Pharmacogenetics of controlled ovarian hyperstimulation: time to corroborate the clinical utility of FSH receptor genetic markers.

Several studies have shown high variability in clinical outcome among women undergoing follicle-stimulating hormone treatment. Pharmacogenetic studies have revealed a series of genetic markers involved in controlled ovarian hyperstimulation (COH) response. FSHR gene-associated SNPs, including the N680S missense variant, are the most promising genetic markers available to date. In this paper the state of the art pharmacogenetic analysis of COH outcome is reviewed and a meta-analysis is conducted with available data that confirms that the N680S marker is associated with poor response during COH. Thus, we propose that by pooling together available information, it is possible to go one step further with this biomarker to definitively validate its utility in the clinical field. We propose to conduct clinical trials, to look for algorithms integrating the N680S genotype and to test if such clinical protocols can optimize recombinant follicle-stimulating hormone dose and detect women at risk of a poor response during a COH cycle.