title: DNA fragmentation in brighter sperm predicts male fertility independently from age and semen parameters.
abstract: OBJECTIVE
  To evaluate whether sperm DNA fragmentation (sDF), measured in brighter, dimmer, and total populations, predicts natural conception, and to evaluate the intra-individual variability of sDF.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Outpatient clinic and diagnostic laboratory.
  
  
  METHODS
  A total of 348 unselected patients and 86 proven fertile men.
  
  
  METHODS
  None.
  
  
  METHODS
  sDF was revealed with the use of terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)/propidium iodide (PI). Receiver operating characteristic (ROC) curves were built before and after matching fertile men to patients for age (76:152) or semen parameters (68:136) or both (49:98). Intra-individual variability of sDF was assessed over 2 years.
  
  
  RESULTS
  Brighter (area under ROC curve [AUC] 0.718 ± 0.54), dimmer (AUC 0.655 ± 0.63), and total (AUC 0.757 ± 0.54) sDF predict male fertility in unmatched and age- or semen parameters-matched subjects. After matching for both age and semen parameters, only brighter (AUC 0.711 ± 0.83) and total (AUC 0.675 ± 0.92) sDF predict male fertility. At high values of total sDF, brighter predicts natural conception better than total sDF. Intra-individual coefficients of variation of sDF were 9.2 ± 8.6% (n = 25), 12.9 ± 12.7% (n = 53), and 14.0 ± 12.6% (n = 70) over, respectively, 100-day and 1- and 2-year periods, appearing to be the most stable of the evaluated semen parameters.
  
  
  CONCLUSIONS
  The predictive power of total sDF partially depends on age and semen parameters, whereas brighter sDF independently predicts natural conception. Therefore, brighter sDF is a fraction of sDF that adds new information to the routine semen analysis. At high levels of sDF, distinguishing the two sperm populations improves the predictive power of sDF. Overall, our results support the idea that TUNEL/PI can be of clinical usefulness in the male fertility workup.
authors.affiliation: Department of Experimental, Clinical and Biomedical Sciences, DeNoth Center of Excellence, University of Florence, Florence, Italy. Electronic address: monica.muratori@unifi.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Muratori
authors.affiliation: Department of Experimental, Clinical and Biomedical Sciences, DeNoth Center of Excellence, University of Florence, Florence, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Marchiani
authors.affiliation: Department of Experimental, Clinical and Biomedical Sciences, DeNoth Center of Excellence, University of Florence, Florence, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Tamburrino
authors.affiliation: Department of Experimental, Clinical and Biomedical Sciences, DeNoth Center of Excellence, University of Florence, Florence, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Cambi
authors.affiliation: Department of Experimental, Clinical and Biomedical Sciences, DeNoth Center of Excellence, University of Florence, Florence, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lotti
authors.affiliation: Seminology Laboratory, Azienda USL3 Pistoia, Pistoia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Natali
authors.affiliation: Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors.forename: Erminio
authors.initials: E
authors.lastname: Filimberti
authors.affiliation: Department of Experimental, Clinical and Biomedical Sciences, DeNoth Center of Excellence, University of Florence, Florence, Italy.
authors.forename: Ivo
authors.initials: I
authors.lastname: Noci
authors.affiliation: Department of Experimental, Clinical and Biomedical Sciences, DeNoth Center of Excellence, University of Florence, Florence, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Forti
authors.affiliation: Department of Experimental, Clinical and Biomedical Sciences, DeNoth Center of Excellence, University of Florence, Florence, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Maggi
authors.affiliation: Department of Experimental, Clinical and Biomedical Sciences, DeNoth Center of Excellence, University of Florence, Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Baldi
mesh_terms: D000328:Adult; D019540:Area Under Curve; D016022:Case-Control Studies; D053938:DNA Fragmentation; D005298:Fertility; D006801:Humans; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010331:Paternal Age; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D012307:Risk Factors; D013076:Sperm Count; D013081:Sperm Motility; D013094:Spermatozoa / Q000473:pathology*
keywords: Sperm DNA fragmentation; TUNEL/PI; male fertility; natural conception