322
Views
24
CrossRef citations to date
0
Altmetric
Review

Sperm DNA damage and its impact on male reproductive health: a critical review for clinicians, reproductive professionals and researchers

, , &
Pages 443-457 | Received 20 Feb 2019, Accepted 01 May 2019, Published online: 13 May 2019

References

  • Irvine DS. Epidemiology and aetiology of male infertility. Hum Reprod. 1998;13(suppl_1):33–44.
  • Lotti F, Maggi M. Sexual dysfunction and male infertility [Review Article]. Nat Rev Urol. 2018 Mar 13;15:287. online.
  • Esteves SC. Clinical relevance of routine semen analysis and controversies surrounding the 2010 World Health Organization criteria for semen examination. Int Braz J Urol. 2014;40(4):433–453.
  • Cho CL, Agarwal A. Role of sperm DNA fragmentation in male factor infertility: A systematic review. Arab J Urol. 2018 Mar;16(1):21–34. PubMed PMID: 29713533; PubMed Central PMCID: PMCPMC5922225. eng.
  • Majzoub A, Agarwal A, Cho CL, et al. Sperm DNA fragmentation testing: a cross sectional survey on current practices of fertility specialists. Transl Androl Urol. 2017 Sep;6(Suppl 4):S710–9. PubMed PMID: 29082205; PubMed Central PMCID: PMCPMC5643631. eng.
  • Amaral A, Lourenço B, Marques M, et al. Mitochondria functionality and sperm quality. Reproduction. 2013;146(5):R163–R174.
  • Jenkins TG, Carrell DT. The sperm epigenome and potential implications for the developing embryo. Reproduction. 2012;143(6):727–734.
  • Kaarouch I, Bouamoud N, Madkour A, et al. Paternal age: negative impact on sperm genome decays and IVF outcomes after 40 years. Mol Reprod Dev. 2018;85(3):271–280.
  • Ward WS. Function of sperm chromatin structural elements in fertilization and development. Mol Hum Reprod. 2010 Jan;16(1):30–36. PubMed PMID: 19748904; PubMed Central PMCID: PMCPMC2790366. eng.
  • Ahmadi A, Ng SC. Fertilizing ability of DNA‐damaged spermatozoa. J Exp Zool. 1999;284(6):696–704.
  • Evenson D, Jost L, Marshall D, et al. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod. 1999;14(4):1039–1049.
  • Zini A, Sigman M. Are tests of sperm DNA damage clinically useful? Pros and cons. J Andrology. 2009;30(3):219–229.
  • O’Neill CL, Parrella A, Keating D, et al. A treatment algorithm for couples with unexplained infertility based on sperm chromatin assessment. J Assist Reprod Genet. 2018 Oct;35(10):1911–1917. PubMed PMID: 30056595; PubMed Central PMCID: PMCPMC6150896. eng.
  • Bareh GM, Jacoby E, Binkley P, et al. Sperm deoxyribonucleic acid fragmentation assessment in normozoospermic male partners of couples with unexplained recurrent pregnancy loss: a prospective study. Fertil Steril. 2016 Feb 01;105(2):329–336.e1.
  • Medicine PCotASfR. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2015 Mar 01;103(3):e18–e25.
  • Jarow J, Sigman M, Kolettis P, editors. The optimal evaluation of the infertile male: best practice statement reviewed and validity confirmed 2011. American Urological Association; 2011. https://www.auanet.org/guidelines/male-infertility-optimal-evaluation-best-practice-statement
  • Jungwirth A, Diemer T, Dohle G, et al. Guidelines on male infertility, European Association of Urology guidelines. Arnhem the Netherlands; 2015. https://uroweb.org/wp-content/uploads/17-Male-Infertility_LR1.pdf
  • Bui AD, Sharma R, Henkel R, et al. Reactive oxygen species impact on sperm DNA and its role in male infertility. Andrologia. 2018;50(8):e13012.
  • Muratori M, Tamburrino L, Marchiani S, et al. Investigation on the origin of sperm DNA fragmentation: role of apoptosis, immaturity and oxidative stress. Mol Med (Cambridge, MA). 2015;21(1):109–122. PubMed PMID: 25786204; PubMed Central PMCID: PMCPMC4461587. eng.
  • De Iuliis GN, Finnie JM, Aitken RJ, et al. Analysis of the relationships between oxidative stress, DNA damage and sperm vitality in a patient population: development of diagnostic criteria. Hum Reprod. 2010;25(10):2415–2426.
  • Shamsi MB, Kumar R, Bhatt A, et al. Mitochondrial DNA Mutations in etiopathogenesis of male infertility. Indian J Urol. 2008 Apr-Jun;24(2):150–154. PubMed PMID: 19468388; PubMed Central PMCID: PMCPMC2684292. eng.
  • Rodríguez S, Goyanes V, Segrelles E, et al. Critically short telomeres are associated with sperm DNA fragmentation. Fertil Steril. 2005 Oct 01;84(4):843–845.
  • Mishra S, Kumar R, Malhotra N, et al. Mild oxidative stress is beneficial for sperm telomere length maintenance. World J Methodol. 2016 Jun 26;6(2):163–170. PubMed PMID: 27376021; PubMed Central PMCID: PMCPMC4921947. eng.
  • Oakes CC, La Salle S, Smiraglia DJ, et al. Developmental acquisition of genome-wide DNA methylation occurs prior to meiosis in male germ cells. Dev Biol. 2007 Jun 15;307(2):368–379.
  • Dada R, Kumar M, Jesudasan R, et al. Epigenetics and its role in male infertility. J Assist Reprod Genet. 2012 Mar;29(3):213–223. PubMed PMID: 22290605; PubMed Central PMCID: PMCPMC3288140. eng.
  • Tunc O, Tremellen K. Oxidative DNA damage impairs global sperm DNA methylation in infertile men. J Assist Reprod Genet. 2009 Oct;26(9–10):537–544. PubMed PMID: 19876730; PubMed Central PMCID: PMCPMC2788683. eng.
  • Olszewska M, Barciszewska MZ, Fraczek M, et al. Global methylation status of sperm DNA in carriers of chromosome structural aberrations. Asian J Androl. 2017 Jan-Feb;19(1):117–124. PubMed PMID: 26908061; PubMed Central PMCID: PMCPMC5227660. eng.
  • Gunes S, Arslan MA, Hekim GNT, et al. The role of epigenetics in idiopathic male infertility. J Assist Reprod Genet. 2016 May;33(5):553–569. PubMed PMID: 26941097; PubMed Central PMCID: PMCPmc4870443. eng.
  • Schütte B, El Hajj N, Kuhtz J, et al. Broad DNA methylation changes of spermatogenesis, inflammation and immune response-related genes in a subgroup of sperm samples for assisted reproduction. Andrology. 2013 Nov;1(6):822–829. PubMed PMID: 23996961; PubMed Central PMCID: PMCPmc4033565. eng.
  • Ferfouri F, Boitrelle F, Ghout I, et al. A genome-wide DNA methylation study in azoospermia. Andrology. 2013;1(6):815–821.
  • Venkatesh S, Thilagavathi J, Kumar K, et al. Cytogenetic, Y chromosome microdeletion, sperm chromatin and oxidative stress analysis in male partners of couples experiencing recurrent spontaneous abortions [journal article]. Arch Gynecol Obstet. 2011 Dec 01;284(6):1577–1584.
  • Krausz C, Cioppi F, Riera-Escamilla A. Testing for genetic contributions to infertility: potential clinical impact. Expert Rev Mol Diagn. 2018 Apr 03;18(4):331–346.
  • Dinesh V, Shamsi M, Dada R. Supraphysiological free radical levels and their pathogenesis in male infertility. Reprod Sys Sexual Disord. 2012;1(114):2.
  • Griswold MD. The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol. 1998 Aug 01;9(4):411–416.
  • Print CG, Loveland KL. Germ cell suicide: new insights into apoptosis during spermatogenesis. BioEssays. 2000;22(5):423–430.
  • Lee J, Richburg JH, Younkin SC, et al. The fas system is a key regulator of germ cell apoptosis in the testis*. Endocrinology. 1997;138(5):2081–2088.
  • Rodriguez I, Ody C, Araki K, et al. An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis. Embo J. 1997 May 1;16(9):2262–2270. PubMed PMID: 9171341; PubMed Central PMCID: PMCPMC1169828. eng.
  • Sakkas D, Mariethoz E, St. John JC. Abnormal sperm parameters in humans are indicative of an abortive apoptotic mechanism linked to the fas-mediated pathway. Exp Cell Res. 1999 Sep 15;251(2):350–355.
  • Marchiani S, Tamburrino L, Maoggi A, et al. Characterization of M540 bodies in human semen: evidence that they are apoptotic bodies. Mol Hum Reprod. 2007;13(9):621–631.
  • Muratori M, Porazzi I, Luconi M, et al. Annexin V binding and merocyanine staining fail to detect human sperm capacitation. J Andrology. 2004;25(5):797–810.
  • Sakkas D, Moffatt O, Manicardi GC, et al. Nature of DNA damage in ejaculated human spermatozoa and the possible involvement of apoptosis. Biol Reprod. 2002;66(4):1061–1067.
  • McPherson SM, Longo FJ. Localization of DNase I-hypersensitive regions during rat spermatogenesis: stage-dependent patterns and unique sensitivity of elongating spermatids. Mol Reprod Dev. 1992;31(4):268–279.
  • McPherson SMG, Longo FJ. Nicking of rat spermatid and spermatozoa DNA: possible involvement of DNA topoisomerase II. Dev Biol. 1993 Jul 01;158(1):122–130.
  • Marcon L, Boissonneault G. Transient DNA strand breaks during mouse and human spermiogenesis: newInsights in stage specificity and link to chromatin remodeling1. Biol Reprod. 2004;70(4):910–918.
  • Moskovtsev SI, Jarvi K, Mullen JBM, et al. Testicular spermatozoa have statistically significantly lower DNA damage compared with ejaculated spermatozoa in patients with unsuccessful oral antioxidant treatment. Fertil Steril. 2010 Mar 01;93(4):1142–1146.
  • De Iuliis GN, Aitken RJ. On the possible origins of DNA damage in human spermatozoa. Mol Hum Reprod. 2009;16(1):3–13.
  • Pourmasumi S, Sabeti P, Rahiminia T, et al. The etiologies of DNA abnormalities in male infertility: an assessment and review. Int J Reprod Biomed (Yazd). 2017 Jun;15(6):331–344. PubMed PMID: 29177237; PubMed Central PMCID: PMCPMC5605854. eng.
  • Aitken J, Buckingham D, Krausz C. Relationships between biochemical markers for residual sperm cytoplasm, reactive oxygen species generation, and the presence of leukocytes and precursor germ cells in human sperm suspensions. Mol Reprod Dev. 1994;39(3):268–279.
  • Darbandi M, Darbandi S, Agarwal A, et al. Reactive oxygen species-induced alterations in H19-Igf2 methylation patterns, seminal plasma metabolites, and semen quality [journal article]. J Assist Reprod Genet. 2018 Oct 31. DOI:10.1007/s10815-018-1350-y
  • Skowronek F, Casanova G, Alciaturi J, et al. DNA sperm damage correlates with nuclear ultrastructural sperm defects in teratozoospermic men. Andrologia. 2012;44(1):59–65.
  • Puga Molina LC, Luque GM, Balestrini PA, et al. Molecular basis of human sperm capacitation [Review]. Front Cell Dev Biol. 2018 Jul 27;6(72). English. DOI:10.3389/fcell.2018.00072
  • Guraya SS. Cellular and molecular biology of capacitation and acrosome reaction in spermatozoa. Int Rev Cytol. 2000;199:1–64.
  • Gunes S, Al-Sadaan M, Agarwal A. Spermatogenesis, DNA damage and DNA repair mechanisms in male infertility. Reprod Biomed Online. 2015;31(3):309–319.
  • Intasqui P, Camargo M, Del Giudice PT, et al. Sperm nuclear DNA fragmentation rate is associated with differential protein expression and enriched functions in human seminal plasma. BJU Int. 2013;112(6):835–843.
  • Intasqui P, Camargo M, Del Giudice PT, et al. Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation. J Assist Reprod Genet. 2013 Sep;30(9):1187–1202. PubMed PMID: 23893156; PubMed Central PMCID: PMCPmc3800528. eng.
  • Behrouzi B, Kenigsberg S, Alladin N, et al. Evaluation of potential protein biomarkers in patients with high sperm DNA damage. Syst Biol Reprod Med. 2013;59(3):153–163.
  • Sharma R, Agarwal A, Mohanty G, et al. Proteomic analysis of seminal fluid from men exhibiting oxidative stress. ReprodBiol Endocrinol. 2013;11:85. PubMed PMID: 24004880; PubMed Central PMCID: PMCPMC3846593. eng.
  • Darbandi M, Darbandi S, Agarwal A, et al. Reactive oxygen species-induced alterations in H19-Igf2 methylation patterns, seminal plasma metabolites, and semen quality [journal article]. J Assist Reprod Genet. 2019 Feb 01;36(2):241–253.
  • Intasqui P, Camargo M, Antoniassi MP, et al. Association between the seminal plasma proteome and sperm functional traits. Fertil Steril. 2016;105(3):617–628.
  • Cho C-L, Agarwal A. Role of sperm DNA fragmentation in male factor infertility: A systematic review. Arab J Urol. 2018;16(1):21–34.
  • Saleh RA, Agarwal A, Nada EA, et al. Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril. 2003;79:1597–1605.
  • Agarwal A, Cho CL, Majzoub A, et al. Risk factors associated with sperm DNA fragmentation. Transl Androl Urol. 2017 Sep;6(Suppl 4):S519–s521. PubMed PMID: 29082947; PubMed Central PMCID: PMCPMC5643615. eng.
  • Saleh RA, Agarwal A, Nelson DR, et al. Increased sperm nuclear DNA damage in normozoospermic infertile men: a prospective study. Fertil Steril. 2002;78(2):313–318.
  • Alshahrani S, Agarwal A, Assidi M, et al. Infertile men older than 40 years are at higher risk of sperm DNA damage. Reprod Biol Endocrinol. 2014;12(1):103.
  • Brahem S, Mehdi M, Elghezal H, et al. The effects of male aging on semen quality, sperm DNA fragmentation and chromosomal abnormalities in an infertile population. J Assist Reprod Genet. 2011;28(5):425–432.
  • Luetjens C, Rolf C, Gassner P, et al. Sperm aneuploidy rates in younger and older men. Hum Reprod. 2002;17(7):1826–1832.
  • Harlev A, Agarwal A, Gunes SO, et al. Smoking and male infertility: an evidence-based review. World J Mens Health. 2015 Dec;33(3):143–160. PubMed PMID: 26770934; PubMed Central PMCID: PMCPMC4709430. eng.
  • Cui X, Jing X, Wu X, et al. Potential effect of smoking on semen quality through DNA damage and the downregulation of Chk1 in sperm. Mol Med Rep. 2016;14(1):753–761.
  • Akang EN, Oremosu AA, Osinubi AA, et al. Alcohol-induced male infertility: is sperm DNA fragmentation a causative? J Exp Clin Anat. 2017;16(1):53.
  • 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.
  • Dupont C, Faure C, Sermondade N, et al. Obesity leads to higher risk of sperm DNA damage in infertile patients. Asian J Androl. 2013;15(5):622.
  • Palmer NO, Bakos HW, Fullston T, et al. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis. 2012;2(4):253–263.
  • Jeng HA. Exposure to endocrine disrupting chemicals and male reproductive health. Front Public Health. 2014;2:55.
  • McPherson NO, Lane M. Male obesity and subfertility, is it really about increased adiposity? Asian J Androl. 2015 May-Jun;17(3):450–458. PubMed PMID: 25652636; PubMed Central PMCID: PMCPMC4430951. eng.
  • Meeker JD, Ehrlich S, Toth TL, et al. Semen quality and sperm DNA damage in relation to urinary bisphenol A among men from an infertility clinic. Reprod Toxicol. 2010 Dec;30(4):532–539. PubMed PMID: 20656017; PubMed Central PMCID: PMCPMC2993767. eng.
  • Ahmad G, Agarwal A. Ionizing Radiation and Male Fertility. In: Gunasekaran K., Pandiyan N. (eds) Male Infertility. Springer, New Delhi. 2017;185-196.
  • Smit M, Van Casteren N, Wildhagen M, et al. Sperm DNA integrity in cancer patients before and after cytotoxic treatment. Hum Reprod. 2010;25(8):1877–1883.
  • Agarwal A, Deepinder F, Sharma RK, et al. Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study. Fertil Steril. 2008 Jan;89(1):124–128. PubMed PMID: 17482179.
  • Gallegos G, Ramos B, Santiso R, et al. Sperm DNA fragmentation in infertile men with genitourinary infection by Chlamydia trachomatis and Mycoplasma. Fertil Steril. 2008;90(2):328–334.
  • Erenpreiss J, Hlevicka S, Zalkalns J, et al. Effect of leukocytospermia on sperm DNA integrity: a negative effect in abnormal semen samples. J Andrology. 2002;23(5):717–723.
  • Auger J, Mesbah M, Huber C, et al. Aniline blue staining as a marker of sperm chromatin defects associated with different semen characteristics discriminates between proven fertile and suspected infertile men. Int JAndrology. 1990;13(6):452–462.
  • Manicardi GC, Bizzaro D, Sakkas D. Basic and clinical aspects of sperm chromomycin A3 assay. In: Zini A, Agarwal A, editors. Sperm chromatin: biological and clinical applications in male infertility and assisted reproduction. New York: Springer New York; 2011. p. 171–179.
  • Manicardi GC, Bianchi PG, Pantano S, et al. Presence of endogenous nicks in DNA of ejaculated human spermatozoa and its relationship to chromomycin A3 accessibility1. Biol Reprod. 1995;52(4):864–867.
  • Sakkas D, Urner F, Bizzaro D, et al. Sperm nuclear DNA damage and altered chromatin structure: effect on fertilization and embryo development. Hum Reprod. 1998;13(suppl_4):11–19.
  • Evenson DP. The Sperm Chromatin Structure Assay (SCSA®) and other sperm DNA fragmentation tests for evaluation of sperm nuclear DNA integrity as related to fertility. Anim Reprod Sci. 2016;169:56–75.
  • Evenson DP, Larson KL, Jost LK. Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. J Andrology. 2002;23(1):25–43.
  • Evenson DP. Sperm Chromatin Structure Assay (SCSA): 30 years’ experience with the SCSA. In: Agarwal A, Zini A. editors. Sperm DNA and Male Infertility and ART, New York, Springer Publishers, 2011;125-149.
  • Fernández JL, Muriel L, Goyanes V, et al. Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion test. Fertil Steril. 2005 Oct 01;84(4):833–842.
  • Fernández JL, Muriel L, Rivero MT, et al. The sperm chromatin dispersion test: a simple method for the determination of sperm DNA fragmentation. J Andrology. 2003;24(1):59–66.
  • Pratap H, Hottigoudar SY, Nichanahalli KS, et al. Assessment of sperm deoxyribose nucleic acid fragmentation using sperm chromatin dispersion assay. J Pharmacol Pharmacotherapeutics. 2017 Apr-Jun;8(2):45–49. PubMed PMID: 28706397; PubMed Central PMCID: PMCPMC5497398. eng.
  • Bissonnette F, Bleau G, Laforest G, et al. Sperm DNA fragmentation: threshold value in male fertility. Hum Reprod. 2005;20(12):3446–3451.
  • Ostling O, Johanson KJ. Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem Biophys Res Commun. 1984 Aug 30;123(1):291–298.
  • Singh NP, Danner DB, Tice RR, et al. Abundant alkali-sensitive sites in DNA of human and mouse sperm. Exp Cell Res. 1989;184(2):461–470.
  • Niederberger C. Re: HT-COMET: a novel automated approach for high throughput assessment of human sperm chromatin quality. J Urol. 2016 Dec 01;196(6):1726.
  • Albert O, Reintsch WE, Chan P, et al. HT-COMET: a novel automated approach for high throughput assessment of human sperm chromatin quality. Hum Reprod. 2016 May;31(5):938–946. PubMed PMID: 26975326; PubMed Central PMCID: PMCPMC4840022. eng.
  • Cortes-Gutierrez EI, Davila-Rodriguez MI, Cerda-Flores RM, et al. Localisation and quantification of alkali-labile sites in human spermatozoa by DNA breakage detection-fluorescence in situ hybridisation. Andrologia. 2015 Mar;47(2):221–227. PubMed PMID: 24576285; eng.
  • Fernandez JL, Vazquez-Gundin F, Delgado A, et al. DNA breakage detection-FISH (DBD-FISH) in human spermatozoa: technical variants evidence different structural features. Mutat Res. 2000 Sep 20;453(1):77–82. PubMed PMID: 11006414; eng.
  • Cortés-Gutiérrez EI, Dávila-Rodríguez MI, López-Fernández C. The comet assay. In: Zini A, Agarwal A, editors. A clinician’s guide to sperm DNA and chromatin damage. Switzerland: Springer Nature; 2018. p. 119.
  • Sharma R, Cakar Z, Agarwal A. TUNEL Assay by Benchtop Flow Cytometer in Clinical Laboratories. In: Zini A., Agarwal A. (eds) A Clinician's Guide to Sperm DNA and Chromatin Damage. Springer, Cham, 2018;103-118.
  • Sharma R, Ahmad G, Esteves SC, et al. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay using bench top flow cytometer for evaluation of sperm DNA fragmentation in fertility laboratories: protocol, reference values, and quality control. J Assist Reprod Genet. 2016 Feb;33(2):291–300. PubMed PMID: 26780327; PubMed Central PMCID: PMCPMC4758999. eng.
  • Ribeiro S, Sharma R, Gupta S, et al. Inter‐and intra‐laboratory standardization of TUNEL assay for assessment of sperm DNA fragmentation. Andrology. 2017;5(3):477–485.
  • Sharma R, Gupta S, Henkel R, et al. Critical evaluation of two models of flow cytometers for the assessment of sperm DNA fragmentation: an appeal for performance verification. Asian J Androl. 2019 Jan 8; doi: 10.4103/aja.aja_109_18.
  • Sharma R, Masaki J, Agarwal A. Sperm DNA Fragmentation Analysis Using the TUNEL Assay. In: Carrell D., Aston K. (eds) Spermatogenesis. Methods in Molecular Biology (Methods and Protocols). Totowa, New Jersey: Humana Press. 2013;927:121-136.
  • Sharma RK, Sabanegh E, Mahfouz R, et al. TUNEL as a test for sperm DNA damage in the evaluation of male infertility. Urology. 2010 Dec 01;76(6):1380–1386.
  • Cho CL, Esteves SC, Agarwal A. Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation. Asian J Androl. 2016 Mar-Apr;18(2):186–193. PubMed PMID: 26732105; PubMed Central PMCID: PMCPMC4770484. eng.
  • Zini A, Dohle G. Are varicoceles associated with increased deoxyribonucleic acid fragmentation? Fertil Steril. 2011 Dec 01;96(6):1283–1287.
  • Wang Y-J, Zhang R-Q, Lin Y-J, et al. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Reprod Biomed Online. 2012;25(3):307–314.
  • Smit M, Romijn JC, Wildhagen MF, et al. Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate. J Urol. 2010 Jan;183(1):270–274. PubMed PMID: 19913801; eng.
  • Mohammed -E-EM, Mosad E, Zahran AM, et al. Acridine orange and flow cytometry: which is better to measure the effect of varicocele on sperm DNA integrity? Adv Urol. 2015;2015:6.
  • Esteves SC, Roque M, Agarwal A. Outcome of assisted reproductive technology in men with treated and untreated varicocele: systematic review and meta-analysis. Asian J Androl. 2016 Mar-Apr;18(2):254–258. PubMed PMID: 26510504; PubMed Central PMCID: PMCPMC4770495. eng.
  • Hamada A, Esteves SC, Nizza M, et al. Unexplained male infertility: diagnosis and management. Int Braz J Urol. 2012;38(5):576–594.
  • Bungum L, Humaidan P, Bungum M, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod. 2006;22(1):174–179.
  • Oleszczuk K, Augustinsson L, Bayat N, et al. Prevalence of high DNA fragmentation index in male partners of unexplained infertile couples. Andrology. 2013;1(3):357–360.
  • Simon L, Proutski I, Stevenson M, et al. Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod Biomed Online. 2013 Jan 01;26(1):68–78.
  • Spanò M, Bonde JP, Hjøllund HI, et al. Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study is a collaborative follow-up study on environmental and biological determinants of fertility. The project is coordinated by the Steno Institute of Public Health, Aarhus University and is undertaken in collaboration with the Department of Growth and Reproduction, National University Hospital, Copenhagen. The team includes Jens Peter E. Bonde, Niels Henrik I. Hjøllund, Tina Kold Jensen, Tine Brink Henriksen, Henrik A. Kolstad, Erik Ernst, Aleksander Giwercman, Niels Erik Skakkebæk, and Jørn Olsen. Fertil Steril. 2000 Jan 01;73(1):43–50.
  • Buck Louis GM, Sundaram R, Schisterman EF, et al. Semen quality and time to pregnancy: the Longitudinal Investigation of fertility and the environment study. Fertil Steril. 2014 Feb;101(2):453–462. PubMed PMID: 24239161; PubMed Central PMCID: PMCPMC3946620. eng.
  • Zini A. Are sperm chromatin and DNA defects relevant in the clinic? Syst Biol Reprod Med. 2011 Jan 01;57(1–2):78–85.
  • Agarwal A, Cho C-L, Esteves SC. Should we evaluate and treat sperm DNA fragmentation? Curr Opin Obstet Gynecol. 2016;28(3):164–171.
  • Duran EH, Morshedi M, Taylor S, et al. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod. 2002;17(12):3122–3128.
  • Simon L, Carrell DT, Zini A. Sperm DNA tests are clinically useful: pro. A Clinician’s guide to sperm DNA and chromatin damage. Cham: Springer; 2018. p. 431–467.
  • Sakkas D, Urner F, Bianchi P, et al. Sperm chromatin anomalies can influence decondensation after intracytoplasmic sperm injection. Hum Reprod. 1996;11(4):837–843.
  • Simon L, Lewis SEM, Brunborg G, et al. Clinical significance of sperm DNA damage in assisted reproduction outcome. Hum Reprod. 2010;25(7):1594–1608.
  • Oleszczuk K, Giwercman A, Bungum M. Sperm chromatin structure assay in prediction of in vitro fertilization outcome. Andrology. 2016;4(2):290–296.
  • Johnson LNC, Sasson IE, Sammel MD, et al. Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well-defined unexplained infertility? A systematic review and meta-analysis. Fertil Steril. 2013 Sep 01;100(3):704–711.
  • Aziz N, Said T, Paasch U, et al. The relationship between human sperm apoptosis, morphology and the sperm deformity index. Hum Reprod. 2007;22(5):1413–1419.
  • Agarwal A, Said TM. Oxidative stress, DNA damage and apoptosis in male infertility: a clinical approach. BJU Int. 2005;95(4):503–507.
  • Tesarik J, Mendoza C, Greco E. Paternal effects acting during the first cell cycle of human preimplantation development after ICSI. Hum Reprod. 2002;17(1):184–189.
  • Tesarik J, Greco E, Mendoza C. Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation. Hum Reprod. 2004;19(3):611–615.
  • Zini A, Jamal W, Cowan L, et al. Is sperm DNA damage associated with IVF embryo quality? A systematic review. J Assist Reprod Genet. 2011 May;28(5):391–397. PubMed PMID: 21327499; PubMed Central PMCID: PMCPMC3151360. eng.
  • Simon L, Zini A, Dyachenko A, et al. 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 Jan-Feb;19(1):80–90. PubMed PMID: 27345006; PubMed Central PMCID: PMCPMC5227680. eng.
  • Collins JA, Barnhart KT, Schlegel PN. Do sperm DNA integrity tests predict pregnancy with in vitro fertilization? Fertil Steril. 2008 Apr 01;89(4):823–831.
  • Rilcheva VS, Ayvazova NP, Ilieva LO, et al. Sperm DNA integrity test and assisted reproductive technology (art) outcome. J Biomed Clin Res. 2016;9(1):21. English.
  • Zhao J, Zhang Q, Wang Y, et al. Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Fertil Steril. 2014 Oct 01;102(4):998–1005.e8.
  • 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. PubMed PMID: 27832085; PubMed Central PMCID: PMCPMC5104467. eng.
  • Robinson L, Gallos ID, Conner SJ, et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod. 2012;27(10):2908–2917.
  • Khadem N, Poorhoseyni A, Jalali M, et al. Sperm DNA fragmentation in couples with unexplained recurrent spontaneous abortions. Andrologia. 2014;46(2):126–130.
  • Agarwal A, Majzoub A, Esteves SC, et al. Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios. Transl Androl Urol. 2016 Dec;5(6):935–950. PubMed PMID: 28078226; PubMed Central PMCID: PMCPMC5182232. eng.
  • Gosálvez J, González-Martínez M, López-Fernández C, et al. Shorter abstinence decreases sperm deoxyribonucleic acid fragmentation in ejaculate. Fertil Steril. 2011 Nov 01;96(5):1083–1086.
  • Matsuura R, Takeuchi T, Yoshida A. Preparation and incubation conditions affect the DNA integrity of ejaculated human spermatozoa. Asian J Androl. 2010 Sep;12(5):753–759. PubMed PMID: 20562894; PubMed Central PMCID: PMCPMC3739315. eng.
  • Agarwal A, Durairajanayagam D, Du Plessis SS. Utility of antioxidants during assisted reproductive techniques: an evidence based review. ReprodBiol Endocrinol. 2014;12:112. PubMed PMID: 25421286; PubMed Central PMCID: PMCPMC4258799. eng.
  • Xue X, Wang WS, Shi JZ, et al. Efficacy of swim-up versus density gradient centrifugation in improving sperm deformity rate and DNA fragmentation index in semen samples from teratozoospermic patients. J Assist Reprod Genet. 2014 Sep;31(9):1161–1166. PubMed PMID: 25015033; PubMed Central PMCID: PMCPMC4156946. eng.
  • Martínez-Soto JC, Domingo JC, Cordobilla B, et al. Dietary supplementation with docosahexaenoic acid (DHA) improves seminal antioxidant status and decreases sperm DNA fragmentation systems biology in reproductive medicine. Syst Biol Reprod Med. 2016 Nov 01;62(6):387–395.
  • Abdelbaki SA, Sabry JH, Al-Adl AM, et al. The impact of coexisting sperm DNA fragmentation and seminal oxidative stress on the outcome of varicocelectomy in infertile patients: a prospective controlled study. Arab J Urol. 2017;15(2):131–139.
  • Bradley C, McArthur S, Gee A, et al. Intervention improves assisted conception intracytoplasmic sperm injection outcomes for patients with high levels of sperm DNA fragmentation: a retrospective analysis. Andrology. 2016;4(5):903–910.
  • Mayorga-Torres JM, Agarwal A, Roychoudhury S, et al. Can a short term of repeated ejaculations affect seminal parameters? J Reprod Infertil. 2016 Jul-Sep;17(3):177–183. PubMed PMID: 27478772; PubMed Central PMCID: PMCPMC4947206. eng.
  • Shen Z-Q, Shi B, Wang T-R, et al. Characterization of the sperm proteome and reproductive outcomes with in vitro fertilization after a reduction in male ejaculatory abstinence period. Mol Cell Proteomics. 2018;mcp.RA117.000541. DOI:10.1074/mcp.RA117.000541
  • Nabi A, Khalili MA, Halvaei I, et al. Prolonged incubation of processed human spermatozoa will increase DNA fragmentation. Andrologia. 2014;46(4):374–379.
  • Muratori M, Tarozzi N, Cambi M, et al. Variation of DNA fragmentation levels during density gradient sperm selection for assisted reproduction techniques: a possible new male predictive parameter of pregnancy? Medicine (Baltimore). 2016 May;95(20):e3624. PubMed PMID: 27196465; PubMed Central PMCID: PMCPMC4902407. eng.
  • Zini A, Finelli A, Phang D, et al. Influence of semen processing technique on human sperm DNA integrity. Urology. 2000 Dec 01;56(6):1081–1084.
  • Smith R, Kaune H, Parodi D, et al. Increased sperm DNA damage in patients with varicocele: relationship with seminal oxidative stress. Hum Reprod. 2005;21(4):986–993.
  • Kamkar N, Ramezanali F, Sabbaghian M. The relationship between sperm DNA fragmentation, free radicals and antioxidant capacity with idiopathic repeated pregnancy loss. Reprod Biol. 2018 Dec 01;18(4):330–335.
  • Showell MG, Mackenzie‐Proctor R, Brown J, et al. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2014;(12). PubMed PMID: CD007411. DOI:10.1002/14651858.CD007411.pub3
  • Ménézo YJR, Hazout A, Panteix G, et al. Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect. Reprod Biomed Online. 2007 Jan 01;14(4):418–421.
  • Roque M, Esteves SC. Effect of varicocele repair on sperm DNA fragmentation: a review [journal article]. Int Urol Nephrol. 2018 Apr 01;50(4):583–603.
  • Ni K, Steger K, Yang H, et al. Sperm protamine mRNA ratio and DNA fragmentation index represent reliable clinical biomarkers for men with varicocele after microsurgical varicocele ligation. J Urol. 2014;192(1):170–176.
  • Mehta A, Bolyakov A, Schlegel PN, et al. Higher pregnancy rates using testicular sperm in men with severe oligospermia. Fertil Steril. 2015 Dec 01;104(6):1382–1387.
  • Esteves SC, Roque M, Bradley CK, et al. 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.e1.
  • Arafa M, AlMalki A, AlBadr M, et al. ICSI outcome in patients with high DNA fragmentation: testicular versus ejaculated spermatozoa. Andrologia. 2018;50(1):e12835.
  • Esteves SC, Roque M, Garrido N. Use of testicular sperm for intracytoplasmic sperm injection in men with high sperm DNA fragmentation: a SWOT analysis. Asian J Androl. 2018 Jan-Feb;20(1):1–8. PubMed PMID: 28440264; PubMed Central PMCID: PMCPMC5753543. eng.
  • Sharma R, Said T, Agarwal A. Sperm DNA damage and its clinical relevance in assessing reproductive outcome. Asian J Androl. 2004;6(2):139–148.
  • Cho CL, Agarwal A, Majzoub A, et al. Future direction in sperm DNA fragmentation testing. Transl Androl Urol. 2017 Sep;6(Suppl 4):S525–s526. PubMed PMID: 29082977; PubMed Central PMCID: PMCPMC5643689. eng.
  • Agarwal A, Cho CL, Majzoub A, et al. The Society for Translational Medicine: clinical practice guidelines for sperm DNA fragmentation testing in male infertility. Transl Androl Urol. 2017 Sep;6(Suppl 4):S720–S733. PubMed PMID: 29082206; PubMed Central PMCID: PMCPmc5643607. eng.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.