SPERM DNA DAMAGE RATE AMONG INFERTILE PATIENTS WITH VARICOCELE
Keywords:
Infertility, SDI, Sperm DNA, Varicocele
Abstract
https://doi.org/10.31386/dmj.2022.16.2.9
Background: Varicocele has a common association with male hypofertility. The prevalence of clinical varicocele is about 15% among adults and adolescents. varicocele patients are at risk of infertility. Sperm deoxyribonucleic acid (DNA) fragmentation rate (SDFR) is considered a major factor in decreased fertilization ability in males with varicocele. Varicocele increases SDFR through heat stress, increased reactive oxygen species, and reduction in the level of total antioxidants.
Objectives: To study the rate of sperm DNA fragmentation in patients with different grades of varicocele.
Patients and methods: A prospective, case-control study was conducted at Azadi Teaching hospital in Duhok city / Iraq from March 2020 to December 2021. The study included 34 infertile patients with varicocele of different grades and 30 infertile patients without varicocele. Seminal fluid analysis was performed followed by sperm DNA analysis by Alkaline Comet Assay. The obtained data were analyzed using a Prism-GraphPad to compare the mean of parameters in patients and control subjects.
Results: Sixty-four infertile patients were included. The mean of sperm immobility and abnormal morphology rates were statistically higher in infertile patients with varicocele compared with those without varicocele (39.56±12.63 Vs 28.07±4.541) and (51.59±23.00 Vs 34.79±15.72) respectively, (P<0.0001).The fluorescence microscopic images of sperm DNA of infertile patients with varicocele showed a clear migration to DNA tail (DNA damage) compared with sperm DNA of those without varicocele (8.195 ± 0.3799 Vs. 4.794 ± 0.2186) respectively (P<0.0001).The degree of sperm DNA damage was directly related to the degree of varicocele and was significant (P<0.0001).
Conclusion: Sperm DNA damage rate was higher in infertile male patients with varicocele in comparison to those without varicocele and directly related to the grade of varicocele.
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References
REFERENCES
1. Jensen CF, Østergren P, Dupree JM, Ohl DA, Sønksen J, Fode M Varicocele and male infertility. Nat Rev Urol. 2017;14(9):523-33. https://www.nature.com/articles/nrurol.2017.98
2. Alsaikhan B, Alrabeeah K, Delouya G, Zini A. Epidemiology of varicocele. Asian J Androl. 2016;18(2):179. https://www.ajandrology.com/article.asp?issn=1008682X;year=2016;volume=18;issue=2;spage=179;epage=181;aulast=Alsaikhan
3. Clavijo RI, Carrasquillo R, Ramasamy R. Varicoceles: prevalence and pathogenesis in adult men. Fertil Steril. 2017;108(3):364-9. https://www.fertstert.org/article/S0015-0282(17)30495-8/fulltext
4. Su JS, Farber NJ, Vij SC. Pathophysiology and treatment options of varicocele: An overview. Andrologia. 2021;53(1):e13576. 10.1111/and.13576
5. Asafu-Adjei D, Judge C, Deibert CM, Li G, Stember D, Stahl PJ. Systematic review of the impact of varicocele grade on response to surgical management. J Urol. 2020;203(1):48-56.https://doi.org/10.1097/JU.0000000000000311
6. Vivas-Acevedo G, Lozano JR, Camejo MI. Effect of varicocele grade and age on seminal parameters. Urol Int. 2010;85(2):194-9. https://pubmed.ncbi.nlm.nih.gov/20424431/
7. Wang YJ, Zhang RQ, Lin YJ, Zhang RG, Zhang WL. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Reprod Biomed online. 2012;25(3):307-14.https://www.rbmojournal.com/article/S1472-6483(12)00324-0/fulltext
8. Agarwal A, Majzoub A, Baskaran S, Selvam MK, Cho CL, Henkel R, Finelli R, Leisegang K, Sengupta P, Barbarosie C, Parekh N. Sperm DNA fragmentation: a new guideline for clinicians. World JMen’s Health. 2020;38(4):412.https://wjmh.org/DOIx.php?id=10.5534/wjmh.200128
9. Wright C, Milne S, Leeson H. Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility. Reprod BiomedOnline. 2014;28(6):684-703.https://pubmed.ncbi.nlm.nih.gov/24745838/
10. Leach M, Aitken RJ, Sacks G. Sperm DNA fragmentation abnormalities in men from couples with a history of recurrent miscarriage. Aust N Z J Obstet Gynecol. 2015;55(4):379-83.https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1111/ajo.12373
11. Hauser R, Paz G, Botchan A, Yogev L, Yavetz H. Varicocele and male infertility: part II: varicocele: effect on sperm functions. Hum ReprodUpdate. 2001;7(5):482-5. https://academic.oup.com/humupd/article/7/5/482/651191
12. Amann RP. Can the fertility potential of a seminal sample be predicted accurately?J Androl. 1989;10(2):89-98. https://onlinelibrary.wiley.com/doi/10.1002/j.1939-4640.1989.tb00066.x
13. Duru NK, Morshedi M, Oehninger S. Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril. 2000;74(6):1200-7. https://www.fertstert.org/article/S0015-0282(00)01591-0/fulltext
14. Chen SS, Huang WJ, Chang LS, Wei YH. Attenuation of oxidative stress after varicocelectomy in subfertile patients with varicocele. J Urol. 2008;179(2):639-42. https://www.auajournals.org/doi/10.1016/j.juro.2007.09.039
15. Dorostghoal M, Kazeminejad SR, Shahbazian N, Pourmehdi M, Jabbari A. Oxidative stress status and sperm DNA fragmentation in fertile and infertile men. Andrologia. 2017;49(10):e12762. https://doi.org/10.1111/and.12762
16. Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, Kirkman-Brown J, Coomarasamy A. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod. 2012;27(10):2908-17. https://academic.oup.com/humrep/article/27/10/2908/749072
17. Bungum M, Bungum L, Giwercman A. Sperm chromatin structure assay (SCSA): a tool in diagnosis and treatment of infertility. Asian J Androl. 2011;13(1):69. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739398/
18. Absalan F, Ghannadi A, Kazerooni M, Parifar R, Jamalzadeh F, Amiri S. Value of sperm chromatin dispersion test in couples with unexplained recurrent abortion. J Assist Reprod Gen. 2012;29(1):11-4. https://pubmed.ncbi.nlm.nih.gov/22009642/
19. Lee JM, Park JH, Kim BY, Kim IH. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay to characterize histopathologic changes following thermal injury. Ann Dermatol. 2018;30(1):41-6. https://anndermatol.org/DOIx.php?id=10.5021/ad.2018.30.1.41
20. Cissen M, Wely MV, Scholten I, Mansell S, Bruin JP, Mol BW, Braat D, Repping S, Hamer G. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PloS one. 2016;11(11):e0165125.
21. Ribas-Maynou J, Garcia-Peiro A, Abad C, Amengual MJ, Navarro J, Benet J. Alkaline and neutral Comet assay profiles of sperm DNA damage in clinical groups. Hum Reprod. 2012;27(3):652-8.https://pubmed.ncbi.nlm.nih.gov/22252081/
22. Belloli G, D'agostino S, Pesce C, Fantuz E. Varicocele in childhood and adolescence and other testicular anomalies: an epidemiological study. Pediatr Med Chir. 1993;15(2):159-62.https://pubmed.ncbi.nlm.nih.gov/8100626/
23. Benoff S, Gilbert BR. Varicocele and male infertility: part I. Hum Reprod Update. 2001;7(1):47-54.https://doi.org/10.1093/humupd/7.1.47
24. Santi D, Spaggiari, G. Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management – meta-analyses. Reprod Biomed Online. 2018;37(3):315 326. https://www.sciencedirect.com/science/article/abs/pii/S1472648318303523
25. Vahidi S, Moein M, Nabi A, Narimani N. Effects of microsurgical varicocelectomy on semen analysis and sperm function tests in patients with different grades of varicocele: Role of sperm functional tests in the evaluation of treatments outcome. Andrologia. 2018; 50(8):e13069.
26. Smith R, Kaune H, Parodi D, Madariaga M, Ríos R, Morales I, Castro A. Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. Hum Reprod. 2006;21(4):986-93.
27. De Lamirande E, Jiang H, Zini A, Kodama H, Gagnon C. Reactive oxygen species and sperm physiology. Rev Reprod. 1997;(2):48-54.
28. Finelli R, Pallotti F, Cargnelutti F, Faja F, Carlini T, Rizzo F, Lenzi A, Paoli D, Lombardo F. Sperm DNA damage and cytokines in varicocele: A case‐control study. Andrologia. 2021;53(5):e14023.
29. Zini A , Dohle G. Are varicoceles associated with increased deoxyribonucleic acid fragmentation?. Fertil Steril, 2011;96 (6):1283-7 https://doi.org/10.1016/j.fertnstert.2011.10.016
30. Zhang Y, Zhang W, Wu X, Liu G, Dai Y, Jiang H, Zhang X Effect of varicocele on sperm DNA damage: A systematic review and meta-analysis. Andrologia 2021;17. https://onlinelibrary.wiley.com/doi/epdf/10.1111/and.14275
31. Jellad S, Hammami F, Khalbous A, Messousi M, Khiari R, Ghozzi S, Chibani M.
32. Sperm DNA status in infertile patients with clinical varicocele. Prog Urol.2021;31(2):105-111. PMID: 32826197 DOI: 10.1016/j.purol.2020.07.241
33. Blumer CG, Fariello RM, Restelli AE, Spaine DM, Bertolla RP, Cedenho AP. Sperm nuclear DNA fragmentation and mitochondrial activity in men with varicocele. Fert Ster. 2008;90(5):1716-22. https://www.fertstert.org/article/S0015-0282(07)03477-2/fulltext
34. Wang YJ, Zhang RQ, Lin YJ, Zhang RG, Zhang WL. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Rerprod Biomed Online. 2012;25(3):307-14. https://www.rbmojournal.com/article/S1472-6483(12)00324-0/fulltext
35. Roque M, Bedoschi, G, Esteves SC. Effect of Varicocele on Sperm DNA Fragmentation: A Systemic Review andMeta-Analysis. Fertil Steril,2018;110(4)sup, E162 https://www.fertstert.org/article/S0015-0282(18)31073-2/fulltext
36. Esfahani MH, Tavalaee M. Origin and role of DNA damage in varicocele. Int J Fertil Steril. 2012;6(3):141. https://www.ijfs.ir/article_45137.html.
37. Blumer CG, Restelli AE, Giudice PT, Soler TB, Fraietta R, Nichi M, Bertolla RP, Cedenho AP. Effect of varicocele on sperm function and semen oxidative stress. BJU Int. 2012;109(2):259-65. https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2011.10240.x
38. Khelifa M, Elloumi H, Mnallah S, Khrouf M, Zhioua F, Terras K, Benkhalifa M, Mahmoud K. Varicocele induces Oxidative Stress and Sperm DNA Damages in Infertile Patients. Fertil Steril. 2020;114(3):e395. https://doi.org/10.1016/j.fertnstert.2020.08.1159
1. Jensen CF, Østergren P, Dupree JM, Ohl DA, Sønksen J, Fode M Varicocele and male infertility. Nat Rev Urol. 2017;14(9):523-33. https://www.nature.com/articles/nrurol.2017.98
2. Alsaikhan B, Alrabeeah K, Delouya G, Zini A. Epidemiology of varicocele. Asian J Androl. 2016;18(2):179. https://www.ajandrology.com/article.asp?issn=1008682X;year=2016;volume=18;issue=2;spage=179;epage=181;aulast=Alsaikhan
3. Clavijo RI, Carrasquillo R, Ramasamy R. Varicoceles: prevalence and pathogenesis in adult men. Fertil Steril. 2017;108(3):364-9. https://www.fertstert.org/article/S0015-0282(17)30495-8/fulltext
4. Su JS, Farber NJ, Vij SC. Pathophysiology and treatment options of varicocele: An overview. Andrologia. 2021;53(1):e13576. 10.1111/and.13576
5. Asafu-Adjei D, Judge C, Deibert CM, Li G, Stember D, Stahl PJ. Systematic review of the impact of varicocele grade on response to surgical management. J Urol. 2020;203(1):48-56.https://doi.org/10.1097/JU.0000000000000311
6. Vivas-Acevedo G, Lozano JR, Camejo MI. Effect of varicocele grade and age on seminal parameters. Urol Int. 2010;85(2):194-9. https://pubmed.ncbi.nlm.nih.gov/20424431/
7. Wang YJ, Zhang RQ, Lin YJ, Zhang RG, Zhang WL. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Reprod Biomed online. 2012;25(3):307-14.https://www.rbmojournal.com/article/S1472-6483(12)00324-0/fulltext
8. Agarwal A, Majzoub A, Baskaran S, Selvam MK, Cho CL, Henkel R, Finelli R, Leisegang K, Sengupta P, Barbarosie C, Parekh N. Sperm DNA fragmentation: a new guideline for clinicians. World JMen’s Health. 2020;38(4):412.https://wjmh.org/DOIx.php?id=10.5534/wjmh.200128
9. Wright C, Milne S, Leeson H. Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility. Reprod BiomedOnline. 2014;28(6):684-703.https://pubmed.ncbi.nlm.nih.gov/24745838/
10. Leach M, Aitken RJ, Sacks G. Sperm DNA fragmentation abnormalities in men from couples with a history of recurrent miscarriage. Aust N Z J Obstet Gynecol. 2015;55(4):379-83.https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1111/ajo.12373
11. Hauser R, Paz G, Botchan A, Yogev L, Yavetz H. Varicocele and male infertility: part II: varicocele: effect on sperm functions. Hum ReprodUpdate. 2001;7(5):482-5. https://academic.oup.com/humupd/article/7/5/482/651191
12. Amann RP. Can the fertility potential of a seminal sample be predicted accurately?J Androl. 1989;10(2):89-98. https://onlinelibrary.wiley.com/doi/10.1002/j.1939-4640.1989.tb00066.x
13. Duru NK, Morshedi M, Oehninger S. Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril. 2000;74(6):1200-7. https://www.fertstert.org/article/S0015-0282(00)01591-0/fulltext
14. Chen SS, Huang WJ, Chang LS, Wei YH. Attenuation of oxidative stress after varicocelectomy in subfertile patients with varicocele. J Urol. 2008;179(2):639-42. https://www.auajournals.org/doi/10.1016/j.juro.2007.09.039
15. Dorostghoal M, Kazeminejad SR, Shahbazian N, Pourmehdi M, Jabbari A. Oxidative stress status and sperm DNA fragmentation in fertile and infertile men. Andrologia. 2017;49(10):e12762. https://doi.org/10.1111/and.12762
16. Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, Kirkman-Brown J, Coomarasamy A. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod. 2012;27(10):2908-17. https://academic.oup.com/humrep/article/27/10/2908/749072
17. Bungum M, Bungum L, Giwercman A. Sperm chromatin structure assay (SCSA): a tool in diagnosis and treatment of infertility. Asian J Androl. 2011;13(1):69. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739398/
18. Absalan F, Ghannadi A, Kazerooni M, Parifar R, Jamalzadeh F, Amiri S. Value of sperm chromatin dispersion test in couples with unexplained recurrent abortion. J Assist Reprod Gen. 2012;29(1):11-4. https://pubmed.ncbi.nlm.nih.gov/22009642/
19. Lee JM, Park JH, Kim BY, Kim IH. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay to characterize histopathologic changes following thermal injury. Ann Dermatol. 2018;30(1):41-6. https://anndermatol.org/DOIx.php?id=10.5021/ad.2018.30.1.41
20. Cissen M, Wely MV, Scholten I, Mansell S, Bruin JP, Mol BW, Braat D, Repping S, Hamer G. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PloS one. 2016;11(11):e0165125.
21. Ribas-Maynou J, Garcia-Peiro A, Abad C, Amengual MJ, Navarro J, Benet J. Alkaline and neutral Comet assay profiles of sperm DNA damage in clinical groups. Hum Reprod. 2012;27(3):652-8.https://pubmed.ncbi.nlm.nih.gov/22252081/
22. Belloli G, D'agostino S, Pesce C, Fantuz E. Varicocele in childhood and adolescence and other testicular anomalies: an epidemiological study. Pediatr Med Chir. 1993;15(2):159-62.https://pubmed.ncbi.nlm.nih.gov/8100626/
23. Benoff S, Gilbert BR. Varicocele and male infertility: part I. Hum Reprod Update. 2001;7(1):47-54.https://doi.org/10.1093/humupd/7.1.47
24. Santi D, Spaggiari, G. Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management – meta-analyses. Reprod Biomed Online. 2018;37(3):315 326. https://www.sciencedirect.com/science/article/abs/pii/S1472648318303523
25. Vahidi S, Moein M, Nabi A, Narimani N. Effects of microsurgical varicocelectomy on semen analysis and sperm function tests in patients with different grades of varicocele: Role of sperm functional tests in the evaluation of treatments outcome. Andrologia. 2018; 50(8):e13069.
26. Smith R, Kaune H, Parodi D, Madariaga M, Ríos R, Morales I, Castro A. Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. Hum Reprod. 2006;21(4):986-93.
27. De Lamirande E, Jiang H, Zini A, Kodama H, Gagnon C. Reactive oxygen species and sperm physiology. Rev Reprod. 1997;(2):48-54.
28. Finelli R, Pallotti F, Cargnelutti F, Faja F, Carlini T, Rizzo F, Lenzi A, Paoli D, Lombardo F. Sperm DNA damage and cytokines in varicocele: A case‐control study. Andrologia. 2021;53(5):e14023.
29. Zini A , Dohle G. Are varicoceles associated with increased deoxyribonucleic acid fragmentation?. Fertil Steril, 2011;96 (6):1283-7 https://doi.org/10.1016/j.fertnstert.2011.10.016
30. Zhang Y, Zhang W, Wu X, Liu G, Dai Y, Jiang H, Zhang X Effect of varicocele on sperm DNA damage: A systematic review and meta-analysis. Andrologia 2021;17. https://onlinelibrary.wiley.com/doi/epdf/10.1111/and.14275
31. Jellad S, Hammami F, Khalbous A, Messousi M, Khiari R, Ghozzi S, Chibani M.
32. Sperm DNA status in infertile patients with clinical varicocele. Prog Urol.2021;31(2):105-111. PMID: 32826197 DOI: 10.1016/j.purol.2020.07.241
33. Blumer CG, Fariello RM, Restelli AE, Spaine DM, Bertolla RP, Cedenho AP. Sperm nuclear DNA fragmentation and mitochondrial activity in men with varicocele. Fert Ster. 2008;90(5):1716-22. https://www.fertstert.org/article/S0015-0282(07)03477-2/fulltext
34. Wang YJ, Zhang RQ, Lin YJ, Zhang RG, Zhang WL. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Rerprod Biomed Online. 2012;25(3):307-14. https://www.rbmojournal.com/article/S1472-6483(12)00324-0/fulltext
35. Roque M, Bedoschi, G, Esteves SC. Effect of Varicocele on Sperm DNA Fragmentation: A Systemic Review andMeta-Analysis. Fertil Steril,2018;110(4)sup, E162 https://www.fertstert.org/article/S0015-0282(18)31073-2/fulltext
36. Esfahani MH, Tavalaee M. Origin and role of DNA damage in varicocele. Int J Fertil Steril. 2012;6(3):141. https://www.ijfs.ir/article_45137.html.
37. Blumer CG, Restelli AE, Giudice PT, Soler TB, Fraietta R, Nichi M, Bertolla RP, Cedenho AP. Effect of varicocele on sperm function and semen oxidative stress. BJU Int. 2012;109(2):259-65. https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2011.10240.x
38. Khelifa M, Elloumi H, Mnallah S, Khrouf M, Zhioua F, Terras K, Benkhalifa M, Mahmoud K. Varicocele induces Oxidative Stress and Sperm DNA Damages in Infertile Patients. Fertil Steril. 2020;114(3):e395. https://doi.org/10.1016/j.fertnstert.2020.08.1159
Published
2023-01-03
How to Cite
SULAIMAN ABDULKAREEM, A., AZO NAJEEB, H., & TAHIR RAJAB, A. (2023). SPERM DNA DAMAGE RATE AMONG INFERTILE PATIENTS WITH VARICOCELE. Duhok Medical Journal, 16(2), 93-103. Retrieved from https://dmj.uod.ac/index.php/dmj/article/view/197
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