Department of Reproductive Medicine and Gynecological Endocrinology, University Medical Centre Maribor, Ljubljanska ulica 5, 2000, Maribor, Slovenia.
Biomedical Research Institute BRIS, Ljubljana, Slovenia.
J Assist Reprod Genet. 2019 Jan;36(1):47-55. doi: 10.1007/s10815-018-1357-4. Epub 2018 Nov 8.
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.
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).
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).
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.
本研究旨在探讨卵泡发生的激素调节相关基因中的单核苷酸多态性（SNP）是否与接受控制性卵巢过度刺激（COH）的反应以及接受体外受精（IVF）方案的女性的临床特征有关。
在一项横断面研究中，60 名接受 GnRH 拮抗剂和重组卵泡刺激素（rFSH）方案 COH 的 IVF 患者被分为三组：低反应组（根据博洛尼亚标准）、中反应组（≤15 个卵母细胞）和高反应组（>15 个卵母细胞）。使用高分辨率熔解曲线分析（HRMA）对 AMH rs10407022、AMHR rs3741664、FSHR rs1394205 和 rs6166 以及 ESR1 rs2234693 的 SNP 进行基因分型。采用酶联免疫吸附试验（ELISA）测定基础 FSH（bFSH）、雌二醇（E2）和抗苗勒管激素（AMH）水平。
与 AA 或 AG 基因型的女性相比，FSHR rs1394205 的 GG 基因型患者的 AMH 水平显著降低（P=0.016），并且每个卵母细胞所需的 rFSH 剂量更高（P=0.036）。我们还发现，在低反应者（76.5%）中 FSHR rs1394205 的 GG 基因型的频率高于高反应者（37.5%，P=0.002）。与 AG 或 GG 基因型的患者相比，FSHR rs6166 的 AA 基因型患者的 bFSH 水平更高（P=0.043）。与携带 AA 或 AG 基因型的患者相比，AMHR rs3741664 的 GG 基因型患者需要更高剂量的 rFSH（P=0.028）。
FSHR rs1394205 位置的 GG 基因型与 COH 卵巢反应不良有关。携带这种基因型的患者可能需要更高剂量的 rFSH 来诱导排卵。
