Analysis of sperm aneuploidy in infertile subjects after chemotherapy treatment

The continuing search for a cure for cancer has developed more aggressive therapies that may damage germ cells, leading to clinical disease in offspring of survivors. Standard therapy for the majority of cancer today consists in combinations of high doses of radiation and chemotherapy drugs. We investigated the effect of cancer treatments on the reproductive potential of men. Multicolor fluorescence in situ hybridization has been used to recognize chromosomes X, Y and 8 in sperm of 10 severely oligozoospermic subjects (sperm concentration < 5,000,000/mL) treated for cancer at least 5 years before the beginning of this study. As controls, we analyzed sperm aneuploidies in 20 fertile men (sperm concentration > 20,000,000/mL) and in 20 severe idiopathic oligozoospermic subjects (sperm concentration < 5,000,000/mL). In all subjects, X- and Y-bearing spermatozoa were present in a normal 1:1 ratio; nevertheless the frequency of 24,XY, 24,XX and 24,YY disomic sperm was significantly higher in patients treated for cancer and in idiopathic oligozoospermic subjects with respect to normozoospermic men. These results suggest that the increase in sperm aneuploidies in treated patients cannot be reported directly to precedent chemotherapy, but reflects the alteration of testicular structure, as in the case of severe idiopathic oligozoospermic subjects. With the advent of intra-cytoplasmic sperm injection, it is possible to offer the opportunity to conceive in men affected by severe oligozoospermia but it is also possible, when the spermatozoa of these subjects are used, to pass sex chromosome abnormalities on to the children. We therefore suggest caution before application of an artificial reproductive technique in severe oligozoospermic patients.