Disentangling the current role of LH activity in assisted reproduction : from biology to patient personalization

Abstract

The importance of determining the precise role of gonadotropins in assisted reproductive technology (ART) is increasingly recognized, as optimizing ovarian stimulation (OS) protocols is crucial for improving outcomes. Recent advances in reproductive biology highlight the multifaceted functions of luteinizing hormone (LH), revealing a complex interplay between its endocrine actions and local ovarian mechanisms. Traditionally, LH was primarily associated with its role in triggering ovulation and supporting the corpus luteum. However, accumulating evidence suggests that LH also influences follicular steroidogenesis, oocyte maturation, and endometrial receptivity. Despite these insights, the role of LH in OS remains controversial, particularly outside of patients with hypogonadotropic hypogonadism, characterized by hypothalamic amenorrhea. Notably, recent molecular and clinical evidence supports the benefits of including LH activity in OS protocols for select patient groups. LH activity can be derived from human menopausal gonadotropin (hMG), which contains both FSH and LH activity, with LH primarily driven by human chorionic gonadotropin (hCG); recombinant LH (rLH), or recombinant FSH + LH (rFSH+rLH). This review clarifies the evolving role of LH activity in ART, bridging foundational biological insights with the emerging paradigm of patient-specific treatment strategies to optimize reproductive outcomes.