Background: The ovarian response to follicle stimulating hormone (FSH) stimulation in assisted conception cycles is variable. Although it would be beneficial to predict accurately the response of patients to FSH, to date no robust predictors of ovarian performance have been identified. Recently, there have been a number of studies on the effect of single nucleotide polymorphisms (SNP) in the FSH receptor gene and its predictive value in the patients undergoing ovarian stimulation. Several reports have shown that two common SNPs at positions 307 and 680 in exon 10 of the FSH receptor gene are associated with ovarian response in in-vitro fertilization (IVF). Some authors have shown predictability of ovarian response to FSH stimulation in patients with different alleles, while others have refuted this finding. Until now, there is no clear clinical benefit in screening FSHR genotypes before IVF treatment. Objective: 1) To study the association between ovarian response and FSHR gene polymorphisms2) To study the association between FSHR gene polymorphisms and markers of ovarian reserve, including Anti Mullerian Hormone, Antral Follicle Count, Follicle Stimulating Hormone.Design: Prospective observational studyMethodology: 421 patients attending a tertiary reproductive medicine unit undergoing first cycle of IVF treatment were recruited into the study. Blood tests were taken on day 2 or 3 of the cycle for assessment of hormones and for DNA extraction. The SNP genotyping was done using Taqman analysis. Non-parametric tests were done to compare the various outcome parameters in patients with different genotypes.Results: FSHR p.Asn680Ser was not predictive of ovarian response. There was no evidence of any difference in basal FSH, AMH or AFC between the patients with different FSHR genotypes, with or without an adjustment for age or BMI. On subgroup analysis, there was no evidence that FSHR p.Asn680Ser genotypes are associated with PCOS, high AMH levels or response to clomiphene citrate. FSHR gene polymorphism was also not related to oocyte maturity or fertilization rate.Conclusions: FSHR p.Asn680Ser was not shown to be predictive of ovarian response, although clinically relevant differences cannot be ruled out. There may be an effect size but smaller than that detected for the power of this study. Other genetic markers may be relevant in the prediction of response to ovarian stimulation.
|Date of Award||31 Dec 2012|
- The University of Manchester
|Supervisor||Luciano Nardo (Supervisor) & William Newman (Supervisor)|
- Single nucleitide polymorphism, SNP, FSH receptor, FSH