Follicle-stimulating hormone and luteinizing hormone polymorphisms and their association with female infertility in North India- a pilot study

Abstract Background Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) play essential roles in the regulation of ovarian function and female fertility. Both of these hormones consist of two subunits (α and β), and genetic variations in the β-subunit or these receptor genes have been linked with reproductive disorders. Single nucleotide polymorphisms (SNPs) in these genes may alter receptor sensitivity, hormone binding and ovarian response potentially leading to infertility. Objective This pilot study aimed to investigate the association between the rs6166 polymorphism in the Follicle stimulating hormone receptor (FSHR) gene and the rs4539842 polymorphism in the Luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene with female infertility among women from North India. Methods A total of 100 women were enrolled, including 50 infertile patients undergoing infertility treatment and 50 fertile controls. Genomic DNA was extracted from peripheral blood samples, and genotyping of rs6166 and rs4539842 polymorphisms was performed using the Restriction Fragment Length Polymorphism–Polymerase Chain Reaction (RFLP–PCR) method. Infertile patients were further categorized into subgroups based on clinical diagnosis—polycystic ovarian disease (PCOD) and poor ovarian reserve (POR). The association of genotypes with infertility status, gonadotropin dosage, and oocyte quality was evaluated using correlation analysis. Results A significant association was observed between the No Insertion (NI) variant of rs4539842 and infertility cases (r = 0.7924). The Serine/Serine (SS) genotype of FSHR rs6166 was predominantly associated with the control group (r = 0.9979), suggesting a possible protective effect. The Asparagine/Serine (NS) variant of FSHR showed a positive correlation with PCOD, whereas the SS genotype was associated with POR among infertile women. High gonadotropin dosage exhibited a negative correlation with oocyte quality (r = –0.1353). Moreover, the SS variant of FSHR was correlated with increased serum FSH levels and higher gonadotropin dosage requirements during controlled ovarian stimulation. Conclusion The findings of this pilot study indicate that specific genotypic variants of FSHR (rs6166) and LHCGR (rs4539842) polymorphisms may contribute to infertility in North Indian women. These polymorphisms appear to influence ovarian response, gonadotropin dosage requirements as well as oocyte quality, underscoring their potential as genetic markers for predicting ovarian stimulation outcomes and tailoring fertility treatments but due to few limitations in this study such as sample size we can not conclude so till we reach a statistical significant sample size.