Aneuploidy and chromosome breakage in swim-up versus unprocessed semen from twenty healthy men

Toxicological and epidemiological studies have investigated several factors that are believed to induce cytogenetic damage in human sperm cells in an effort to estimate heritable risk to future generations. Most of these studies have not differentiated damage based on cell fertility or motility. In the clinical setting, intracytoplasmic sperm injection (ICSI) bypasses the natural process of sperm selection. Although practitioners attempt to select motile sperm for ICSI, the sperm may not always demonstrate motility, maturity, or even viability. Knowing whether cytogenetic damage differs in motile versus unselected sperm would improve our ability to estimate heritable risk and lead to improved ICSI procedures, and would expand the body of toxicology and epidemiology research. We divided semen samples from 20 healthy donors and compared aneuploidy and chromosome breakage in sperm cells gathered directly from the ejaculate (unprocessed semen) with cells enriched for motility using the swim-up assay. Sperm fluorescence in situ hybridization was used to detect aneuploidy for chromosomes 13, 18, 21, X, and Y. Tandem labeling probes were used to detect breakage in the 1cen-1q12 region of chromosome 1. The occurrence of disomy 18-18 and XY18 was significantly lower in specimens enriched for motility (P = .004 and P = .001, respectively). Sperm that carried duplication errors and diploid sperm were also seen less frequently in semen analyzed by the swim-up assay (P < .008). Chromosome 1 breakage did not differ between swim up-assayed and unprocessed specimens. Findings suggest that unprocessed semen may overestimate heritable aneuploidy risk in sperm biomarker studies, and may be biologically relevant to ICSI in disomy categories 18-18 and XY18, demonstrating 1.4-fold to 1.8-fold differences.