Background: Macrocephalic or large headed sperm with multiflagella is a rare abnormality often associated with infertility. Sperm chromosomal abnormalities could be associated with this specific morphological abnormality.
Methods: The cytogenetic content of large-headed sperm was assessed by dual and three-colour fluorescence in-situ hybridization in three patients carrying this specific morphological abnormality.
Results: In all patients nearly all sperm contained at least one copy of each sex chromosome, and in more than half of them at least two copies of either chromosome 1 or 18 were identified. In some sperm a tetraploidy was found.
Conclusions: These observations suggested that both meiotic I and II divisions were affected by incomplete partition of homologous chromosomes during meiosis I and of sister chromatids during meiosis II associated with a failure of nuclear cleavage. Furthermore, they provide evidence for a clear relationship between a specific morphological abnormality of the sperm and their abnormal cytogenetic content. The treatment of infertility using ICSI would probably be unsuccessful and have a high genetic risk in these cases.