Sperm Genomic Integrity by TUNEL Varies Throughout the Male Genital Tract.
To assess sperm chromatin fragmentation (SCF) at different levels of the male genital tract.Ejaculated specimens from consenting male partners were screened for SCF by terminal deoxynucleotidyl dUTP nick-end labeling (TUNEL). Men with ICSI failure and high ejaculated SCF underwent surgery to retrieve spermatozoa from different levels of the male genital tract, which were then reassessed for SCF. Approximately ≥500 spermatozoa were assessed per patient, with a 15% threshold. ICSI results from cycles using spermatozoa from different levels of the male genital tract were compared.Topographical assessment of the male genital tract showed a 20.4±10% SCF in the vas deferens, 15.8±8% in the epididymis, and 11.4±6% in the testis; all lower than the ejaculated controls (32.9±20%; P<0.05). Couples (n=25) who underwent ICSI with surgically retrieved (SR) spermatozoa had lower SCF (P<0.001) and higher implantation, clinical pregnancy, and delivery rates (P<0.01). Couples (n=45) with history of ICSI failure elsewhere with ejaculate were treated solely with SR spermatozoa at our center. Compared to historical cycles, SR spermatozoa had a lower fertilization rate (65%, P<0.05) but enhanced implantation (19.1%), clinical pregnancy (40.0%), and delivery rates (34.3%; P<0.01).For the first time, we demonstrate that SCF increases progressively from the testicle, to the epididymis, vas deferens, and is highest in the ejaculate. Men with high ejaculated SCF can benefit from using SR sperm for IVF/ICSI.