促卵泡生成素受体多态性在预测多囊卵巢综合征女性排卵诱导期间对来曲唑的卵巢反应中的作用。
Role of follicle-stimulating hormone receptor polymorphism in predicting ovarian response to letrozole in women with polycystic ovary syndrome during ovulation induction.
作者信息
Zhu Xiuxian, Wang Qiaoling, Lang Jingwen, Zhi Yunqing, Fu Yonglun, Bao Shihua
机构信息
Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
出版信息
Front Endocrinol (Lausanne). 2025 Jun 19;16:1585655. doi: 10.3389/fendo.2025.1585655. eCollection 2025.
BACKGROUND
Letrozole is a first-line treatment for anovulatory infertility in women with polycystic ovary syndrome (PCOS). Despite its widespread use, a significant proportion of patients exhibit non-responsive cycles, limiting treatment efficacy. Identifying predictive markers for ovarian response could enhance the efficiency and cost-effectiveness of ovulation induction. Previous studies have suggested an association between follicle-stimulating hormone receptor (FSHR) polymorphisms and ovarian response, though the precise relationship between these polymorphisms and ovarian response to letrozole remains poorly defined.
METHODS
This retrospective study analyzed data from 133 women with PCOS (93 responsive to letrozole and 40 resistant) between January 2021 and May 2024. Demographic data were collected, and genotyping of FSHR single nucleotide polymorphisms (c.2039A>G, rs6166 at position 680, and c.919A>G, rs6165 at position 307) was performed using predesigned TaqMan SNP assays. A binary logistic regression model was employed to evaluate the predictive value of FSHR polymorphisms in letrozole resistance.
RESULTS
The Asn/Asn polymorphism at position 680 was significantly more prevalent in the letrozole-resistant group (57.5%) compared to the letrozole-responsive group (34.41%) [OR: 1.543 (95% CI, 1.046-2.278), P = 0.013]. Similarly, the Thr/Thr polymorphism at position 307 was more common in the resistance group (57.5% vs. 30.11%) [OR: 1.645 (95% CI, 1.120-2.415), P = 0.003]. Participants with either the Asn/Asn or Thr/Thr polymorphism were more likely to exhibit resistance to letrozole. Logistic regression analysis indicated that the Asn/Asn polymorphism was a potential risk factor for letrozole resistance [OR: 5.227 (95% CI, 0.994-27.490), P = 0.051], while the Thr/Thr polymorphism significantly influenced letrozole response [OR: 7.04 (95% CI, 1.394-35.559), P = 0.018].
CONCLUSIONS
The Asn/Asn polymorphism at position 680 and the Thr/Thr polymorphism at position 307 of the FSHR gene may serve as potential predictors of ovulatory failure during letrozole therapy in PCOS patients.
背景
来曲唑是多囊卵巢综合征（PCOS）女性无排卵性不孕症的一线治疗药物。尽管其广泛应用，但仍有相当一部分患者出现无反应周期，限制了治疗效果。识别卵巢反应的预测标志物可以提高促排卵的效率和成本效益。既往研究提示促卵泡激素受体（FSHR）基因多态性与卵巢反应有关，但这些多态性与来曲唑治疗卵巢反应的确切关系仍不明确。
方法
这项回顾性研究分析了2021年1月至2024年5月期间133例PCOS女性的数据（93例对来曲唑有反应，40例耐药）。收集人口统计学数据，并使用预先设计的TaqMan SNP分析对FSHR单核苷酸多态性（第680位c.2039A>G、rs6166，以及第307位c.919A>G、rs6165）进行基因分型。采用二元逻辑回归模型评估FSHR基因多态性在来曲唑耐药中的预测价值。
结果
与来曲唑反应组（34.41%）相比，第680位Asn/Asn多态性在来曲唑耐药组中显著更常见（57.5%）[比值比（OR）：1.543（95%置信区间，1.046 - 2.278）；P = 0.013]。同样，第307位Thr/Thr多态性在耐药组中更常见（57.5%对30.11%）[OR：1.645（95%置信区间1.120 - 2.415）；P = 0.003]。具有Asn/Asn或Thr/Thr多态性的参与者更有可能对来曲唑耐药。逻辑回归分析表明，Asn/Asn多态性是来曲唑耐药的潜在危险因素[OR：5.227（95%置信区间，0.994 - 27.490）；P = 0.051]，而Thr/Thr多态性显著影响来曲唑反应[OR：7.04（95%置信区间，1.394 - 35.559）；P = 0.018]。
结论
FSHR基因第680位的Asn/Asn多态性和第307位的Thr/Thr多态性可能是PCOS患者来曲唑治疗期间排卵失败的潜在预测指标。
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