Impact of endogenous LH and LH supplementation on clinical outcome following a long GnRH agonist protocol in younger and older patients

Background The optimal luteinizing hormone (LH) concentration on the day of hCG trigger during long-protocol IVF/ICSI remains uncertain. Although some studies associate profound LH suppression with impaired reproductive outcomes, others report no adverse effects. Importantly, most existing evidence does not consider maternal age as a potential effect modifier, despite its well established role in ovarian response and oocyte competence. Methods This retrospective cohort study included 9,979 IVF/ICSI cycles performed between 2009 and 2017, comprising 8,786 cycles in women younger than 38 years and 1,193 cycles in women aged 38 years or older. First, cycles were stratified into five groups according to serum LH concentration on the day of hCG trigger: <0.5, 0.5 to <1.0, 1.0 to <2.0, 2.0 to <5.0, and ≥5.0 IU/L, to evaluate associations with clinical outcomes. Second, among cycles with LH ≤1.0 IU/L on stimulation day 7, when r-hLH supplementation was considered according to institutional protocol, we compared outcomes between those who received r-hLH and those who did not, adjusting for age, antral follicle count, BMI and basal FSH. The primary outcomes were good-quality embryo rate, clinical pregnancy rate, and live birth rate. Results In young patients (<38 years), LH levels on the hCG trigger day were not associated with oocyte yield, embryo quality, clinical pregnancy, or live birth rates, and r-hLH supplementation conferred no benefit. In older patients (≥38 years), LH <0.5 IU/L was associated with a lower good-quality embryo rate and greater gonadotropin consumption with prolonged stimulation, reflecting deeper pituitary suppression; however, it was not linked to differences in live birth rates, and r-hLH supplementation was not associated with a statistically significant improvement in good-quality embryo rate after multivariable adjustment. Conclusions In women <38 years, profound LH suppression does not impair IVF outcomes and r-hLH is unnecessary. In those ≥38 years, low LH correlates with poorer embryo quality, but r-hLH supplementation shows no significant benefit after adjustment. Routine r-hLH add-back based solely on low LH levels is not supported.