Diminished ovarian reserve (DOR) and luteal phase defect (LPD) are common endocrine disorders affecting the fertility of women of reproductive age. Traditionally, these conditions have been considered and treated independently. However, clinical observations frequently reveal that patients with DOR also exhibit features of LPD, suggesting a potential pathophysiological link between them. This review aims to explore the interplay between DOR and LPD from a novel perspective by integrating epidemiological data, current diagnostic and therapeutic practices, and recent insights into molecular mechanisms. Special emphasis is placed on the role of hypothalamic-pituitary-gonadal (HPG) axis dysfunction, oxidative stress-inflammatory microenvironment imbalance, and key signaling pathways, such as PI3K/Akt/mTOR, in mediating their interaction. We propose a central hypothesis: LPD may not merely be a complication of DOR; rather, intrinsic features of LPD-such as insufficient or prematurely withdrawn progesterone secretion-may exert negative feedback on the HPG axis and exacerbate oxidative damage within the ovarian microenvironment, thereby actively contributing to the onset or progression of DOR. Based on this hypothesis, we further suggest that treating LPD-particularly through luteal phase support therapy-may have benefits beyond improving endometrial receptivity. Such interventions could potentially modulate the endocrine milieu at both the systemic and local ovarian levels, thereby playing a role in managing DOR and possibly improving antral follicle count (AFC). These insights open up new directions for future therapeutic strategies targeting DOR.
Zhang et al. (2026) studied this question.