# Significance of Follicle-Stimulating Hormone Receptor Gene Single-Nucleotide Polymorphism rs6165/rs6166 Analysis for Infertility-Associated Ovarian Disease Susceptibility Prediction and Optimized Individualized Ovulation Induction/Ovarian Stimulation

## TL;DR

This review explores how genetic variations in the FSHR gene affect infertility and treatment responses, suggesting personalized approaches could improve outcomes.

## Contribution

The paper highlights the potential of genotype-guided ovulation stimulation based on FSHR rs6165/rs6166 polymorphisms to improve infertility treatment outcomes.

## Key findings

- FSHR gene polymorphisms rs6165 and rs6166 are linked to susceptibility to infertility-related ovarian diseases.
- Genotype-guided treatment may reduce poor or excessive ovarian responses during ovulation induction.
- Current evidence supports further research to validate clinical implementation of genotype-based approaches.

## Abstract

Follicle-stimulating hormone receptor (FSHR) is expressed on the plasma membrane of granulosa cells in the ovarian follicles. FSHR is involved in the development and maturation of Graafian follicles, along with granulosa proliferation and estrogen synthesis. There are two well-characterized non-synonymous single-nucleotide gene polymorphisms in the exon 10 of the human FSHR gene, namely rs6165 (c.919G>A, Ala307Thr) and rs6166 (c.2039A>G, Ser680Asn). Recent research clarifies the association of rs6165/rs6166 with susceptibility to infertility-associated ovarian diseases, ranging from polycystic ovarian syndrome, premature ovarian insufficiency, endometriosis, to ovarian cancer, along with response/resistance to ovulation induction/ovarian stimulation with clomiphene citrate, letrozole, metformin, FSH preparations, and adjunctive growth hormone in infertility treatment. This narrative review aims to update the knowledge on the relationship among rs6165/rs6166, infertility etiology, and differential responses to oral ovulation induction agents, FSH preparations, and adjunctive growth hormone. The re6165/rs6166 genotype-guided choice of individualized ovulation stimulation preparations has great potential to reduce unexpected poor or high ovarian responses in ovulation induction and ovarian stimulation and improve clinical outcomes in reproductive medicine. Current evidence is insufficient, and further studies are warranted to ascertain its potential for clinical implementation.