Optimization of art programs in women of late reproductive age by co-cultivation of oocytes with donor extracellular vesicles from follicular fluid
- Авторлар: Akhmedova Z.F.1, Sysoeva A.P.1, Gavrilov M.Y.1, Zingerenko B.V.1, Shevtsova Y.A.1, Silachev D.N.1, Ekimov А.N.1, Makarova N.P.1, Kulakova E.V.1, Kalinina E.A.1
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Мекемелер:
- Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
- Шығарылым: № 8 (2025)
- Беттер: 133-142
- Бөлім: Original Articles
- URL: https://journals.eco-vector.com/0300-9092/article/view/690404
- DOI: https://doi.org/10.18565/aig.2025.104
- ID: 690404
Дәйексөз келтіру
Аннотация
Background: The effectiveness of infertility treatment using assisted reproductive technologies (ART) decreases with the age of the woman due to the aging of the germ cells. It has been previously shown that co-cultivation of embryos with autologous extracellular vesicles from follicular fluid (EVFF) improves the embryological stage of treatment. However, in women of late reproductive age, biological fluids senesce and lose their effectiveness. Therefore, a hypothesis about the use of donor EVFF to improve the results of ART has been proposed.
Objective: To evaluate the effectiveness of donor EVFF in co-cultivation of embryos of women over 40 years.
Materials and methods: The study was conducted among 79 married infertile couples. Inclusion criteria: the woman's age > 40 years, normal karyotype both in a woman and a man. The patients were divided into two groups: the main group (n=40) with co-cultivation of oocytes with donor EVFF and the comparison group (n=39) with standard cultivation. Stimulation of ovarian function was performed according to the protocol with gonadotropin-releasing hormone antagonists. Transvaginal puncture was done under anesthesia. In group 1, donor EVFF were added to fertilized oocytes. The next day, they were transferred to fresh culture medium. The main evaluation parameters included: fertilization rate, blastocyst formation, and clinical pregnancy.
Results: In the group with donor EVFF, the fertilization rate was higher (84.8% vs. 70%, p=0.008), the proportion of embryo transfer cancellations was lower (22.5% vs. 46.1%, p=0.021). The frequency of pregnancy and genetically normal embryos did not statistically differ.
Conclusion: Donor EVFF improve embryological parameters but do not affect clinical outcomes in women of late reproductive age.
Негізгі сөздер
Толық мәтін

Авторлар туралы
Z. Akhmedova
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Хат алмасуға жауапты Автор.
Email: zyuka-1997@mail.ru
ORCID iD: 0000-0002-4483-8820
PhD student at the Prof. B.V. Leonov Department for Assisted Technologies in Infertility Treatment
Ресей, MoscowA. Sysoeva
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: sysoeva.a.p@gmail.com
ORCID iD: 0000-0002-6502-4498
PhD, Clinical Embryologist at the Prof. B.V. Leonov Department for Assisted Technologies in Infertility Treatment
Ресей, MoscowM. Gavrilov
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: maxgavr67@gmail.com
ORCID iD: 0000-0001-6189-0287
Junior Researcher at the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment
Ресей, MoscowB. Zingerenko
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: b_zingerenko@oparina4.ru
ORCID iD: 0000-0002-8784-5502
Junior Researcher at the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment
Ресей, MoscowYu. Shevtsova
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: u_shevtsova@oparina4.ru
Junior Researcher at the Cell Technologies Laboratory
Ресей, MoscowD. Silachev
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: d_silachev@oparina4.ru
ORCID iD: 0000-0003-0581-9755
Dr. Bio. Sci., Head of the Cell Technologies Laboratory
Ресей, MoscowА. Ekimov
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: a_ekimov@oparina4.ru
ORCID iD: 0000-0001-5029-0462
PhD, Head of the Laboratory of Preimplantation Genetic Testing and Genetic Diagnostics
Ресей, MoscowN. Makarova
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: np_makarova@oparina4.ru
ORCID iD: 0000-0003-1396-7272
Dr. Bio. Sci., Leading Researcher at the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment
Ресей, MoscowE. Kulakova
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: e_kulakova@oparina4.ru
ORCID iD: 0000-0002-4433-4163
Dr. Med. Sci., Senior Researcher at the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment
Ресей, MoscowE. Kalinina
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia
Email: e_kalinina@oparina4.ru
ORCID iD: 0000-0002-8922-2878
Dr. Med. Sci., Professor, Head of the Prof. B.V. Leonov Department of Assistive Technologies in Infertility Treatment
Ресей, MoscowӘдебиет тізімі
- Долгушина Н.В., Адамян Л.В., Шешко Е.Л. Поздний репродуктивный возраст женщины: риски нарушения репродуктивной функции (обзор литературы). Проблемы репродукции. 2023; 29(4): 99-106. [Dolgushina N.V., Adamyan L.V., Sheshko E.L. Late reproductive age of a woman: risks of reproductive dysfunction (literature review). Russian Journal of Human Reproduction. 2023; 29(4): 99-106 (in Russian)]. https://dx.doi.org/10.17116/repro20232904199
- Зингеренко Б.В., Бурменская О.В., Сысоева А.П., Шевцова Ю.А., Силачев Д.Н., Макарова Н.П., Калинина Е.А. Изменение транскрипции генов в клетках кумулюса возрастных женщин под действием внеклеточных везикул фолликулярной жидкости молодых доноров. Бюллетень экспериментальной биологии и медицины. 2024; 178(12): 767-73. [Zingerenko B.V., Burmenskaya O.V., Sysoeva A.P., Shevtsova Yu.A., Silachev D.N., Makarova N.P., Kalinina E.A. Gene transcription changes in advanced maternal aged women cumulus cells under influence of young donors follicular fluid extracellular vesicles. Bulletin of experimental biology and medicine. 2024; 178(12): 767-73 (in Russian)]. https://dx.doi.org/10.47056/0365-9615-2024-178-12-767-773
- Патент №2801339 C1 Российская Федерация, МПК G01N 33/50, A61B 17/435. Способ использования внеклеточных везикул фолликулярной жидкости для увеличения подвижности сперматозоидов человека в программах экстракорпорального оплодотворения: №2022131353: заявл. 01.12.2022: опубл. 07.08.2023. А.П. Сысоева, Н.П. Макарова, Д.Н. Силачев [и др.]; заявитель Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова" Министерства здравоохранения Российской Федерации. [Patent No. 2801339 C1 Russian Federation, IPC G01N 33/50, A61B 17/435. Method of using extracellular vesicles of follicular fluid to increase the motility of human sperm in in vitro fertilization programs: No. 2022131353: appl. 01.12.2022: publ. 07.08.2023. A.P. Sysoeva, N.P. Makarova, D.N. Silachev [et al.]; applicant Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. (in Russian)].
- Sysoeva A., Akhmedova Z., Nepsha O., Makarova N., Silachev D., Shevtsova Y. et al. Characteristics of the follicular fluid extracellular vesicle molecular profile in women in different age groups in ART programs. Life (Basel). 2024; 14(5): 541. https://dx.doi.org/10.3390/life14050541
- Sysoeva A.P., Nepsha O.S., Makarova N.P., Silachev D.N., Lobanova N.N., Timofeeva A.V. et al. Influence of extracellular vesicles from the follicular fluid of young women and women of advanced maternal age with different miRNA profiles on sperm functional properties. Bull. Exp. Biol. Med. 2022; 173(4): 560-8. https://dx.doi.org/10.1007/s10517-022-05589-x
- Nepsha O.S., Burmenskaya O.V., Akhmedova Z.F., Romanov E.A., Sysoeva A.P., Goryunov K.V. et al. Changes in the transcription of proliferation- and apoptosis-related genes in embryos in women of different ages under the influence of extracellular vesicles from donor follicular fluid in vitro. Bull. Exp. Biol. Med. 2024; 176(5): 658-65. https://dx.doi.org/10.1007/ s10517-024-06087-y
- da Silveira J.C., Andrade G.M., Del Collado M., Sampaio R.V., Sangalli J.R., Silva L.A. et al. Supplementation with small-extracellular vesicles from ovarian follicular fluid during in vitro production modulates bovine embryo development. PLOS One. 2017; 12(6): e0179451. https://dx.doi.org/10.1371/journal.pone.0179451
- Российская Aссоциация Репродукции Человека. Оценка ооцитов и эмбрионов в лаборатории ВРТ. Методические рекомендации. М.; 2021. 17 с. [Russian Association of Human Reproduction. Assessment of oocytes and embryos in the ART laboratory. Methodological guidelines. Moscow; 2021. 17 p. (in Russian)].
- Sallem A., Santulli P., Barraud-Lange V., Foll N.L., Ferreux L., Maignien C. et al. Extended culture of poor-quality supernumerary embryos improves ART outcomes. J. Assist. Reprod. Genet. 2018; 35(2): 311-9. https://dx.doi.org/10.1007/s10815-017-1063-7
- Биопсия эмбриона на стадии бластоцисты: учебно-методическое пособие для практических занятий по специальности «эмбриология». М.: ФГБУ «НМИЦ АГП им. В.И. Кулакова» Минздрава России; 2024. 51 с. [Embryo biopsy at the blastocyst stage: a teaching manual for practical exercises in the specialty "embryology". Moscow: V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology; 2024. 51 p. (in Russian)].
- Довгань А.А., Ахмедова З.Ф., Сысоева А.П., Зингеренко Б.В., Романов Е.А., Силачев Д.Н., Макарова Н.П., Калинина Е.А. Внеклеточные везикулы фолликулярной жидкости: клинические аспекты и молекулярная биология. Акушерство и гинекология. 2023; 6: 38-43. [Dovgan A.A., Akhmedova Z.F., Sysoeva A.P., Zingerenko B.V., Romanov E.A., Silachev D.N., Makarova N.P., Kalinina E.A. Extracellular vesicles in follicular fluid: clinical aspects and molecular biology. Obstetrics and Gynecology. 2023; (6): 38-43 (in Russian)]. https://dx.doi.org/10.18565/aig.2022.320
- Pan Y., Pan C., Zhang C. Unraveling the complexity of follicular fluid: insights into its composition, function, and clinical implications. J. Ovarian Res. 2024; 17(1): 237. https://dx.doi.org/10.1186/s13048-024-01551-9
- Nejabati H.R., Roshangar L., Nouri M. Follicular fluid extracellular vesicle miRNAs and ovarian aging. Clin. Chim. Acta. 2023; 538: 29-35. https://dx.doi.org/10.1016/j.cca.2022.11.003
- Gabryś J., Pietras N., Kowal-Mierzwa W., Karnas E., Andronowska A., Nowak A. et al. Investigating the impact of extracellular vesicle addition during IVM on the fertilization rate of equine oocytes following ICSI. Reprod. Biol. 2024; 24(4): 100967. https://dx.doi.org/10.1016/j.repbio.2024.100967
- Mas-Bargues C., Alique M. Extracellular vesicles as «very important particles» (VIPs) in aging. Int. J. Mol. Sci. 2023; 24(4): 4250. https://dx.doi.org/10.3390/ijms24044250
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