Center for Human Reproduction Prof Franco Jr, Ribeirao Preto, SP, Brazil.
Paulista Center for Diagnosis, Research and Training, Ribeirao Preto, SP, Brazil.
JBRA Assist Reprod. 2023 Mar 30;27(1):78-84. doi: 10.5935/1518-0557.20230009.
Follicle-stimulating hormone (FSH) is essential for folliculogenesis, acting through the follicle-stimulating hormone receptor (FSHR) that is present on the membrane of granulosa cells. Polymorphisms in the FSHR gene may lead to an altered pattern of receptor expression on the cell surface or to changes in affinity for FSH. The aim of this prospective study was to detect any association between the follicle-stimulating hormone receptor (FSHR) gene Ala307Thr polymorphism (rs6165) and ovarian reserve, ovarian response or clinical results in IVF/ICSI treatment.
This prospective cohort study included 450 women who underwent IVF/ICSI cycles. DNA was extracted from peripheral blood, and the Ala307Thr FSHR polymorphism (rs6165) was genotyped using the TaqMan SNP genotyping assay. Participants were divided into three groups according to their Ala307Thr FSHR genotype: Thr/Thr (n:141), Thr/Ala (n=213) and Ala/Ala (n=96). The results were tested for associations with age, anti-Mullerian hormone (AMH) levels, antral follicle count (AFC), total dose of r-FSH, follicle size, number of retrieved oocytes, and clinical outcome of IVF/ICSI cycles. The statistical analyses were performed using Fisher's exact test and the Kruskal‒Wallis test.
An association between the genotype of the FSHR (Ala307Thr) polymorphism and the dose of r-FSH was observed. Patients with the Ala/Ala genotype received a higher r-FSH dose than patients with the Ala/Thr (p=0.0002) and Thr/Thr (p=0.02) genotypes. No other correlation was observed.
The Ala/Ala genotype was associated with the use of higher doses of recombinant FSH (r-FSH), suggesting that homozygosis of this allelic variant (Ala) provides lower sensitivity to r-FSH.
卵泡刺激素(FSH)对卵泡发生至关重要,通过存在于颗粒细胞膜上的卵泡刺激素受体(FSHR)发挥作用。FSHR 基因的多态性可能导致细胞表面受体表达模式的改变或对 FSH 的亲和力发生变化。本前瞻性研究旨在检测卵泡刺激素受体(FSHR)基因 Ala307Thr 多态性(rs6165)与卵巢储备、卵巢反应或 IVF/ICSI 治疗的临床结果之间是否存在任何关联。
本前瞻性队列研究纳入了 450 名接受 IVF/ICSI 周期的女性。从外周血中提取 DNA,并使用 TaqMan SNP 基因分型检测法对 Ala307Thr FSHR 多态性(rs6165)进行基因分型。根据其 Ala307Thr FSHR 基因型将参与者分为三组:Thr/Thr(n=141)、Thr/Ala(n=213)和 Ala/Ala(n=96)。检测结果与年龄、抗苗勒管激素(AMH)水平、窦卵泡计数(AFC)、r-FSH 总剂量、卵泡大小、获卵数和 IVF/ICSI 周期的临床结局进行关联分析。统计分析采用 Fisher 确切检验和 Kruskal-Wallis 检验。
观察到 FSHR(Ala307Thr)多态性的基因型与 r-FSH 剂量之间存在关联。Ala/Ala 基因型患者接受的 r-FSH 剂量高于 Ala/Thr(p=0.0002)和 Thr/Thr(p=0.02)基因型患者。未观察到其他相关性。
Ala/Ala 基因型与使用更高剂量重组 FSH(r-FSH)相关,表明该等位基因变异(Ala)的纯合性降低了对 r-FSH 的敏感性。