Sabine Kliesch, Centre of Reproductive Medicine and Andrology (CeRA) (Homepage)
Couple infertility goes along with about 70% of men revealing decreased total sperm counts, either due to known major causes in one third of patients or unexplained (so-called idiopathic) infertility in two thirds of men. Etiology-based treatment options are lacking in most patients and assisted reproductive techniques (ART) are applied with intracytoplasmic sperm injection (ICSI) being the most frequently used. As ICSI includes hormonal stimulation and ovum-pick in the female partner, and also raises some concerns for progeny health, we realise a growing demand to identify treatment options for infertile men. Within the ongoing CRU 326 projects we could identify in oligozoospermic men with unexplained infertility single nucelotide polmorphisms (SNPs) (SNP c.-211G>T in the FSHB gene promotor region) that influence the synthesis and action of the follicle stimulating hormone (FSH), which is the key hormone for spermatogenesis. This FSHB gene region is of crucial importance in the regulation of FSH, as the results of our GWAS study reveal. T-allele carriers display inadequately low FSH serum levels in the presence of low sperm counts in comparison to GG homozygous men, representing a hypogonadotropic hypogonadism with isolated FSH deficieny.
Due to this knowledge we suggest for the next funding period a randomised, prospective, open-label, controlled multicentric interventional study (RCT) based on a pharmacogenetic approach including stratificaton by FSHB -211G>T polymorphism prior to FSH treatment based on our hypothesis that this approach will improve sperm count in infertile men. We aim to proof an efficient treatment in infertile men, therewith reduce the need for ART and increase the chance for spontanous conception.