Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) serve distinct but interdependent roles in follicular development. FSH drives granulosa cell proliferation and follicular growth, while LH stimulates theca cell androgen production, which is required for estrogen synthesis.1 As follicles mature, LH contributes to steroidogenesis and the later stages of follicular development, supporting a competent, estrogenic follicular environment.
The shift from gonadotropin preparations with inherent LH bioactivity to recombinant FSH-only products introduced a new clinical variable: reduced LH exposure during stimulation. For many patients, endogenous LH is sufficient to maintain follicular development throughout a stimulation cycle.2 However, for specific patient subgroups, including women of advanced reproductive age, those with diminished ovarian reserve, and patients with hypogonadotropic hypogonadism, LH bioactivity may be functionally insufficient, with consequences for steroidogenesis and oocyte quality.2,3
Differences in ovarian sensitivity to gonadotropins may contribute to variability in follicular response beyond traditional ovarian reserve measures, potentially helping explain why some patients experience suboptimal outcomes despite apparently adequate ovarian reserve and stimulation.1–3 In this context, maintaining adequate LH “tone” during stimulation has been increasingly recognized as a potential factor in optimizing follicular development and cycle performance in selected patients.2
The evidence base for LH supplementation has historically relied on population-level, age-stratified trials, which have produced inconsistent findings and limited guidance for individual patient management.2 More recent work suggests that endocrine parameters, including pituitary LH response during gonadotropin-releasing hormone (GnRH) antagonist protocols, may offer more clinically meaningful criteria for identifying patients with relative LH deficiency.2 These findings support a more individualized approach to assessing LH sufficiency during stimulation rather than a uniform supplementation strategy across all patients.2,4
As recombinant FSH and LH combination products continue to be evaluated and access expands in the context of evolving in vitro fertilization (IVF) policy, reproductive endocrinologists are well positioned to apply this biologic rationale in clinical decision-making. Ongoing regulatory and policy evolution in several regions may further clarify the role of recombinant LH-containing regimens within individualized ovarian stimulation strategies.
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