Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-wzw2p Total loading time: 0 Render date: 2024-05-29T09:37:38.643Z Has data issue: false hasContentIssue false

Chapter 23 - Clinical Value of Sperm DNA Fragmentation Tests

from Section 4 - Laboratory Evaluation and Treatment of Male Infertility

Published online by Cambridge University Press:  06 December 2023

By
Armand Zini
Edited by
Douglas T. Carrell ,
Alexander W. Pastuszak  and
James M. Hotaling
Douglas T. Carrell
Affiliation:
Utah Center for Reproductive Medicine
Alexander W. Pastuszak
Affiliation:
University of Utah
James M. Hotaling
Affiliation:
Utah Center for Reproductive Medicine
Get access

Summary

Over the past 20 years, there has been growing interest in understanding the genomic integrity of human spermatozoa and the clinical relevance of sperm chromatin and DNA defects. We have learned that the etiology of human sperm DNA damage is multi-factorial and that sperm DNA defects are associated with abnormal semen parameters. While we have observed that tests of sperm DNA integrity are correlated with reproductive outcomes, use of these complementary biomarkers in the management of male infertility remains controversial. In this chapter, we review the etiologic factors associated with sperm DNA damage and the utility of these tests in clinical practice. We also review the treatment options for infertile men with sperm DNA damage.

Keywords

men’s healthinfertilitysperm DNA damagesperm DNA fragmentation testsARTICSIoxidative stresssperm chromatin damagemale agingvaricocelehormonal treatmentsperm sorting
Type
Chapter
Information
Men's Reproductive and Sexual Health Throughout the Lifespan
An Integrated Approach to Fertility, Sexual Function, and Vitality
 , pp. 183 - 190
Publisher: Cambridge University Press
Print publication year: 2023

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Cooper, TG, Noonan, E, von Eckardstein, S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–245.Google Scholar
Vinnakota, C, Cree, L, Peek, J, Morbeck, DE. Incidence of high sperm DNA fragmentation in a targeted population of subfertile men. Syst Biol Reprod Med. 2019;65(6):451–457.Google Scholar
Fernández-Gonzalez, R, Moreira, PN, Pérez-Crespo, M, et al. Long-term effects of mouse intracytoplasmic sperm injection with DNA-fragmented sperm on health and behavior of adult offspring. Biol Reprod. 2008;78(4):761–772.Google Scholar
Bungum, M, Bungum, L, Lynch, KF, Wedlund, L, Humaidan, P, Giwercman, A. Spermatozoa DNA damage measured by sperm chromatin structure assay (SCSA) and birth characteristics in children conceived by IVF and ICSI. Int J Androl. 2012;35(4):485–490.CrossRefGoogle ScholarPubMed
Ji, BT, Shu, XO, Linet, MS, et al. Paternal cigarette smoking and the risk of childhood cancer among offspring of nonsmoking mothers. J Natl Cancer Inst. 1997;89(3):238–244.Google Scholar
Al-Jebari, Y, Glimelius, I, Berglund Nord, C, et al. Cancer therapy and risk of congenital malformations in children fathered by men treated for testicular germ-cell cancer: a nationwide register study. PLoS Med. 2019;16(6):e1002816.Google Scholar
Zini, A, Sigman, M. Are tests of sperm DNA damage clinically useful? Pros and cons. J Androl. 2009;30(3):219–229.Google Scholar
De Iuliis, GN, Thomson, LK, Mitchell, LA, et al. DNA damage in human spermatozoa is highly correlated with the efficiency of chromatin remodeling and the formation of 8-hydroxy-2’-deoxyguanosine, a marker of oxidative stress. Biol Reprod. 2009;81(3):517–524.Google Scholar
Suganuma, R, Yanagimachi, R, Meistrich, ML. Decline in fertility of mouse sperm with abnormal chromatin during epididymal passage as revealed by ICSI. Hum Reprod. 2005;20(11):3101–3108.Google Scholar
Muratori, M, Marchiani, S, Tamburrino, L, Baldi, E. Sperm DNA fragmentation: mechanisms of origin. Adv Exp Med Biol. 2019;1166:75–85.Google Scholar
Moskovtsev, SI, Willis, J, White, J, Mullen, JB. Sperm DNA damage: correlation to severity of semen abnormalities. Urology. 2009;74(4):789–793.CrossRefGoogle ScholarPubMed
Johnson, L. Spermatogenesis and aging in the human. J Androl. 1986;7(6):331–354.Google Scholar
Sartorius, GA, Nieschlag, E. Paternal age and reproduction. Hum Reprod Update. 2010;16(1):65–79.Google Scholar
Belloc, S, Benkhalifa, M, Cohen-Bacrie, M, Dalleac, A, Amar, E, Zini, A. Sperm DNA damage in normozoospermic men is related to age and sperm progressive motility. Fertil Steril. 2014;101(6):1588–1593.Google Scholar
Wyrobek, AJ, Eskenazi, B, Young, S, et al. Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proc Natl Acad Sci U S A. 2006;103(25):9601–9606.Google Scholar
Yatsenko, AN, Turek, PJ. Reproductive genetics and the aging male. J Assist Reprod Genet. 2018;35(6):933–941.Google Scholar
Smit, M, van Casteren, NJ, Wildhagen, MF, Romijn, JC, Dohle, GR. Sperm DNA integrity in cancer patients before and after cytotoxic treatment. Hum Reprod. 2010;25(8):1877–1883.Google Scholar
Ståhl, O, Eberhard, J, Cavallin-Ståhl, E, et al. Sperm DNA integrity in cancer patients: the effect of disease and treatment. Int J Androl. 2009;32(6):695–703.Google Scholar
Bujan, L, Walschaerts, M, Moinard, N, et al. Impact of chemotherapy and radiotherapy for testicular germ cell tumors on spermatogenesis and sperm DNA: a multicenter prospective study from the CECOS network. Fertil Steril. 2013;100(3):673–680.CrossRefGoogle ScholarPubMed
Brydøy, M, Fosså, SD, Klepp, O, et al. Norwegian Urology Cancer Group (NUCG) III study group. Sperm counts and endocrinological markers of spermatogenesis in long-term survivors of testicular cancer. Br J Cancer. 2012;107(11):1833–1839.Google Scholar
Paoli, D, Gallo, M, Rizzo, F, et al. Testicular cancer and sperm DNA damage: short- and long-term effects of antineoplastic treatment. Andrology. 2015;3(1):122–128.CrossRefGoogle Scholar
Robbins, WA, Meistrich, ML, Moore, D, et al. Chemotherapy induces transient sex chromosomal and autosomal aneuploidy in human sperm. Nat Genet. 1997;16(1):74–78.Google Scholar
Martin, RH, Ernst, S, Rademaker, A, et al. Chromosomal abnormalities in sperm from testicular cancer patients before and after chemotherapy. Hum Genet. 1997;99(2):214–218.CrossRefGoogle ScholarPubMed
Lee, SJ, Schover, LR, Partridge, AH, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006;24(18):2917–2931.Google Scholar
Krishnamurthy, H, Kumar, KM, Joshi, CV, Krishnamurthy, HN, Moudgal, RN, Sairam, MR. Alterations in sperm characteristics of follicle-stimulating hormone (FSH)-immunized men are similar to those of FSH-deprived infertile male bonnet monkeys. J Androl. 2000;21(2):316–327.CrossRefGoogle ScholarPubMed
Xing, W, Krishnamurthy, H, Sairam, MR. Role of follitropin receptor signaling in nuclear protein transitions and chromatin condensation during spermatogenesis. Biochem Biophys Res Commun. 2003;312(3):697–701.Google Scholar
Meeker, JD, Singh, NP, Hauser, R. Serum concentrations of estradiol and free T4 are inversely correlated with sperm DNA damage in men from an infertility clinic. J Androl. 2008;29(4):379–388.Google Scholar
Erenpreiss, J, Hlevicka, S, Zalkalns, J, Erenpreisa, J. Effect of leukocytospermia on sperm DNA integrity: a negative effect in abnormal semen samples. J Androl. 2002;23(5):717–723.Google Scholar
La Vignera, S, Condorelli, R, D’Agata, R, Vicari, E, Calogero, AE. Semen alterations and flow-citometry evaluation in patients with male accessory gland infections. J Endocrinol Invest. 2012;35(2):219–223.Google Scholar
Gallegos, G, Ramos, B, Santiso, R, Goyanes, V, Gosálvez, J, Fernández, JL. Sperm DNA fragmentation in infertile men with genitourinary infection by chlamydia trachomatis and mycoplasma. Fertil Steril. 2008;90(2):328–334.Google Scholar
Cortés‐Gutiérrez, EI, Dávila‐Rodríguez, MI, Fernández, JL, de la O‐Pérez, LO,Garza‐Flores, ME, Eguren-Garza, R,Gosálvez, J. The presence of human papillomavirus in semen does not affect the integrity of sperm DNA. Andrologia. 2017;49(10):e12774.CrossRefGoogle Scholar
Damsgaard, J, Joensen, UN, Carlsen, E, et al. Varicocele is associated with impaired semen quality and reproductive hormone levels: a study of 7035 healthy young men from six European countries. Eur Urol. 2016;70(6):1019–1029.Google Scholar
Zini, A, Dohle, G. Are varicoceles associated with increased deoxyribonucleic acid fragmentation? Fertil Steril. 2011;96(6):1283–1287.Google Scholar
Roque, M, Esteves, SC. Effect of varicocele repair on sperm DNA fragmentation: a review. Int Urol Nephrol. 2018;50(4):583–603.CrossRefGoogle ScholarPubMed
Smith, R, Kaune, H, Parodi, D, et al. Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. Hum Reprod. 2006;21(4):986–993.CrossRefGoogle ScholarPubMed
Kaufman, DW, Kelly, JP, Rosenberg, L, Anderson, TE, Mitchell, AA. Effect of prescriber education on the use of medications contraindicated in older adults in a managed Medicare population. JAMA. 2002;287(3):337–344.CrossRefGoogle Scholar
Kantor, ED, Rehm, CD, Haas, JS, Chan, AT, Giovannucci, EL. Trends in prescription drug use among adults in the United States from 1999–2012. JAMA. 2015;314(17):1818–1831.Google Scholar
Safarinejad, MR. Sperm DNA damage and semen quality impairment after treatment with selective serotonin reuptake inhibitors detected using semen analysis and sperm chromatin structure assay. J Urol. 2008;180(5):2124–2128.Google Scholar
Tanrikut, C, Feldman, AS, Altemus, M, Paduch, DA, Schlegel, PN. Adverse effect of paroxetine on sperm. Fertil Steril. 2010;94(3):1021–1026.Google Scholar
Samplaski, MK, Lo, K, Grober, E, Jarvi, K. Finasteride use in the male infertility population: effects on semen and hormone parameters. Fertil Steril. 2013;100(6):1542–1546.CrossRefGoogle ScholarPubMed
Sharma, R, Harlev, A, Agarwal, A, Esteves, SC. Cigarette smoking and semen quality: a new meta-analysis examining the effect of the 2010 World Health Organization Laboratory Methods for the Examination of Human Semen. Eur Urol. 2016;70(4):635–645.Google Scholar
Fraga, CG, Motchnik, PA, Wyrobek, AJ, Rempel, DM, Ames, BN. Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat Res. 1996;351(2):199–203.Google Scholar
Jenkins, TG, James, ER, Alonso, DF, et al. Cigarette smoking significantly alters sperm DNA methylation patterns. Andrology. 2017;5(6):1089–1099.Google Scholar
Hammadeh, ME, Hamad, MF, Montenarh, M, Fischer-Hammadeh, C. Protamine contents and P1/P2 ratio in human spermatozoa from smokers and non-smokers. Hum Reprod. 2010;25(11):2708–2720.Google Scholar
Boeri, L, Capogrosso, P, Ventimiglia, E, et al. Heavy cigarette smoking and alcohol consumption are associated with impaired sperm parameters in primary infertile men. Asian J Androl. 2019;21(5):478–485.Google Scholar
Sailer, BL, Sarkar, LJ, Bjordahl, JA, Jost, LK, Evenson, DP. Effects of heat stress on mouse testicular cells and sperm chromatin structure. J Androl. 1997;18(3):294–301.CrossRefGoogle ScholarPubMed
Thonneau, P, Bujan, L, Multigner, L, Mieusset, R. Occupational heat exposure and male fertility: a review. Hum Reprod. 1998;13(8):2122–2125.Google Scholar
Jurewicz, J, Dziewirska, E, Radwan, M, Hanke, W. Air pollution from natural and anthropic sources and male fertility. Reprod Biol Endocrinol. 2018;16(1):109.Google Scholar
Snijder, CA, te Velde, E, Roeleveld, N, Burdorf, A. Occupational exposure to chemical substances and time to pregnancy: a systematic review. Hum Reprod Update. 2012;18(3):284–300.CrossRefGoogle ScholarPubMed
Spano, M, Bonde, JP, Hjollund, HI, Kolstad, HA, Cordelli, E, Leter, G. Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team. Fertil Steril. 2000;73:43–50.Google Scholar
Sugihara, A, Van Avermaete, F, Roelant, E, Punjabi, U, De Neubourg, D. The role of sperm DNA fragmentation testing in predicting intra-uterine insemination outcome: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2020;244:8–15.Google Scholar
Simon, L, Zini, A, Dyachenko, A, Ciampi, A, Carrell, DT. A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome. Asian J Androl. 2017;19:80–90.Google Scholar
Cissen, M, Wely, MV, Scholten, I, et al. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PLoS ONE. 2016;11(11):e0165125.Google Scholar
Zini, A, Boman, J, Belzile, E, Ciampi, A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008;23:2663–2668.Google Scholar
McQueen, DB, Zhang, J, Robins, JC. Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril. 2019;112(1):54–60.e3.Google Scholar
Gawecka, JE, Boaz, S, Kasperson, K, Nguyen, H, Evenson, DP, Ward, WS. Luminal fluid of epididymis and vas deferens contributes to sperm chromatin fragmentation. Hum Reprod. 2015;30(12):2725–2736.Google Scholar
Majzoub, A, Agarwal, A, Cho, CL, Esteves, SC. Sperm DNA fragmentation testing: a cross sectional survey on current practices of fertility specialists. Transl Androl Urol. 2017;6(Suppl. 4):S710–S719.Google Scholar
Practice Committee of the American Society for Reproductive Medicine. The clinical utility of sperm DNA integrity testing: a guideline. Fertil Steril. 2013;99(3):673–677.Google Scholar
Agarwal, A, Majzoub, A, Esteves, SC, Ko, E, Ramasamy, R, Zini, A. Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios. Transl Androl Urol. 2016;5(6):935–950.CrossRefGoogle ScholarPubMed
Kroese, ACJ, de Lange, NM, Collins, J, Evers, JLH. Surgery or embolization for varicoceles in subfertile men. Cochrane Database Syst Rev. 2012;10:CD000479.Google Scholar
Attia, AM, Abou-Setta, AM, Al-Inany, HG. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database Syst Rev. 2013;23(8):CD005071.Google Scholar
Kamischke, A, Behre, HM, Bergmann, M, Simoni, M, Schäfer, T, Nieschlag, E. Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: a randomized, double-blind, placebo-controlled, clinical trial. Hum Reprod. 1998;13(3):596–603.CrossRefGoogle ScholarPubMed
Santi, D, Spaggiari, G, Simoni, M. 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.CrossRefGoogle ScholarPubMed
Smits, RM, Mackenzie-Proctor, R, Yazdani, A, Stankiewicz, MT, Jordan, V, Showell, MG. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2019;3(3):CD007411.Google ScholarPubMed
Hanson, BM, Aston, KI, Jenkins, TG, Carrell, DT, Hotaling, JM. The impact of ejaculatory abstinence on semen analysis parameters: a systematic review. J Assist Reprod Genet. 2018;35(2):213–220.Google Scholar
Ramos, L, De Boer, P, Meuleman, EJ, Braat, DD, Wetzels, AM. Evaluation of ICSI-selected epididymal sperm samples of obstructive azoospermic males by the CKIA system. J Androl. 2004;25(3):406–411.Google Scholar
Said, TM, Land, JA. Effects of advanced selection methods on sperm quality and ART outcome: a systematic review. Hum Reprod Update. 2011;17(6):719–733.Google Scholar
Strassburger, D, Friedler, S, Raziel, A, Schachter, M, Kasterstein, E, Ron-el, R. Very low sperm count affects the result of intracytoplasmic sperm injection. J Assist Reprod Genet. 2000;17(8):431–436.Google Scholar
Greco, E, Scarselli, F, Lacobelli, M, et al. Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Hum Reprod. 2005;20(1):226–230.Google Scholar
Esteves, SC, Roque, M, Bradley, CK, Garrido, N. Reproductive outcomes of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with high levels of DNA fragmentation in semen: systematic review and meta-analysis. Fertil Steril. 2017;108(3):456–467.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×