Endometriosis-Associated Implantation Failure: Pathophysiology, Biomarkers, and Emerging Therapeutic Strategies

Vaia Sarli, Charikleia Papageorgiou, Chrysi Christodoulaki, Periklis Panagopoulos, Nikolaos Machairiotis
In: Cureus · 2026 · doi:10.7759/cureus.113299 · W7170665682
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Abstract

Implantation failure remains a major challenge in assisted reproductive technology (ART) and is a significant contributor to infertility in women with endometriosis. Beyond mechanical distortion and ovarian dysfunction, increasing evidence suggests that endometriosis profoundly alters endometrial receptivity through complex inflammatory, immunological, and molecular mechanisms. Chronic inflammation, progesterone resistance, dysregulated immune cell populations, and aberrant cytokine signaling converge to create a hostile endometrial microenvironment that compromises embryo-endometrial crosstalk and implantation success. This narrative review provides a comprehensive overview of the pathophysiological pathways linking endometriosis to implantation failure, with particular emphasis on immune dysregulation and defects in endometrial receptivity. We summarize the current evidence regarding key immune cell populations, including uterine natural killer (uNK) cells and macrophages, and their role in modulating implantation. We further discuss established and emerging biomarkers of impaired receptivity, including BCL6, integrins, endometrial receptivity assays, and epigenetic markers, highlighting their diagnostic potential and current limitations. Finally, we review contemporary and emerging therapeutic strategies aimed at restoring endometrial receptivity in women with endometriosis-associated implantation failure. These include hormonal pretreatment protocols, immunomodulatory approaches, and novel regenerative therapies such as platelet-rich plasma (PRP) and granulocyte colony-stimulating factor (G-CSF). By integrating mechanistic insights with clinical evidence, this review aims to provide a practical framework for the personalized management of implantation failure in women with endometriosis and to identify key directions for future research in this rapidly evolving field.

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