Abstract
PurposeThe 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.MethodsIn 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).ResultsPatients 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).ConclusionsThe 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.
Highlights
Since introduction of in vitro fertilization (IVF) in the clinical practice of infertility treatment, the follicular response to ovarian stimulation protocols has been largely investigated
Applicated recombinant follicle-stimulating hormone (rFSH) dose was significantly higher in the group of poor responders, compared to normo- (P = 0.002) and hyper-responders (P < 0.0005)
When comparing genotype and allele frequencies between groups, we found higher frequency of GG genotype of single nucleotide polymorphisms (SNPs) rs1394205 in follicle-stimulating hormone receptor (FSHR) gene in poor- than in hyperresponders (76.5 vs. 37.5%, P = 0.002)
Summary
Since introduction of IVF in the clinical practice of infertility treatment, the follicular response to ovarian stimulation protocols has been largely investigated. The ovarian response to gonadotrophin stimulation is difficult to predict even in patients with similar endocrine profiles. This has led to the investigation of specific new biomarkers that could serve as predictors of ovarian response to an exogenous hormonal stimulation. Very common coding SNPs rs6165, rs6166, and rs1394205 are currently most extensively studied to assess the response of the FSHR protein to FSH stimulation. Some authors have reported predictability of the ovarian
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