Use of extracellular vesicles from multipotent mesenchymal stromal cells in preparation for in vitro fertilization programs in patients with diminished ovarian reserve
Martirosyan Ya.O., Biryukova A.M., Silachev D.N., Popov K.V., Nazarenko T.A., Sukhikh G.T.
Objective: To evaluate the clinical efficacy of intraovarian injection of extracellular vesicles isolated from placental multipotent mesenchymal stromal cells in patients with diminished ovarian reserve undergoing in vitro fertilization (IVF).
Materials and methods: This prospective randomized controlled trial (open-label design) included 100 women with a diminished ovarian reserve. Patients randomized to the study group (n=50) received intraovarian injections of extracellular vesicles before stimulation, whereas those in the control group (n=50) underwent standard stimulation. The primary outcome was the clinical pregnancy rate, and secondary outcomes included the number of retrieved and mature oocytes, number of 2PN zygotes, blastocysts, blastulation rate, and live births.
Results: The study group showed a statistically significant increase in the number of mature oocytes (4.1 (1.3) vs. 1.5 (1.0), p<0.001), blastocysts (1.4 (0.6) vs. 0.8 (0.4), p<0.001), and blastulation rate (58.2% vs. 31.1%, p=0.008). The clinical pregnancy rate was 24% in the study group compared to 6% in the control group (RR=4.0; 95% CI 1.2–13.3), and the live birth rate was 18% in the study group and 2% in the control group (RR=9.0; 95% CI 1.2–68.4).
Conclusion: Intraovarian administration of extracellular vesicles from mesenchymal stromal cells in patients with diminished ovarian reserve enhances ovarian response, embryo quality, clinical pregnancy rates, and live birth rates in IVF. This technique shows high potential but requires confirmation through larger studies.
Authors' contributions: Sukhikh G.T. – conception and design of the study; Silachev D.N., Popov K.V. – review of relevant literature; Nazarenko T.A. – Analysis and interpretation of data; Martirosyan Ya.O., Biryukova A.M. – drafting of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: R&D 121040600410-7 Nazarenko T.A. Solving the problem of infertility in modern conditions by developing a clinical and diagnostic model of infertile marriage and using innovative technologies in assisted reproduction programs.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Martirosyan Ya.O., Biryukova A.M., Silachev D.N., Popov K.V., Nazarenko T.A., Sukhikh G.T.
Use of extracellular vesicles from multipotent mesenchymal stromal cells in preparation for
in vitro fertilization programs in patients with diminished ovarian reserve.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (9): 117-125 (in Russian)
https://dx.doi.org/10.18565/aig.2025.228
Keywords
diminished ovarian reserve
poor response
extracellular vesicles
exosomes
mesenchymal stromal cells
assisted reproductive technology
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Received 21.08.2025
Accepted 03.09.2025
About the Authors
Yana O. Martirosyan, PhD, Researcher at the F. Paulsen Research and Educational Center for ART with the Clinical Department, V.I. Kulakov NMRC for OG&P,Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(925) 124-99-99, marti-yana@yandex.ru, https://orcid.org/0000-0002-9304-4410
Almina M. Biryukova, PhD, Clinical Supervisor at the F. Paulsen Research and Educational Center for ART with the Clinical Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, alma21@list.ru
Denis N. Silachev, Dr. Bio. Sci., Head of the Laboratory of Cell Technologies, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow,
Ac. Oparin str., 4, +7(905)792-13-01, d_silachev@oparina4.ru, https://orcid.org/0000-0003-0581-9755
Konstantin V. Popov, PhD (Bio), Head of the Center for Personalized High-Tech Drugs, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, +7(916)580-68-05, k_popov@oparina4.ru, https://orcid.org/0000-0002-3436-3235
Tatiana A. Nazarenko, Dr. Med. Sci., Professor, Head of the Institute of Reproductive Medicine, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
117997, Russia, Moscow, Ac. Oparin str., 4, t_nazarenko@oparina4.ru, https://orcid.org/0000-0002-5823-1667
Gennady T. Sukhikh, Academician of the RAS, Dr. Med. Sci., Professor, Director, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow,
Ac. Oparin str., 4, g_sukhikh@oparina4.ru, https://orcid.org/0000-0002-7712-1260
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