The question of which patients benefit from luteinizing hormone (LH) supplementation during ovarian stimulation has gained renewed attention as evidence accumulates and combination gonadotropin options become more broadly available.1 While follicle-stimulating hormone (FSH)-only stimulation is appropriate for many patients, a growing body of research supports a more differentiated approach based on individual clinical and endocrine characteristics.
Patients most consistently identified as candidates for LH supplementation include women of advanced reproductive age, in whom a less functional LH system contributes to reduced androgen production and impaired follicular steroidogenesis, and those with hypogonadotropic hypogonadism, for whom LH activity during stimulation is not optional but necessary for adequate follicular recruitment. Patients classified as hypo-responders represent an additional subgroup where supplemental LH activity warrants consideration.2,3
A propensity score-matched analysis comparing recombinant follicle-stimulating hormone (FSH) plus recombinant LH to human menopausal gonadotropin (HMG) found an association with higher mature oocyte and euploid blastocyst yields.4 The benefit was most pronounced in women with normal ovarian reserve, while those with low or high reserve showed less pronounced effects, reinforcing the importance of patient selection.4 Notably, as human menopausal gonadotropin (HMG) contains endogenous urinary LH and human chorionic gonadotropin (hCG) activity, this comparison reflects differences between two LH-containing approaches rather than recombinant LH versus no LH, a distinction relevant to interpreting the magnitude of effect.
Despite this progress, most existing evidence has been generated through population-based designs that limit patient-level applicability. Endocrine-based criteria, pharmacogenetic approaches including LH receptor polymorphism analysis, and multivariate modeling represent emerging directions for more precise identification of LH-responsive patients.5,6 For reproductive endocrinologists, the current evidence supports an individualized approach to gonadotropin selection rather than uniform supplementation, with ongoing research continuing to refine which patients derive the greatest benefit.
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