couples in whom the man has a high percentage of spermatozoa with DNA damage have very low potential for natural fertility, and will have to wait a long time before conceiving.Couples whose pregnancy resulted in miscarriage demonstrate a trend toward poorer sperm DNA integrity compared with highly fertile couples.With the advent of IVF and intracytoplasmic sperm injection, the concern over using damaged DNA has become apparent.Human spermatozoa that bind to oviduct cells have better DNA integrity than spermatozoa that do not bind to these cells, which suggests that nature can select spermatozoa with enhanced DNA integrity during natural fertilization.Numerous studies have examined the possible influence of sperm DNA integrity on reproductive outcomes after both standard IVF and IVFICSI. There is no consistent relation between sperm DNA damage and fertilization rates during IVF or IVFICSI.Neither fertilization nor early embryo development is dependent on sperm DNA integrity, since the embryonic genome is not expressed until after the second cleavage division. There is also no consistent relation between sperm DNA damage and embryo quality after ICSI. However, high levels of sperm DNA damage are inversely related to pregnancy rates in most, but not all, studies.This is probably because the stringent process of sperm and embryo selection during ICSI will mitigate the potential adverse effects of sperm DNA damage on reproductive outcomes.It is now known that IVFICSI is associated with an increased risk of birth defects and genetic and epigenetic abnormalities in the child.To date, it is unclear whether it is the ICSI procedure or the underlying infertility that is responsible for these defects.Clearly, the understanding that sperm DNA damage is common in infertile men, together with the concerning preliminary reports on genetic and epigenetic abnormalities in children conceived through ICSI, urge us to explore the subject of sperm DNA damage further.DNA that possesses measurable damage may cause misreading errors to occur during DNA replication, and this might cause de novo mutations.For example, studies have found that children of fathers who smoked cigarettes preconceptually have a higher risk of childhood cancers than do children of nonsmoking fathers.These studies suggest that there may be a link between sperm DNA damage and the subsequent development of childhood diseases.There appears to be a threshold of sperm DNA damage beyond which embryo development and subsequent pregnancy outcome are impa ired. Clinical evidence now shows that sperm DNA damage is detrimental to reproductive outcomes and that the spermatozoa of infertile men possess substantially more DNA damage than do the spermatozoa of fertile men.However, our understanding of the causes of sperm DNA damage and the full impact of this sperm defect on reproductive outcomes in humans remains rudimentary.DNA integrity in human spermatozoa: relationships with semen quality.Armand Zini, Rm, St. Marys Hospital, Lacombe Ave, reasch Phloretin Montral QC HTM; fax; armand.zinissss.gouv.qc.ca CMAJ August, There is an urgent need to develop new and more effective therapeutic strategies to combat these devastating diseases.Models from cellbased systems, to unicellular organisms, to complex animals have proven to be a useful tool to help the research community shed light on the mechanisms underlying neurodegenerative diseases, and these advances have now begun to provide promising therapeutic avenues.