Antioxidant therapy in male infertility: Fact or fiction?

Asian Journal of Andrology

Volumn 13, Issue 3, 2011, Pages 374-381

  Zini, Armand ^a   Al Hathal, Naif ^a  

^a ROYAL VICTORIA HOSPITAL   (Canada)

Author keywords

antioxidant; male infertility; oxidative stress; sperm DNA fragmentation; vitamins

Indexed keywords

ANTIOXIDANT; REACTIVE OXYGEN METABOLITE;

ARTICLE; CRYOPRESERVATION; DIET SUPPLEMENTATION; DNA DAMAGE; HUMAN; MALE; MALE GENITAL SYSTEM DISEASE; MALE INFERTILITY; OXIDATIVE STRESS; PREGNANCY; SPERM; SPERM DYSFUNCTION; SPERMATOZOON; SPERMATOZOON MOTILITY; THAWING;

ANTIOXIDANTS; DIETARY SUPPLEMENTS; DNA DAMAGE; HUMANS; INFERTILITY, MALE; MALE; OXIDATIVE STRESS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; REACTIVE OXYGEN SPECIES; SEMEN; SPERMATOZOA;

EID: 79955653567     PISSN: 1008682X     EISSN: 17457262     Source Type: Journal    
DOI: 10.1038/aja.2010.182     Document Type: Article

References (114)

1. Zini A, San Gabriel M, Baazeem A. Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod Genet 2009; 26: 427-32.
2. Aitken RJ, de Iuliis GN, Finnie JM, Hedges A, Mc Lachlan RI. Analysis of the relationships between oxidative stress, DNA damage and sperm vitality in a patient population: development of diagnostic criteria. Hum Reprod 2010; 25: 2415-26.
3. Fraga CG, Motchnik PA, Shigenaga MK, Helbock HJ, Jacob RA et al. Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci USA 1991; 88: 11003-6. (Pubitemid 21915967)
4. Iwasaki A, Gagnon C. Formation of reactiveoxygenspecies inspermatozoaof infertile patients. Fertil Steril 1992; 57: 409-16.
5. Zini A, Sigman M. Are tests of sperm DNA damage clinically useful? Pros and cons. J Androl 2009; 30: 219-29.
6. Agarwal A, Nallella KP, Allamaneni SS, Said TM. Role of antioxidants in treatment of male infertility: an overviewofthe literature. Reprod Biomed Online 2004; 8: 616-27. (Pubitemid 38744936)
7. Aitken RJ, Paterson M, Fisher H, Buckingham DW, van Duin M. Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function. J Cell Sci 1995; 108 (Pt 5): 2017-25.
8. Griveau JF, Le Lannou D. Reactive oxygen species and human spermatozoa: physiology and pathology. Int J Androl 1997; 20: 61-9. (Pubitemid 27390290)
9. de Lamirande E, Jiang H, Zini A, Kodama H, Gagnon C Reactive oxygen speciesand sperm physiology. Rev Reprod 1997; 2: 48-54. (Pubitemid 27165966)
10. Aitken RJ, Clarkson JS. Cellular basis of defectivesperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 1987;81: 459-69. (Pubitemid 17160425)
11. de Lamirande E, Gagnon C Reactive oxygen species and human spermatozoa. I. Effects on the motility of intact spermatozoa and on sperm axonemes. J Androl 1992;13:368-78.
12. Zini A, Garrels K, Phang D. Antioxidant activity in the semen of fertile and infertile men. Urology 2000; 55: 922-6. (Pubitemid 30330801)
13. Alvarez JG, Touchstone JC, Blasco L, Storey BT. Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as major enzyme protectant against oxygen toxicity. J Androl 1987; 8: 338-48.
14. Twigg J, Fulton N, Gomez E, Irvine DS, Aitken RJ. Analysis of the impact of intracellular reactive oxygen species generation on the structural and functional integrity of human spermatozoa: lipid peroxidation, DNA fragmentation and effectiveness of antioxidants. Hum Reprod 1998; 13: 1429-36. (Pubitemid 28310468)
15. Tremellen K. Oxidative stress and male infertility\a clinical perspective. Hum Reprod Update 2008; 14: 243-58. (Pubitemid 351566975)
16. Saleh RA, Agarwal A. Oxidative stress and male infertility: from research bench to clinical practice. J Androl 2002; 23: 737-52. (Pubitemid 36300961)
17. Chabory E, Damon C, Lenoir A, Kauselmann G, Kern H et al. Epididymis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice. J Clin Invest 2009; 119: 2074-85.
18. Weir CP, Robaire B. Spermatozoa havedecreasedantioxidantenzymaticcapacityand increased reactive oxygen species production during aging in the Brown Norway rat. J Androl 2007; 28: 229-40. (Pubitemid 46423904)
19. Zini A, de Lamirande E, Gagnon C Low levels of nitric oxide promote human sperm capacitation in vitro. J Androl 1995; 16: 424-31.
20. Smith R, Vantman D, Ponce J, Escobar J, Lissi E. Total antioxidant capacity of human seminal plasma. Hum Reprod 1996; 11: 1655-60. (Pubitemid 26318905)
21. Zini A, de Lamirande E, Gagnon C Reactive oxygen species in semen of infertile patients: levels of superoxide dismutase-and catalase-like activities in seminal plasma and spermatozoa. Int J Androl 1993; 16: 183-8. (Pubitemid 23241013)
22. Kobayashi T, Miyazaki T, Natori M, Nozawa S. ProtectiveRole of superoxidedismutase in human sperm motility: superoxidedismutase activity and lipid peroxide in human seminal plasma and spermatozoa. Hum Reprod 1991; 6: 987-91.
23. Zini A, Schlegel PN. Catalase mRNA expression in the male rat reproductive tract. J Androl 1996; 17: 473-80. (Pubitemid 26403607)
24. Thiele JJ, Friesleben HJ, Fuchs J, Ochsendorf FR. Ascorbic acid and urate in human seminal plasma: determination and interrelationships with chemiluminescence in washedsemen. Hum Reprod 1995; 10: 110-5.
25. Kalthur G, Adiga SK, Upadhya D, Rao S, Kumar P. Effect of cryopreservation onsperm DNA integrityin patientswithteratospermia. Fertil Steril 2008; 89: 1723-7. (Pubitemid 351749640)
26. Tauber PF, Zaneveld LJ, Propping D, Schumacher GF. Components of human split ejaculates. I. Spermatozoa, fructose, immunoglobulins, albumin, lactoferrin, transferrin and other plasma proteins. J Reprod Fertil 1975; 43: 249-67.
27. Lewis SE, Sterling ES, Young IS, Thompson W. Comparison of individual antioxidants of sperm and seminal plasma in fertile and infertile men. Fertil Steril 1997; 67: 142-7. (Pubitemid 26428428)
28. Sanocka D, Miesel R, Jedrzejczak P, Kurpisz MK. Oxidativestressandmale infertility. J Androl 1996; 17: 449-54.
29. Appasamy M, Muttukrishna S, Pizzey AR, Ozturk O, Groome NP et al. Relationship between male reproductive hormones, sperm DNA damage and markers of oxidative stress in infertility. Reprod Biomed Online 2007; 14: 159-65. (Pubitemid 46296498)
30. Verit FF, Verit A, Kocyigit A, Ciftci H, Celik H et al. No increase insperm DNAdamage andseminaloxidativestressinpatientswith idiopathic infertility. Arch Gynecol Obstet 2006; 274: 339-44. (Pubitemid 44440531)
31. Lewis SE, Boyle PM, Mc Kinney KA, Young IS, Thompson W.Total antioxidant capacity of seminal plasma is different in fertile and infertile men. Fertil Steril 1995; 64: 868-70.
32. Hampl JS, Taylor CA, Johnston CS. Vitamin C deficiency and depletion in the United States: the Third National Health and Nutrition Examination Survey, 1988 to 1994. Am J Public Health 2004; 94: 870-5. (Pubitemid 38560397)
33. Jacob RA. Assessment of human vitamin C status. J Nutr 1990; 120 (Suppl 11): 1480-5.
34. Ryle PR, Thomson AD. Nutrition and vitamins in alcoholism. Contemp Issues Clin Biochem 1984; 1: 188-224.
35. Silver EW, Eskenazi B, Evenson DP, Block G, Young Set al. Effect of antioxidant intake onspermchromatinstability in healthynonsmokingmen. J Androl 2005; 26: 550-6. (Pubitemid 40847868)
36. Henkel RR. Leukocytes and oxidative stress: dilemma for sperm function and male fertility. Asian J Androl 2011; 13: 43-52.
37. Comhaire FH, El Garem Y, Mahmoud A, Eertmans F, Schoonjans F. Combined conventional/antioxidant "Astaxanthin" treatment for male infertility: a double blind, randomizedtrial. Asian J Androl 2005; 7: 257-62. (Pubitemid 41288547)
38. Comhaire FH, Christophe AB, Zalata AA, Dhooge WS, Mahmoud AM et al. The Effects of combined conventional treatment, oral antioxidants and essential fatty acids on sperm biology in subfertilemen. Prostaglandins Leukot Essent Fatty Acids 2000; 63: 159-65.
39. Suleiman SA, Ali ME, Zaki ZM, el-Malik EM, Nasr MA. Lipid peroxidation and human sperm motility: protectiveRole ofvitamin E. J Androl 1996; 17: 530-7. (Pubitemid 26403614)
40. Lenzi A, Culasso F, Gandini L, Lombardo F, Dondero F. Placebo-controlled, double-blind, cross-overtrial of glutathionetherapyin male infertility. Hum Reprod 1993; 8: 1657-62. (Pubitemid 23299785)
41. Keskes-Ammar L, Feki-Chakroun N, Rebai T, Sahnoun Z, Ghozzi H et al. Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Arch Androl 2003; 49: 83-94. (Pubitemid 36269762)
42. Balercia G, Regoli F, Armeni T, Koverech A, Mantero F et al. Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoo-spermia. Fertil Steril 2005; 84: 662-71. (Pubitemid 41317725)
43. Scott R, Mac Pherson A, Yates RW, Hussain B, Dixon J. The effect of oral selenium supplementation on human sperm motility. Br J Urol 1998; 82: 76-80. (Pubitemid 28316672)
44. Cavallini G, Ferraretti AP, Gianaroli L, Biagiotti G, Vitali G. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia. J Androl 2004; 25: 761-70; discussion 71-2. (Pubitemid 39096312)
45. Ciftci H, Verit A, Savas M, Yeni E, Erel O. Effects of N-acetylcysteine on semen parametersand oxidative/antioxidant status. Urology 2009; 74: 73-6.
46. Dawson EB, Harris WA, Teter MC, Powell LC. Effect of ascorbicacidsupplementation on the sperm qualityof smokers. Fertil Steril 1992; 58: 1034-9.
47. Ebisch IM, Pierik FH, de Jong FH, Thomas CM, Steegers-Theunissen RP. Does folic acid and zinc sulphate intervention affect endocrine parameters and sperm characteristics in men? Int J Androl 2006; 29: 339-45. (Pubitemid 43383400)
48. Hawkes WC, Alkan Z, Wong K. Selenium supplementation does not affect testicular selenium status or semen quality in North American men. J Androl 2009; 30: 525-33.
49. Lenzi A, Lombardo F,Sgro P,Salacone P,Caponecchia Let al. Use of carnitinetherapy in selected cases of malefactor infertility: a double-blind crossovertrial. Fertil Steril 2003; 79: 292-300. (Pubitemid 36144052)
50. Mahajan SK, Abbasi AA, Prasad AS, Rabbani P, Briggs WA et al. Effect of oral zinc therapy on gonadal function in hemodialysis patients. A double-blind study. Ann Intern Med 1982; 97: 357-61. (Pubitemid 12061583)
51. Omu AE, Al-Azemi MK, Kehinde EO, Anim JT, Oriowo MA et al. Indications of the mechanisms involved in improvedsperm parametersbyzinctherapy. Med Princ Pract 2008; 17: 108-16. (Pubitemid 351301295)
52. Omu AE, Dashti H, Al-Othman S. Treatment Of asthenozoospermia with zincsulphate: andrological, immunological and obstetric outcome. Eur J Obstet Gynecol Reprod Biol 1998;79:179-84. (Pubitemid 28294911)
53. Piomboni P, Gambera L, Serafini F, Campanella G, Morgante G et al. Sperm quality improvement after natural anti-oxidant treatment of asthenoteratospermic men with leukocytospermia. Asian J Androl 2008; 10: 201-6. (Pubitemid 351337980)
54. Safarinejad MR, Safarinejad S. Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. J Urol 2009; 181: 741-51.
55. Wong WY, Merkus HM, Thomas CM, Menkveld R, Zielhuis GA et al. Effects of folicacid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlledtrial. Fertil Steril 2002; 77: 491-8. (Pubitemid 34177203)
56. Kessopoulou E, Powers HJ, Sharma KK, Pearson MJ, Russell JM et al. Adouble-blind randomized placebocross-overcontrolledtrial usingtheantioxidantvitamin Etotreat reactiveoxygen species associated male infertility. Fertil Steril 1995; 64: 825-31.
57. Moilanen J, Hovatta O, Lindroth L.Vitamin E levels inseminal plasmacan beelevated by oral administration of vitamin E in infertile men. Int J Androl 1993; 16: 165-6. (Pubitemid 23185890)
58. Rolf C, Cooper TG, Yeung CH, Nieschlag E. Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. Hum Reprod 1999; 14: 1028-33. (Pubitemid 29176484)
59. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S et al. Reduction of the incidence of sperm DNA fragmentationbyoral antioxidant treatment. J Androl 2005; 26: 349-53. (Pubitemid 40628971)
60. Sigman M, Glass S, Campagnone J, Pryor JL. Carnitineforthetreatment of idiopathic asthenospermia: a randomized, double-blind, placebo-controlled trial. Fertil Steril 2006;85:1409-14.
61. Paradiso Galatioto G, Gravina GL, Angelozzi G, Sacchetti A, Innominato PF et al. May antioxidant therapy improve sperm parameters of men with persistent oligospermia after retrogradeembolization for varicocele? World J Urol 2008; 26: 97-102.
62. Gil-Villa AM, Cardona-Maya W, Agarwal A, Sharma R, Cadavid A. Role of malefactor inearly recurrent embryo loss: do antioxidants have any effect? Fertil Steril 2009; 92: 565-71.
63. Greco E, Romano S, Iacobelli M, Ferrero S, Baroni E et al. ICSI in cases of sperm DNA damage: beneficial Effect of oral antioxidanttreatment. Hum Reprod 2005; 20: 2590-4. (Pubitemid 41222514)
64. Greco E, Scarselli F, Iacobelli M, Rienzi L, Ubaldi F et al. Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Hum Reprod 2005; 20: 226-30.
65. Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertil Steril 1997; 68: 519-24. (Pubitemid 27412924)
66. Menezo YJ, Hazout A, Panteix G, Robert F, Rollet J et al. Antioxidant storeducesperm DNA fragmentation: an unexpected adverse effect. Reprod Biomed Online 2007; 14: 418-21. (Pubitemid 46584375)
67. 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 NZJ Obstet Gynaecol 2007; 47: 216-21. (Pubitemid 46909301)
68. Tunc O, Thompson J, Tremellen K. Improvement in sperm DNAquality using an oral antioxidant therapy. Reprod Biomed Online 2009; 18: 761-8.
69. Steenken S. Structure, acid/base properties and transformation reactions of purine radicals. Free Radic Res Commun 1989; 6: 117-20. (Pubitemid 19141941)
70. Zini A, Kamal K, Phang D, Willis J, Jarvi K. Biologic variability of sperm DNA denaturation in infertile men. Urology 2001; 58: 258-61. (Pubitemid 32728067)
71. Smit M, Dohle GR, Hop WC, Wildhagen MF, Weber RF et al. Clinical correlates of the biological variation of sperm DNA fragmentation in infertile men attending an andrology outpatient clinic. Int J Androl 2007; 30: 48-55. (Pubitemid 46161040)
72. Evenson DP, Jost LK, Baer RK, Turner TW, Schrader SM. Individuality of DNA denaturation patterns in human sperm as measured by the sperm chromatin structure assay. Reprod Toxicol 1991; 5: 115-25.
73. De Iuliis GN, Thomson LK, Mitchell LA, Finnie JM, Koppers AJ et al. DNAdamage in human spermatozoa is highly correlated withthe efficiencyof chromatin remodeling and the formation of 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress. Biol Reprod 2007; 81: 517-24.
74. Aitken RJ, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod 1989; 41: 183-97. (Pubitemid 19246344)
75. Aitken RJ, Baker HW. Seminal leukocytes: passengers, terroristsor good samaritans? Hum Reprod 1995; 10: 1736-9.
76. Aitken RJ, Buckingham DW, Brindle J, Gomez E, Baker HW et al. Analysis of sperm movement in relation to the oxidative stress created by leukocytes in washed sperm preparationsandseminal plasma. Hum Reprod 1995; 10: 2061-71.
77. Anderson D, Schmid TE, Baumgartner A, Cemeli-Carratala E, Brinkworth MH et al. Oestrogeniccompoundsandoxidativestress(in humansperm and lymphocytes inthe Cometassay). Mutat Res 2003; 544: 173-8.
78. Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P et al. Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod 1998; 59: 1037-46. (Pubitemid 28498912)
79. Aitken RJ, Clarkson JS. Significance of reactive oxygen species and antioxidants in definingtheefficacyof sperm preparation techniques. J Androl 1988; 9: 367-76. (Pubitemid 19022029)
80. Aitken RJ, Buckingham D, Harkiss D. Use of axanthineoxidasefree radical generating system to investigate the cytotoxic effects of reactive oxygen species on human spermatozoa. J Reprod Fertil 1993; 97: 441-50. (Pubitemid 23127680)
81. Lopes S,Jurisicova A, Sun JG, Casper RF. Reactiveoxygenspecies: potentialcausefor DNA fragmentation in human spermatozoa. Hum Reprod 1998; 13: 896-900. (Pubitemid 28239194)
82. Potts RJ, Notarianni LJ, Jefferies TM. Seminal plasma reduces exogenous oxidative damageto human sperm, determined bythe measurementof DNAstrand breaksand lipid peroxidation. Mutat Res 2000; 447: 249-56. (Pubitemid 30177171)
83. Russo A, Troncoso N, Sanchez F, Garbarino JA, Vanella A. Propolis protects human spermatozoa from DNA damage caused by benzo[a]pyrene and exogenous reactive oxygen species. Life Sci 2006; 78: 1401-6. (Pubitemid 43233806)
84. Sierens J, Hartley JA, Campbell MJ, Leathem AJ, Woodside JV. In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm. Teratog Carcinog Mutagen 2002; 22: 227-34. (Pubitemid 34437650)
85. Bungum M, Humaidan P, Axmon A, Spano M, Bungum L et al. Sperm DNA integrity assessment in prediction of assisted reproduction technologyoutcome. Hum Reprod 2007; 22: 174-9. (Pubitemid 44942682)
86. Collins JA, Barnhart KT, Schlegel PN. Dosperm DNA integritytestspredict pregnancy with in vitrofertilization? Fertil Steril 2008; 89: 823-31. (Pubitemid 351491237)
87. Aitken RJ, Fisher HM, Fulton N, Gomez E, Knox W et al. Reactive oxygen species generation by human spermatozoa is induced byexogenous NADPH and inhibited by the flavoprotein inhibitors diphenylene iodonium and quinacrine. Mol Reprod Dev 1997; 47: 468-82. (Pubitemid 27273158)
88. Cemeli E, Schmid TE, Anderson D. Modulation byflavonoidsof DNAdamage induced by estrogen-like compounds. Environ Mol Mutagen 2004; 44: 420-6. (Pubitemid 40128661)
89. Dobrzynska MM, Baumgartner A, Anderson D. Antioxidants modulate thyroid hormone-and noradrenaline-induced DNA damage in human sperm. Mutagenesis 2004; 19: 325-30. (Pubitemid 39028958)
90. Muratori M, Piomboni P, Baldi E, Filimberti E, Pecchioli P et al. Functional and ultrastructural featuresof DNA-fragmented humansperm. J Androl 2000; 21: 903-12.
91. Said TM, Agarwal A,Sharma RK,Thomas AJ Jr,Sikka SC. Impact of sperm morphology on DNA damage caused by oxidative stress induced by beta-nicotinamide adenine dinucleotide phosphate. Fertil Steril 2005; 83: 95-103. (Pubitemid 40103581)
92. Libman J, Gabriel MS, Sairam MR, Zini A. Catalase can protect spermatozoa of FSH receptor knock-out mice against oxidant-induced DNA damage in vitro. Int J Androl 2010; 33: 818-22.
93. Griveau JF, Le Lannou D. Effects of antioxidants on human sperm preparation techniques. Int J Androl 1994; 17: 225-31. (Pubitemid 24351548)
94. Oeda T, Henkel R, Ohmori H, Schill WB. Scavenging effect of N-acetyl-L-cysteine against reactive oxygen species in human semen: a possible therapeutic modality for malefactor infertility? Andrologia 1997; 29: 125-31. (Pubitemid 27259313)
95. Verma A, Kanwar KC. Effect of vitamin E on human sperm motility and lipid peroxidation in vitro. Asian J Androl 1999; 1: 151-4.
96. Zheng RL, Zhang H. Effects of ferulic acid on fertile and asthenozoospermic infertile humansperm motility, viability, lipid peroxidation, andcyclic nucleotides. Free Radic Biol Med 1997; 22: 581-6. (Pubitemid 27043394)
97. Calamera JC, Fernandez PJ, Buffone MG,Acosta AA, Doncel GF. Effects of long-term invitro incubation of humanspermatozoa: functional parametersandcatalaseeffect. Andrologia 2001; 33: 79-86. (Pubitemid 33757134)
98. Chi HJ, Kim JH, Ryu CS, Lee JY, Park JS et al. Protective effect of antioxidant supplementation in sperm-preparation medium against oxidative stress in human spermatozoa. Hum Reprod 2008; 23: 1023-8. (Pubitemid 351757326)
99. Donnelly ET, Mc Clure N, Lewis SE. Glutathione and hypotaurine in vitro: effects on human sperm motility, DNA integrity and production of reactive oxygen species. Mutagenesis 2000; 15: 61-8. (Pubitemid 30071762)
100. Donnelly ET, Mc Clure N, Lewis SE. The effect of ascorbate and alpha-tocopherol supplementation in vitro on DNA integrity and hydrogen peroxide-induced DNA damage in human spermatozoa. Mutagenesis 1999; 14: 505-12.
101. Hughes CM, Lewis SE, Mc Kelvey-Martin VJ, Thompson W. The Effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity. Hum Reprod 1998; 13: 1240-7. (Pubitemid 28279177)
102. Esteves SC, Sharma RK, Thomas AJ Jr, Agarwal A. Cryopreservation of human spermatozoa with pentoxifylline improves the post-thaw agonist-induced acrosome reaction rate. Hum Reprod 1998; 13: 3384-9. (Pubitemid 29002627)
103. Brennan AP, Holden CA. Pentoxifylline-supplemented cryoprotectant improves human sperm motility after cryopreservation. Hum Reprod 1995; 10: 2308-12.
104. Bell M, Wang R, Hellstrom WJ, Sikka SC. Effect of cryoprotective additives and cryopreservation protocol on sperm membrane lipid peroxidation and recovery of motile human sperm. J Androl 1993; 14: 472-8. (Pubitemid 24001035)
105. Wang R, Sikka SC, Veeraragavan K, Bell M, Hellstrom WJ. Platelet activating factor and pentoxifyllineas human sperm cryoprotectants. Fertil Steril 1993; 60: 711-5. (Pubitemid 23298521)
106. Check DJ, Kiefer D, Katsoff D, Check JH. Effect of pentoxifylline added to freezing media on subsequent post-thaw hypoosmotic swelling test and other semen parameters. Arch Androl 1995; 35: 161-3.
107. Park NC, Park HJ, Lee KM, Shin DG. Free radical scavenger effect of rebamipide in sperm processingand cryopreservation. Asian J Androl 2003; 5: 195-201. (Pubitemid 37099034)
108. Askari HA, Check JH, Peymer N, Bollendorf A. Effect of natural antioxidants tocopherol and ascorbic acids in maintenance of sperm activity during freeze-thaw process. Arch Androl 1994; 33: 11-5. (Pubitemid 24229994)
109. Branco CS, Garcez ME, Pasqualotto FF, Erdtman B, Salvador M. Resveratrol and ascorbic acid prevent DNA damage induced by cryopreservation in human semen. Cryobiology 2010; 60: 235-7.
110. Li Z, Lin Q, Liu R,Xiao W, Liu W. Protective Effects of ascorbate and catalas eonhuman spermatozoa duringcryopreservation. J Androl 2010; 31: 437-44.
111. Martinez-Soto JC,deDioshourcade J,Gutierrez-Adan A, Landeras JL, Gadea J. Effect of genistein supplementation of thawing medium on characteristics of frozen human spermatozoa. J Androl 2010; 12: 431-41.
112. Thomson LK, Fleming SD, Aitken RJ, de Iuliis GN, Zieschang JA et al. Cryopreservation-induced human sperm DNA damage is predominantly mediated by oxidativestress ratherthan apoptosis. Hum Reprod 2009; 24: 2061-70.
113. Taylor K, Roberts P, Sanders K, Burton P. Effect of antioxidant supplementation of cryopreservation medium on post-thaw integrity of human spermatozoa. Reprod Biomed Online 2009; 18: 184-9.
114. Nallella KP, Sharma RK, Allamaneni SS, Aziz N, Agarwal A. Cryopreservation of human spermatozoa: comparison of two cryopreservation methods and three cryoprotectants. Fertil Steril 2004; 82: 913-8. (Pubitemid 39346438)