P-605 The predictive role of follicle-stimulating hormone receptor polymorphism on letrozole resistance in women with polycystic ovary syndrome

Abstract Study question Whether follicle stimulating hormone receptor (FSHR) polymorphism can predict letrozole resistance in women with polycystic ovarian syndrome (PCOS) during ovulation induction therapy. Summary answer The Asn/Asn polymorphism at FSHR 680 position and Thr/Thr polymorphism at FSHR 307 position were potential predictors for letrozole resistance in women with PCOS. What is known already Letrozole is an oral medication for ovulation induction, which gradually becomes an essential first-line treatment for anovulatory infertility. However, there are still a proportion of non-responsive cycles during letrozole therapy, which is defined as “letrozole resistance”. Exploring potential markers to predict the ovarian response during ovulation induction will help women with PCOS achieve conception in a shorter time with a lower expense. Previous studies have shown that FSHR polymorphism is associated with ovarian response. However, the relationship between FSHR polymorphism and the ovarian response to letrozole has not been reported. Study design, size, duration This was a retrospective study that included 133 women with PCOS (93 with letrozole response and 40 with letrozole resistance) between January 2021 and May 2024. Participants/materials, setting, methods Data on demographics were collected, and the genotyping of the FSHR single nucleotide polymorphisms (c.2039A>G, rs6166 at position 680, and c.919A>G, rs6165 at position 307) was carried out using the predesigned TaqMan SNP assays. Binary logistic regression model was used for the prediction of FSHR polymorphisms on letrozole resistance. Main results and the role of chance The distribution rate of Asn/Asn polymorphism at position 680 was significantly higher [OR: 1.543 (95% CI, 1.046-2.278), P = 0.013] in letrozole resistance group (57.5%) compared to letrozole response group (34.41%), so as to the distribution rate of Thr/Thr polymorphism at position 307 [57.5% vs. 30.11%; OR: 1.645 (95% CI, 1.120-2.415), P = 0.003]. As a result, significantly more participants with Asn/Asn polymorphism or Thr/Thr polymorphism were resistant to letrozole compared to other polymorphisms. Logistic regression model showed that Asn/Asn polymorphism tended to be a risk factor [OR: 5.227 (95% CI, 0.994-27.490), P = 0.051] for letrozole response, while Thr/Thr polymorphism significantly influenced [OR: 7.04 (95% CI, 1.394-35.559), P = 0.018] letrozole response. Limitations, reasons for caution Our study is limited by the retrospective design and the small sample size, thus additional prospective trials with a larger sample size are needed to verify our findings. In addition, the mechanism on how FSHR genotype affects ovarian response to letrozole treatment needs to be further explored. Wider implications of the findings Our study provided evidence for making individualized ovulation induction strategies according to the FSHR genotypes, which help to better guide the selection of ovulation-induction medications in clinic. Trial registration number No