Effects of a Polymorphism in the Promoter Region of the Follicle-Stimulating Hormone Subunit Beta (FSHB) Gene on Female Reproductive Outcomes

Background: Follicle-stimulating hormone (FSH) is essential to the hypothalamic-pituitary-gonadal axis, playing a key role in human reproduction. It is a heterodimer comprised of a hormone-specific beta-chain (FSH-beta) that is associated with an alpha-chain. It exerts its biological activities by binding to the FSH receptor (FSHR). The beta-subunit, which is encoded by the FSHB gene, is responsible for ensuring binding specificity to the FSHR. There is a promoter polymorphism in this gene, c.-211G>T (rs10835638), upstream of the transcription start site; and in vitro studies have reported that the T allele decreases FSHB transcription in gonadotrophic cells. Aims: Investigate the possible effects of the FSHB c.-211G/T polymorphism on hormonal profile and in in vitro fertilization (IVF)/intracytoplasmic sperm injection outcomes in normoovulatory Brazilian women. Methods: A cross-sectional study of 140 women (median age = 33 years [CI: 32-34]) with infertility mainly caused by male (n = 85) or tuboperitoneal (n = 55) factors. In this study we evaluated FSH, estradiol, luteinizing hormone (LH), progesterone, prolactin and anti-Mullerian hormone levels, and antral follicle counting (AFC). Genotyping was performed using the TaqMan real-time polymerase chain reaction methodology. Results: The wild-type allele G was found in 86.4% and the polymorphic allele T in 13.6% of the women respectively. The TT genotype was not found in any women. Women carrying the GT genotype had a poorer response more frequently to controlled ovarian hyperstimulation when compared to individuals with the GG genotype (47.4% vs. 26.5%, p = 0.010), higher LH levels (3.1 IU/mL vs. 2.4 IU/mL, p = <0.001), lower AFC (8.0 vs. 10.0, p = 0.03), oocytes retrieved (3.0 vs. 5.0, p = 0.03), MII (3.0 vs. 4.0, p = 0.02), and embryos (2.0 vs. 3.0, p = 0.02). Despite these findings, no difference was observed in pregnancy rate. Conclusion: Our findings suggest that the FSHB c.-211G/T polymorphism may modestly alter some aspects of the female reproductive system, but they are not associated with significantly different IVF outcomes.