Luteinizing hormone supplementation and cumulative live birth rate in assisted reproductive technology cycles among women of advanced reproductive age

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Background The effectiveness of luteinizing hormone (LH) supplementation during assisted reproductive technology (ART) cycles remains controversial, particularly among women of advanced reproductive age. This study aimed to compare the cumulative live birth rate (CLBR) associated with ovarian stimulation using recombinant follicle stimulating hormone (rFSH) alone or in combination with recombinant LH (rLH) or human menopausal gonadotropin (HMG). Methods In this retrospective cohort study, 2, 316 women of advanced reproductive age undergoing ART between 2015 and 2024 were included. Cycles were categorized into three groups according to the stimulation regimen: rFSH alone, rFSH+rLH, and rFSH+HMG. Propensity score matching was applied to balance baseline characteristics across three pairwise comparisons. The primary outcome, CLBR, was estimated using cumulative incidence function curves and compared using Fine–Gray models, with permanent failure treated as a competing event. Results After propensity score matching, baseline characteristics were well balanced across all comparisons. The rFSH+HMG group required significantly higher total gonadotropin doses and longer stimulation duration than both the rFSH+rLH and rFSH groups (all P < 0.001). Although the number of retrieved oocytes was comparable, the rFSH+rLH group exhibited a higher number of follicles ≥14 mm on trigger day, whereas the rFSH+HMG group had fewer (both P < 0.05). Fresh embryo transfer outcomes did not differ significantly between groups. The rFSH+rLH group showed a higher CLBR compared with the rFSH group (61.31% vs. 51.48%, P = 0.036), while the difference compared with the rFSH+HMG group did not reach statistical significance in unadjusted analyses (59.78% vs. 52.99%, P = 0.102). In multivariable Fine–Gray models, rFSH+rLH was associated with a higher probability of cumulative live birth compared with rFSH alone (adjusted sHR 1.29, 95% CI 1.04–1.61, P = 0.020) and rFSH+HMG (adjusted sHR 1.23, 95% CI 1.01–1.50, P = 0.039). Conclusions Among women of advanced reproductive age undergoing ART, recombinant LH supplementation was associated with a higher CLBR compared with rFSH alone or rFSH combined with HMG, whereas the difference versus rFSH combined with HMG was not statistically significant in unadjusted analyses. These findings suggest a potential benefit of rLH, but causality cannot be inferred and results should be interpreted with caution.