Mitochondrial dysfunction and embryo quality: prospects for antioxidant correction containing myo-inositol and D-chiroinositol in a 5:1 ratio, manganese and folic acid

Ob’edkova K.V., Ryzhov Ju.R., Khalenko V.V., Ishchuk M.A., Sagurova Ya.M., Lesik E.A., Komarova E.M., Gzgzyan A.M., Bespalova O.N., Kogan I.Yu., Tapilskaya N.I.

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction, St. Petersburg, Russia

Objective: To evaluate the functional activity of mitochondria of cumulus cells and embryo quality in protocols of assisted reproductive technologies (ART) in reproductive-aged patients with anovulatory infertility and obesity taking myo-inositol (MI) and D-chiroinositol (DCI) complex in a 5:1 ratio in combination with manganese and folic acid.
Materials and methods: The study included 22 patients with obesity and anovulatory infertility. The patients of the main group (n=11) received one sachet of Dikirogen complex two times/day for six months before the ART protocol, the comparison group (n=11) did not receive Dikirogen. The obtained embryos were cultured in the EmbryoVisor incubator with time-lapse function. Confocal laser scanning microscopy was used to study the mitochondrial activity of cumulus cells.
Results: No statistically significant differences were found in the comparison of morphokinetic parameters of embryos, but the blastulation rate in the main group was significantly higher than in the comparison group (57.01±1.99 vs 48.19±3.13, p=0.04). The evaluation of mitochondrial networks in cumulus cells showed a significantly higher emission intensity in the main group than in the comparison group (48.28±1.14 and 42.03±1.24, p=0.002).
Conclusion: The combined therapy with antioxidants, vitamins and trace elements (2000 mg MI, 400 mg DHI, 400 μg folic acid, 10 mg manganese) administered for six months before the initiation of the ART protocol can reduce mitochondrial dysfunction of cumulus cells, decrease oxidative stress and lead to the improvement of oocyte quality.

Authors’ contributions: Ob’edkova K.V. – preparing the publication, analysis of the obtained data; Ryzhov Ju.R. – preparing the publication; Khalenko V.V. – statistical processing of the data, confocal microscopy; Ishchuk M.A., Sagurova Ya.M., Lesik E.A. – conducting the embryological stage of the ART protocols; Komarova E.M.: conducting the embryologic stage of ART protocols, developing the study design, preparing the publication; Gzgzyan A.M., Bespalova O.N., Kogan I.Yu. – developing the study design; Tapilskaya N.I. – developing the study design, preparing the publication, analysis of the obtained data.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The study was supported by the Exploratory scientific research “Creation of innovative approaches in the field of assisted human reproductive technologies using biobanking and import-substituting genetic, regenerative and embryological platforms” No. 1024062500021-3-3.2.2 (FGWN-2024-0020).
Ethical Approval: The study was approved by the Ethical Review Board of D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction, St. Petersburg, Russia dated 12.05.2023 and was performed in accordance with the principles of the Declaration of Helsinki (1964).
Patient Consent for Publication: All patients participating in the study provided an informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Ob’edkova K.V., Ryzhov Ju.R., Khalenko V.V., Ishchuk M.A., Sagurova Ya.M., Lesik E.A., Komarova E.M., Gzgzyan A.M., Bespalova O.N., Kogan I.Yu., Tapilskaya N.I. Mitochondrial dysfunction and embryo quality: prospects for antioxidant correction containing myo-inositol and D-chiroinositol in a 5:1 ratio, manganese and folic acid.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (12): 148-156 (in Russian)
https://dx.doi.org/10.18565/aig.2024.299

Keywords

in vitro fertilization
assisted reproductive technology
mitochondrial dysfunction
time-lapse
inositol
manganese
Dikirogen
embryo
antioxidants

References

  1. Piomboni P., Focarelli R., Capaldo A., Stendardi A., Cappelli V., Cianci A. et al. Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin. J. Assist. Reprod. Genet. 2014; 31(10): 1269-76. https://dx.doi.org/10.1007/s10815-014-0307-z.
  2. Сафронова Н.А., Калинина Е.А., Донников А.Е., Бурменская О.В., Макарова Н.П., Кулакова Е.В., Алиева К.У. Перспективы исследования маркеров клеток кумулюса для оценки качества ооцитов и эмбрионов в программах вспомогательных репродуктивных технологий. Акушерство и гинекология. 2015; 12: 21-5. [Safronova N.A., Kalinina E.A., Donnikov A.E., Burmenskaya O.V., Makarova N.P., Kulakova E.V., Alieva K.U. Prospects for studying cumulus cell markers to assess the quality of oocytes and embryos in assisted reproductive technology programs. Obstetrics and Gynecology. 2015; (12): 21-5. (in Russian)].
  3. Bausenwein J., Serke H., Eberle K., Hirrlinger J., Jogschies P., Hmeidan F.A. et al. Elevated levels of oxidized low-density lipoprotein and of catalase activity in follicular fluid of obese women. Mol. Hum. Reprod. 2010; 16(2): 117-24. https://dx.doi.org/10.1093/molehr/gap078.
  4. Chattopadhayay R., Ganesh A., Samanta J., Jana S.K., Chakravarty B.N., Chaudhury K. Effect of follicular fluid oxidative stress on meiotic spindle formation in infertile women with polycystic ovarian syndrome. Gynecol. Obstet. Invest. 2010; 69(3): 197-202. https://dx.doi.org/10.1159/000270900.
  5. Esencan E., Beroukhim G., Seifer D.B. Age-related changes in Folliculogenesis and potential modifiers to improve fertility outcomes - A narrative review. Reprod. Biol. Endocrinol. 2022; 20(1): 156. https://dx.doi.org/10.1186/s12958-022-01033-x.
  6. Nestler J.E., Jacubowicz D.J., Reamer P., Gunn R.D., Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N. Engl. J. Med. 1999; 340(17): 1314-20. https://dx.doi.org/10.1056/NEJM199904293401703.
  7. Schimberni M. The use of nutritional supplements in the treatment of male factor infertility. In: Supplements and herbal remedies. Featured in obstetrics and gynecology. 2006 CIC international Ed.: 38-40.
  8. Baillargeon J.P., Nestler J.E., Ostlund R.E., Apridonidze T., Diamanti-Kandarakis E. Greek hyperinsulinemic women, with or without polycystic ovary syndrome, display altered inositols metabolism. Hum. Reprod. 2008; 23(6): 1439-46. https://dx.doi.org/10.1093/humrep/den097.
  9. Papaleo E., Unfer V., Baillargeon J.P., Fusi F., Occhi F., De Santis L. Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil. Steril. 2009; 91(5): 1750-4. https://dx.doi.org/10.1016/j.fertnstert.2008.01.088.
  10. Morgante G., Orvieto R., Di Sabatino A., Musacchio M.C., De Leo V. The role of inositol supplementation in patients with polycystic ovary syndrome, with insulin resistance, undergoing the low-dose gonadotropin ovulation induction regimen. Fertil. Steril. 2011; 95(8): 2642-4. https://dx.doi.org/10.1016/j.fertnstert.2011.01.035.
  11. Тапильская Н.И., Сажина И.Н., Андреева М.Д., Сорокина О.В. Эффективность применения комбинации миоинозитола и D-хирои­нозитола в соотношении 5:1 с марганцем и фолиевой кислотой у пациенток репродуктивного возраста с нерегулярным менструальным циклом и ожирением. Гинекология. 2022; 24(2): 101-7. [Tapilskaya N.I., Sazhina I.N., Andreeva M.D., Sorokina O.V. Clinical effect of the combination of myoinositol and D-chiroinositol in the ratio 5:1 with manganese and folic acid on female reproductive function in patients with anovulatory infertility in patients with abnormal menstrual cycles and obesity. Gynecology. 2022; 24(2): 101-7.(in Russian)]. https://dx.doi.org/10.26442/20795696.2022.2.201393.
  12. Комарова Е.М., Лесик Е.А., Объедкова К.В., Рыжов Ю.Р., Гзгзян А.М., Тапильская Н.И. Прогностическое значение маркеров митохондриальной дисфункции клеток кумулюса в получении эмбрионов оптимального качества в протоколах вспомогательных репродуктивных технологий. Проблемы репродукции. 2023; 29(6): 57-64. [Komarova E.M., Lesik E.A., Ob’edkova K.V., Ryzhov Ju. R., Gzgzyan A.M., Tapilskaya N.I. Prognostic significance of cumulus cells mitochondrial dysfunction markers in obtaining optimal quality embryos in assisted reproductive technologies protocols. Russian Journal of Human Reproduction. 2023; 29(6): 57-64. (in Russian)]. https://dx.doi.org/10.17116/repro20232906157.
  13. Панферов Е.В., Тапильская Н.И., Масиева К.С., Объедкова К.В., Гзгзян А.М. Митохондриальные сети клеток кумулюса и качество ооцитов. Известия Российской Военно-медицинской академии. 2022; 41(3): 303-8. [Panferov E.V., Tapilskaya N.I., Masieva K.S., Ob’edkova K.V., Gzgzyan A.M. Mitochondrial networks of cumulus cells and oocyte quality. Russian Military Medical Academy Reports. 2022; 41(3): 303-8. (in Russian)]. https://dx.doi.org/ 10.17816/rmmar109074.
  14. ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine. Electronic address: coticchio.biogenesi@grupposandonato.it. The Vienna consensus: report of an expert meeting on the development of ART laboratory performance indicators. Reprod. Biomed. Online. 2017; 35(5): 494-510. https://dx.doi.org/10.1016/j.rbmo.2017.06.015.
  15. Tan T.C.Y., Dunning K.R. Non-invasive assessment of oocyte developmental competence. Reprod. Fertil. Dev. 2022; 35(2): 39-50. https://dx.doi.org/ 10.1071/RD22217.

Received 21.11.2024

Accepted 11.12.2024

About the Authors

Ksenia V. Ob’edkova, PhD, Senior Researcher at the Department of Reproductology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology,
199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, https://orcid.org/0000-0002-2056-7907
Julian R. Ryzhov, Junior Researcher at the Department of Reproductology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology,
199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, julian.ryzhov@gmail.com, https://orcid.org/0000-0002-5073-8279
Vladislava V. Khalenko, Junior Researcher at the Department of Reproductology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology,
199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51.
Mariia A. Ishchuk, Embryologist at the Assisted Reproductive Technology Department, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology,
199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, https://orcid.org/0000-0002-4443-4287
Yanina M. Sagurova, Embryologist at the Assisted Reproductive Technology Department, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, https://orcid.org/0000-0003-4947-8171
Elena A. Lesik, PhD, Senior Embryologist at the Assisted Reproductive Technology Department, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, https://orcid.org/0000-0003-1611-6318
Evgenia M. Komarova, PhD, Head of the Early Embryogenesis Laboratory of the Department of Reproductology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, https://orcid.org/0000-0002-9988-9879
Alexander M. Gzgzyan, Dr. Med. Sci., Professor, Leading Researcher at the Department of Reproductology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, https://orcid.org/0000-0003-3917-9493
Olesya N. Bespalova, Dr. Med. Sci., Deputy Director for Scientific Work, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia,
Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, https://orcid.org/0000-0002-6542-5953
Igor Yu. Kogan, Dr. Med. Sci., Professor, Corresponding Member of Russian Academy of Sciences, Director, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, https://orcid.org/0000-0002-7351-6900
Natalia I. Tapilskaya, Dr. Med. Sci., Professor, Head of the Department of Reproductology, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034, Russia, Saint-Petersburg, Mendeleevskaya line, 3, +7(812)679-55-51, https://orcid.org/0000-0001-5309-0087
Corresponding author: Julian R. Ryzhov, julian.ryzhov@gmail.com

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