Long-term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
Por:
Farnetani G., Fino M.G., Cioppi F., Riera-Escamilla A., Tamburrino L., Vannucci M., Rosta V., Vinci S., Casamonti E., Turki L., Degl'Innocenti S., Spinelli M., Marchiani S., Lotti F., Muratori M., Krausz C.
Publicada:
29 mar 2023
Ahead of Print:
1 mar 2023
Resumen:
IntroductionTesticular germ cell tumor is the most frequent neoplasia in men of reproductive age, with a 5-year survival rate of 95%. Antineoplastic treatments induce sperm DNA fragmentation, especially within the first year post-therapy. Data in the literature are heterogeneous concerning longer follow-up periods, and the large majority is limited to 2 years. ObjectiveTo define the timing for the recovery of sperm DNA damage and the proportion of patients with severe DNA damage at 2 and 3 years from the end of therapy. Materials and methodsSperm DNA fragmentation was evaluated in 115 testicular germ cell tumor patients using terminal deoxynucleotidyl transferase dUTP nick end labeling assay coupled with flow cytometry before (T-0) and 2 (T-2) and 3 (T-3) years post-treatment. Patients were divided based on the type of treatment: carboplatin, bleomycin-etoposide-cisplatin, and radiotherapy. For 24 patients, paired sperm DNA fragmentation data were available at all time-points (T-0-T-2-T-3). Seventy-nine cancer-free, fertile normozoospermic men served as controls. Severe DNA damage was defined as the 95th percentile in controls (sperm DNA fragmentation = 50%). ResultsComparing patients versus controls, we observed: (i) no differences at T-0 and T-3 and (ii) significantly higher sperm DNA fragmentation levels (p < 0.05) at T-2 in all treatment groups. Comparing pre- and post-therapy in the 115 patients, the median sperm DNA fragmentation values were higher in all groups at T-2, reaching significance (p < 0.05) only in the carboplatin group. While the median sperm DNA fragmentation values were also higher in the strictly paired cohort at T-2, about 50% of patients returned to baseline. The proportion of severe DNA damage in the entire cohort was 23.4% and 4.8% of patients at T-2 and T-3, respectively. DiscussionCurrently, testicular germ cell tumor patients are advised to wait 2 years post-therapy before seeking natural pregnancy. Our results suggest that this period may not be sufficient for all patients. ConclusionThe analysis of sperm DNA fragmentation may represent a useful biomarker for pre-conception counseling following cancer treatment.
Filiaciones:
Farnetani G.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Fino M.G.:
Univ Hosp Careggi AOUC, Florence, Italy
Cioppi F.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Univ Florence, Dept Expt & Clin Med, Florence, Italy
Riera-Escamilla A.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Univ Autonoma Barcelona, Dept Androl, Fundacio Puigvert, Inst Invest Biomed St Pau IIB St Pau, Barcelona, Catalonia, Spain
Tamburrino L.:
Univ Florence, Dept Expt & Clin Med, Florence, Italy
Vannucci M.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Univ Hosp Careggi AOUC, Florence, Italy
Rosta V.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Vinci S.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Casamonti E.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Turki L.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Degl'Innocenti S.:
Univ Hosp Careggi AOUC, Florence, Italy
Spinelli M.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Marchiani S.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Lotti F.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Univ Hosp Careggi AOUC, Florence, Italy
Muratori M.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Krausz C.:
Univ Florence, Dept Clin & Expt Biomed Sci Mario Serio, Florence, Italy
Univ Hosp Careggi AOUC, Florence, Italy
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