Impact of Mutations and Polymorphisms of Gonadotrophins and Their Receptors on the Outcome of Controlled Ovarian Stimulation

Abstract

Controlled ovarian stimulation is a mainstay of assisted reproductive technologies and leads to optimal follicular growth and steroidogenesis in the majority of cases. Nonetheless, some women defined as “hyporesponders” require higher amount of exogenous gonadotrophin to achieve an adequate number of oocytes retrieved despite an apparently good prognosis. Clinical observational trials suggest that hyporesponse to exogenous gonadotrophins, including initial poor response, could be a genetically determined trait with specific genotype profile associated with this condition. Specifically, mutation and polymorphisms involving luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and their receptors LH-R and FSH-R have been thoroughly investigated. Among all the mutations discovered, it seems that that carriers of common LH variant and FSH receptor Ser/680 variants require higher doses of exogenous FSH to achieve a normal ovarian response.

In conclusion, the idea of a tailored gonadotrophin administration based on a pharmacogenomic approach may be considered in specific situations and could represent the future research target for a better understanding of the underlying mechanisms that regulate human fertility.