The Impact of FSHR Polymorphisms (rs6165 and rs6166) on Ovarian Response to Stimulation in Infertile Women with Diminished Ovarian Reserve.

Abstract

Background: Diminished ovarian reserve (DOR) remains a significant challenge in IVF, as it is closely associated with poor ovarian response. Beyond well-established predictive of ovarian response, genetic polymorphisms in the FSH receptor (FSHR) gene rs6165 and rs6166 have been reported as potential markers.

Purpose: Evaluating the expression of FSHR rs6165 and rs6166 in DOR patients and their impact on ovarian response to stimulation.

Materials and methods: This prospective cross-sectional included 79 DOR patients (AMH < 1.2 ng/mL and/or AFC < 5) undergoing IVF treatment at the National Hospital of Obstetrics and Gynecology, Vietnam. GnRH antagonist protocol was applied, using alpha follitropin with individualized dosages combined with clomiphene citrate, followed by dual-trigger ovulation induction. FSHR rs6165 and rs6166 were genotyped by Next-Generation Sequencing (NGS) assays, with Sanger sequencing for validation. Ovarian response was assessed based on follicular development and oocyte retrieval.

Results: The overall prevalence of the rs6165 and rs6166 polymorphisms was 10.1% (8/79), with strong linkage disequilibrium observed between the two loci (OR = 490, p < 0.0001). No significant differences in age, AMH, baseline FSH, and AFC were found in all genotypes (AA, AG, GG) of rs6165 and rs6166. In the rs6165 dominant model, patients with G alleles (AG/GG) had lower total oocyte retrieval, FOI and FORT than the AA genotype. In rs6166 codominant, dominant, and recessive models, the GG phenotype retrieved fewer oocytes (p1 = 0.02, p2 = 0.03, p3 = 0.01). FORT was significantly lower in G allele carriers (AG/GG) than AA (p = 0.04).

Conclusion: In the diminished ovarian reserve patients, FSHR rs6165 and rs6166 were associated with ovarian response to stimulation in IVF treatment. Specifically, the presence of G alleles in both rs6165 and rs6166 was correlated with reduced oocyte retrieval, independent of baseline ovarian reserve markers.