Genetic aspects of disorders of spermatogenesis

The cause for infertility which affects about 10-15% of all couples may be found in approximately half of the cases in the male partners who usually exhibit reduced sperm counts in the ejaculate (i.e. oligozoospermia or azoospermia). The clinically most relevant genetic causes of spermatogenic failure are chromosomal aberrations including Klinefelter's syndrome and Y chromosomal microdeletions of the AZF loci. Aside from the full clinical picture of cystic fibrosis, mutations in the CFTR gene can cause an isolated obstructive azoospermia without spermatogenic impairment. Genetic investigations should depend on the results of andrological examinations. Chromosomal aberrations are detected more frequently with decreasing sperm counts, where autosomes (e.g. translocations) are predominantly involved in men with oligozoospermia whereas in 10-15% azoospermia is caused by Klinefelter's syndrome. Classical AZF deletions are found only in men with severe oligospermia or azoospermia and have a prognostic value. In contrast to men with AZFc deletions, carriers of complete AZFa and AZFb deletions have virtually no chance for testicular sperm extraction and a testicular biopsy is not advised. Rare cases of male infertility may be caused by specific syndromes or sperm defects (e.g. globozoospermia and disorders of ciliary structure).