P-602 Impact of recombinant LH supplementation versus FSH alone on cumulative live birth rates: a comprehensive observational study in poor ovarian responders undergoing ART

Abstract

Study question Does luteinizing hormone supplementation improve cumulative live birth rates in poor ovarian responders. Summary answer LH supplementation (LHS) enhances CLBR in moderate and severe poor ovarian responders (POR), with the effect becoming more pronounced as severity increases. What is known already Poor ovarian responders (POR) typically produce fewer oocytes during standard controlled ovarian stimulation (COS), leading to lower live birth rates. Various treatments, including high-dose gonadotropins, mild stimulation, and growth hormones, aim to improve ovarian response. LH supplementation (LHS) has been explored as a potential solution, but results remain conflicting. LHS may enhance follicular maturation and oocyte quality, particularly in hypogonadotropic women. While suppressed LH during GnRH agonist/antagonist COS does not negatively impact IVF outcomes, adding LH in patients with reduced LH does not always improve live birth rates. The potential benefits of LHS in POR remain uncertain and require investigation. Study design, size, duration This retrospective, multicenter controlled study utilized data from 5 ART centers in Pakistan, focusing on poor ovarian responders (POR) treated with follitropin-alfa (FSH-α), with or without lutropin-α, based on an intention-to-treat principle during 2008 to 2020. POR was defined per the ESHRE Bologna criteria and categorized as mild, moderate, or severe using the PROP score. The primary endpoint was CLBR from fresh and frozen embryos derived from the same ovarian stimulation cycle. Participants/materials, setting, methods A total of 12,000 controlled ovarian stimulation (COS) cycles were analyzed, with 6,658 receiving luteinizing hormone supplementation (LHS) and 5,342 receiving FSH-α alone. The intent-to-treat sample included all COS cycles for POR treated with recombinant FSH-α alone or with recombinant LH. A generalized linear mixed model with logistic regression assessed cumulative live birth rate (CLBR), adjusted for PROsPeR score and severity. Random factors included center and matched sub-classes. Missing data (5.9%) were missing at random. Main results and the role of chance The total cycles were classified into Mild (32.6%), Moderate (54.5%), and Severe (12.9%) categories based on POR. A mixed logistic regression model, adjusted for matched sub-classes and baseline severity, revealed a significant improvement in CLBR with luteinizing hormone supplementation (LHS) in patients with moderate (15.7% vs. 12.4%, OR = 1.41, [1.05, 1.40], RR = 1.29, p = 0.015) and severe (9.9% vs. 3.3%, OR = 2.39 [1.34, 3.11], RR = 1.99, p < 0.001) POR. However, no significant benefit was observed in the mild category (16.6% vs. 20.5%, OR = 0.98 [0.68, 2.11], RR = 0.98, p = 0.05). Additionally, the effect of LHS appeared to increase with the severity of baseline POR. In the control group, CLBR was slightly higher for mild POR but declined significantly with increasing severity, reaching just 5.6% for severe POR. In contrast, the LHS group showed a slightly lower CLBR for mild POR, with a more gradual decline observed for moderate (15.1%) and severe (10.01%) POR. The LHS effect was consistent across centers for both moderate ([1.33, 1.47], p = 0.521) and severe POR ([1.99, 3.10], p = 0.325). A substantial proportion of patients in both groups (80.1% in control and 61% in LHS) had no available embryos after the final transfer. A supplementary model showed no significant effect of total gonadotropin dose (p = 0.321). Limitations, reasons for caution This study, based on data from five non-randomly selected Pakistani ART centers, may be subject to bias from unknown patient characteristics. While significant differences in live birth rates were observed across centers, the LHS effect remained consistent, ensuring that the main findings were not influenced by center selection. Wider implications of the findings Luteinizing hormone supplementation (LHS) does not benefit normal responders in IVF but may improve outcomes for poor ovarian responders (POR). This effect appears more pronounced with increasing severity of POR, suggesting LHS could enhance cumulative live birth rates (CLBR) in patients with varying degrees of ovarian response. Trial registration number No