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A reduction in recombination in the pseudoautosomal region is associated with an increased frequency of aneuploid 24,XY human sperm. Similarly, individuals with paternally derived Klinefelter syndrome (47,XXY) also have a paucity of recombination in the chromosomes that have undergone nondisjunction. Meiotic studies using newly developed immunocytogenetic techniques have demonstrated errors of chromosome synapsis and significantly reduced recombination in infertile men with nonobstructive azoospermia. These men have an increased risk of aneuploidy in sperm that have been surgically removed from the testes. Thus, evidence is starting to accumulate that reduced recombination has a marked effect on the generation of aneuploid sperm.

Sperm karyotype analysis was performed on testicular cancer patients before and after treatment with BEP (bleomycin, etoposide, and cisplatin). A total of 788 sperm chromosome complements was studied, 236 before chemotherapy (CT) and 552 post-CT. There was no significant difference in the total frequency of sperm chromosomal abnormalities pre-CT (10.2%) compared to post-CT (10.7 %). Similarly, there were no significant differences in the frequencies of numerical abnormalities (2.5% pre-CT vs. 2.4% post-CT) or structural abnormalities (6.4% pre-CT vs. 7.4% post-CT). The percentage of X-bearing sperm was also not significantly different before (46.3%) and after CT (50.1%). The results in cancer patients were not significantly different from those in control donors. This study corroborates results from our previous analysis of these same men using multicolor fluorescence in situ hybridization for assessment of aneuploidy for chromosomes 1, 12, X, Y, and XY. Together, these two studies suggest that the sperm of men receiving BEP chemotherapy are not at increased risk of chromosomal abnormalities two or more years after treatment.

Acrocentric chromosomes may be particularly predisposed to nondisjunction because of the frequency of trisomy for these chromosomes in human spontaneous abortions and liveborns. Studies of aneuploidy in human sperm have provided data on only a few acrocentric chromosomes, with evidence that chromosome 21 has a significantly increased frequency of disomy. To determine whether other acrocentric chromosomes have a higher frequency of nondisjunction or if chromosome 21 is anomalous, disomy frequencies for chromosomes 13 and 22 were studied by fluorescence in situ hybridization (FISH) analysis of 51,043 sperm nuclei from five normal men for whom the frequency of disomy for chromosomes 15 and 21 was known. The mean frequency of disomy for chromosome 13 (0.19%) did not differ significantly from that for other autosomes; however, the frequency of disomy 22 (1.21%) was significantly elevated (P < 0.001, Mantel-Haenszel χ2 test). The G-group chromosomes (Nos. 21 and 22) also showed a significantly increased frequency of disomy (0.75%) compared to acrocentric D-group chromosomes (viz., chromosomes 13 and 15; 0.15%) (P < 0.001, Mantel-Haenszel χ2 test) and other autosomes (chromosomes 1, 2, 4, 9, 12, 13, 15, 16, 18, and 20; 0.13%) studied in the same men (P < 0.001, Mantel-Haenszel χ2 test).