Clinical use of recombinant human luteinizing hormone beyond hypogonadotropic hypogonadism: a multicenter descriptive...

Recombinant human luteinizing hormone (rLH) was originally introduced to supplement recombinant human follicle-stimulating hormone (rFSH) for controlled ovarian stimulation (COS) in patients with hypogonadotropic hypogonadism. Promising evidence is emerging regarding the efficacy of rLH in conditions which mimic hypogonadotropic hypogonadism; however, current data remain insufficient to draw definitive conclusions. The aim of the present multicentre observational study was to characterize the in vitro fertilization (IVF) population in which a fixed combination of rFSH/rLH is prescribed, and to analyse both point-specific and cumulative outcomes associated with its use.

This study was conducted across the Infertility Units of 5 different large public hospitals in northern Italy. All women who were referred to the 5 IVF Units between January 2018 and December 2023 to undergo either conventional IVF or intracytoplasmic sperm injection (ICSI) were reviewed. Only homologous in vitro fertilization cycles were included. Patients who were prescribed a fixed-ratio (2:1) combination of rFSH and rLH, were deemed eligible for study entry. Patients whose partners had severe forms of male infertility (i.e., men with sperm concentration < 1000000/ml or who underwent surgical sperm retrieval) were excluded. The primary outcome was the cumulative live birth rate (cLBR) per oocyte retrieval defined as the number of deliveries with at least one live birth resulting from one initiated or aspirated IVF/ICSI cycle.

Overall, 9,703 IVF/ICSI cycles were included in the study. The median female age was 39 [36-41] years. The main IVF indications were mixed infertility (28%), followed by reduced ovarian reserve (24%) and tubal factor (15%). Ovarian reserve markers showed a median AMH of 1.00 [0.55-1.80] ng/ml and a median AFC of 6 [4-9]. A LBR of 24% [95%CI: 23-25] per cycle and 27% [95%CI: 26-29] per oocyte retrieval and a CPR of 33% [95% confidence interval (CI): 32-34] per cycle and 38% [95%CI: 37-39] per oocyte retrieval were observed. No differences emerged in LBR and CPR when patients were divided according to baseline LH levels (< 6 mIU/ml vs. ≥ 6 mIU/ml).

The present study showed that the fixed-ratio rFSH/rLH combination was primarily employed in AMA women with poor or very poor prognosis. Our data also suggest that baseline serum LH concentrations do not significantly impact clinical outcomes in patients undergoing COS with the fixed rFSH/rLH combination. Future research directions should include well-designed, real-world comparative studies involving large multicentre datasets and robust patient stratification.