The verified and tested system is based on specialized genetic counselling to detect genetic and environmental risk factors at least in the last 3 generations and to indicate further laboratory and clinical examinations. Cytogenetic examination is indicated for the detection of heterochromosomal and autosomal aberrations. In the case of unclear severe oligo- or azoospermia, FISH analysis of ejaculated sperm is recommended together with classical and CASA sperm analysis, accompanied by Y chromosome microdeletion analysis of AZF a, b and c, including the recently introduced Y subdeletion detection within AZFc. The detection of most frequent 38 CFTR gene mutations and variants IVS8(TG)/IVS8(Tn) and 1540 A/G are performed in men with the nonobstructive azoospermia and severe oligospermia. The androgene receptor is analysed to elucidate disorders of sex development, as well as phenotypically unapparent males with XXY (Klinefelter) syndrome. The detection of thrombophilic mutations is important to improve the strategy of early prenatal care, especially if female partner is carrying alleles increasing thrombophilic disposition in developing embryo/fetus, that might endanger reproduction or their prenatal developement. This combined approach of genetic counselling together with genetic testing will allow the precise contribution of genetic factors causing male infertility.