Intravenous intralipid therapy in recurrent implantation failure: Biological rationale, clinical evidence, and...

Recurrent implantation failure (RIF) remains a major challenge in assisted reproductive technology (ART), reflecting multifactorial and incompletely understood etiologies. Although embryonic competence is widely regarded as the primary determinant of implantation success, increasing attention has been directed toward endometrial and immunological factors that may contribute to repeated failure in selected patient populations. Among proposed immunomodulatory interventions, intravenous lipid emulsions (intralipids) have been investigated as a strategy to modulate uterine immune responses, particularly natural killer (NK) cell activity, in women undergoing in vitro fertilization (IVF). The biological rationale for intralipid therapy derives from observations that uterine NK (uNK) cells play essential roles in early placentation, including regulation of angiogenesis, trophoblast invasion, and cytokine balance. However, the clinical significance of altered NK cell numbers or function in RIF remains debated, and evidence linking immune modulation to improved live birth rates is inconsistent. Variability across studies is further compounded by heterogeneity in diagnostic criteria, immune testing methodologies, and treatment protocols. This narrative review aims to critically evaluate the available mechanistic and clinical evidence regarding intravenous intralipid infusion in IVF patients, with emphasis on recurrent implantation failure. We examine proposed mechanisms of action, summarize randomized controlled trials and meta-analyses, assess methodological limitations, and consider current professional society recommendations. Although some reports describe improvements in clinical pregnancy rates, conflicting findings and the absence of large, adequately powered trials preclude definitive conclusions. Current guidelines do not recommend routine intralipid use outside research settings. Future investigations should prioritize immune assessment and live birth as the primary endpoint.