Single-nucleotide polymorphisms in the FSH receptor gene and ovarian performance: future role in IVF.

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 absolute predictors of ovarian performance have been identified. Recently, there have been a number of studies on the effect of single-nucleotide polymorphisms (SNPs) in the FSH receptor gene and its predictability in ovarian response to FSH stimulation. Several reports have shown that two very common SNPs at positions 307 and 680 in exon 10 of the FSH receptor gene are associated with ovarian response in IVF. The SNPs in exon 10 result in four discrete allelic variants characterised by the amino acid combinations Thr(307)-Asn(680), Ala(307)-Ser(680), Ala(307)-Asn(680) and Thr(307)-Ser(680). Because Thr(307) is almost always in linkage disequilibrium with Asn(680), and Ala(307) almost always with Ser(680), most studies are focussed solely on position 680. Some authors have shown predictability of ovarian response to FSH stimulation in patients with different alleles, while others have refuted this finding. In vitro models have not shown any difference in response among various alleles. Most of the available studies are retrospective, observational. Until now, there is no clear clinical benefit in the screening for SNP before IVF treatment. However, there is the prospect of devising mathematical models using a group of polymorphisms to provide an important tool for improving ovulation induction, especially in poor responders.