Assessment of the potential use of antioxidant support in infertility of various etiologies

Berezina D.A., Karimova A.A.

Ural State Medical University, Ministry of Health of Russia, Yekaterinburg, Russia

The options for infertility treatment increase and it is necessary to assess rationally the value of including additional substances in the algorithms for the management of patients. One of the most controversial issues remains the use of antioxidants. Although these substances have a positive effect on molecular levels, the results of their use in clinical practice can be very contradictory. To obtain an up-to-date and comprehensive view of the role of antioxidants in combating oxidative stress observed in various reproductive pathologies, we reviewed the world literature sources in Scopus, Web of Science, MedLine, Cochrane and other databases for the last five years. The data on potential mechanisms of antioxidant action in relation to molecular targets in the female reproductive system were summarized and analyzed. It was observed that the majority of foreign scientists were interested in the potential use of antioxidants in the treatment of infertility associated with endocrine disorders. The review pays special attention to the analysis of experience in the use of the most widely studied antioxidants in the treatment of unexplained infertility.
Conclusion: The analysis of the literature data demonstrated the considerable potential of natural antioxidants, but in most cases their use did not result in statistically significant clinical effects, even for the molecules most studied, such as vitamins C and E, alpha-lipoic acid, L-carnitine, and melatonin. The use of antioxidants in the treatment of unexplained infertility has had disappointing results so far. Nevertheless, there is still hope for achieving this ambitious therapeutic goal which justifies the need to continue further research on this issue.

Authors’ contributions: Berezina D.A. – developing the concept of the article; editing the text; Berezina D.A., Karimova A.A. – analysis of literature data, writing the text.
Conflicts of interest: Authors declare lack of the possible conflicts of interests.
Funding: The study was conducted without sponsorship.
For citation: Berezina D.A., Karimova A.A. Assessment of the potential use 
of antioxidant support in infertility of various etiologies.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (7): 22-27 (in Russian)
https://dx.doi.org/10.18565/aig.2024.68

Keywords

antioxidants
treatment of infertility
unexplained infertility

References

  1. Киракосян Е.В., Назаренко Т.А., Павлович С.В. Поиск причин формирования нарушений репродуктивной системы: обзор научных исследований. Акушерство и гинекология. 2021; 11: 18-25. [Kirakosyan E.V., Nazarenko T.A., Pavlovich S.V. Search for the causes of reproductive system disorders: a research review. Obstetrics and Gynecology. 2021; (11): 18-25.(in Russian)]. https://dx.doi.org/10.18565/aig.2021.11.18-25.
  2. Practice Committee of the American Society for Reproductive Medicine. Evidence-based treatments for couples with unexplained infertility: a guideline. Fertil. Steril. 2020; 113(2): 305-22. https://dx.doi.org/10.1016/j.fertnstert.2019.10.014.
  3. Rodríguez-Varela C., Labarta E. Clinical application of antioxidants to improve human oocyte mitochondrial function: a review. Antioxidants (Basel). 2020; 9(12): 1197. https://dx.doi.org/10.3390/antiox9121197.
  4. Cacciottola L., Donnez J., Dolmans M.M. Can endometriosis-related oxidative stress pave the way for new treatment targets? Int. J. Mol. Sci. 2021; 22(13): 7138. https://dx.doi.org/10.3390/ijms22137138.
  5. Orlova V.V., Suslikova L.V., Orlova O.A., Dmytriienko D.V., Malysheva I.V. Assisted reproductive technology efficiency improvement of tubal-peritoneal infertility. Wiad. Lek. 2020; 73(11): 2370-7.
  6. Березина Д.А., Кудрявцева Е.В., Гаврилов И.В. Роль окислительного стресса в женской репродуктивной системе: обзор литературы. Пермский медицинский журнал. 2023; 40(4): 62-72. [Berezina D.A., Kudryavtseva E.V., Gavrilov I.V. Role of oxidative stress in female reproductive system: literature review. Perm Medical Journal. 2023; 40(4): 62-72. (in Russian)]. https://dx.doi.org/10.17816/pmj40462-72.
  7. Cheng X., He B. Clinical and biochemical potential of antioxidants in treating polycystic ovary syndrome. Int. J. Womens Health. 2022; 14: 467-79. https://dx.doi.org/10.2147/IJWH.S345853.
  8. Dutta S., Sengupta P., Izuka E., Menuba I., Nwagha U. Oxidative and nitrosative stress and female reproduction: roles of oxidants and antioxidants. J. Integr. Sci. Technol. 2024; 12(3): 754. https://dx.doi.org/10.62110/sciencein.jist.2024.v12.754.
  9. Wang L., Tang J., Wang L., Tan F., Song H., Zhou J. et al. Oxidative stress in oocyte aging and female reproduction. J. Cell. Physiol. 2021; 236(12): 7966-83. https://dx.doi.org/10.1002/jcp.30468.
  10. Самойлова Ю.Г., Матвеева М.В., Петров И.А., Мицеля Е.В., Кудлай Д.А., Гайфулина Ж.Ф. Оксидативный стресс и фертильность. Природа, диагностика, терапия. Вопросы гинекологии, акушерства и перинатологии. 2021; 20(4): 131-9. [Samoilova Yu.G., Matveeva M.V., Petrov I.A., Mitselya E.V., Kudlai D.A., Gaifulina Zh.F. Oxidative stress and fertility. Nature, diagnosis, and treatment. Gynecology, Obstetrics and Perinatology. 2021; 20(4): 131-9.(in Russian)]. https://dx.doi.org/10.20953/1726-1678-2021-4-131-139.
  11. Showell M.G., Mackenzie-Proctor R., Jordan V., Hart R.J. Antioxidants for female subfertility. Cochrane Database Syst. Rev. 2020; 8(8): CD007807. https://dx.doi.org/10.1002/14651858.CD007807.pub4.
  12. Budani M.C., Tiboni G.M. Effects of supplementation with naturalantioxidants on oocytes and preimplantation embryos. Antioxidants(Basel). 2020; 9(7): 612. https://dx.doi.org/10.3390/antiox9070612.
  13. De Cosmi V., Cipriani S., Esposito G., Fedele F., La Veccyia I., Trojano G. et al. Vitamin and carotenoid intake and outcomes of in vitro fertilization in women referring to an Italian fertility service: a cross-sectional analysis of a prospective cohort study. Antioxidants (Basel). 2023; 12(2): 286.https://dx.doi.org/10.3390/antiox12020286.
  14. Mendoza N., Losa F., Palacios S. Strategy to improve the female fertility in the general gynecologist's office: use of a nutritional supplement based on myo-inositol/D-chiro-inositol and antioxidants. Gynecol. Endocrinol. 2022; 38(4): 275-8. https://dx.doi.org/10.1080/09513590.2021.2015759.
  15. Bhardwaj J.K., Panchal H., Saraf P. Ameliorating effects of natural antioxidant compounds on female infertility: a review. Reprod. Sci. 2021; 28(5): 1227-56. https://dx.doi.org/10.1007/s43032-020-00312-5.
  16. Сыркашева А.Г., Лисицына О.И. Роль микронутриентов в сохранении женского репродуктивного потенциала, сниженного на фоне инфекционных заболеваний. Медицинский совет. 2022; 16(16): 101-7. [Syrkasheva A.G., Lisitsyna O.I. The role of micronutrients in maintaining women's reproductive potential reduced due to infectious diseases. Medical Council. 2022; 16(16): 101-7. (in Russian)]. https://dx.doi.org/10.21518/2079-701X-2022-16-16-101-107.
  17. Давыдов А.И., Чилова Р.А., Лебедев В.А., Таирова М.Б. Аденомиоз и оксидативный стресс. Обоснование комплексного подхода к лечению пациенток репродуктивного возраста. Вопросы гинекологии, акушерства и перинатологии. 2021; 20(6): 155-61. [Davydov A.I., Chilova R.A., Lebedev V.A., Tairova M.B. Adenomyosis and oxidative stress. Rationale for comprehensive approach to treatment of patients of reproductive age. Gynecology, Obstetrics and Perinatology. 2021; 20(6): 155-61. (in Russian)]. https://dx.doi.org/10.20953/1726-1678-2021-6-155-161.
  18. Купина А.Д., Петров Ю.А. Роль витамина D в репродуктивном здоровье женщин. Вопросы питания. 2021; 90(1): 6-14. [Kupina A.D., Petrov Yu.A. Role of vitamin D in women's reproductive health. Problems of Nutrition. 2021; 90(1): 6-14. (in Russian)]. https://dx.doi.org/10.33029/0042-8833-2021-90-1-6-14.
  19. Хабаров С.В., Стерликова Н.А. Мелатонин и его роль в циркадной регуляции репродуктивной функции (обзор литературы). Вестник новых медицинских технологий. 2022; 29(3): 17-31. [Khabarov S.V., Sterlikova N.A. Melatonin and its role in circadian regulation of reproductive function (literature review). Journal of New Medical Technologies. 2022; 29(3): 17-31. (in Russian)]. https://dx.doi.org/10.24412/1609-2163-2022-3-17-31.
  20. Zheng S.H., Chen X.X., Chen Y., Wu Z.C., Chen X.Q., Li X.L. Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis. Reprod. Biol. Endocrinol. 2023; 21(1): 79. https://dx.doi.org/10.1186/s12958-023-01126-1.
  21. Md Amin N.A., Sheikh Abdul Kadir S.H., Arshad A.H., Abdul Aziz N., Abdul Nasir N.A., Ab Latip N. Are vitamin E supplementation beneficial for female gynaecology health and diseases? Molecules. 2022; 27(6): 1896. https://dx.doi.org/10.3390/molecules27061896.
  22. Chen J., Guo Q., Pei Y., Ren Q., Chi L., Hu R.K. et al. Effect of a short-term vitamin E supplementation on oxidative stress in infertile PCOS women under ovulation induction: a retrospective cohort study. BMC Womens Health. 2020; 20(1): 69. https://dx.doi.org/10.1186/s12905-020-00930-w.
  23. Di Tucci C., Galati G., Mattei G., Bonanni V., Capri O., D’Amelio R. et al. The role of alpha lipoic acid in female and male infertility: a systematic review. Gynecol. Endocrinol. 2021; 37(6): 497-505. https://dx.doi.org/10.1080/09513590.2020.1843619.
  24. Aldeghiree Z.A., Streibert M., Mossa H.A.L. The effect of L-carnitine on oocyte maturity in women with polycystic ovarian syndrome undergoing ICSI. IJEIR. 2021; 10(1): 65-79. https://dx.doi.org/10.28969/IJEIR.v11.i1.r5.21.
  25. Yuzko V.O., Yuzko O.M., Yuzko T.A., Pryimak S.H., Voloshynovych N.S., Chobaniuk S.I. Comparative characteristics of infertile women when applying melatonin in complex preparation for assisted reproductive technologies. J. Med. Life. 2022; 15(8): 1013-7. https://dx.doi.org/10.25122/jml-2022-0154.
  26. Hu K.L., Ye X., Wang S., Zhang D. Melatonin application in assisted reproductive technology: a systematic review and meta-analysis of randomized trials. Front. Endocrinol. (Lausanne). 2020; 11: 160. https://dx.doi.org/10.3389/fendo.2020.00160.
  27. Cao Y., Zhao H., Wang Z., Zhang C., Bian Y., Liu X. et al. Quercetin promotes in vitro maturation of oocytes from humans and aged mice. Cell Death Dis. 2020; 11(11): 965. https://dx.doi.org/10.1038/s41419-020-03183-5.
  28. Vašková J., Klepcová Z., Špaková I., Urdzík P., Štofilová J., Bertková I. et al. The importance of natural antioxidants in female reproduction. Antioxidants (Basel). 2023; 12(4): 907. https://dx.doi.org/10.3390/antiox12040907.
  29. Moreira-Pinto B., Costa L., Felgueira E., Fonseca B.M., Rebelo I. Low doses of resveratrol protect human granulosa cells from induced-oxidative stress. Antioxidants (Basel). 2021; 10(4): 561. https://dx.doi.org/10.3390/antiox10040561.
  30. Teymoori A., Khaki A., Rahmanifar G., Khatami F., Rezaii A. Effect of anthocyanin on the ovarian damage and oxidative stress markers in adult female rat after torsion/detorsion. Int. J. Women's Health Reprod. Sci. 2023; 11(4): 172-7. https://dx.doi.org/10.15296/ijwhr.2023.8005.
  31. Mintziori G., Mousiolis A., Duntas L.H., Goulis D.G. Evidence for a manifold role of selenium in infertility. Hormones (Athens). 2020; 19(1): 55-9. https://dx.doi.org/10.1007/s42000-019-00140-6.
  32. Ma L., Chen G., Xu W., Chen P., Lan Y., Huang Y. et al. The relationship between vitamin E level and premature ovarian insufficiency. J. Obstet. Gynaecol. Res. 2021; 47(4): 1481-6. https://dx.doi.org/10.1111/jog.14659.
  33. Jeremic A., Mikovic Z., Soldatovic I., Sudar-Milovanovic E., Isenovic E.R., Perovic M. Follicular and serum levels of vitamin D in women with unexplained infertility and their relationship with in vitro fertilization outcome: an observational pilot study. Arch. Med. Sci. 2021; 17(5): 1418-22. https://dx.doi.org/10.5114/aoms/141185.
  34. Ekapatria C., Hartanto B., Wiryawan P., Tono D., Maringan Diapari Lumban T., Meita D. et al. The effects of follicular fluid 25(OH)D concentration on [intrafollicular estradiol level, oocyte quality, and fertilization rate in women who underwent IVF Program. J. Obstet. Gynaecol. India. 2022; 72(Suppl. 1): 313-8. https://dx.doi.org/10.1007/s13224-021-01615-6.
  35. Ji X., Ye Y., Wang L., Liu S., Dong X. Association between nutrient intake and female infertility: a study based on NHANES database. J. Obstet. Gynaecol. 2023; 43(2): 2285025. https://dx.doi.org/10.1080/01443615.2023.2285025.
  36. Soliman M.Y., Idris O.A.F., Momtaz M., Kortam M.A., ELNoury M.A., Saleh H.A. et al. Expert consensus on the role of supplementation in obstetrics and gynecology using modified delphi method. Arch. Gynecol. Obstet. 2024; 309(2): 639-50. https://dx.doi.org/10.1007/s00404-023-07310-3.

Received 22.03.2024

Accepted 10.07.2024

About the Authors

Dinara A. Berezina, PhD student, Department of Obstetrics and Gynecology, Ural State Medical University, Ministry of Health of Russia, 620028, Russia, Yekaterinburg, Repina str., 3, +7(908)906-37-57, dinara-berezina@mail.ru, https://orcid.org/0000-0003-2797-1926
Alisa A. Karimova, PhD, Associate Professor at the Department of Pharmacy, Ural State Medical University, Ministry of Health of Russia, 620028, Russia, Yekaterinburg,
Repina str., 3, +7(950)549-29-64, otd.mspo@gmail.com, https://orcid.org/0000-0003-3500-096X
Corresponding author: Dinara A. Berezina, dinara-berezina@mail.ru

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