Association of a promoter polymorphism in FSHR with ovarian reserve and response to ovarian stimulation in women undergoing assisted reproductive treatment

Abstract

Previous studies have suggested an association between a variant in the promoter region of the FSHR gene and diminished response to controlled ovarian hyperstimulation (COH) in women undergoing assisted reproduction. FSHR -29G>A was genotyped in 559 women undergoing their first cycle of COH for IVF/intracytoplasmic sperm injection (ICSI) using TaqMan allelic discrimination assay. Correlation and regression analysis was performed to assess the relationship between FSHR promoter genotypes and markers of ovarian reserve and measures of response to COH, including the number of oocytes retrieved, gonadotrophin dose used and the live-birth rate. There were no statistically significant differences between the genotype frequencies and the markers of ovarian reserve or the early measures of response to COH. However, the live-birth rate was higher for women carrying the variant A allele (odds ratio [OR] 1.37; 95% confidence interval [CI] 1.02-1.84 per allele). This relationship did not reach statistical significance after adjustment for the number of embryos transferred (OR 1.33; 95% CI 0.98-1.83 per allele). Results from this study do not provide evidence that the FSHR -29G>A variant can be used in the individualization of the treatment protocol for women undergoing IVF/ICSI.

The carriers of the A/G-G/G allelic combination of the c.2039 A>G and c.-29 G>A FSH receptor polymorphisms retrieve the highest number of oocytes in IVF/ICSI cycles

“…Moreover, A/G-G/G was associated with higher AFC, lower basal FSH, lower 17β-estradiol and lower FORT in comparison with other genetic variants, supporting its positive predictive factor for the success of ovarian stimulation. The positive association between A/G-G/G and basal FSH contradicts the published studies which considered the different allelic combinations of c.2039 A>G and c.-29 G>A [4,28,31], where no correlation with basal FSH was found. The negative association with FORT could be explained by the selection of the antral follicles with the greatest developmental potential.…”

“…Specifically, Wunsch et al [4] have found no correlation of this polymorphism with ovarian reserve or ovarian response to stimulation. The same conclusion was reached very recently by Tohlob et al [28]. On the other hand, and with reference to the paper by Achrekar et al [29], patients with the A/A variant required a higher total dose of gonadotropins in order to reach significantly lower levels of estradiol on the day of hCG administration with a lower number of retrieved oocytes.…”

“…In the study by Wunsch et al [4], the authors considered the peak estradiol levels as an outcome measure of ovarian response, and they did not identify any correlation with the single polymorphism and their combination. The second study [28] showed that patients carrying the diplotype with variant alleles for both the polymorphisms (G for c.2039 A>G and A for c.-29 G>A) were more likely to have a hyper-response to stimulation but, again, no correlation was observed with poor response. Considering the third study [30], conducted on an Indian population, the authors found that A/A (Asn/Asn)-G/ G and A/G (Asn/Ser)-G/G were the genetic combinations associated with the highest number of collected oocytes.…”

“…As far as we know, only three studies have analyzed the association of c.2039 A>G and c.-29 G>A [4,28,31]. In the study by Wunsch et al [4], the authors considered the peak estradiol levels as an outcome measure of ovarian response, and they did not identify any correlation with the single polymorphism and their combination.…”

“…As regards the Bnew^FSHR polymorphism c.-29 G>A, few studies have been published [4,[28][29][30][31]. Specifically, Wunsch et al [4] have found no correlation of this polymorphism with ovarian reserve or ovarian response to stimulation.…”