Association between FSHR and ESR1 gene variants and ovarian response to gonadotropin in Egyptian women undergoing ICSI treatment

Abstract

The unpredictable variability in patients' responses to gonadotropins represents one of the most intractable IVF treatment problems. Identifying the genetic variants associated with ovarian responses to gonadotropins is an important step towards developing individualised pharmacogenetics protocols for ovarian stimulation. The purpose of the current study was to evaluate correlations between FSHR rs6165, FSHR rs616, and ESR1 rs2234693 gene variants and the degree of ovarian response to gonadotropin in Egyptian women undergoing ICSI treatment. Two hundred and eighty Egyptian women (mean age of 20-35) undergoing ICSI treatment were enrolled in a cross-sectional study conducted between January 2017 and May 2019. The women were classified into three groups based on ovarian response: normal responders (retrieved oocytes = 4-15) (n = 80), poor responders (retrieved oocytes < 4) (n = 92), and high responders (retrieved oocytes> 15) (n = 108). Genomic DNA was extracted from blood samples, and PCR and DNA sequencing were performed to identify genetic variations in the different study groups. FSHR and ESR1 genetic variants were then compared in normal, poor, and high responders. DNA sequencing results showed significant differences in the frequencies of FSHR rs6166 and ESR1 rs2234693 genotypes in poor responders compared with normal responders (P ≤ 0.001 and P ≤ 0.001, respectively). In contrast, no significant differences in the frequencies of FSHR rs6166, FSHR rs6165, or ESR1 rs2234693 genotypes were observed in high responders compared with normal responders (P ≤ 0.074, P ≤ 0.353, and P ≤ 0.060, respectively). These results suggest that FSHR and ESR1 gene variants could predict the degree of ovarian response to Controlled ovarian hyperstimulation in Egyptian women.

Keywords: ESR1 variant; FSHR variants; Female fertility; ICSI; Ovarian response.