Systemic oxidative stress could predict assisted reproductive technique outcome

Purpose Previous studies have indicated that OxS (oxidative stress) may appear as a possible reason for poor ART outcome. Our aim was to study OxS levels in both partners of couples seeking Assisted reproduction Technology (ART).

Altogether 79 couples were recruited. Oxidative DNA damage (8-OHdG) and lipid peroxidation (8-EPI) were measured, and clinical background and ART outcomes were recorded.

Both OxS markers accurately reflected clincal conditions with prominent negative effects attributable to genital tract infections, endometriosis, uterine myoma and smoking. Furthermore, the level of OxS was also affected by partner’s state of health. The highest 8-EPI levels were detected in both partners when biochemically detectable pregnancies did not develop into clinically detectable pregnancies (in women, 97,8 ± 16,7 vs 72.9 ± 22,9, p = 0.007; in men, 89.6 ± 20,4 vs 72,1 ± 22,6, p = 0.049).

To conclude, high grade systemix OxS in both partners may negatively affect the maintenance and outcome of pregnancy. Applying the detection of OxS in ART patients may select patients with higher success rate and/or those who require antioxidant therapy. This would lead to improvement of ART outcome as well as natural fertility. Similar content being viewed by others

Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, et al. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology. Fertil Steril. 2009;92:1520–4. National Health and Medical Research Council. Ethical guidelines on assisted reproductive technology. Available at: http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/e28.pdf. Accessed 2 Feb 2014. Ferraretti AP, Goossens V, de Mouzon J, Bhattacharya S, Castilla JA, Korsak V, et al. Assisted reproductive technology in Europe, 2008: results generated from European registers by ESHRE. Hum Reprod. 2012;27:2571–84. Loft S, Kold-Jensen T, Hjollund NH, Giwercman A, Gyllemborg J, Ernst E, et al. Oxidative DNA damage in human sperm influences time to pregnancy. Hum Reprod. 2003;18:1265–72. Schulte RT, Ohl DA, Sigman M, Smith GD. Sperm DNA damage in male infertility: etiologies, assays, and outcomes. J Assist Reprod Genet. 2010;27:3–12. Simon L, Proutski I, Stevenson M, Jennings D, McManus J, Lutton D, et al. Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod BioMed Online. 2013;26:68–78. Knox CL, Allan JA, Allan JM, Edirisinghe WR, Stenzel D, Lawrence FA, et al. Ureaplasma parvum and Ureaplasma urealyticum are detected in semen after washing before assisted reproductive technology procedures. Fertil Steril. 2003;80:921–9. Li MQ, Jin LP. Ovarian stimulation for in vitro fertilization alters the protein profile expression in endometrial secretion. Int J Clin Exp Pathol. 2013;6:1964–7. Margalioth EJ, Ben-Chetrit A, Gal M, Eldar-Geva T. Investigation and treatment of repeated implantation failure following IVF–ET. Hum Reprod. 2006;2:3036–43. Fiedler K, Ezcurra D. Predicting and preventing ovarian hyperstimulation syndrome (OHSS): the need for individualized not standardized treatment. Reprod Biol Endocrinol. 2012;10:32. Zorn B, Vidmar G, Meden-Vrtovec H. Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm injection. Int J Androl. 2003;26:279–85. Meseguer M, Martínez-Conejero JA, O’Connor JE, Pellicer A, Remohí 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. Agarwal A, Aponte-Mellado A, Premkumar BJ, Shaman A, Gupta S. The effects of oxidative stress on female reproduction: a review. Reprod Biol Endocrinol. 2012;10:49. Montuschi P, Barnes P, Roberts LJ. Insights into oxidative stress: the isoprostanes. Curr Med Chem. 2007;14:703–17. Cambi M, Tamburrino L, Marchiani S, Olivito B, Azzari C, Forti G, et al. Development of a specific method to evaluate 8-hydroxy, 2-deoxyguanosine in sperm nuclei: relationship with semen quality in a cohort of 94 subjects. Reproduction. 2013;145:227–35. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol. 1991;29:297–301. WHO. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010. WHO, editor. Laboratory manual for examination of human semen and sperm–cervical mucus interaction. 4th ed. New York: Cambridge University Press; 1999. Punab M, Lõivukene K, Kermes K, Mändar R. The limit of leucocytospermia from the microbiological viewpoint. Andrologia. 2003;35:271–8. Kullisaar T, Songisepp E, Mikelsaar M, Zilmer K, Vihalemm T, Zilmer M. Antioxidative probiotic fermented goats’ milk decreases oxidative stress-mediated atherogenecity in human subjects. Br J Nutr. 2003;90:449–56. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. New York: Oxford University Press; 1999. Sies H. Oxidative stress: oxidants and antioxidants. London: Academic; 1991. Jones DP. Redefining oxidative stress. Antioxid Redox Signal. 2006;8:1865–79. Laurent A, Nicco C, Chereau C, Goulvestre C, Alexandre J, Alves A, et al. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res. 2005;65:948–56. Al-Gubory KH, Fowler PA, Garrel C. The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. Int J Biochem Cell Biol. 2010;42:1634–50. Combelles CMH, Gupta S, Agarwal A. Could oxidative stress influence the in-vitro maturation of oocytes? Reprod BioMed Online. 2009;18:864–80. Rizzo A, Roscino MT, Binetti F, Sciorsci RL. Roles of reactive oxygen species in female reproduction. Reprod Domest Anim. 2011;47:344–52. Burton GJ, Jauniaux E. Oxidative stress. Best Pract Res Clin Obstet Gynaecol. 2011;25:287–99. Sharma I, Dhaliwal L, Saha S, Sangwan S, Dhawan V. Role of 8-iso-prostaglandin F2alpha and 25-hydroxycholesterol in the pathophysiology of endometriosis. Fertil Steril. 2010;94:63–70. Bogavac M, Lakic N, Simin N, Nikolic A, Sudji J, Bozin B. Bacterial vaginosis and biomarkers of oxidative stress in amniotic fluid. J Matern Fetal Neonatal Med. 2012;25:1050–4. Kothari S, Thompson A, Agarwal A, du Plessis SS. Free radicals: their beneficial and detrimental effects on sperm function. Indian J Exp Biol. 2010;48:425–35. de Lamirande E, Leclerc P, Gagnon C. Capacitation as a regulatory event that primes spermatozoa for the acrosome reaction and fertilization. Mol Hum Reprod. 1997;3:175–94. Benedetti S, Tagliamonte MC, Catalani S, Primiterra M, Canestrari F, De Stefani S, et al. Differences in blood and semen oxidative status in fertile and infertile men, and their relationship with sperm quality. Reprod BioMed Online. 2012;25:300–6. Aitken RJ, Jones KT, Robertson SA. Reactive oxygen species and sperm function — in sickness and in health. J Androl. 2012;33:1096–106. Aitken RJ, De Iuliis GN, Finnie JM, Hedges A, McLachlan 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. Gharagozloo P, Aitken RJ. The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod. 2011;26:1628–40. Ménézo Y, Entezami F, Lichtblau I, Belloc S, Cohen M, Dale B. Oxidative stress and fertility: incorrect assumptions and ineffective solutions? Zygote. 2014;22(1):80–90. Frohner IE, Bourgeois C, Yatsyk K, Majer O, Kuchler K. Candida albicans cell surface superoxide dismutases degrade host-derived reactive oxygen species to escape innate immune surveillance. Mol Microbiol. 2009;71:240–52. Kullisaar T, Türk S, Punab M, Mändar R. Oxidative stress – cause or consequence of male genital tract disorders? Prostate. 2012;72:977–83. Kullisaar T, Türk S, Punab M, Korrovits P, Kisand K, Rehema A, et al. Oxidative stress in leucocytospermic prostatitis patients: preliminary results. Andrologia. 2008;40:161–72. Taha EA, Ez-Aldin AM, Sayed SK, Ghandour NM, Mostafa T. Effect of smoking on sperm vitality, DNA integrity, seminal oxidative stress, zinc in fertile men. Urology. 2012;80:822–5. Mändar R, Kullisaar T, Borovkova N, Punab M. Sexual intercourse with leucocytospermic men may be a possible booster of oxidative stress in female partners of infertile couples. Andrology. 2013;1:464–8. Borovkova N, Korrovits P, Ausmees K, Türk S, Jõers K, Punab M, et al. Influence of sexual intercourse on genital tract microbiota in infertile couples. Anaerobe. 2011;17:414–8. Velthut A, Zilmer M, Zilmer K, Kaart T, Karro H, Salumets A. Elevated blood plasma antioxidant status is favourable for achieving IVF/ICSI pregnancy. Reprod BioMed Online. 2013;26:345–52. Acknowledgments The present study was supported by Enterprise Estonia (Grant no. EU 30020), Estonian Ministry of Education and Research (Target Financing SF0180132s08, Institutional Research Funding IUT 20–42, Institutional Research Funding IUT 15–19 and Scientific Collection Financing KOGU-HUMB) and University of Tartu (Grant no. SARMBARENG). Conflict of interest The authors declare that they have no conflict of interest. Author information Authors and Affiliations Corresponding author Additional information Capsule High grade systemic oxidative stress in both partners affects negatively the maintenance of pregnancy, therefore its testing in ART patients may select the patients with higher success rate and/or those who need antioxidant therapy. Electronic supplementary material Below is the link to the electronic supplementary material. ESM 1 (download DOC ) (DOC 88 kb) ESM 2 (download DOC ) (DOC 42 kb) ESM 3 (download DOC ) (DOC 32 kb) Rights and permissions About this article Cite this article Ahelik, A., Mändar, R., Korrovits, P. et al. Systemic oxidative stress could predict assisted reproductive technique outcome. J Assist Reprod Genet 32, 699–704 (2015). https://doi.org/10.1007/s10815-015-0466-6 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s10815-015-0466-6