Objective

To study the consequences of specific genotype profiles of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone choriogonadotropin receptor (LHCGR) on assisted reproductive technology outcomes when preimplantation genetic testing for aneuploidy is used for controlling the embryo ploidy status. The most common reported single-nucleotide polymorphisms in the amino acid position for the FSHR (N680S; N: asparagine, S: serine; [rs6166]) and the LHCGR (N312S variant; N: asparagine, S: serine [rs2293275]) were chosen for this study.

Design

Retrospective cohort study.

Setting

Private Fertility Clinic.

Patient(s)

All women aged 18–40 years undergoing their first assisted reproductive technology cycle with aneuploidy screening between 2006 and 2017 with body mass index of >18 and <40 kg/m² were included.

Intervention(s)

All patients received both recombinant follicle-stimulating hormone and human menopausal gonadotropin or low dose human chorionic gonadotropin. Genomic DNA was isolated from patients’ blood. Genotyping of the FSHR and LHCGR polymorphisms was performed using TaqMan genotyping assays. Associations between both receptor genotypes and clinical outcomes were assessed using generalized regression and ANOVA.

Main Outcomes Measure(s)

Live birth rate was the primary outcome. Secondary outcomes included oocyte yield, mature oocytes, blastulation rate, usable blastocyst rate, and implantation rate.

Result(s)

A total of 1,183 patients met the inclusion criteria and generated reliable genotype results. The overall genotype frequencies in the study population for the FSHR gene were as follows: 21.7% homozygous for S in codon 680, 29.2% homozygous for N680, and 48.1% heterozygous (N680S). As for the LHCGR, 15.6% were homozygous for N312, 38.5% homozygous for S312 and 45.9% heterozygous (N312S). Our study population consisted of 53.8% non-Hispanic white; 6.1% Hispanic white; 4.1% Afro-American; 15.4% Asian; and 20.6% other or unknown. No significant association was found with any of the studied variables (oocyte yield, usable blastocyst rate, implantation rate, live birth) when genotypes were analyzed per receptor or in combination with one another. There was a statistically significant but clinically irrelevant difference in the rate of mature oocytes across different variant combinations.

Conclusion(s)

Our findings suggest that the presence of gonadotropin receptor polymorphisms in both FSHR N680S and LHCGR N312S are not associated with assisted reproductive technology outcomes; therefore, these variants should not be considered reproductive predictors.

中文翻译：

---

促性腺激素受体多态性（FSHR N680S 和 LHCGR N312S）不能预测辅助生殖技术中的临床结果和活产

客观的

研究卵泡刺激素受体 (FSHR) 和促黄体生成素绒毛膜促性腺激素受体 (LHCGR) 的特定基因型谱对非整倍体植入前基因检测用于控制胚胎倍性状态时辅助生殖技术结果的影响。FSHR（N680S；N：天冬酰胺，S：丝氨酸；[rs6166]）和 LHCGR（N312S 变体；N：天冬酰胺，S：丝氨酸 [rs2293275]）的氨基酸位置中最常见的单核苷酸多态性是为这项研究选择。

设计

回顾性队列研究。

环境

私人生育诊所。

病人）

^{所有在 2006 年至 2017 年间接受非整倍体筛查且体重指数 >18 且 <40 kg/m 2}的辅助生殖技术周期的 18-40 岁女性均被纳入。

干预措施

所有患者均接受重组促卵泡激素和人绝经期促性腺激素或低剂量人绒毛膜促性腺激素。从患者的血液中分离出基因组 DNA。使用 TaqMan 基因分型测定法对 FSHR 和 LHCGR 多态性进行基因分型。使用广义回归和方差分析评估受体基因型和临床结果之间的关联。

主要成果措施

活产率是主要结果。次要结果包括卵母细胞产量、成熟卵母细胞、囊胚形成率、可用囊胚率和着床率。

结果）

共有 1,183 名患者符合纳入标准并产生了可靠的基因型结果。研究人群中FSHR的总体基因型频率 gene were as follows: 21.7% homozygous for S in codon 680, 29.2% homozygous for N680, and 48.1% heterozygous (N680S). As for the LHCGR, 15.6% were homozygous for N312, 38.5% homozygous for S312 and 45.9% heterozygous (N312S). Our study population consisted of 53.8% non-Hispanic white; 6.1% Hispanic white; 4.1% Afro-American; 15.4% Asian; and 20.6% other or unknown. No significant association was found with any of the studied variables (oocyte yield, usable blastocyst rate, implantation rate, live birth) when genotypes were analyzed per receptor or in combination with one another. There was a statistically significant but clinically irrelevant difference in the rate of mature oocytes across different variant combinations.

Conclusion(s)

我们的研究结果表明，FSHR N680S 和 LHCGR N312S 中促性腺激素受体多态性的存在与辅助生殖技术结果无关；因此，不应将这些变异视为生殖预测因子。