Endometrial receptivity failure in assisted reproduction: immune-cellular niches, mechanistic evidence, and translational boundaries

Endometrial receptivity failure and recurrent implantation failure (RIF) are clinically heterogeneous outcomes shaped by embryo competence, uterine anatomy, endocrine support, immune adaptation, and the timing of embryo-endometrial synchrony. This Review focuses on how immune-cellular niches, cell-specific and spatiotemporal mechanisms, disease-modified receptivity states, and evidence-to-translation boundaries should be interpreted in assisted reproduction. Single-cell, spatial, and multi-omics studies increasingly resolve abnormalities in stromal, sepithelial, vascular, perivascular, and immune compartments, including altered decidualization, epithelial competence, inflammatory tone, metabolic signaling, and microbiota-immune communication. However, most of these signals remain mechanistic, preclinical, associative, or candidate-biomarker evidence rather than proof of clinical utility. Therefore, biological plausibility should not be conflated with routine care: transcriptome-based receptivity timing tests, empirical immune profiling or treatment, microbiota-directed interventions, endometrial scratching, and regenerative add-ons require cautious interpretation unless they improve clinically meaningful outcomes. Future progress depends on standardized RIF phenotyping, cycle-phase and sampling control, euploid embryo transfer where relevant, external validation of cell-specific markers, prospective trials, live-birth endpoints, safety follow-up, and transparent separation of discovery evidence from clinically actionable strategies.