregnancy at the Gynecology and Obstetrics Clinic of Balcalı Hospital, Faculty of Medicine, Çukurova University were clinically evaluated between days 19-21 of the menstrual cycle and included in the study. Endometrial biopsies, prepared for light and electron microscopy, received Hematoxylin and Eosin staining and anti-α4β1 integrin, anti-MUC-2, and anti-PNAd antibodies for immunohistochemistry. Blood samples were collected on the 2nd and 3rd days of the menstrual cycle to assess serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and thyroid-stimulating hormone (TSH).

Results: While FSH, LH, and E2 levels showed no significant difference, TSH was elevated in the recurrent implantation failure group. Structural differences in the endometrium included increased microvilli cells and reduced pinopod counts in infertile women compared to controls. In women with recurrent implantation failure MUC-2 expression were found to be elevated in the endometrial surface epithelium, while PNAd expression was reduced compared to the control group.

Conclusion: These findings suggest structural and molecular disparities during the endometrial receptivity window in recurrent implantation failure women may underlie infertility by hindering blastocyst adherence. Molecular studies are needed to elucidate the pathophysiology of the biomarkers whose presence in the endometrium we examined immunohistochemically and to discover new molecules.

Capsule: Changing expressions of adhesion molecules (PNAd, α4β1 and MUC-2) under the influence of steroid hormones, remodeling of intercellular connections and stromal epithelial communication play an important role in endometrial receptivity.