Impact Of Chemotherapeutics And Advanced Testicular Cancer Or Hodgkin Lymphoma On Sperm Deoxyribonucleic Acid Integrity

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Cancer / Oncology;  Fertility
Article Date: 30 Dec 2009 - 0:00 PDT

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UroToday.com - The incidence of testicular cancer (TC) and Hodgkin lymphoma (HL) has increased recently. Although improved chemotherapeutic regimens have augmented survival in men with these malignancies, they are associated with a negative impact on reproductive health, including a decrease in fertilization rate and an increase in embryo loss. Specifically, chemotherapy produces azoospermia or severe oligozoospermia in some cancer patients and may have a negative impact on sperm DNA integrity. Thus, we determined the impact of combination chemotherapy on the quality of newly generated spermatozoa from advanced TC and HL patients. Semen parameters, hormone levels, testis volume and presence of sperm DNA strand breaks (by the alkaline comet assay) were compared in community volunteers (CV, n=11), TC (n=16), and HL (n=16) patients pre- and post-chemotherapy at 6, 12, 18 and 24 months.

Pre-chemotherapy, both cancer groups had poorer semen quality compared to CV. TC patients showed a trend to a decrease in sperm concentration and normal forms (NF), a significant decrease of progressive motility (PM) and significant sperm DNA damage compared to CV; while HL patients had normozoospospermic samples, their spermatozoa also showed significant DNA damage. Six months post-chemotherapy, 67% and 60%, respectively of the TC and HL patients had < 5x106 sperm/ml. Azoospermia was observed in 53% and 40%, while severe oligozoospermia was detected in 44% and 38% of TC and HL patients, respectively. At 24 months, 60% and 57% of TC and HL patients, respectively, were normozoospermic. PM remained significantly lower in TC subjects compared to CV. In contrast, the sperm parameters of HL subjects did not differ from CV. After chemotherapy, PM was significantly lower at every time compared to baseline. PM remained low up to 18 months only in the TC group; in HL patients, PM was similar to CV from 18 months to the end of the study. The percentage of sperm with NF was the parameter least affected by chemotherapy. At 6 months, there was a significant decrease in NF, but from 12 months on NF did not differ from CV. At 24 months, cancer patients had a normal semen analysis outcome.

FSH was significantly higher in the cancer groups compared with CV at 6-12 months post-chemotherapy. LH was significantly elevated only in TC patients after treatment. These hormones remained elevated during the entire follow-up period in these patients. Free testosterone or 17β-estradiol levels in cancer patients did not differ from those from CV.

Cancer patients had significantly elevated sperm DNA damage compared to CV prior to chemotherapy, and at 6 months post-treatment, sperm DNA damage was even higher in comparison to the baseline for each cancer group. The sperm DNA damage remained high in the 18-24 months period.

In this prospective, longitudinal study, we determined semen parameters, hormone levels and sperm DNA damage in patients with either advanced TC or HL prior to and post-chemotherapy. Detrimental effects on sperm DNA integrity were observed in both TC and HL patients even prior to the initiation of chemotherapy. Abnormal sperm DNA may impair the fertilizing ability of these men. As previously reported, there was a recovery of sperm parameters in the 12-24-month period after chemotherapy in both cancer patient groups. However, despite the improvement, or even the normalization of standard semen analysis parameters, sperm DNA damage remained elevated in cancer patients compared to CV. Thus, although spermatogenesis was resumed, the spermatogonial stem cells were affected; consequently, the spermatozoa that were produced may not be normal and may be at risk for the production of an abnormal progeny outcome. In another study, we observed an increase in aneuploidy associated with chemotherapy in spermatozoa from TC and HL patients. These findings, and the increased, persistent DNA damage in spermatozoa from TC and HL patients after chemotherapy reported here, indicate that spermatozoa from chemotherapy-treated cancer survivors may be at a significant risk of adverse reproductive outcomes. Healthcare providers should be aware of these potential risks and provide counseling to these patients on fertility preservation early on in the course of cancer treatment, prior to the initiation of chemotherapy. Moreover, it is of paramount importance to explore new therapeutic strategies to diminish the damage inflicted by the current chemotherapy protocols to male reproduction.

Written by Cristian O'Flaherty, Ph.D., a‡ Barbara F. Hales, Ph.D., a Peter Chan, M.D., b,d and Bernard Robaire, Ph.D.a,b,c,d as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.

Departments of Pharmacology and Therapeuticsa, Urologyb and Obstetrics and Gynecologyc, McGill University and the McGill University Health Centred, Montréal, Québec, Canada. ‡Present affiliation: Department of Urology, McGill University and the McGill University Health Centre, Montréal, Québec, Canada.

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