Association of FSH receptor and CYP19A1 gene variations with sterility and ovarian hyperstimulation syndrome

Severe ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication during assisted reproduction technology (ART). The aetiology of this condition is still not fully understood. Several gene variations in the FSH receptor (FSHR) gene have been identified for the very rare cases of spontaneous OHSS. There are only few published data on gene variations in sterility and iatrogenic OHSS and no data regarding aromatase (cytochrome P450 19A1; CYP19A1). Ninety-one ART patients with OHSS, eighty-eight ART patients without DHSS and ninety-seven women with assumed normal fecundity were analysed for the FSHR single nucleotide polymorphism (SNP) gene variations Asn680Ser (rs6166), Ala189Val, Ile160Thr, Thr449Ile (rs28928870) and the CYP19A1 rs10046 locus using real-time PCR. In addition, exon 10 of FSHR of two patients with spontaneous hyperreactio luteinalis (H L) was sequenced. Significantly lower frequencies of homozygous Ser(680)/Ser(680) (P=0.035) and heterozygous Thr(160)/Ile(160) (P=0.039) were found in patients with normal fecundity than those undergoing ART. The Ile160Thr SNP with a frequency of 6.7 and 6.1% in ART patients with and without OHSS respectively does not represent a rare mutation as previously published. There were no differences in the frequencies of all other gene variations. Of two patients with HL, both had homozygous point mutations for Ser(680)/Ser(680) and one was heterozygous for Ile160Thr and CYP19A1 rs10046. The FSHRgene variations Asn680ser as well as Ile160Thr maybe contributing factors in unexplained sterility. The other FSHR coding gene variations and CYP19A1 rs10046 investigated are mostlikely not involved in the aetiology of iatrogenic OHSS or sterility.