Could polymorphisms of some hormonal receptor genes, involved in folliculogenesis help in predicting patient response to controlled ovarian stimulation?

• Published in: Journal of assisted reproduction and genetics Vol. 36; no. 1; pp. 47 - 55
• Main Authors: Čuš, Maruška, Vlaisavljević, Veljko, Repnik, Katja, Potočnik, Uroš, Kovačič, Borut
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2019; Springer Nature B.V
• Subjects: 17β-Estradiol; Adult; Anti-Mullerian Hormone - blood; Anti-Mullerian Hormone - genetics; Cross-Sectional Studies; Enzyme-linked immunosorbent assay; ESR1 protein; Estrogen Receptor alpha - genetics; Female; Fertilization in Vitro; Follicle-stimulating hormone; Folliculogenesis; Gene regulation; Genetics; Genotype; Genotype & phenotype; Genotyping; Gonadotropin-releasing hormone; Gonadotropins; Gynecology; Hormone Antagonists - therapeutic use; Human Genetics; Humans; In vitro fertilization; Infertility, Female; Medicine; Medicine & Public Health; Oocytes; Ovarian Follicle - cytology; Ovarian Follicle - drug effects; Ovarian Follicle - metabolism; Ovulation; Ovulation Induction - methods; Pituitary (anterior); Polymorphism, Single Nucleotide; Pregnancy; Pregnancy Rate; Receptors, FSH - genetics; Receptors, Peptide - genetics; Receptors, Transforming Growth Factor beta - genetics; Reproductive Medicine; Single-nucleotide polymorphism; AMHR; Single nucleotide polymorphisms; Controlled ovarian hyperstimulation; Genotyping; FSHR
• ISSN: 1058-0468; 1573-7330
• DOI: 10.1007/s10815-018-1357-4

Purpose The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in selected genes, responsible for hormonal regulation of folliculogenesis, are associated with response to controlled ovarian hyperstimulation (COH) and clinical characteristics of women enrolled in in vitro fertilization (IVF) programs. Methods In a cross-sectional study, 60 (IVF) patients underwent COH by using gonadotropin-releasing hormone (GnRH) antagonist and recombinant follicle-stimulating hormone (rFSH) protocol. Patients were classified into three groups: poor-responders (according to Bologna criteria), normo-responders (≤ 15 oocytes), and hyper-responders (> 15 oocytes). Genotyping of SNPs AMH rs10407022, AMHR rs3741664, FSHR rs1394205 and rs6166, and ESR1 rs2234693 was performed using high-resolution melting analysis (HRMA). Basal FSH (bFSH), estradiol (E2), and anti-Müllerian hormone (AMH) were measured by enzyme-linked immunosorbent assay (ELISA). Results Patients with GG genotype of FSHR rs1394205 had significantly lower AMH level ( P  = 0.016) and required higher rFSH dose per oocyte compared to women with AA or AG genotype ( P  = 0.036). We also found higher frequency of GG genotype of FSHR rs1394205 in poor- (76.5%) than in hyper-responders (37.5%, P  = 0.002). Patients with AA genotype of FSHR rs6166 had higher level of measured bFSH compared to those with AG or GG genotypes ( P  = 0.043). Women with GG genotype of AMHR rs3741664 required higher rFSH dose in comparison with patients carrying genotypes AA or AG ( P  = 0.028). Conclusions The GG genotype at position rs1394205 is associated with poor ovarian response to COH. Patients with this genotype may require higher doses of rFSH for ovulation induction.