Vieira Inês H, Carvalho Alexandra F, Almeida Reis Sandra, Carreira Ana L, Dias Conceição, Fernandes Silvana, Ferreira Ana Filipa, Rodrigues Dircea, Sousa Ana Paula, Ramalho-Santos João, Ramalhinho Ana Cristina, Moura Ramos Mariana, Paiva Isabel, Cortesão Paulo, Almeida-Santos Ana Teresa
Department of Endocrinology, Diabetes, and Metabolism, Coimbra Hospital and University Center, Coimbra, PRT.
Reproductive Medicine Unit, Department of Gynecology, Obstetrics, Reproduction, and Neonatology, Coimbra Hospital and University Center, Coimbra, PRT.
Cureus. 2023 Mar 2;15(3):e35690. doi: 10.7759/cureus.35690. eCollection 2023 Mar.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder often leading to anovulatory infertility. PCOS pathophysiology is still unclear and several potential genetic susceptibility factors have been proposed. The effect of polymorphisms in two genesrelated to follicular recruitment and development, the follicle-stimulating hormone receptor () and the estrogen receptor 1 (), have been studied in different populations with contradictory results.
To evaluate the influence of rs6166 (c.2039A>G) and of rs2234693 (Pvull c.453-397 T > C) polymorphisms on PCOS risk, phenotype, and response to controlled ovarian stimulation (COS).
Genotyping of the rs6166 and the rs2234693 polymorphisms was performed in PCOS women and a control group undergoing in vitro fertilization (IVF). Demographic, clinical, and biochemical data, genotype frequency, and IVF outcomes were compared between groups.
We evaluated 88 PCOS women and 80 controls. There was no significant difference in the genotype distribution of rs6166 polymorphism between PCOS women and controls (AA 31.8%/AS 48.9%/SS 19.3% in PCOS women vs AA 37.5%/AS 40.0%/SS 22.5% in controls; p = 0.522). The same was true for the rs2234693 (CC 24.1%/CT 46.0%/TT 29.9% in PCOS women vs CC 18.8%/CT 48.8%/TT 32.5% in controls; p = 0.697). In PCOS women, we found higher follicle-stimulating hormone (FSH) levels on the third day of the menstrual cycle associated with the SS variant of the polymorphism (9.2 vs6.2 ± 1.6 and 5.6 ± 1.6 mUI/mL; p = 0.011). We did not find other associations between the baseline hormonal parameters, antral follicle count, and response measures to COS with or genotypes. We found, however, a need for higher cumulative doses of FSH for COS in patients with the SS variant of the rs6166 polymorphism (1860.5 ± 627.8 IU for SSvs1498.1 ± 359.3 for AA and 1425.4 ± 474.8 for SA; p = 0.046 and p = 0.046).
Our data suggest that in the population, rs6166and polymorphisms do not influence the risk of developing PCOS nor do they influence the patient's phenotype and IVF success. However, the SS variant of the rs6166 polymorphism may be associated with FSH resistance requiring higher FSH doses for COS.
多囊卵巢综合征（PCOS）是一种常见的内分泌紊乱疾病，常导致无排卵性不孕。PCOS的病理生理学仍不清楚，并且已经提出了几种潜在的遗传易感性因素。在不同人群中研究了与卵泡募集和发育相关的两个基因，即促卵泡激素受体（FSHR）和雌激素受体1（ESR1）中的多态性的影响，但结果相互矛盾。
评估FSHR基因rs6166（c.2039A>G）和ESR1基因rs2234693（Pvull c.453-397 T>C）多态性对PCOS风险、表型及控制性卵巢刺激（COS）反应的影响。
对PCOS女性患者和接受体外受精（IVF）的对照组进行FSHR基因rs6166和ESR1基因rs2234693多态性的基因分型。比较两组之间的人口统计学、临床和生化数据、基因型频率及IVF结局。
我们评估了88例PCOS女性患者和80例对照。PCOS女性患者和对照之间FSHR基因rs6166多态性的基因型分布无显著差异（PCOS女性患者中AA占31.8%/AS占48.9%/SS占19.3%，对照中AA占37.5%/AS占40.0%/SS占22.5%；p = 0.522）。ESR1基因rs2234693也是如此（PCOS女性患者中CC占24.1%/CT占46.0%/TT占29.9%，对照中CC占18.8%/CT占48.8%/TT占32.5%；p = 0.697）。在PCOS女性患者中，我们发现月经周期第3天较高的促卵泡激素（FSH）水平与FSHR基因多态性的SS变异型相关（分别为9.2 vs 6.2±1.6和5.6±1.6 mUI/mL；p = 0.011）。我们未发现基线激素参数、窦卵泡计数及COS反应指标与FSHR或ESR1基因型之间存在其他关联。然而，我们发现FSHR基因rs6166多态性的SS变异型患者进行COS时需要更高的FSH累积剂量（SS型为1860.5±627.8 IU，AA型为1498.1±359.3 IU，SA型为1425.4±474.8 IU；p = 0.046和p = 0.046）。
我们的数据表明，在该人群中，FSHR基因rs6166和ESR1基因多态性不影响PCOS的发病风险，也不影响患者的表型及IVF成功率。然而，FSHR基因rs6166多态性的SS变异型可能与FSH抵抗相关，进行COS时需要更高剂量的FSH。
