Current limitation and future perspective of sperm DNA fragmentation tests

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. The commentary by Drs. Garrido, Rivera and Luján (1), in response to the practice recommendations by Agarwal et al. (2), is a valuable addition to the debate on sperm DNA fragmentation (SDF). We want to supplement their information as well as provide our opinion on several important points raised by the authors. The authors (Garrido et al.) raised concern on the possible negative consequences of sperm DNA damage by stating that “...damaged DNA in sperm could lead to worse reproductive results or mid-long term health problems in offspring, given that this is the way genetic information is delivered to the next generation” (1). We certainly concur with their concern but, as opposed to the authors’ view, we believe that the current evidence is not reassuring. Although it is well known that intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of male infertility and allowed the most severe form of male factors to be bypassed, however, animal studies have provided unequivocal result that sperm DNA damage leads to deleterious effect on offspring (3-5). ICSI with DNAfragmented sperm in mouse can result in premature ageing, aberrant growth, and increased incidence of tumors in the offspring (6).The possible link between SDF and defects in human offsprings is best illustrated by the effect of smoking and paternal age. Heavy smokers have higher levels of SDF (7) and this may correspond to the higher incidence of childhood cancer in the offspring of heavy smokers (8,9). Impaired sperm DNA integrity is also associated with advanced paternal age (10). The advanced paternal age has been linked to dominant genetic diseases (11), schizophrenia (12), and birth defects (13). Despite this evidence, the relationship between SDF and genetic defect can only be fully answered by longitudinal studies with sufficient samples and duration. It is definitely too early to conclude the safety of ICSI since it was introduced into clinical practice only three decades ago. The unknown and potentially lethal consequence of passing aberrant genetic information to the next generation should be taken seriously. Correction of SDF before recommending assisted reproductive technologies (ART) should be the preferred approach as far as possible. The presence of oocyte repair machinery for sperm DNA damage may serve as another safety check to avoid passage of defective genetic information. However, not all types of sperm DNA break, for example, extensive double stranded DNA breaks, are repairable (14). Irradiated sperm with DNA damage was shown to retain the ability to fertilize the oocyte, but the embryonic development was significantly affected in a dose-response fashion. The oocyte has the ability to repair sperm DNA damage of less than 8% (15). Even though there is a lack of human data at this time, animal studies show that female mice with defective DNA double-stranded break repair had increased frequencies of zygotes with sperm-derived chromosomal aberrations when fertilized by sperm with irradiation-induced double-stranded DNA breaks. The chromosome-type aberration, which affect both sister chromatids, resulted in high embryonic lethality (16). It is suggested that good oocyte quality may overcome the negative impact of high SDF (17). Results of a retrospective clinical study showed that the live-birth and Editorial