The effect of energy metabolism on embryonic development and endometrial receptivity in patients with repeated implantation failure

Repeated implantation failure (RIF) remains a formidable challenge in in vitro fertilization-embryo transfer (IVF-ET). The etiology of RIF is multifactorial, involving complex interactions between embryo quality, the endometrium, and the maternal microenvironment. Adequate energy metabolism is pivotal for successful embryo implantation, supporting both embryonic development and the establishment of endometrial receptivity. Conversely, metabolic dysregulation contributes to RIF by arresting embryonic development, impairing endometrial receptivity, and disrupting the essential crosstalk between the embryo and the endometrium. Embryos and endometrial tissues from patients with RIF frequently exhibit distinct metabolomic abnormalities, including glycolysis utilization disorders, lipid metabolism disorders, and mitochondrial dysfunction. Clinical evidence suggests that therapeutic interventions involving antioxidants and specific metabolic modulators can enhance pregnancy rates in this population. This article reviews the critical role of energy metabolism in embryonic development and implantation, elucidates the pathological mechanisms linking metabolic dysfunction to RIF, and explores potential therapeutic strategies. We highlight that a comprehensive management strategy integrating diet, exercise, and targeted nutritional and antioxidant supplementation is expected to restore metabolic homeostasis in RIF patients and improve reproductive outcomes.