Luteinizing Hormone/Human Chorionic Gonadotropin Receptor N312S Single-Nucleotide Polymorphism and Its Impact on Clinical and Reproductive Outcomes in Assisted Reproductive Technology: A Prospective Cohort Study

Abstract

Objective The aim of this study was to determine the genotypic distribution of luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) N312S single-nucleotide polymorphism (SNP) and to investigate its impact on clinical and reproductive outcomes in infertile Indian women undergoing assisted reproductive technology (ART). Study design and settings This was a prospective cohort study conducted at a tertiary care university hospital. Subjects and methods Infertile women aged between 21 and 40 years undergoing ART with an antagonist protocol were enrolled in this study. A 2-ml sample of peripheral venous blood was collected from each woman and genotyped for the LHCGR N312S SNP. Participants were divided into three groups based on their SNP: NN, NS, and SS. All subjects underwent controlled ovarian hyperstimulation (COH) through a gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). Of the 140 women recruited based on selection criteria, 128 underwent embryo transfer. We compared the genotypic distribution of the LHCGR N312S SNP, baseline characteristics, clinical outcomes, and reproductive outcomes in ART among the three groups. Data were analyzed using IBM SPSS Statistics for Windows, Version 29 (Released 2022; IBM Corp., Armonk, New York, United States). The chi-square test and Fisher-Irwin test were employed to evaluate significant differences among the qualitative categorical variables. A p-value of less than 0.05 was considered statistically significant. Results Among the test subjects, 19.3% were homozygous for the LHCGR N312 SNP (NN group), 38.6% were heterozygous (NS group), and 42.1% were homozygous for the LHCGR S312 SNP (SS group). Baseline characteristics were similar among the three groups. In terms of ovarian reserve tests, significantly lower anti-Müllerian hormone (AMH) levels were observed in the SS group compared to the NS and NN groups (2.8 ± 2.1 vs. 3.2 ± 2.5 vs. 4.3 ± 3.3; p=0.03). No significant differences were observed in COH outcomes such as duration of stimulation, total gonadotropin requirement, oocyte yield, or the number of good-quality embryos among the three groups. The cumulative pregnancy rate (82.9% vs. 50.0% vs. 38.2%, p=0.0005), cumulative clinical pregnancy rate (78.8% vs. 44.7% vs. 34.5%, p = 0.0005), and cumulative live birth rate (50.0% vs. 20.2% vs. 20.0%, p=0.005) were significantly higher in the NN group than in the NS and SS groups. Conclusion The study's findings suggest that LHCGR N312 may help predict reproductive outcomes in ART, which may aid in providing better counseling to infertile couples. We need more studies on individualized/personalized COH using pharmacogenomics for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) supplementation based on combined FSH and LH receptor SNP and to assess their effects on ART outcomes.

Keywords: assisted reproductive technology; clinical outcomes; genotypic distrubution; lhcgr n312s snp; reproductive outcomes.

Figure 1. LHCGR N312S single-nucleotide polymorphism (SNP) genotypic distribution