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Diagnostic accuracy of sperm DNA degradation index (DDSi) as a potential noninvasive biomarker to identify men with varicocele-associated infertility

  • Urology - Original Paper
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Abstract

Purpose

Varicocele is a frequent cause of impaired testicular function that has been associated with increased levels of sperm DNA fragmentation (SDF). Sperm with degraded DNA (DDS), as observed using the sperm chromatin dispersion (SCD) test, represent a subpopulation of spermatozoa with extensive DNA and nuclear protein damage. The aim of this work was to determine the usefulness of sperm DNA degradation index (DDSi) as a novel noninvasive biomarker to identify infertile men with varicocele.

Methods

A total of 593 semen samples obtained from men attending infertility clinics were analyzed for SDF and DDS with the SCD test. These samples were classified as: (1) fertile donors; (2) infertile patients with least two failed assisted reproduction cycles; (3) leukocytospermia; (4) Chlamydia trachomatis infection; (5) testicular cancer, and (6) infertile men with varicocele. The DDSi was obtained by determining the proportion of DDS in the whole sperm population presenting with fragmented DNA. The diagnostic accuracy of DDSi was evaluated by correlation coefficient and receiver operating characteristics analyses.

Results

A positive correlation (r ≥ 0.52) was observed between the SDF and the frequency of degraded sperm in all patient groups. The sperm DNA degradation index (DDSi) was at least twice as higher in infertile men with varicocele (mean: 0.54) compared with other clinical conditions and fertile donors (means ranging from 0.02 to 0.21; P < 0.0001). A DDSi ≥ 0.33 identified patients with varicocele with 94 % accuracy.

Conclusion

Although DDS is not pathognomonic of varicocele, the DDSi is a useful noninvasive biomaker to identify infertile individuals with varicocele when examining sperm DNA damage during a routine semen analysis. This finding may alert practitioners and laboratories performing semen analysis that in the presence of an abnormal DDSi it is likely that a given patient has varicocele. It is therefore strongly recommended that such patients be referred to urologists in order to undergo a full andrological examination and be properly counseled.

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References

  1. Saypol DC (1981) Varicocele. J Androl 2:61–71

    Google Scholar 

  2. Hauser R, Paz G, Botchan A, Yogev L, Yavetz H (2001) Varicocele: effect on sperm functions. Hum Reprod Update 7:482–485

    Article  CAS  PubMed  Google Scholar 

  3. Silber SJ (2001) The varicocele dilemma. Hum Reprod Update 7:70–77

    Article  CAS  PubMed  Google Scholar 

  4. Gat Y, Bachar GN, Zukerman Z, Belenky A, Gorenish M (2004) Physical examination may miss the diagnosis of bilateral varicocele: a comparative study of 4 diagnostic modalities. J Urol 172:1414–1417

    Article  PubMed  Google Scholar 

  5. Miyaoka R, Esteves SC (2012) A critical appraisal on the role of varicocele in male infertility. Adv Urol 2012:597495

    Article  PubMed Central  PubMed  Google Scholar 

  6. Esteves SC, Miyaoka R, Agarwal A (2011) An update on the clinical assessment of the infertile male. Clinics 66:691–700

    Article  PubMed Central  PubMed  Google Scholar 

  7. World Health Organization (1992) The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil Steril 57:1289–1293

    Google Scholar 

  8. Esteves SC (2014) Clinical relevance of routine semen analysis and controversies surrounding the 2010 World Health Organization criteria for semen examination. Int Braz J Urol 40:433–453

    Article  Google Scholar 

  9. van der Steeg JW, Steures P, Eijkemans MJ, Habbema JDF, Hompes PG, Kremer JA et al (2011) Role of semen analysis in subfertile couples. Fertil Steril 95:1013–1019

    Article  PubMed  Google Scholar 

  10. Agarwal A, Prabakaran S, Allamaneni S (2006) Relationship between oxidative stress, varicocele and infertility: a meta-analysis. RBM Online 12:630–633

    CAS  PubMed  Google Scholar 

  11. Smith R, Kaune H, Parodi D, Madariaga M, Rios R et al (2006) Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. Hum Reprod 21:986–993

    Article  CAS  PubMed  Google Scholar 

  12. Pasqualotto FF, Sundaram A, Sharma RK, Borges E, Pasqualotto EB et al (2008) Semen quality and oxidative stress scores in fertile and infertile patients with varicocele. Fertil Steril 89:602–607

    Article  PubMed  Google Scholar 

  13. Saleh RA, Agarwal A, Sharma RK, Said TM, Sikka SC et al (2003) Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele. Fertil Steril 80:1431–1436

    Article  PubMed  Google Scholar 

  14. Chen CH, Lee SS, Chen DC, Chien HH, Chen IC et al (2004) Apoptosis and kinematics of ejaculated spermatozoa in patients with varicocele. J Androl 25:348–353

    PubMed  Google Scholar 

  15. Fernández JL, Muriel L, Goyanes V, Segrelles E, Gosálvez J et al (2005) Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion (SCD) test. Fertil Steril 84:833–842

    Article  PubMed  Google Scholar 

  16. Enciso M, Muriel L, Fernández JL, Goyanes V, Segrelles E et al (2006) Infertile men with varicocele show a high relative proportion of sperm cells with more intense nuclear damage level in the population with fragmented DNA, evidenced by the sperm chromatin dispersion (SCD) test. J Androl 27:106–111

    Article  PubMed  Google Scholar 

  17. Gosálvez J, Rodríguez-Predreira M, Mosquera A, López-Fernández C, Esteves SC et al (2014) Characterization of a subpopulation with massive nuclear damage, as recognized with the sperm chromatin dispersion (SCD) test. Andrologia 46:602–609

    Article  PubMed  Google Scholar 

  18. García-Peiró A, Oliver-Bonet M, Navarro J, Abad C, Amengual MJ et al (2012) Differential clustering of sperm subpopulations in infertile males with clinical varicocele and carriers of rearranged genomes. J Androl 33:361–367

    Article  PubMed  Google Scholar 

  19. Gosálvez J, López-Fernández C, Fernández JL (2011) Sperm chromatin dispersion (SCD) test: technical aspects and clinical applications. In: Zini A, Agarwal A (eds) Sperm DNA damage: biological and clinical applications in male infertility and assisted reproduction. Springer, New York, pp 151–170

    Google Scholar 

  20. Zini A, Libman J (2006) Sperm DNA damage: importance in the era of assisted reproduction. Curr Opin Urol 16:428–434

    Article  PubMed  Google Scholar 

  21. Evenson DP, Wixon R (2008) Data analysis of two in vivo fertility studies using Sperm Chromatin Structure Assay-derived DNA fragmentation index vs pregnancy outcome. Fertil Steril 90:1229–1231

    Article  PubMed  Google Scholar 

  22. Bungum M, Bungum L, Giwercman A (2011) Sperm chromatin structure assay (SCSA): a tool in diagnosis and treatment of infertility. Asian J Androl 13:69–75

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Baazeem A, Belzile E, Ciampi A, Dohle G, Jarvi K et al (2011) Varicocele and male factor infertility treatment: a new meta-analysis and review of the role of varicocele repair. Eur Urol 60:796–808

    Article  PubMed  Google Scholar 

  24. Zini A, Azhar R, Baazeem A, Gabriel MS (2011) Effect of microsurgical varicocelectomy on human sperm chromatin and DNA integrity: a prospective trial. Int J Androl 34:14–19

    Article  CAS  PubMed  Google Scholar 

  25. Hamada A, Esteves SC, Agarwal A (2013) Insight into oxidative stress in varicocele-associated male infertility: part 2. Nat Rev Urol 10:26–37

    Article  CAS  PubMed  Google Scholar 

  26. Agarwal A, Deepinder F, Cocuzza M, Agarwal R, Short RA, Sabanegh E et al (2007) Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. Urology 70:532–538

    Article  PubMed  Google Scholar 

  27. Esteves SC, Oliveira FV, Bertolla RP (2010) Clinical outcome of intracytoplasmic sperm injection in infertile men with treated and untreated clinical varicocele. J Urol 184:1442–1446

    Article  PubMed  Google Scholar 

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Acknowledgments

We are grateful to Ms. Paqui Arroyo for technical assistance. This study was partially supported by a Spanish Government research grant BFU2013-44290-R.

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Correspondence to Sandro C. Esteves or José Luis Fernández.

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The authors declare no conflict of interest.

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Esteves, S.C., Gosálvez, J., López-Fernández, C. et al. Diagnostic accuracy of sperm DNA degradation index (DDSi) as a potential noninvasive biomarker to identify men with varicocele-associated infertility. Int Urol Nephrol 47, 1471–1477 (2015). https://doi.org/10.1007/s11255-015-1053-6

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  • DOI: https://doi.org/10.1007/s11255-015-1053-6

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