Evaluation of the Quality and Health of Embryos Resulting from In Vitro Maturation (IVM) under the Influence of Stem Cell Secretome
Subject Areas : Journal of Animal Biology
Hilda Rastegari
1
,
Nasim Hayati Roodbari
2
*
,
Somaieh Kazemnejad
3
,
Soheila Ansaripour
4
1 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
2 - Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
3 - Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
4 - Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
Keywords: Stem cells, In Vitro Maturations, Polycystic Ovary, Preimplantation Genetic Screening, aneuploidy,
Abstract :
The role of mesenchymal stem cells (MSCs) is mainly dependent on their paracrine components, namely their secretome. The use of stem cells has been recognized as a novel approach in the treatment of infertility and in vitro oocyte maturation (IVM) and has shown promising results, especially in women with polycystic ovary syndrome (PCOS). However, the health of the resulting embryos remains a major challenge. In this study, menstrual blood stem cell secretome was used for in vitro oocyte maturation in 100 patients with PCOS, and the health of the embryos was assessed by preimplantation genetic screening for aneuploidy (PGT-A). The resulting embryos were cultured to the blastocyst stage and their chromosomal status was assessed by next-generation sequencing (NGS). The results showed that the total number of embryos produced did not differ significantly between the two groups. In the age group under 30 years, the difference in the total number of embryos between the control and experimental groups was not statistically significant, and although the percentage of high-quality embryos in the secretome group increased compared to the control group, this difference was not statistically significant (p = 0.207). In the age group over 30 years, the number of embryos between the two groups was not significantly different, but the percentage of high-quality embryos in the secretome group was significantly higher than the control group. Also, in people over 30 years, the quality of the embryos improved and there was no significant difference in terms of aneuploidy, euploidy, and mosaicism. IVM had no significant effect on the health of the embryos in terms of aneuploidy and mosaicism. These findings indicate the safety and efficacy of the in vitro maturation method of oocytes using stem cell secretome in the treatment of infertility.
1. Walls M, Hunter T, Ryan JP, Keelan JA, Nathan E, Hart RJ. In vitro maturation as an alternative to standard in vitro fertilization for patients diagnosed with polycystic ovaries: a comparative analysis of fresh, frozen and cumulative cycle outcomes. Hum Reprod. 2015;30(1):88-96.
2. Halvaei I, Ali Khalili M, Razi MH, Nottola SA. The effect of immature oocytes quantity on the rates of oocytes maturity and morphology, fertilization, and embryo development in ICSI cycles. J Assist Reprod Genet. 2012;29:803-810.
3. Chen L, Qu J, Cheng T, Chen X, Xiang C. Menstrual blood-derived stem cells: toward therapeutic mechanisms, novel strategies, and future perspectives in the treatment of diseases. Stem Cell Res Ther. 2019;10(1):406.
4. Rastegari H, Kazemnejad S, Hayati Roodbari N, Ansaripour S. Role of menstrual blood stem cell-derived secretome, follicular fluid, and melatonin in oocyte maturation and embryo development in polycystic ovary syndrome. Curr Stem Cell Res Ther. 2025;20(3):291-301.
5. Zafardoust S, Kazemnejad S, Darzi M, Fathi-Kazerooni M, Rastegari H, Mohammadzadeh A. Improvement of pregnancy rate and live birth rate in poor ovarian responders by intraovarian administration of autologous menstrual blood derived-mesenchymal stromal cells: phase I/II clinical trial. Stem Cell Reviews and Reports, 2020;16(4):755-763.
6. Fathi-Kazerooni M, Fattah-Ghazi S, Darzi M, Makarem J, Nasiri R, Salahshour F, Dehghan-Manshadi SA, Kazemnejad S. Safety and efficacy study of allogeneic human menstrual blood stromal cells secretome to treat severe COVID-19 patients: clinical trial phase I & II. Stem Cell Res Ther. 2022;13(1):96.
7. Fesahat F, Kalantar SM, Sheikhha MH, Saeedi H, Montazeri F, Firouzabadi RD, Khalili MA. Developmental and cytogenetic assessments of preimplantation embryos derived from in-vivo or in-vitro matured human oocytes. Eur J Med Genet. 2018;61(4):235-241.
8. Amini MS, Naderi MM, Shirazi A, Aminafshar M, Boroujeni SB, Pournourali M, Malekpour A. Bioactive materials derived from menstrual blood stem cells enhance the quality of in vitro bovine embryos. Avicenna J Med Biotechnol. 2022;14(4):287.
9. Lee SH. Effects of human endothelial progenitor cell and its conditioned medium on oocyte development and subsequent embryo development. Int J Mol Sci. 2020;21(21):7983.
10. Practice Committees of the American Society for Reproductive Medicine, the Society of Reproductive Biologists and Technologists, and the Society for Assisted Reproductive Technology. Electronic address: jgoldstein@asrm.org. In vitro maturation: a committee opinion. Fertil Steril. 2021;115(2):298-304.
11. Smith AD, Tilling K, Lawlor DA, Nelson SM. Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles. BMC Med. 2019;17(1):202.
12. Li J, Chen J, Sun T, Zhang S, Jiao T, Chian RC, Li Y, Xu Y. Chromosome aneuploidy analysis in embryos derived from in vivo and in vitro matured human oocytes. J Transl Med. 2021;19(1):416.
13. Jafarzadeh H, Nazarian H, Ghaffari Novin M, Shams Mofarahe Z, Eini F, Piryaei A., Improvement of oocyte in vitro maturation from mice with polycystic ovary syndrome by human mesenchymal stromal cell–conditioned media. J Cell Biochem. 2018;119(12):10365-10375.
14. Madkour A, Bouamoud N, Kaarouch I, Louanjli N, Saadani B, Assou S, Aboulmaouahib S, Sefrioui O, Amzazi S, Copin H, Benkhalifa M. Follicular fluid and supernatant from cultured cumulus-granulosa cells improve in vitro maturation in patients with polycystic ovarian syndrome. Fertil Steril. 2018;110(4):710-719.
15. Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73(6):1155-1158.
16. Chen L, Qu J, Xiang C. The multi-functional roles of menstrual blood-derived stem cells in regenerative medicine. Stem Cell Res Ther. 2019;10(1):1-10.
17. He Y, Chen D, Yang L, Hou Q, Ma H, Xu X. The therapeutic potential of bone marrow mesenchymal stem cells in premature ovarian failure. Stem Cell Res Ther. 2018;9(1):263.
18. Chen L, Qu J, Mei Q, Chen X, Fang Y, Chen L, Li Y, Xiang C. Small extracellular vesicles from menstrual blood-derived mesenchymal stem cells (MenSCs) as a novel therapeutic impetus in regenerative medicine. Stem Cell Res Ther. 2021;12(1):433.20.
19. Nikoloff N. The key role of cumulus cells in oocytes in vitro maturation protocols. Fertil Steril. 2021;116(6):1663.
20. Massoud G, Spann M, Vaught KC, Das S, Dow M, Cochran R, et al. Biomarkers assessing the role of cumulus cells on IVF outcomes: a systematic review. J Assist Reprod Genet. 2024;41(2):253-275.
21. Montazeri F, Kalantar M, Hoseini SM, Agha-Miri A, Abdoli M, Nikuei P. Comparing aneuploidy rate in arrested human embryos derived from in-vivo and in-vitro matured oocytes, 19 September 2023, PREPRINT (Version 1) available at Research Square, 2023; https://doi.org/10.21203/ rs.3.rs-3309756/v1
22. Song H, Zhang R, Liu Y, Wu J, Fan W, Wu J, Liu Y, Lin J. Menstrual blood-derived endometrial stem cells ameliorate ovarian senescence by relieving oxidative stress-induced inflammation. Reprod Sci. 2025; 32(5):1566-1579.
23. Morales C. Current applications and controversies in preimplantation genetic testing for aneuploidies (PGT-A) in In vitro fertilization. Reprod Sci. 2024;31(1):66-80.
24. Siristatidis C, Sergentanis TN, Vogiatzi P., Kanavidis P, Chrelias C, Papantoniou N, Psaltopoulou T. In vitro maturation in women with vs. without polycystic ovarian syndrome: a systematic review and meta-analysis. PLoS One. 2015;10(8):e0134696.
25. Fesahat F, Montazeri F, Hoseini SM. Preimplantation genetic testing in assisted reproduction technology. J Gynecol Obstet Hum Reprod. 2020;49(5):101723.