Relationship Between Serum Levels of Antioxidant Vitamins and Semen Analysis Parameters in Men with Idiopathic Infertility in Yugra

Introduction. Male fertility disorders, particularly idiopathic male infertility (IMI), remain a pressing medical and social issue. The pathogenesis of IMI is often associated with oxidative stress, which highlights the relevance of antioxidant vitamins. However, comprehensive studies of their serum concentrations in regional populations, such as the Yugra, are lacking.

Objective is to compare serum concentrations of vitamins A, E, C, D and semen parameters in men with IMI and fertile men residing in Yugra, and to assess the relationship between vitamin levels and semen parameters in the total sample of examined individuals.

Materials and methods. A prospective case-control study was conducted. The main group consisted of 70 patients with IMI, the comparison group — 50 fertile men with normozoospermia. All participants underwent semen analysis (WHO 2021 criteria) and determination of serum concentrations of vitamins A and E by high-performance liquid chromatography (HPLC), vitamin C by HPLC with ultraviolet detection, and 25-hydroxyvitamin D by chemiluminescent immunoassay. Statistical analysis was performed using MedCalc.

Results. Patients with IMI showed a significant decrease in serum levels of vitamins A, E, and C and deterioration in all semen parameters compared to controls (p < 0.001). No differences were found for vitamin D. Correlation analysis in the pooled sample (n = 120) revealed significant positive associations of vitamins A, E, and C with the main semen parameters. The most pronounced correlations were found for vitamin C with the proportion of progressively motile sperm (rS = 0.758; p < 0.001) and total motility (rS = 0.699; p < 0.001). Vitamins A and E also significantly correlated with motility, morphology, and sperm concentration (p < 0.001–0.010). No significant correlations were found between vitamin D and semen parameters (p > 0.050).

1. Sun H, Gong TT, Jiang YT, Zhang S, Zhao YH, Wu QJ. Global, regional, and national prevalence and disability-adjusted life-years for infertility in 195 countries and territories, 1990–2017: Results from a global burden of disease study, 2017. Aging. 2019;11(23):10952–10991. DOI: https://doi.org/10.18632/aging.102497.

2. Agarwal A, Baskaran S, Parekh N, Cho CL, Henkel R, Vij S, et al. Male infertility. The Lancet. 2021;397(10271):319–333. DOI: https://doi.org/10.1016/S0140-6736(20)32667-2.

3. Boeri L, Kandil H, Ramsay J. Idiopathic male infertility — what are we missing? Arab Journal of Urology. 2024;23(3):215–229. DOI: https://doi.org/10.1080/20905998.2024.2381972.

4. Efremov EA, Kasatonova EV. Current and promising methods for the treatment of idiopathic male infertility. Andrology and Genital Surgery. 2022;23(3):48–53. (In Russ.). EDN: https://elibrary.ru/AXMIRE.

5. Minhas S, Boeri L, Capogrosso P, Cocci A, Corona G, Dinkelman-Smit M, et al. European Association of Urology Guidelines on Male Sexual and Reproductive Health: 2025 update on male infertility. European Urology. 2025;87(5):601–616. DOI: https://doi.org/10.1016/j.eururo.2025.02.026.

6. Ovchinnikov RI. Male infertility associated with oxidative stress of spermatozoa: Pathogenesis and therapeutic approach. Medical Council. 2022;(5):46–53. (In Russ.). DOI: https://doi.org/10.21518/2079-701X-2022-16-5-46-53.

7. Sengupta P, Roychoudhury S, Nath M, Dutta S. Oxidative stress and idiopathic male infertility. In: Kesari KK, Roychoudhury S (eds.). Oxidative stress and toxicity in reproductive biology and medicine. Cham: Springer; 2022. P. 181–204. DOI: https://doi.org/10.1007/978-3-030-89340-8_9.

8. Zhao Y, Deng S, Li C, Cao J, Wu A, Chen M, et al. The role of retinoic acid in spermatogenesis and its application in male reproduction. Cells. 2024;13(13):1092. DOI: https://doi.org/10.3390/cells13131092.

9. Zhou X, Shi H, Zhu S, Wang H, Sun S. Effects of vitamin E and vitamin C on male infertility: A meta-analysis. International Urology and Nephrology. 2022;54(8):1793–1805. DOI: https://doi.org/10.1007/s11255-022-03237-x.

10. Kaltsas A. Oxidative stress and male infertility: The protective role of antioxidants. Medicina. 2023;59(10):1769. DOI: https://doi.org/10.3390/medicina59101769.

11. Kuchmin AN, Diskalenko OV, Izotova AB, Ekimov VV. The future of vitamin D: Extraskeletal effects. Bulletin of the Russian Military Medical Academy. 2025;27(2):267–276. (In Russ.). DOI: https://doi.org/10.17816/brmma639981.

12. Shahid M, Khan S, Ashraf M, Akram Mudassir H, Rehman R. Male infertility: Role of vitamin D and oxidative stress markers. Andrologia. 2021;53(8):e14147. DOI: https://doi.org/10.1111/and.14147.

13. Boiko YE. Method approaches to studying effects of North factors on human body. Herald of Education and Science Development of Russian Academy of Natural Sciences. 2020;(1):82–88. (In Russ.). DOI: https://doi.org/10.26163/RAEN.2020.46.81.013.

14. Agarwal A, Parekh N, Panner Selvam MK, Henkel R, Shah R, Homa ST. Male Oxidative Stress Infertility (MOSI): Proposed terminology and clinical practice guidelines for management of idiopathic male infertility. The World Journal of Men’s Health. 2019;37(3):296–312. DOI: https://doi.org/10.5534/wjmh.190055.

15. Takalani B, Monageng EM, Mohlala K, Monsees TK, Henkel R, Opuwari CS. Role of oxidative stress in male infertility. Reproduction & Fertility. 2023;4(3):e230024. DOI: https://doi.org/10.1530/RAF-23-0024.

16. Saito Y. Lipid peroxidation products as a mediator of toxicity and adaptive response — the regulatory role of selenoprotein and vitamin E. Archives of Biochemistry and Biophysics. 2021;703:108840. DOI: https://doi.org/10.1016/j.abb.2021.108840.

17. Wang Y, Fu X, Li H. Mechanisms of oxidative stress-induced sperm dysfunction. Frontiers in Endocrinology. 2025;16:1520835. DOI: https://doi.org/10.3389/fendo.2025.1520835.

18. Bruno RS, Leonard SW, Atkinson J, Montine TJ, Ramakrishnan R, Bray TM, et al. Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Free Radical Biology & Medicine. 2006;40(4):689–697. DOI: https://doi.org/10.1016/j.freeradbiomed.2005.10.051.

19. Gromova OA, Torshin IYu, Grishina TR, Malyavskaya SI. The roles of vitamin D in the prevention and the therapy of male infertility. Good Clinical Practice. 2017;(3):61–71. (In Russ.). EDN: https://elibrary.ru/YLSNQY.

20. Güngör K, Güngör ND, Başar MM, Cengiz F, Erşahin SS, Çil K. Relationship between serum vitamin D levels semen parameters and sperm DNA damage in men with unexplained infertility. European Review for Medical and Pharmacological Sciences. 2022;26(2):499–505. DOI: https://doi.org/10.26355/eurrev_202201_27875.

21. Blomberg Jensen M. Vitamin D metabolism, sex hormones, and male reproductive function. Reproduction. 2012;144(2):135–152. DOI: https://doi.org/10.1530/REP-12-0064.

22. Colagar AH, Marzony ET. Ascorbic acid in human seminal plasma: Determination and its relationship to sperm quality. Journal of Clinical Biochemistry and Nutrition. 2009;45(2):144–149. DOI: https://doi.org/10.3164/jcbn.08-251.

23. Hungerford AJ, Harrison N, Bakos HW, Aitken RJ. Development of an improved medium for the preservation of human spermatozoa. Journal of Assisted Reproduction and Genetics. 2025;42(7):2167–2180. DOI: https://doi.org/10.1007/s10815-025-03525-2.

24. Margiana R, Pakpahan C, Pangestu M. A systematic review of retinoic acid in the journey of spermatogonium to spermatozoa: From basic to clinical application [version 2; peer review: 2 approved]. F1000Research. 2022;11:552. DOI: https://doi.org/10.12688/f1000research.110510.2.

25. Bozhedomov VA, Kononenko IA. Male preconceptional training: The role of nutrition and nutrient complexes. Part 1. Experimental and Clinical Urology. 2023;16(1):128–136. DOI: https://doi.org/10.29188/2222-8543-2023-16-1-128-136.

26. Wang R, Wang S, Song Y, Zhou H, Pan Y, Liu L, et al. Effect of vitamin E on semen quality parameters: A meta-analysis of a randomized controlled trial. Urology Journal. 2022;19(5):343–351. DOI: https://doi.org/10.22037/uj.v19i.7160.

27. Service CA, Puri D, Al Azzawi S, Hsieh TC, Patel DP. The impact of obesity and metabolic health on male fertility: A systematic review. Fertility and Sterility. 2023;120(6):1098–1111. DOI: https://doi.org/10.1016/j.fertnstert.2023.10.017.