Ukrainska S. I., Lytvynenko A. P., Kaleinikova O. M.


About the author:

Ukrainska S. I., Lytvynenko A. P., Kaleinikova O. M.



Type of article:

Scentific article


The sperm DNA fragmentation index (DFI) is widely regarded as a key measure for assessing male fertility and can also impair the outcome of assisted reproductive technologies. The effect of antioxidant therapy on sperm DNA fragmentation index remains not fully understood. The aim of this study was to search and analyze data of the effect of antioxidant therapy on sperm DNA fragmentation. It is known, that an increase in DFI of more than 30% is a significant confirmation of a decrease in the reproductive potential of a man and the spontaneous onset of labor. Many assays are currently available for the measurement of sperm DNA fragmentation, that is, the sperm chromatin dispersion assay (SCDA), the TUNEL (the terminal deoxynucleotidyl transferase-mediated dUDP nick endlabeling) assay, the comet assay (single-cell gel electrophoresis), or the sperm chromatin structure assay (SCSA). Oxidative stress (OS) has been identified as one of the many mediators of male infertility by causing sperm dysfunction. OS is a state related to increased cellular damage triggered by oxygen and oxygen-derived free radicals known as reactive oxygen species (ROS). OS and the excessive production of ROS have been associated with impaired sperm motility, concentration, and morphology. The production of ROS is a normal physiological event in the spermatozoa, its key signaling molecules in capacitation (a complex process which involves profound structural and functional changes thereby preparing it for egg fertilization). The seminal plasma is endowed with many enzymatic and nonenzymatic antioxidants which protect the spermatozoa against oxidative stress. The main antioxidative defence in the seminal plasma includes superoxide dismutase, catalase, glutathione peroxidase, ascorbic acid, tocopherol and zinc. Therefore, oxidative stress has been considered as a potential mechanism of the sperm DNA damage in infertile men. ROS cause damage to sperm, lipid and proteins, alteration to critical sperm structures and signaling pathways, leading to a decreased sperm activity and fertilizing capacity. DFI is an important marker of male infertility and can greatly reduce the effectiveness of measures taken under assisted reproductive technologies. Thus, there are a number of ways to reduce the production of ROS and stimulate the work of endogenous antioxidant systems, which is achieved, including by the appointment of antioxidants and trace elements. Currently, the role of antioxidant therapy in the treatment of male infertility requires further study, both in vivo and in vitro.


sperm DNA fragmentation index, oxidative stress, reactive oxygen species.


  1. Kaleynikova OM, Sribna VO, Vynohradova-Anyk OO, Voznesensʹka TYu, Blashkiv TV. Reproduktsiya i frahmentatsiya DNK spermatozoyidiv. Visnyk problem biolohiyi i medytsyny. 2019;4.1(152):31-4. [in Ukrainian].
  2. Chornokulskiy IS, Reznichenko IV. Izmeneniya kinezisgramy v sluchaye dobavleniya metabolitov i antioksidantov v eyakulyat in vitro. Slovo o zdorov’ye. 2019 may;(9). Dostupno: [in Russiаn].
  3. Chen H, Zhao H, Huang X, Chen G, Yang Z, Sun W, et al. Does high load of oxidants in human semen contribute to male factor infertility? Antioxid Redox Signal. 2012;16:754-9.
  4. Martin-Hidalgo D, Bragado M, Batista A, Oliveira P, Alves M. Antioxidants and Male Fertility: from Molecular Studies to Clinical Evidence. Antioxidants (Basel). 2019;8(4):89.
  5. Siddhartha N, Reddy N, Pandurangi M, Muthusamy T, Vembu R, Kasinathan K. The Effect of Sperm DNA Fragmentation Index on the Outcome of Intrauterine Insemination and Intracytoplasmic Sperm Injection. J Hum Reprod Sci. 2019;12(3):189-98.
  6. Zhang H, Xuan X, Yang S, Li X, Xu C, Gao X. Selection of viable human spermatozoa with low levels of DNA fragmentation from an immotile population using density gradient centrifugation and magnetic-activated cell sorting. Andrologia. 2018 Feb;50(1). DOI: 10.1111/and.12821
  7. Bungum M. Sperm DNA integrity assessment: a new tool in diagnosis and treatment of fertility. Obstet Gynecol Int. 2012;2012:531042.
  8. Oleszczuk K, Giwercman A, Bungum M. Intra-individual variation of the sperm chromatin structure assay DNA fragmentation index in men from infertile couples. Hum Reprod. 2011;26:3244-8.
  9. Chi H, Chung D, Choi S, Kim J, Kim G, Lee J, et al. Integrity of human sperm DNA assessed by the neutral comet assay and its relationship to semen parameters and clinical outcomes for the IVF-ET program. Clin Exp Reprod Med. 2011;38:10-7.
  10. Mehdi M, Khantouche L, Ajina M, Saad A. Detection of DNA fragmentation in human spermatozoa: correlation with semen parameters. Andrologia. 2009;41:383-6.
  11. Das M, Al-Hathal N, San-Gabriel M, Phillips S, Kadoch I, Bissonnette F, et al. High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age. J Assist Reprod Genet. 2013;30:843-8.
  12. Smit M, Romijn J, Wildhagen M, Weber R, Dohle G. Sperm chromatin structure is associated with the quality of spermatogenesis in infertile patients. Fertil Steril. 2010;94:1748-52.
  13.  Alvarez J, Sharma R, Ollero M, Saleh R, Lopez M, Thomas A, et al. Increased DNA damage in sperm from leukocytospermic semen samples as determined by the sperm chromatin structure assay. Fertil Steril. 2002;78:319-29.
  14.  Fariello R, Del Giudice P, Spaine D, Fraietta R, Bertolla R, Cedenho A. Effect of leukocytospermia and processing by discontinuous density gradient on sperm nuclear DNA fragmentation and mitochondrial activity. J Assist Reprod Genet. 2009;26:151-7.
  15. Moskovtsev S, Willis J, White J, Mullen J. Leukocytospermia: relationship to sperm deoxyribonucleic acid integrity in patients evaluated for male factor infertility. Fertil Steril. 2007;88:737-40.
  16. Gosalvez J, Tvrda E, Agarwal A. Free radical and superoxide reactivity detection in semen quality assessment: past, present, and future. J Assist Reprod Genet. 2017;34(6):697-707.
  17. Rengan A, Agarwal A, van der Linde M, du Plessis S. An investigation of excess residual cytoplasm in human spermatozoa and its distinction from the cytoplasmic droplet. Reprod Biol Endocrinol. 2012;10(92):1-8.
  18. Dona G, Fiore C, Andrisani A, Ambrosini G, Brunati A, Ragazzi E, et al. Evaluation of correct endogenous reactive oxygen species content for human sperm capacitation and involvement of the NADPH oxidase system. Hum Reprod. 2011;26:3264-73.
  19. Esteves S, Roque M, Bradley C, 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):456-67.
  20. Esteves S, 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;20(1):1-8.
  21. Beigi H, Rahmani H, Tahmasbpour E, Shahriary A. Hyperviscous Semen Causes Poor Sperm Quality and Male Infertility through Induction of Oxidative Stress. Curr Urol. 2019;13(1):1-6.
  22. Dutta S, Majzoub A, Agarwal A. Oxidative stress and sperm function: A systematic review on evaluation and management. Arab J Urol. 2019;17(2):87-97.
  23. Aktan G, Dogru-Abbasoglu S, Kucukgergin C, Kadioglu A, Ozdemirler-Erata G, Kocak-Toker N. Mystery of idiopathic male infertility: is oxidative stress an actual risk? Fertil Steril. 2013;99:1211-5.
  24. Yanushpolsky E, Politch J, Hill J, Anderson D. Is leukocytospermia clinically relevant? Fertil Steril. 1996;66:822-5.
  25. Plante M, de Lamirande E, Gagnon C. Reactive oxygen species released by activated neutrophils, but not by deficient spermatozoa, are sufficient to affect normal sperm motility. Fertil Steril. 1994;62:387-93.
  26. Hamada A, Agarwal A, Sharma R, French D, Ragheb A, Sabanegh E. Empirical treatment of low-level leukocytospermia with doxycycline in male infertility patients. Urology. 2011;78:1320-5.
  27. Lanzafame F, La Vignera S, Vicari E, Calogero A. Oxidative stress and medical antioxidant treatment in male infertility. Reprod Biomed Online. 2009;19:638-59.
  28. Salehi P, Zahra S, Kamran T, Ajami A, Taghiyar S, Reza D. Effect of antioxidant therapy on the sperm DNA integrity improvement; a longitudinal cohort study. Int J Reprod Biomed (Yazd). 2019;17(2):99-106.
  29. Gharagozloo P, Gutiérrez-Adán A, Champroux A, Noblanc A, Kocer A, Calle A, et al. A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models. Hum Reprod. 2016;31(2):252-62.
  30. Saddein E, Haghpanah T, Nematollahi-Mahani S, Seyedi F, Ezzatabadipour M. Preventative Effects of Vitamin E on Testicular Damage and Sperm Parameters in the First-Generation Mice Pups due to Pre- and Postnatal Mancozeb Exposure. J Toxicol. 2019;2019:1-12.
  31.  Zhou X, Liu F, Zhai S. Effect of L-carnitine and/or L-acetylcarnitine in nutrition treatment for male infertility: a systematic review. Asia Pac J Clin Nutr. 2007;16:383-90.
  32. Littarru G, Tiano L. Bioenergetic and antioxidant properties of coenzyme Q10: recent developments. Mol Biotechnol. 2007;37:31-7.
  33. Abad C, Amengual M, Gosalvez J, Coward K, Hannaoui N, Benet J, et al. Effects of oral antioxidant treatment upon the dynamics of human sperm DNA fragmentation and subpopulations of sperm with highly degraded DNA. Andrologia. 2013;45:211-6.
  34. Giustarini D, Dalle-Donne I, Colombo R, Milzani A, Rossi R. Is ascorbate able to reduce disulfide bridges? A cautionary note. Nitric Oxide. 2008;19:252-8.
  35. Ebisch I, Thomas C, Peters W, Braat D, Steegers-Theunissen RP. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007;13:163-74.
  36. Calvin H. Selective incorporation of selenium-75 into a polypeptide of the rat sperm tail. J Exp Zool. 1978;204(3):445-52.
  37. Mruk D, Silvestrini B, Mo M, Cheng C. Antioxidant superoxide dismutase – a review: its function, regulation in the testis, and role in male fertility. Contraception. 2002;65:305-11.
  38. Kothari R, Chaudhari A. Zinc Levels in Seminal Fluid in Infertile Males and its Relation with Serum Free Testosterone. J Clin Diagn Res. 2016;10(5):5-8.
  39. Zhao J, Dong X, Hu X, Long Z, Wang L, Liu Q, et al. Zinc levels in seminal plasma and their correlation with male infertility: A systematic review and meta-analysis. Sci Rep. 2016;6:22386.
  40. Tinggi U. Selenium: its role as antioxidant in human health. Environ Health Prev Med. 2008;13:102-8.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 1 (155), 2020 year, 58-61 pages, index UDK 616.699-07:577.2.088.7