Introduction and background

Endometriosis is a chronic inflammatory disease affecting approximately 10% of women of reproductive age and represents one of the leading causes of female infertility. Beyond its well-established association with pelvic pain and anatomical distortion, endometriosis has increasingly been recognized as a systemic and endometrial disorder that profoundly interferes with reproductive function. Women with endometriosis exhibit reduced spontaneous conception rates and significantly lower success rates following assisted reproductive technology (ART), even in the absence of severe pelvic adhesions or ovarian compromise [1].

Implantation failure remains a major limiting factor in ART outcomes and constitutes a particularly challenging clinical entity in women with endometriosis. Traditionally, impaired fertility in endometriosis has been attributed to mechanical factors, altered folliculogenesis, and compromised oocyte quality. However, accumulating evidence indicates that defective endometrial receptivity plays a central role in implantation failure in this population. Alterations in hormonal responsiveness, chronic inflammation, immune dysregulation, and aberrant molecular signaling converge to create a hostile endometrial microenvironment that impairs embryo-endometrium crosstalk and compromises implantation.

Endometrial receptivity is a finely regulated process that depends on coordinated endocrine, immune, and molecular events occurring within a narrow window of implantation. In women with endometriosis, progesterone resistance, altered expression of receptivity markers, dysregulated immune cell populations, and persistent inflammatory activation have been consistently reported. These abnormalities not only disrupt decidualization and trophoblast invasion but may also lead to repeated implantation failure (RIF), even when high-quality embryos are transferred. A range of molecular and immune biomarkers have been proposed to identify impaired endometrial receptivity in this population. Nevertheless, their clinical utility remains controversial, and standardized diagnostic algorithms are still lacking [2].

Therapeutic strategies aiming to restore endometrial receptivity in women with endometriosis-associated implantation failure have evolved substantially over the past decade. Hormonal pretreatment protocols, immunomodulatory interventions, and novel regenerative approaches such as platelet-rich plasma (PRP) and granulocyte colony-stimulating factor (G-CSF) have been increasingly explored, with heterogeneous and often conflicting results. The absence of consensus regarding optimal patient selection and treatment sequencing continues to represent a major unmet need in clinical practice.

This narrative review aims to provide a comprehensive overview of the pathophysiological mechanisms linking endometriosis to implantation failure, with particular emphasis on immune dysregulation and endometrial receptivity defects. We further summarize current evidence regarding established and emerging biomarkers of impaired receptivity and critically discuss available and novel therapeutic strategies. By integrating mechanistic insights with clinical data, this review seeks to propose a practical framework for the personalized management of implantation failure in women with endometriosis.