FSHB -211G>T stratification for follicle-stimulating hormone treatment of male infertility patients: making the case for a pharmacogenetic approach in genetic functional secondary hypogonadism.

Male infertility contributes to a substantial share to couple infertility. Despite scientific efforts, most cases of male infertility remain 'idiopathic' and male-specific therapeutic options are sparse. Given the crucial role of the follicle-stimulating hormone (FSH) for spermatogenesis, FSH is used empirically to improve semen parameters. Furthermore, a recently updated Cochrane review points to a beneficial effect of FSH treatment in idiopathic infertile men on spontaneous pregnancy rates. However, since response to FSH varies strongly even in selected patients and given the lack of powerful evidence of FSH treatment regimens, intra-cytoplasmic spermatozoa injection (ICSI) is widely used in idiopathic male infertility, though the treatment burden is high for the couple and it entails considerable costs and some risks. Single nucleotide polymorphisms (SNPs) within FSH ligand/receptor genes (FSHB/FSHR), significantly influencing reproductive parameters in men, represent promising candidates to serve as pharmacogenetic markers to improve prediction of response to FSH. However, there is an evident lack of information which patients should be treated and how many patients in an andrological outpatient clinic would be eligible for such a treatment, a crucial decision criterion for clinicians and also pharmaceutical industry to start such a pharmacogenetic intervention therapy. After screening our andrological patient cohort, we present a realistic scenario and a basis for further prospective studies using FSH in idiopathic infertile men.