Use of extracellular vesicles from multipotent mesenchymal stromal cells in preparation for in vitro fertilization programs in patients with diminished ovarian reserve

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Abstract

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.

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About the authors

Yana O. Martirosyan

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Author for correspondence.
Email: marti-yana@yandex.ru
ORCID iD: 0000-0002-9304-4410

PhD, Researcher at the F. Paulsen Research and Educational Center for ART with the Clinical Department

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

Almina M. Biryukova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: alma21@list.ru

PhD, Clinical Supervisor at the F. Paulsen Research and Educational Center for ART with the Clinical Department

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

Denis N. Silachev

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: d_silachev@oparina4.ru
ORCID iD: 0000-0003-0581-9755

Dr. Bio. Sci., Head of the Laboratory of Cell Technologies

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

Konstantin V. Popov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: k_popov@oparina4.ru
ORCID iD: 0000-0002-3436-3235

PhD (Bio), Head of the Center for Personalized High-Tech Drugs

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

Tatiana A. Nazarenko

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: t.nazarenko@mail.ru
ORCID iD: 0000-0002-5823-1667

Dr. Med. Sci., Professor, Head of the Institute of Reproductive Medicine

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

Gennady T. Sukhikh

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of the Russian Federation

Email: g_sukhikh@oparina4.ru
ORCID iD: 0000-0002-7712-1260

Academician of the RAS, Dr. Med. Sci., Professor, Director

Russian Federation, 117997, Moscow, Ac. Oparin str., 4

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