Sperm Genomic Integrity by TUNEL Varies throughout the Male Genital Tract

We assessed sperm chromatin fragmentation at different levels of the male genital tract.

Ejaculated specimens from consenting male partners were screened for sperm chromatin fragmentation by TUNEL (terminal deoxynucleotidyl deoxyuridine triphosphate nick end labeling). Men with intracytoplasmic sperm injection failure and high ejaculated sperm chromatin fragmentation underwent surgery to retrieve spermatozoa from different levels of the male genital tract, which were then reassessed for sperm chromatin fragmentation. Approximately 500 or more spermatozoa were assessed per patient with a 15% threshold. Intracytoplasmic sperm injection results of cycles using spermatozoa from different levels of the male genital tract were compared.

Topographical assessment of the male genital tract showed a mean ± SD of 20.4% ± 10% sperm chromatin fragmentation in the vas deferens, 15.8% ± 8% in the epididymis and 11.4% ± 6% in the testis. All values were lower than in ejaculated controls (mean 32.9% ± 20%, p <0.05). A total of 25 couples who underwent intracytoplasmic sperm injection with surgically retrieved spermatozoa had lower sperm chromatin fragmentation (p <0.001), and higher implantation, clinical pregnancy and delivery rates (p <0.01). A total of 45 couples with a history of intracytoplasmic sperm injection failure with ejaculate performed elsewhere were treated solely with surgically retrieved spermatozoa at our center. Compared to historical cycles, surgically retrieved spermatozoa had a lower fertilization rate (65%, p <0.05) but enhanced rates of implantation (19.1%), clinical pregnancy (40.0%) and delivery (34.3%) (each p <0.01).

To our knowledge we report for the first time that sperm chromatin fragmentation increases progressively from the testicle to the epididymis and the vas deferens, and is highest in the ejaculate. Men with high ejaculated sperm chromatin fragmentation can benefit from using surgically retrieved sperm for in vitro fertilization and/or intracytoplasmic sperm injection.