Genetics of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is typically iatrogenic following the administration of gonadotrophins. Sporadic and familial cases of spontaneous OHSS have generated an interest in genetic mechanisms for OHSS independent of exogenous gonadotrophins. The genetic studies have addressed the genes and receptors for FSH and luteinizing/human chorionic gonadotrophin hormones. Mutations in the FSH receptor (FSHR) could be activating, leading to a predisposition to OHSS, or inactivating, resulting in sterility. Polymorphisms of FSHR have been investigated and, to date, 744 single nucleotide polymorphisms have been identified in the FSHR gene, of which only eight are located in the coding region, exons, with the rest being intronic. Ovarian response is dependent on FSHR genotype. Clinical studies on the p.N680S polymorphism of the FSHR gene have demonstrated the homozygous Ser/Ser variant to be less sensitive to endogenous or exogenous FSH in terms of oestradiol production. Polymorphism of the FSHR, Ser680Asn, in the FSHR gene is a predictor of the severity of symptoms in patients who develop OHSS. OHSS is characterized by leakage of intravascular fluids resulting in ascites and haemoconcentration. These pathological changes are mediated for the most part by vascular endothelial growth factor (VEGF). Targeting the VEGF system at different levels has been the focus of intense research for the prevention of OHSS.