Recombinant LH supplementation with rFSH significantly boosts cumulative live birth rate in advanced maternal age ART cycles

For women of advanced reproductive age undergoing Assisted Reproductive Technology (ART), optimizing ovarian stimulation protocols is critical for improving success rates. The role of luteinizing hormone (LH) supplementation during these cycles remains a subject of debate, with conflicting evidence on its impact on cumulative live birth rates (CLBR). Current standard-of-care often involves recombinant follicle stimulating hormone (rFSH) alone, but some protocols incorporate recombinant LH (rLH) or human menopausal gonadotropin (HMG) to potentially enhance follicular development and oocyte quality, addressing potential LH deficiencies or suboptimal LH signaling in older patients.

This retrospective cohort study analyzed 2,316 women of advanced reproductive age undergoing ART between 2015 and 2024. Participants were categorized into three ovarian stimulation groups: rFSH alone, rFSH + rLH, and rFSH + HMG. Propensity score matching was applied to ensure balanced baseline characteristics across pairwise comparisons. The primary outcome measured was cumulative live birth rate (CLBR), estimated using cumulative incidence function curves and compared via Fine-Gray models, treating permanent failure as a competing event.

After propensity score matching, baseline characteristics were well balanced. 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). While the number of retrieved oocytes was comparable across groups, 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. > The rFSH+rLH group showed a significantly higher CLBR compared with the rFSH group (61.31% vs. 51.48%, P = 0.036). 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 also compared to rFSH+HMG (adjusted sHR 1.23, 95% CI 1.00-1.51, P = 0.048).