Exp Clin Endocrinol Diabetes 2015; 123 - OP1_02
DOI: 10.1055/s-0035-1547603

FSHB -211G>T stratification for FSH treatment of male infertility patients: Making the case for a pharmacogenetic approach

A Busch 1, J Gromoll 2, S Kliesch 3, M Zitzmann 4, F Tüttelmann 5
  • 1Centrum für Reproduktionsmedizin und Andrologie, Münster; And; Department of Growth and Reproduction, Rigshospitalet, Copenhagen
  • 2Centrum für Reproduktionsmedizin und Andrologie, Universität Münster; Cera
  • 3Centrum für Reproduktionsmedizin und Andrologie, Universitätsklinikum Münster; Albert-Schweitzer-Campus 1, Gebäude D11; Klinische Andrologie, Centrum für Reproduktionsmedizin und Andrologie, Universitätsklinikum Münster
  • 4Universitätsklinikum Münster; Cera
  • 5Universitätsklinikum Münster; Institut für Humangenetik

[15:40 – 15:50]
Context:

The FSHB -211G>T (rs10835638) single-nucleotide polymorphism (SNP) has previously been identified to be associated with reduced serum FSH levels and downstream reproductive parameters, e.g., sperm concentration/count, in men. Given the negative impact of the minor allele on FSH levels and spermatogenesis, T allele carriers might particularly benefit from FSH treatment. In this study, we asked how many male patients with couple infertility could benefit from FSH treatment with special regard to this predictive marker for constitutively reduced FSH level and subfertility.

Subjects & Methods:

Male patients seeking medical assistance for couple infertility (excluding cancer and Klinefelter patients) at a university-based andrology centre were genotyped for the SNP over a period of 2 years.

Results:

Within 2 years 1085 male patients attended. 424 displayed oligozoospermia of which 213 patients had FSH levels below the upper normal range of 7 U/l. While this subgroup exhibited a trend for a higher T allele frequency compared to the complete study group, TT homozygotes were significantly overrepresented (19.0 vs. 15.6%, p = 0.08 and 4.7 vs. 2.2%, p = 0.04, respectively). T allele carriers in this subgroup displayed significantly lower FSH levels (GG vs. GT+TT, 4.4 ± 1.5 vs. 3.8 ± 1.6 U/l, p = 0.02). 71 patients within the subgroup (6.5% of the study group) were T allele carriers.

Fig. 1

Conclusion:

Previous small studies provided first data that T allele carriers benefit from FSH treatment. Our stratification approach revealed that among the group of idiopathic infertile patients a subgroup 6.5% of men are eligible for FSH treatment. Routine screening for this SNP could lead to the identification of a subgroup among idiopathic infertile men characterized by a secondary hypogonadotropic hypogonadism due to a variant-mediated relative FSH deficiency. Large, randomized controlled trials are needed to provide evidence for this pharmacogenetic approach towards male infertility.