The combination of ICSI and a sperm chromosome assay provides a useful opportunity to directly investigate relationships between chromosomal aberrations and head morphology, motility or in vitro aging. An increase of aneuploidy was identified in sperm with large heads. Structural chromosome aberrations were frequently found in elongated heads. These types of sperm should therefore be avoided for ICSI and can easily be identified under a microscope. In sperm with normal heads, the chromosomal aberration rate was initially low but increased gradually after removal of the seminal plasma (3.3% to 15.9%); in immotile sperm, the increase of DNA damage was more pronounced (4.5% to 48.1%). Therefore, there are motile and immotile sperm populations in human ejaculates that are potentially vulnerable to in vitro culture conditions. Since these sperm can maintain DNA integrity in the seminal plasma for at least 3 h, and even after cryopreservation, the seminal plasma appears to be an efficient suppressor of DNA damage. We report here our attempts at using ICSI using sperm stored in the seminal plasma (SP-ICSI) to treat infertile patients with normozoospermia and provide data to confirm the safety of this technique. For poor quality semen, SP-ICSI may be more effective in achieving a successful outcome.