Long‐term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor

Medientyp: E-Artikel
Titel: Long‐term effect of cytotoxic treatments on sperm DNA fragmentation in patients affected by testicular germ cell tumor
Beteiligte: Farnetani, Ginevra; Fino, Maria Grazia; Cioppi, Francesca; Riera‐Escamilla, Antoni; Tamburrino, Lara; Vannucci, Matteo; Rosta, Viktoria; Vinci, Serena; Casamonti, Elena; Turki, Leila; Degl'Innocenti, Selene; Spinelli, Matilde; Marchiani, Sara; Lotti, Francesco; Muratori, Monica; Krausz, Csilla
Erschienen: Wiley, 2023
Erschienen in: Andrology
Sprache: Englisch
DOI: 10.1111/andr.13429
ISSN: 2047-2919; 2047-2927
Schlagwörter: Urology ; Endocrinology ; Reproductive Medicine ; Endocrinology, Diabetes and Metabolism
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Testicular 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.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To 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.</jats:p></jats:sec><jats:sec><jats:title>Materials and methods</jats:title><jats:p>Sperm 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 (<jats:italic>T</jats:italic><jats:sub>0</jats:sub>) and 2 (<jats:italic>T</jats:italic><jats:sub>2</jats:sub>) and 3 (<jats:italic>T</jats:italic><jats:sub>3</jats:sub>) 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 (<jats:italic>T</jats:italic><jats:sub>0</jats:sub>–<jats:italic>T</jats:italic><jats:sub>2</jats:sub>–<jats:italic>T</jats:italic><jats:sub>3</jats:sub>). 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%).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Comparing patients versus controls, we observed: (i) no differences at <jats:italic>T</jats:italic><jats:sub>0</jats:sub> and <jats:italic>T</jats:italic><jats:sub>3</jats:sub> and (ii) significantly higher sperm DNA fragmentation levels (<jats:italic>p</jats:italic> < 0.05) at <jats:italic>T</jats:italic><jats:sub>2</jats:sub> 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 <jats:italic>T</jats:italic><jats:sub>2</jats:sub>, reaching significance (<jats:italic>p</jats:italic> < 0.05) only in the carboplatin group. While the median sperm DNA fragmentation values were also higher in the strictly paired cohort at <jats:italic>T</jats:italic><jats:sub>2</jats:sub>, 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 <jats:italic>T</jats:italic><jats:sub>2</jats:sub> and <jats:italic>T</jats:italic><jats:sub>3</jats:sub>, respectively.</jats:p></jats:sec><jats:sec><jats:title>Discussion</jats:title><jats:p>Currently, 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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The analysis of sperm DNA fragmentation may represent a useful biomarker for pre‐conception counseling following cancer treatment.</jats:p></jats:sec>

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