Sperm integrity pre- and post-chemotherapy in men with testicular germ cell cancer.
BACKGROUND
While (partial) recovery of spermatogenesis, observed by means of standard semen analysis, has been seen in testicular cancer patients after chemotherapy with cisplatin, sperm genomic integrity and its implication for the patient's fertility are poorly understood.


METHODS
Semen and serum from 22 patients treated for testicular cancer were analysed pre- and post-chemotherapy. Besides routine semen analysis, sperm samples were evaluated by computerized karyometric image analysis (CKIA), chromomycin-A3 assay (CMA3, chromatin condensation) and TdT-mediated dUTP nick-end labelling assay (TUNEL, DNA damage). Serum FSH, LH and testosterone concentrations were measured.


RESULTS
Ejaculate volume decreased post-chemotherapy (P<0.05). External sperm characteristics (CKIA morphometry) and sperm counts did not deteriorate after chemotherapy. An improvement in DNA condensation was assessed after chemotherapy (37 versus 50% and 47.5 versus 63.7% for CMA3 and CKIA respectively; both P<0.005); yet a high percentage of TUNEL-positive sperm was found in the samples (21 versus 25% for pre- and post-chemotherapy samples respectively). These values were significantly higher than those of a convenience sample of normozoospermic males attending pre-IVF screening. Serum FSH and LH (IU/l) increased after chemotherapy compared with pretreatment levels (8.1 versus 16.7 and 4.5 vs 6.8; both P<0.05, respectively).


CONCLUSIONS
Despite the improvement in sperm chromatin packaging after chemotherapy, an abnormally high percentage of DNA-damaged sperm was found in these samples. As sperm quality does not reach normal levels after treatment, it remains difficult to outline the best strategy and guidance concerning fertility potential of testicular cancer patients.
Spermon
J R
JR
Department of Urology, Radboud University Nijmegen Medical Centre, The Netherlands. spermon@hotmail.com
Ramos
L
L
Wetzels
A M M
AM
Sweep
C G J
CG
Braat
D D M
DD
Kiemeney
L A L M
LA
Witjes
J A
JA
D000328:Adult; D001761:Bleomycin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000627:therapeutic use; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D020287:In Situ Nick-End Labeling; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000503:physiopathology*; D012661:Semen / Q000737:chemistry; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects; D013094:Spermatozoa / Q000166:cytology* / Q000187:drug effects; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D013739:Testosterone / Q000097:blood
D001761:Bleomycin; D013739:Testosterone; C025703:bleomycetin; D005047:Etoposide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002945:Cisplatin