Effect of the supplementation of recombinant Luteinizing Hormone on Cumulative Live Birth rate compared to Follitropin alfa alone on Poor Ovarian Responders. A real-world large study

Abstract Research question The benefit of Luteinizing Hormone supplementation (LHS) to FSH alone during Controlled Ovarian Stimulation (COS) remains controversial. Meta-analyses provided some evidence that the LHS benefit is limited to Poor Ovarian Responders (POR). Our objective is the assessment of the effectiveness of LHS on Cumulative Live Birth rate (CLBR) for POR based on a large controlled study in a real-world context. Design Retrospective multicentre controlled study, from a registry of 12 French ART centres. All the COS undertaken in POR treated with follitropin-alfa (FSH-α) with or without lutropin-α (LH) were selected following the intent to treat principle. POR was defined according to ESHRE Bologna criteria (EBC), and subsequently classified in three categories (Mild, Moderate and Severe) according to PROsPeR score. The primary endpoint was the CLBR from the fresh and frozen embryos originating from the same COS. Results 9787 COS (5218 LHS, 4569 FSHα-only) were analysed, divided in 31.5, 52.7 and 15.7% of Mild, Moderate and Severe PROsPeR categories. Through a mixed Logistic model adjusting for matched sub-classes and baseline severity, compared with FSHα alone, a significant benefit of LHS was found on the CLBR for patients with Moderate category (14.3% vs 11.3%, odds ratio OR=1.37, [1.07, 1.35], Risk Ratio RR=1.30, p=0.013), and Severe category (9.8% vs 4.4%, OR=2.40 [1.48,3.89], RR=1.88, p Conclusion the LHS supplementation has a significant effect in increasing the CLBR on moderately and severely poor ovarian responders.