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What should be done for men with sperm DNA fragmentation?

  • Received : 2018.08.17
  • Accepted : 2018.08.24
  • Published : 2018.09.30

Abstract

In an age when a small quantity of sperm can lead to pregnancy through in vitro fertilization or intracytoplasmic sperm injection, selecting healthy sperm is important. Sperm DNA fragmentation (SDF) is known to be higher in infertile men. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and the alkaline comet test are SDF tests that directly measure DNA damage and have shown closer correlations with assisted reproduction results than indirect tools such as the sperm chromatin structure assay or the sperm chromatic dispersion test. It is difficult; however, to endorse a single test as the best test overall; instead, it is best to select a testing method based on each patient's clinical condition and goals. In a couple struggling with infertility, if the male partner has a high level of SDF, he should aim to decrease SDF through lifestyle modifications, antioxidant treatment, and ensuring an appropriate duration of abstinence, and physicians need to treat the underlying diseases of such patients. If sperm DNA damage continues despite the patient's and physician's efforts, other methods, such as micromanipulation-based sperm selection or testicular sperm extraction, should be used to select healthy sperm with nuclear DNA integrity.

Keywords

References

  1. Fleming S, Green S, Hall J. Analysis and alleviation of male infertility. Microsc Anal 1995;35:37-9.
  2. Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST, Coutifaris C, et al. Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med 2001;345:1388-93. https://doi.org/10.1056/NEJMoa003005
  3. Agarwal A, Allamaneni SS. Sperm DNA damage assessment: a test whose time has come. Fertil Steril 2005;84:850-3. https://doi.org/10.1016/j.fertnstert.2005.03.080
  4. Irvine DS, Twigg JP, Gordon EL, Fulton N, Milne PA, Aitken RJ. DNA integrity in human spermatozoa: relationships with semen quality. J Androl 2000;21:33-44.
  5. Agarwal A, Said TM. Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update 2003;9:331-45. https://doi.org/10.1093/humupd/dmg027
  6. Zini A, Bielecki R, Phang D, Zenzes MT. Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertil Steril 2001;75:674-7. https://doi.org/10.1016/S0015-0282(00)01796-9
  7. Oleszczuk K, Augustinsson L, Bayat N, Giwercman A, Bungum M. Prevalence of high DNA fragmentation index in male partners of unexplained infertile couples. Andrology 2013;1:357-60. https://doi.org/10.1111/j.2047-2927.2012.00041.x
  8. Evgeni E, Lymberopoulos G, Gazouli M, Asimakopoulos B. Conventional semen parameters and DNA fragmentation in relation to fertility status in a Greek population. Eur J Obstet Gynecol Reprod Biol 2015;188:17-23. https://doi.org/10.1016/j.ejogrb.2015.02.026
  9. Twigg JP, Irvine DS, Aitken RJ. Oxidative damage to DNA in human spermatozoa does not preclude pronucleus formation at intracytoplasmic sperm injection. Hum Reprod 1998;13:1864-71. https://doi.org/10.1093/humrep/13.7.1864
  10. Gorczyca W, Gong J, Darzynkiewicz Z. Detection of DNA strand breaks in individual apoptotic cells by the in situ terminal deoxynucleotidyl transferase and nick translation assays. Cancer Res 1993;53:1945-51.
  11. Tarozzi N, Bizzaro D, Flamigni C, Borini A. Clinical relevance of sperm DNA damage in assisted reproduction. Reprod Biomed Online 2007;14:746-57. https://doi.org/10.1016/S1472-6483(10)60678-5
  12. Sergerie M, Laforest G, Bujan L, Bissonnette F, Bleau G. Sperm DNA fragmentation: threshold value in male fertility. Hum Reprod 2005;20:3446-51. https://doi.org/10.1093/humrep/dei231
  13. Sun JG, Jurisicova A, Casper RF. Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro. Biol Reprod 1997;56:602-7. https://doi.org/10.1095/biolreprod56.3.602
  14. Lopes S, Sun JG, Jurisicova A, Meriano J, Casper RF. Sperm deoxyribonucleic acid fragmentation is increased in poor-quality semen samples and correlates with failed fertilization in intracytoplasmic sperm injection. Fertil Steril 1998;69:528-32. https://doi.org/10.1016/S0015-0282(97)00536-0
  15. Duran EH, Morshedi M, Taylor S, Oehninger S. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod 2002;17:3122-8. https://doi.org/10.1093/humrep/17.12.3122
  16. Benchaib M, Braun V, Lornage J, Hadj S, Salle B, Lejeune H, et al. Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. Hum Reprod 2003;18:1023-8. https://doi.org/10.1093/humrep/deg228
  17. Borini A, Tarozzi N, Bizzaro D, Bonu MA, Fava L, Flamigni C, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod 2006;21:2876-81. https://doi.org/10.1093/humrep/del251
  18. Evgeni E, Charalabopoulos K, Asimakopoulos B. Human sperm DNA fragmentation and its correlation with conventional semen parameters. J Reprod Infertil 2014;15:2-14.
  19. Gold R, Schmied M, Rothe G, Zischler H, Breitschopf H, Wekerle H, et al. Detection of DNA fragmentation in apoptosis: application of in situ nick translation to cell culture systems and tissue sections. J Histochem Cytochem 1993;41:1023-30. https://doi.org/10.1177/41.7.8515045
  20. Evenson DP, Darzynkiewicz Z, Melamed MR. Comparison of human and mouse sperm chromatin structure by flow cytometry. Chromosoma 1980;78:225-38. https://doi.org/10.1007/BF00328394
  21. 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 Androl 2002;23:25-43. https://doi.org/10.1002/j.1939-4640.2002.tb02599.x
  22. 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. https://doi.org/10.1016/S0015-0282(99)00462-8
  23. Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril 2004;81:1289-95. https://doi.org/10.1016/j.fertnstert.2003.09.063
  24. Fraser L. Structural damage to nuclear DNA in mammalian spermatozoa: its evaluation techniques and relationship with male infertility. Pol J Vet Sci 2004;7:311-21.
  25. Spano M, Kolstad AH, Larsen SB, Cordelli E, Leter G, Giwercman A, et al. The applicability of the flow cytometric sperm chromatin structure assay in epidemiological studies. Asclepios Hum Reprod 1998;13:2495-505. https://doi.org/10.1093/humrep/13.9.2495
  26. Boe-Hansen GB, Ersboll AK, Christensen P. Variability and laboratory factors affecting the sperm chromatin structure assay in human semen. J Androl 2005;26:360-8. https://doi.org/10.2164/jandrol.04056
  27. McKelvey-Martin VJ, Melia N, Walsh IK, Johnston SR, Hughes CM, Lewis SE, et al. Two potential clinical applications of the alkaline single-cell gel electrophoresis assay: (1) human bladder washings and transitional cell carcinoma of the bladder; and (2) human sperm and male infertility. Mutat Res 1997;375:93-104. https://doi.org/10.1016/S0027-5107(97)00005-5
  28. Ostling O, Johanson KJ. Microelectrophoretic study of radiationinduced DNA damages in individual mammalian cells. Biochem Biophys Res Commun 1984;123:291-8. https://doi.org/10.1016/0006-291X(84)90411-X
  29. Klaude M, Eriksson S, Nygren J, Ahnstrom G. The comet assay: mechanisms and technical considerations. Mutat Res 1996;363:89-96. https://doi.org/10.1016/0921-8777(95)00063-1
  30. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988;175:184-91. https://doi.org/10.1016/0014-4827(88)90265-0
  31. Simon L, Murphy K, Shamsi MB, Liu L, Emery B, Aston KI, et al. Paternal influence of sperm DNA integrity on early embryonic development. Hum Reprod 2014;29:2402-12. https://doi.org/10.1093/humrep/deu228
  32. Lewis SE, Agbaje IM. Using the alkaline comet assay in prognostic tests for male infertility and assisted reproductive technology outcomes. Mutagenesis 2008;23:163-70. https://doi.org/10.1093/mutage/gem052
  33. Donnelly ET, Steele EK, McClure N, Lewis SE. Assessment of DNA integrity and morphology of ejaculated spermatozoa from fertile and infertile men before and after cryopreservation. Hum Reprod 2001;16:1191-9. https://doi.org/10.1093/humrep/16.6.1191
  34. Olive PL, Durand RE, Banath JP, Johnston PJ. Analysis of DNA damage in individual cells. Methods Cell Biol 2001;64:235-49.
  35. Enciso M, Sarasa J, Agarwal A, Fernandez JL, Gosalvez J. A twotailed Comet assay for assessing DNA damage in spermatozoa. Reprod Biomed Online 2009;18:609-16. https://doi.org/10.1016/S1472-6483(10)60003-X
  36. Fernandez JL, Muriel L, Rivero MT, Goyanes V, Vazquez R, Alvarez JG. The sperm chromatin dispersion test: a simple method for the determination of sperm DNA fragmentation. J Androl 2003;24:59-66. https://doi.org/10.1002/j.1939-4640.2003.tb02748.x
  37. Zini A. Are sperm chromatin and DNA defects relevant in the clinic? Syst Biol Reprod Med 2011;57:78-85. https://doi.org/10.3109/19396368.2010.515704
  38. Bungum M, Humaidan P, Axmon A, Spano M, Bungum L, Erenpreiss J, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod 2007;22:174-9. https://doi.org/10.1093/humrep/del326
  39. Muriel L, Meseguer M, Fernandez JL, Alvarez J, Remohi J, Pellicer A, et al. Value of the sperm chromatin dispersion test in predicting pregnancy outcome in intrauterine insemination: a blind prospective study. Hum Reprod 2006;21:738-44. https://doi.org/10.1093/humrep/dei403
  40. Seli E, Gardner DK, Schoolcraft WB, Moffatt O, Sakkas D. Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. Fertil Steril 2004;82:378-83. https://doi.org/10.1016/j.fertnstert.2003.12.039
  41. Meseguer M, Martinez-Conejero JA, O'Connor JE, Pellicer A, Remohi J, Garrido N. The significance of sperm DNA oxidation in embryo development and reproductive outcome in an oocyte donation program: a new model to study a male infertility prognostic factor. Fertil Steril 2008;89:1191-9. https://doi.org/10.1016/j.fertnstert.2007.05.005
  42. Simon L, Liu L, Murphy K, Ge S, Hotaling J, Aston KI, et al. Comparative analysis of three sperm DNA damage assays and sperm nuclear protein content in couples undergoing assisted reproduction treatment. Hum Reprod 2014;29:904-17. https://doi.org/10.1093/humrep/deu040
  43. Zhang Z, Zhu L, Jiang H, Chen H, Chen Y, Dai Y. Sperm DNA fragmentation index and pregnancy outcome after IVF or ICSI: a meta-analysis. J Assist Reprod Genet 2015;32:17-26. https://doi.org/10.1007/s10815-014-0374-1
  44. Collins JA, Barnhart KT, Schlegel PN. Do sperm DNA integrity tests predict pregnancy with in vitro fertilization? Fertil Steril 2008;89:823-31. https://doi.org/10.1016/j.fertnstert.2007.04.055
  45. Anifandis G, Bounartzi T, Messini CI, Dafopoulos K, Markandona R, Sotiriou S, et al. Sperm DNA fragmentation measured by Halosperm does not impact on embryo quality and ongoing pregnancy rates in IVF/ICSI treatments. Andrologia 2015;47:295-302. https://doi.org/10.1111/and.12259
  46. Wdowiak A, Bakalczuk S, Bakalczuk G. The effect of sperm DNA fragmentation on the dynamics of the embryonic development in intracytoplasmatic sperm injection. Reprod Biol 2015;15:94-100. https://doi.org/10.1016/j.repbio.2015.03.003
  47. Osman A, Alsomait H, Seshadri S, El-Toukhy T, Khalaf Y. The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis. Reprod Biomed Online 2015;30:120-7. https://doi.org/10.1016/j.rbmo.2014.10.018
  48. 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.
  49. Zini A, Sigman M. Are tests of sperm DNA damage clinically useful? Pros and cons. J Androl 2009;30:219-29. https://doi.org/10.2164/jandrol.108.006908
  50. Simon L, Emery BR, Carrell DT. Review: diagnosis and impact of sperm DNA alterations in assisted reproduction. Best Pract Res Clin Obstet Gynaecol 2017;44:38-56. https://doi.org/10.1016/j.bpobgyn.2017.07.003
  51. Ola B, Afnan M, Sharif K, Papaioannou S, Hammadieh N, Barratt CL. Should ICSI be the treatment of choice for all cases of in-vitro conception? Considerations of fertilization and embryo development, cost effectiveness and safety. Hum Reprod 2001;16:2485-90. https://doi.org/10.1093/humrep/16.12.2485
  52. Zini A, Boman JM, 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;23:2663-8. https://doi.org/10.1093/humrep/den321
  53. Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod 2012;27:2908-17. https://doi.org/10.1093/humrep/des261
  54. Carrell DT, Liu L, Peterson CM, Jones KP, Hatasaka HH, Erickson L, et al. Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss. Arch Androl 2003;49:49-55. https://doi.org/10.1080/01485010290099390
  55. Check JH, Graziano V, Cohen R, Krotec J, Check ML. Effect of an abnormal sperm chromatin structural assay (SCSA) on pregnancy outcome following (IVF) with ICSI in previous IVF failures. Arch Androl 2005;51:121-4. https://doi.org/10.1080/014850190518125
  56. Khadem N, Poorhoseyni A, Jalali M, Akbary A, Heydari ST. Sperm DNA fragmentation in couples with unexplained recurrent spontaneous abortions. Andrologia 2014;46:126-30. https://doi.org/10.1111/and.12056
  57. Pacey AA. Environmental and lifestyle factors associated with sperm DNA damage. Hum Fertil (Camb) 2010;13:189-93. https://doi.org/10.3109/14647273.2010.531883
  58. Askienazy-Elbhar M. Male genital tract infection: the point of view of the bacteriologist. Gynecol Obstet Fertil 2005;33:691-7. https://doi.org/10.1016/j.gyobfe.2005.07.008
  59. Sakkas D, Alvarez JG. Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil Steril 2010;93:1027-36. https://doi.org/10.1016/j.fertnstert.2009.10.046
  60. Imamovic Kumalic S, Pinter B. Review of clinical trials on effects of oral antioxidants on basic semen and other parameters in idiopathic oligoasthenoteratozoospermia. Biomed Res Int 2014;2014:426951.
  61. Hosen MB, Islam MR, Begum F, Kabir Y, Howlader MZ. Oxidative stress induced sperm DNA damage, a possible reason for male infertility. Iran J Reprod Med 2015;13:525-32.
  62. Zini A, San Gabriel M, Baazeem A. Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod Genet 2009;26:427-32. https://doi.org/10.1007/s10815-009-9343-5
  63. Greco E, Romano S, Iacobelli M, Ferrero S, Baroni E, Minasi MG, et al. ICSI in cases of sperm DNA damage: beneficial effect of oral antioxidant treatment. Hum Reprod 2005;20:2590-4. https://doi.org/10.1093/humrep/dei091
  64. Tremellen K, Miari G, Froiland D, Thompson J. A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment. Aust N Z J Obstet Gynaecol 2007;47:216-21. https://doi.org/10.1111/j.1479-828X.2007.00723.x
  65. Kimura M, Nagao K. Role of varicocele repair for male infertility in the era of assisted reproductive technologies. Reprod Med Biol 2014;13:185-92. https://doi.org/10.1007/s12522-014-0181-5
  66. Zini A, Dohle G. Are varicoceles associated with increased deoxyribonucleic acid fragmentation? Fertil Steril 2011;96:1283-7. https://doi.org/10.1016/j.fertnstert.2011.10.016
  67. 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;18:186-93. https://doi.org/10.4103/1008-682X.170441
  68. Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril 2015;103:e18-25.
  69. Moskovtsev SI, Alladin N, Lo KC, Jarvi K, Mullen JB, Librach CL. A comparison of ejaculated and testicular spermatozoa aneuploidy rates in patients with high sperm DNA damage. Syst Biol Reprod Med 2012;58:142-8. https://doi.org/10.3109/19396368.2012.667504
  70. Esteves SC, Agarwal A. Reproductive outcomes, including neonatal data, following sperm injection in men with obstructive and nonobstructive azoospermia: case series and systematic review. Clinics (Sao Paulo) 2013;68 Suppl 1:141-50.
  71. Esteves SC, Sanchez-Martin F, Sanchez-Martin P, Schneider DT, Gosalvez J. Comparison of reproductive outcome in oligozoospermic men with high sperm DNA fragmentation undergoing intracytoplasmic sperm injection with ejaculated and testicular sperm. Fertil Steril 2015;104:1398-405. https://doi.org/10.1016/j.fertnstert.2015.08.028
  72. Esteves SC. Should a couple with failed in vitro fertilization or intracytoplasmic sperm injection and elevated sperm DNA fragmentation use testicular sperm for the next cycle? Eur Urol Focus 2018 Jun 20 [Epub]. http://doi.org/10.1016/j.euf.2018.06.001.

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