SPERM DNA DAMAGE-INFERTILITY-GENOMIC INSTABILITY

NEW YORK (Reuters Health) Jul 02 - DNA strand breaks in sperm of men who survived childhood cancer may contribute to increased rates of infertility, according to a report in Clinical Cancer Research online June 2nd.

"Childhood cancer survivors (CCS) quite often have impaired fertility due to deranged standard semen parameters, but even those with normal values might have impaired fertility because of high load of DNA damage in the spermatozoa," Dr. Patrik Romerius told Reuters Health in an email. "Therefore, DNA fragmentation index (DFI) analysis should be included in the investigation of infertility in CCS."

An elevated sperm DFI was recently shown to be associated with lower clinical pregnancy rates after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

In their study, Dr. Romerius from Skane University Hospital, Lund, Sweden, and colleagues investigated whether childhood cancer per se and/or different treatment modalities had an impact on sperm DFI in 151 men who had been treated for childhood cancer. A control group of 193 Norwegian men was recruited from the general population.

Sperm DNA integrity was measured for 99 samples from the CCS group and for samples from all the controls.

Average DFI was higher, but not significantly, for CCS than for controls (mean difference, 1.8%, p=0.051), but the risk of having DFI above 20% was 2.2-fold higher in CCS compared with controls (p=0.032).

DFI was significantly higher in CCS treated with surgery than in controls. CCS treated with surgery were 2.7 times as likely as controls to have DFI above 20%.

Results were similar for radiotherapy, with significantly higher DFI and 4.9-fold greater likelihood of DFI above 20% among CCS treated with radiotherapy compared with controls.

In contrast, CCS treated with chemotherapy (or combined radiotherapy and chemotherapy) had significantly lower sperm concentrations than controls, but the groups did not differ in DFI or in the proportion having DFI above 20%.

"These findings have clinical relevance, since DFI, measured with Sperm Chromatin Structure Assay, more than 20% has been shown to be associated with decreased fertility in vivo," Dr. Romerius concluded. "The CCS with the most pronounced increase in DFI did not have decreased sperm concentration; thus these men may have impaired fertility despite having normal (or only moderately deranged) 'traditional' sperm parameters."

Furthermore, the investigators say, "Our data might indicate childhood cancer is associated with genomic instability, and the consequences of possible transmission of sperm DNA damage to the offspring need to be considered."

http://clincancerres.aacrjournals.org/content/early/2010/06/02/1078-0432.CCR-10-0140

Clin Cancer Res 2010.