Human Reproduction, Vol. 15, No. 4, 762-766,
April 2000
© 2000 European Society of Human Reproduction and Embryology
Testicular and sperm DNA damage after treatment with fludarabine for chronic lymphocytic leukaemia
1 Departments of Obstetrics and Gynaecology and 2 Haematology, University College Hospital, London WC1E 6AU, and 3 Division of Physiology, Pharmacology and Toxicology, School of Biological Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK
This study investigated whether chemotherapy using fludarabine (FLU) caused testicular damage and if cytotoxicity could be detected as sperm DNA damage in the single cell Comet assay. A patient with chronic lymphocytic leukaemia requesting preservation of fertility was treated with seven monthly cycles of fludarabine (45.8 mg total dose per cycle). Testicular assessments, serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone measurements, semen analysis and sperm Comet assays were carried out at presentation (pre-FLU therapy), after 1 and 7 months of FLU treatment, and finally at 11 months after completion of chemotherapy. We found that testicular damage occurred within a month, as indicated by reduced testicular volume, oligozoospermia, elevated FSH and LH, and lower testosterone concentrations. Spermatozoa with a large range of DNA damage were detected in the samples from both the control and treated men. DNA damage in the spermatozoa was marked by 7 months of FLU treatment. The high levels of sperm DNA damage seen during and possibly persisting after treatment suggests that caution should be exercised if the ejaculates from these men are used for in-vitro fertility treatment. Further experiments are needed to assess the biological significance of these DNA changes; it may, however, be prudent at present to be cautious when counselling these patients.
Key words: chemotherapy/Comet assay/DNA damage/fertility/spermatozoa
4 To whom correspondence should be addressed at: Obstetric Hospital, Reproductive Medicine Unit (OH2), Huntley Street, London WC1E 6AU, UK
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