Volume 10, Issue 2 (2025)
SJMR 2025, 10(2): 95-102 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Shafti V, Azarboo A. Ovarian Tissue Cryopreservation for An Extended Reproductive Lifespan: A Natural Means to Delay Menopause. SJMR 2025; 10 (2) : 7
URL: http://saremjrm.com/article-1-370-en.html
URL: http://saremjrm.com/article-1-370-en.html
1- Sarem Gynecology, Obstetrics and Infertility Research Center, Sarem Women’s Hospital, Iran University of Medical Sciences, Tehran, Iran. & School of Medicine, Tehran Branch, Islamic Azad University, Tehran, Iran.
2- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract: (19 Views)
Background: Ovarian tissue cryopreservation (OTC) is an evolving method of fertility preservation that also holds promise as a natural approach to delaying menopause. Unlike oocyte or embryo freezing, OTC can restore both endocrine and reproductive function, potentially improving quality of life in women facing premature ovarian insufficiency, gonadotoxic therapy, or elective fertility delay.
Methods: This narrative review summarizes the historical development, surgical techniques, cryopreservation protocols, transplantation approaches, clinical outcomes, and future perspectives of OTC. Literature from preclinical studies, clinical trials, and recent meta-analyses was examined to assess efficacy, safety, and limitations of the procedure.
Discussion and Conclusion: OTC involves laparoscopic harvesting of ovarian cortex, cryopreservation (slow freezing or vitrification), and autotransplantation at orthotopic or heterotopic sites. Reported outcomes include restoration of ovarian endocrine function in up to 85% of cases, resumption of menstruation, and more than 200 live births worldwide. Graft survival typically ranges from 4 to 5 years and may be prolonged with repeated transplantation. Major indications include cancer therapy, genetic or autoimmune conditions, severe endometriosis, gender-affirming surgery, and elective fertility preservation. Limitations include ischemic follicle loss, risk of malignant cell reintroduction, reduced efficacy in women >40 years, and ethical concerns regarding prolongation of reproductive lifespan. Emerging strategies such as in vitro maturation of follicles, artificial ovary constructs, and vascularization enhancement are under investigation. OTC is now an established fertility preservation technique with expanding clinical applications. Beyond safeguarding fertility, it offers a potential means of extending reproductive longevity and delaying menopause. However, further research is needed to optimize outcomes, minimize risks, and address ethical implications before its widespread use as an anti-aging intervention.
Methods: This narrative review summarizes the historical development, surgical techniques, cryopreservation protocols, transplantation approaches, clinical outcomes, and future perspectives of OTC. Literature from preclinical studies, clinical trials, and recent meta-analyses was examined to assess efficacy, safety, and limitations of the procedure.
Discussion and Conclusion: OTC involves laparoscopic harvesting of ovarian cortex, cryopreservation (slow freezing or vitrification), and autotransplantation at orthotopic or heterotopic sites. Reported outcomes include restoration of ovarian endocrine function in up to 85% of cases, resumption of menstruation, and more than 200 live births worldwide. Graft survival typically ranges from 4 to 5 years and may be prolonged with repeated transplantation. Major indications include cancer therapy, genetic or autoimmune conditions, severe endometriosis, gender-affirming surgery, and elective fertility preservation. Limitations include ischemic follicle loss, risk of malignant cell reintroduction, reduced efficacy in women >40 years, and ethical concerns regarding prolongation of reproductive lifespan. Emerging strategies such as in vitro maturation of follicles, artificial ovary constructs, and vascularization enhancement are under investigation. OTC is now an established fertility preservation technique with expanding clinical applications. Beyond safeguarding fertility, it offers a potential means of extending reproductive longevity and delaying menopause. However, further research is needed to optimize outcomes, minimize risks, and address ethical implications before its widespread use as an anti-aging intervention.
Article number: 7
Keywords: Ovarian Tissue Cryopreservation, Fertility Preservation, Menopause, Ovarian Tissue Transplantation.
Article Type: Systematical Review |
Subject:
Women Diseases
Received: 2025/09/2 | Accepted: 2025/09/11 | Published: 2025/09/16
Received: 2025/09/2 | Accepted: 2025/09/11 | Published: 2025/09/16
References
1. 1. Karimizadeh Z, Saltanatpour Z, Tarafdari A, Rezaeinejad M, Hamidieh AA. Ovarian tissue cryopreservation: a narrative review on cryopreservation and transplantation techniques, and the clinical outcomes. Ther Adv Reprod Health. 2025;19:26334941251340517. [DOI:10.1177/26334941251340517] [PMID] []
2. Marin L, Bedoschi G, Kawahara T, Oktay KH. History, Evolution and Current State of Ovarian Tissue Auto-Transplantation with Cryopreserved Tissue: a Successful Translational Research Journey from 1999 to 2020. Reprod Sci. 2020;27(4):955-62. [DOI:10.1007/s43032-019-00066-9] [PMID] []
3. Sehring J, Hussain A, Grimm L, Rosen E, Esguerra J, Matevossian K, et al. A call to action: unified clinical practice guidelines for oncofertility care. J Assist Reprod Genet. 2021;38(7):1745-54. [DOI:10.1007/s10815-021-02142-z] [PMID] []
4. Kristensen SG, Andersen CY. Cryopreservation of Ovarian Tissue: Opportunities Beyond Fertility Preservation and a Positive View Into the Future. Front Endocrinol (Lausanne). 2018;9:347. [DOI:10.3389/fendo.2018.00347] [PMID] []
5. Arapaki A, Christopoulos P, Kalampokas E, Triantafyllidou O, Matsas A, Vlahos NF. Ovarian Tissue Cryopreservation in Children and Adolescents. Children (Basel). 2022;9(8). [DOI:10.3390/children9081256] [PMID] []
6. Ovarian tissue cryopreservation: a committee opinion. Fertility and Sterility. 2014;101(5):1237-43. [DOI:10.1016/j.fertnstert.2014.02.052] [PMID]
7. Sterling J, Garcia MM. Fertility preservation options for transgender individuals. Transl Androl Urol. 2020;9(Suppl 2):S215-s26. [DOI:10.21037/tau.2019.09.28] [PMID] []
8. Raimondo D, Raspollini A, Bertoldo L, Ferla S, Vicenti R, Magnani V, et al. Laparoscopic medulla-sparing ovarian tissue biopsy for cryopreservation: step-by-step surgical technique. Fertility and Sterility. 2024;122(1):184-6. [DOI:10.1016/j.fertnstert.2024.03.011] [PMID]
9. Rivas Leonel EC, Lucci CM, Amorim CA. Cryopreservation of Human Ovarian Tissue: A Review. Transfus Med Hemother. 2019;46(3):173-81. [DOI:10.1159/000499054] [PMID] []
10. Amini M, Benson JD. Technologies for Vitrification Based Cryopreservation. Bioengineering (Basel). 2023;10(5). [DOI:10.3390/bioengineering10050508] [PMID] []
11. Hossay C, Donnez J, Dolmans MM. Whole Ovary Cryopreservation and Transplantation: A Systematic Review of Challenges and Research Developments in Animal Experiments and Humans. J Clin Med. 2020;9(10). [DOI:10.3390/jcm9103196] [PMID] []
12. Bakhach J. The cryopreservation of composite tissues: Principles and recent advancement on cryopreservation of different type of tissues. Organogenesis. 2009;5(3):119-26. [DOI:10.4161/org.5.3.9583] [PMID] []
13. Cottle C, Porter AP, Lipat A, Turner-Lyles C, Nguyen J, Moll G, et al. Impact of Cryopreservation and Freeze-Thawing on Therapeutic Properties of Mesenchymal Stromal/Stem Cells and Other Common Cellular Therapeutics. Curr Stem Cell Rep. 2022;8(2):72-92. [DOI:10.1007/s40778-022-00212-1] [PMID] []
14. von Wolff M, Imboden S, Stute P. Fertility preservation in females requiring gonadotoxic therapy should be more than freezing measures before therapy - secondary fertility preservation and menopause care management after therapy should also be considered. Arch Gynecol Obstet. 2025. [DOI:10.1007/s00404-025-08104-5] []
15. von Wolff M, Stute P. Cryopreservation and transplantation of ovarian tissue exclusively to postpone menopause: technically possible but endocrinologically doubtful. Reprod Biomed Online. 2015;31(6):718-21. [DOI:10.1016/j.rbmo.2015.08.010] [PMID]
16. Massarotti C, Selmi C, La Marca A. "Forever fertile": ovarian tissue cryopreservation for an extended reproductive lifespan. J Assist Reprod Genet. 2025. [DOI:10.1007/s10815-025-03554-x] []
17. Gullo G, Etrusco A, Cucinella G, Basile G, Fabio M, Perino A, et al. Ovarian tissue cryopreservation and transplantation in menopause: new perspective of therapy in postmenopausal women and the importance of ethical and legal frameworks. Eur Rev Med Pharmacol Sci. 2022;26(24):9107-16.
18. Sacinti KG, Sadat R, Ozkavukcu S, Sonmezer M, Sonmezer M. Ovarian tissue cryopreservation and transplantation as a natural means to delay menopause. Arch Gynecol Obstet. 2024;310(5):2305-13. [DOI:10.1007/s00404-024-07752-3] [PMID]
19. Torrealday S, Pal L. Premature Menopause. Endocrinol Metab Clin North Am. 2015;44(3):543-57. [DOI:10.1016/j.ecl.2015.05.004] [PMID]
20. Oktay KH, Marin L, Petrikovsky B, Terrani M, Babayev SN. Delaying Reproductive Aging by Ovarian Tissue Cryopreservation and Transplantation: Is it Prime Time? Trends Mol Med. 2021;27(8):753-61. [DOI:10.1016/j.molmed.2021.01.005] [PMID] []
21. Rozen G, Sii S, Agresta F, Gook D, Polyakov A, Stern C. Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts. Reprod Med Biol. 2021;20(3):277-88. [DOI:10.1002/rmb2.12380] [PMID] []
22. Oktay KH, Marin L. Comparison of orthotopic and heterotopic autologous ovarian tissue transplantation outcomes. Fertil Steril. 2024;121(1):72-9. [DOI:10.1016/j.fertnstert.2023.10.015] [PMID] []
23. Soleimani R, Heytens E, Oktay K. Enhancement of neoangiogenesis and follicle survival by sphingosine-1-phosphate in human ovarian tissue xenotransplants. PLoS One. 2011;6(4):e19475. [DOI:10.1371/journal.pone.0019475] [PMID] []
24. Taylan E, Oktay K. Application of Decellularized Tissue Scaffolds in Ovarian Tissue Transplantation. Methods Mol Biol. 2018;1577:177-81. [DOI:10.1007/7651_2017_35] [PMID]
25. Faubion SS, Kapoor E, Kuhle CL, Sood R, Thielen JM, Miller VM. Recommendations for hormone therapy in hysterectomized women: importance of new data in clinical management. Expert Rev Endocrinol Metab. 2015;10(1):55-63. [DOI:10.1586/17446651.2015.957182] [PMID]
26. Female age-related fertility decline. Committee Opinion No. 589. Fertil Steril. 2014;101(3):633-4. [DOI:10.1016/j.fertnstert.2013.12.032] [PMID]
27. Pacheco F, Oktay K. Current Success and Efficiency of Autologous Ovarian Transplantation: A Meta-Analysis. Reprod Sci. 2017;24(8):1111-20. [DOI:10.1177/1933719117702251] [PMID]
28. Diaz-Garcia C, Domingo J, Garcia-Velasco JA, Herraiz S, Mirabet V, Iniesta I, et al. Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study. Fertil Steril. 2018;109(3):478-85.e2. [DOI:10.1016/j.fertnstert.2017.11.018] [PMID]
29. Llarena NC, Falcone T, Flyckt RL. Fertility Preservation in Women With Endometriosis. Clin Med Insights Reprod Health. 2019;13:1179558119873386. [DOI:10.1177/1179558119873386] [PMID] []
30. Dolmans MM, Manavella DD. Recent advances in fertility preservation. J Obstet Gynaecol Res. 2019;45(2):266-79. [DOI:10.1111/jog.13818] [PMID]
31. Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto S, et al. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015;30(3):608-15. [DOI:10.1093/humrep/deu353] [PMID]
32. Lee S, Ozkavukcu S, Ku SY. Current and Future Perspectives for Improving Ovarian Tissue Cryopreservation and Transplantation Outcomes for Cancer Patients. Reprod Sci. 2021;28(6):1746-58. [DOI:10.1007/s43032-021-00517-2] [PMID] []
33. Dolmans MM, Luyckx V, Donnez J, Andersen CY, Greve T. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue. Fertil Steril. 2013;99(6):1514-22. [DOI:10.1016/j.fertnstert.2013.03.027] [PMID]
34. Kristensen SG, Liu Q, Mamsen LS, Greve T, Pors SE, Bjørn AB, et al. A simple method to quantify follicle survival in cryopreserved human ovarian tissue. Hum Reprod. 2018;33(12):2276-84. [DOI:10.1093/humrep/dey318] [PMID]
35. Zaninović L, Bašković M, Ježek D, Habek D, Pogorelić Z, Katušić Bojanac A, et al. Enhancement of Vascularization and Ovarian Follicle Survival Using Stem Cells in Cryopreserved Ovarian Tissue Transplantation-A Systematic Review. Biology (Basel). 2024;13(5). [DOI:10.3390/biology13050342] [PMID] []
36. Gotschel F, Sonigo C, Becquart C, Sellami I, Mayeur A, Grynberg M. New Insights on In Vitro Maturation of Oocytes for Fertility Preservation. Int J Mol Sci. 2024;25(19). [DOI:10.3390/ijms251910605] [PMID] []
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
