The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment.
Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract, the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency. Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. With all of these fertility check points, it shows more promise than conventional semen parameters from a diagnostic perspective. Despite this, few infertility clinics use it routinely. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the strengths and weaknesses and clinical applicability of current sperm DNA fragmentation tests. Next, the biological significance of DNA damage in the male germ line is considered. Finally, as sperm DNA damage is often the result of increased oxidative stress in the male reproductive tract, the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. As those working in this field of clinical research, we conclude that DNA damage in human spermatozoa is an important attribute of semen quality which should be carefully assessed in the clinical work up of infertile couples and that properly controlled trials addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency.
Centre for Public Health, Institute of Clinical Sciences, Queen's University Belfast, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK. Electronic address: s.e.lewis@qub.ac.uk.
Sheena E M
SE
Lewis
R
R
John Aitken
Sarah J
SJ
Conner
Geoffry De
GD
Iuliis
Donald P
DP
Evenson
Ralph
R
Henkel
Aleksander
A
Giwercman
Parviz
P
Gharagozloo
D000975:Antioxidants / Q000627:therapeutic use; D015415:Biomarkers; D002843:Chromatin / Q000648:ultrastructure; D020552:Comet Assay; D018736:DNA Adducts; D004249:DNA Damage; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D008297:Male; D011247:Pregnancy; D055101:Semen Analysis; D013094:Spermatozoa / Q000502:physiology* / Q000648:ultrastructure
D000975:Antioxidants; D015415:Biomarkers; D002843:Chromatin; D018736:DNA Adducts
DNA fragmentation; Male infertility; antioxidant therapy; assisted reproduction; oxidized bases; spermatozoa