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Hum. Reprod. Advance Access published online on August 5, 2005

Human Reproduction, doi:10.1093/humrep/dei231
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Received December 7, 2004
Revised June 23, 2005
Accepted July 1, 2005

Article

Sperm DNA fragmentation: threshold value in male fertility

M. Sergerie 1, G. Laforest 2, L. Bujan 3, F. Bissonnette 2, and G. Bleau 2*

1 Département d’Obstétrique-Gynécologie, Centre hospitalier de l’Université de Montréal (CHUM) - Hôpital Saint-Luc, Montréal, Québec, Canada; CECOS Midi-Pyrénées, Équipe d’accueil 3694 ‘Fertilité Humaine’ - CHU Paule de Viguier, Toulouse, France; Santé environnementale et santé au travail, Faculté de médecine, Université de Montréal, Montréal, Québec, Canada
2 Département d’Obstétrique-Gynécologie, Centre hospitalier de l’Université de Montréal (CHUM) - Hôpital Saint-Luc, Montréal, Québec, Canada
3 CECOS Midi-Pyrénées, Équipe d’accueil 3694 ‘Fertilité Humaine’ - CHU Paule de Viguier, Toulouse, France

* To whom correspondence should be addressed.
G. Bleau, E-mail: gilles.bleau{at}umontreal.ca


   Abstract

BACKGROUND: The extent of sperm DNA fragmentation, which can be measured by the TUNEL assay, is one of the determinants of male fertility. However, the clinical application of this test to in-vivo situations is difficult owing to the absence of a statistically validated threshold value. METHODS: The aim of this study was to compare the results of TUNEL assay applied to semen samples from men of proven fertility (n = 47) and patients from an infertile population (n = 66), in order to establish a discriminating threshold value. RESULTS: Infertile patients had a higher mean level of DNA fragmentation than men of proven fertility (40.9 ± 14.3% versus 13.1 ± 7.3%, respectively; P < 0.001). The area under the receiver operating characteristics curve was 0.93 for 20% sperm DNA fragmentation. The calculated threshold value for TUNEL assay to distinguish between fertile controls and infertile men was 20%. At this threshold, specificity was 89.4 [95% confidence interval (CI) 83.7-95.1] and sensitivity was 96.9% (95% CI 93.8-100). The positive and negative predictive values of the 20% sperm DNA fragmentation threshold were high: 92.8% (95% CI 87.9-97.5) and 95.5% (95% CI 91.6-99.3), respectively. CONCLUSION: This study demonstrates that sperm DNA fragmentation, as measured by TUNEL assay, is a highly valuable indicator of male fertility.

Keywords: DNA integrity/male infertility/spermatozoa/threshold value/TUNEL.
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