The overlooked uterine factor: unlocking endometrium potential in premature ovarian insufficiency

To date, research on premature ovarian insufficiency (POI) primarily centers on ovarian dysfunction and systemic hormonal imbalances, with limited attention given to associated endometrial alterations. Given the critical role of the endometrium in reproductive function and its potential contribution to POI-related infertility, in this review, we bridge the knowledge gap regarding endometrial aspects of POI. We discuss the physiology and pathophysiology alterations in the POI endometrium, the multilevel endometrial changes spanning histological architecture, molecular signatures, and functional capacity, and clinical ramifications for fertility potential. In addition, we critically evaluate both established and novel therapeutic interventions targeting these endometrial abnormalities, paying particular attention to their potential to restore reproductive function.