Journal of Assisted Reproduction and Genetics

, Volume 34, Issue 11, pp 1469–1474 | Cite as

A transportation network for human ovarian tissue is indispensable to success for fertility preservation

  • K KyonoEmail author
  • T Hashimoto
  • M Toya
  • M Koizumi
  • C Sasaki
  • S Shibasaki
  • N Aono
  • Y Nakamura
  • R Obata
  • N Okuyama
  • Y Ogura
  • H Igarashi
Fertility Preservation



The purpose of this study was to examine the efficacy of an ovarian tissue transportation network for fertility preservation (FP) for cancer patients in Japan.


PubMed was searched for papers on transportation of human ovarian tissue for FP. We analyzed population, area, number of cancer patients for ovarian tissue cryopreservation (OTC), quality control/assessment and safety, cost of a cryopreservation center for the building for 30 years, and medical fees of cancer patients (operation, cryopreservation, and storage of ovarian tissue).


More than twenty babies have been born in Denmark and Germany through a transportation system. Up to 400 new patients a year need OTC. The fees for removal, cryopreservation, and storage for 5 years, and transplantation of ovarian tissue are around €5,000, €4,000, and €5,000, respectively. It costs more than €5 million to establish and maintain one cryopreservation center for 30 years. If we have a few cryopreservation centers in Japan, we can cryopreserve 400 patients’ ovarian tissue per year by safer slow freezing and maintain quality control/assessment. We need to lighten the patients’ burden for easy to use FP by a government subsidy and medical insurance coverage.


This model has been termed the Danish model (“the woman stays - the tissue moves”). This is truly patient-centered medicine. We can have maximum effects with the minimum burden. A transportation network like those of Denmark and Germany is the best strategy for FP in Japan. It may be the best system for cancer patients, medical staff, and the Ministry of Health, Labor, and Welfare.


Fertility preservation Transportation Human ovarian tissue Cryopreservation Network 


  1. 1.
    Jensen AK, Macklon KT, Fedder J, Ernst E, Humaidan P, Andersen CY. 86 successful births and 9 ongoing pregnancies worldwide in women transplanted with frozen-thawed ovarian tissue: focus on birth and perinatal outcome in 40 of these children. J Assist Reprod Genet. 2016; DOI:
  2. 2.
    Jensen AK, Kristensen SG, Macklon KT, Jeppesen JV, Fedder J, Ernst E, et al. Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark. Hum Reprod. 2015;30:2838–45.CrossRefPubMedGoogle Scholar
  3. 3.
    Van der Ven H, Liebenthron J, Beckmann M, Toth B, Korell M, Krussel J, et al. Dittrich R on behalf of the FertiPROTEKT network. Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates. Hum Reprod. 2016;31:2031–41.CrossRefPubMedGoogle Scholar
  4. 4.
    Donnez J, Dolmans MM, Demylle D, Jadoul P, Picard C, Squifflet J, et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;364:1405–10.CrossRefPubMedGoogle Scholar
  5. 5.
    Meirow D, Levron J, Eldar-Geva T, Hardan I, Fridman E, Zalel Y, et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med. 2005;353:318–21.CrossRefPubMedGoogle Scholar
  6. 6.
    Andersen CY, Rosendahl M, Byskov AG, Loft A, Ottosen C, Dueholm M, et al. Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue. Hum Reprod. 2008;23:2266–72.CrossRefPubMedGoogle Scholar
  7. 7.
    Kyono K. Fertility preservation:Transportation and cryopreservation of human ovarian tissue. 34th Annual meeting of Japan society of Fertilization and implantation. Super-hot topic2. Abstract 2016. p84.Google Scholar
  8. 8.
    CANCER STATISTICS IN JAPAN-2015; 82–83.Google Scholar
  9. 9.
    Ruddy KJ, Gelber SI, Tamimi RM, Ginsburg ES, Schapira L, Come SE, et al. Prospective study of fertility concerns and preservation strategies in young women with breast cancer. J Clin Oncol. 2014;32:1–6.Google Scholar
  10. 10.
    Wallace WHB, Smith AG, Kelsey TW, Edgar AE, Anderson RA. Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation. Lancet Oncol. 2014;15:1129–36.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Furui T, Takenaka M, Makino H, Terazawa K, Yamamoto A, Morishige K. An evaluation of the Gifu model in a trial for a new regional oncofertility network in Japan, focusing on its necessity and effects. Reprod Med Biol. 2016;15:107–13.CrossRefGoogle Scholar
  12. 12.
    Klock SC, Zhang JX, Kazer RR. Fertility preservation for female cancer patients: early clinical experience. Fertil Steril. 2010;94:149–55.CrossRefPubMedGoogle Scholar
  13. 13.
    Ben-Aharon I, Abir R, Perl G, Stein J, Gilad G, Toledano H, et al. Optimizing the process of fertility preservation in pediatric female cancer patients—a multidisciplinary program. BMC Cancer. 2016;16:620.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Sigismondi C, Papaleo E, Vigano P, Vailati S, Caniani M, Ottolina J, et al. Fertility preservation in female cancer patients: a single center experience. Chin J Cancer. 2015;34:56–60.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Lawrenz B, Jauckus J, Kupka MS, Strowitzki T, von Wolff M. Fertility preservation in >1,000 patients: patient’s characteristics, spectrum, efficacy and risks of applied preservation techniques. Arch Gynecol Obstet. 2011;283:651–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Nishijima C, Iwahata H, Yoshioka N, Sugishita Y, Takae S, Horage Y, Kawamura K, Suzuki N. Oncofertility care of the St. Marianna University School of Medicine Hospital. The 4th World Congress of International Society for Fertility Preservation. 2015;Abstract A-010,166.Google Scholar
  17. 17.
    Imberts R, Moffa F, Tsepelidis S, Simon P, Delbaere A, Devreker F, et al. Safety and useful of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis. Hum Reprod. 2014;29:1931–40.CrossRefGoogle Scholar
  18. 18.
    Kyono K, Doshida M, Toya M, Sato Y, Akahira J, Sasano H. Potential indications for ovarian autotransplantation based on the analysis of 5,571 autopsy findings of females under the age of 40 in Japan. Fertil Steril. 2010;93:2429–30. [Medline] [CrossRef] CrossRefCrossRefPubMedGoogle Scholar
  19. 19.
    ISFP Practice Committee, Kim SS, Donnez J, Barri P, Pellicer A, Patrizio P, et al. Recommendations for fertility preservation in patients with lymphoma, leukemia, and breast cancer. J Assist Reprod Genet. 2012;29:465–8.CrossRefPubMedCentralGoogle Scholar
  20. 20.
    Kataoka A, Tokunaga E, Matsuda N, Shien T, Kawabata K, Miyashita M. Clinicopathological features of young patients (<35% years of age ) with breast cancer in a Japanese Breast Cancer Society supported study. Breast Cancer 2013 Apr 16.Google Scholar
  21. 21.
    Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006;24:1940–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Liedtke CC, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.CrossRefPubMedGoogle Scholar
  23. 23.
    Kim SS, Klemp J, Fabian C. Breast cancer and fertility preservation. Fertil Steril. 2011;95:1535–43.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Dolmans MM, Luyckx V, Donnez J, Andersen CY, Greve T. Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue. Fertil Steril. 2013;99:1514–22.CrossRefPubMedGoogle Scholar
  25. 25.
    Bittinger S, Nazaretian SP, Gook DA, Parmar C, Harrup RA, Stern CJ. Detection of Hodgkin lymphoma within ovarian tissue. Fertil Steril. 2011;95:803.e3–6.CrossRefGoogle Scholar
  26. 26.
    von Wolff M, Montag M, Dittrich R, Denschlag D, Nawroth F, Lawrenz B. Fertility preservation in women—a practical guide to preservation techniques and therapeutic strategies in breast cancer, Hodgkin’s lymphoma and borderline ovarian tumours by the fertility preservation network FertiPROTEKT. Arch Gynecol Obstet. 2011;284:427–35.CrossRefGoogle Scholar
  27. 27.
    Liebenthron J, Koster M, Drengner C, Reinsberg J, van der Ven H, Montag M. The impact of culture conditions on early follicle recruitment and growth from human ovarian cortex biopsies in vitro. Fertil Steril. 2013;100:483–491.e5.CrossRefPubMedGoogle Scholar
  28. 28.
    Bastings L, Liebenthron J, Westphal JR, Beerendonk CCM, van der Ven H, Meinecke B, et al. Efficacy of ovarian tissue cryopreservation in a major European center. J Assist Reprod Genet. 2014;31:1003–12.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Meirow D, Ra’anani H, Shapira M, Brenghausen M, Chaim SD, Aviel-Ronen S, et al. Transplantations of frozen-thawed ovarian tissue demonstrate high reproductive performance and the need to revise restrictive criteria. Fertil Steril. 2016;106:467–74.CrossRefPubMedGoogle Scholar
  30. 30.
    Rodriguez-Iglesias B, Novella-Maestre E, Herraiz S, Diaz-Garcia C, Pellicer N, Pellicer A. New methods to improve the safety assessment of cryopreserved ovarian tissue for fertility preservation in breast cancer patients. Fertil Steril. 2015;104:1493–1502.e2.CrossRefPubMedGoogle Scholar
  31. 31.
    Schmidt KL, Ernst E, Byskov AG, Andersen AN, Andersen CY. Survival of primordial follicles following prolonged transportation of ovarian tissue prior to cryopreservation. Hum Reprod. 2003;12:2654–9.CrossRefGoogle Scholar
  32. 32.
    Kyoya T, Nakamura Y, Miyatani S, Miyagawa T, Tomiyama T, Kyono K. Evaluation of oxygen consumption in human vitrified and warmed pre-antral follicles after prolonged low temperatures. ReprodMed Biol. 2014;13:47–52.CrossRefGoogle Scholar
  33. 33.
    Kyono K. Fertility preservation. J Mamm Ova Res. 2013;30:101–8.CrossRefGoogle Scholar
  34. 34.
    Isachenko E, Isachenko V, Nawroth F, Rahimi G, Weiss JM. Effect of long-term exposure at suprazero temperatures on activity and viability of human ovarian cortex. Fertil Steril. 2009;91:1556–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Isachenko V, Mallmann P, Petrunkina AM, Rahimi G, Nawroth F, Hancke K, et al. Comparison of in vitro- and chorioallantoic membrane (CAM)-culture systems for cryopreserved medulla-contained human ovarian tissue. PLoS One. 2012;7:e32549.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Isachenko V, Dittrich R, Keck G, Isachenko E, Rahimi G, van der Ven H, et al. Cryopreservation of ovarian tissue: detailed description of methods for transport, freezing and thawing. Geburtshilfe Frauenheilkd. 2012;72:927–32.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Dittrich R, Lotz L, Keck G, Hoffmann I, Mueller A, Beckmann MW, et al. Live birth after ovarian tissue autotransplantation following overnight transportation before cryopreservation. Fertil Steril. 2012;97:387–90.CrossRefPubMedGoogle Scholar
  38. 38.
    Muller A, Keller K, Wacker J, Dittrich R, Keck G, Montag M, et al. Retransplantation of cryopreserved ovarian tissue: the first live birth in Germany. Deutsches Arzteblatt International. 2012;109:8–13.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Rosendahl M, Schmidt KT, Ernst E, Rasmussen PE, Loft A, Byskov AG, et al. Cryopreservation of ovarian tissue for a decade in Denmark: a view of the technique. Reprod BioMed Online. 2011;22:162–71.CrossRefPubMedGoogle Scholar
  40. 40.
    Kamoshita K, Okamoto N, Nakajima M, Hino T, Sugimoto K, Okamoto A, et al. Investigation of in vitro parameters and fertility of mouse ovary after storage at an optimal temperature and duration for transportation. Hum Reprod. 2016;31:774–81.CrossRefPubMedGoogle Scholar
  41. 41.
    Laronda MM, Duncan FE, Hornick JE, Xu M, Pahnke JE, Whelan KA, et al. Alginate encapsulation supports the growth and differentiation of human primordial follicles within ovarian cortical tissue. J Assist Reprod Genet. 2014;31:1013–28.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Duncan FE, Zelinski M, Gunn AH, Pahnke JE, O'Neill CL, Songsasen N, et al. Ovarian tissue transport to expand access to fertility preservation: from animals to clinical practice. Reproduction. 2016;152:R201–10.CrossRefPubMedGoogle Scholar
  43. 43.
    Henry L, Fransolet M, Labied S, Blacher S, Masereel MC, Foidart JM, et al. Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival. Journal of Ovarian Research. 2016;9:4.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Kawamura K, Cheng Y, Suzuki N, Deguchi M, Sato Y, Takae S, et al. Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment. Proc Natl Acad Sci U S A. 2013;110:17474–9.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Kagawa N, Silber S, Kuwayama M. Successful vitrification of bovine and human ovarian tissue. RBM Online. 2009;18:568–77.PubMedGoogle Scholar
  46. 46.
    Hashimoto S, Suzuki N, Yamanaka M, Hosoi Y, Ishizuka B, Morimoto Y. Effects of vitrification solutions and equilibration times on the morphology of cynomolgus ovarian tissues. Reprod BioMed Online. 2010;21:501–9.CrossRefPubMedGoogle Scholar
  47. 47.
    Obata R, Nakamura Y, Okuyama N, Sasaki C, Ogura Y, Aono N, Hamano S, Hashimoto T, Kyono K. Comparison of residual dimethyl sulfoxide (DMSO) and ethylene glycol (EG) concentration in bovine ovarian tissue during warming steps between slow freezing and vitrification methods. 2017;P-513, The 33rd Meeting of the ESHRE.Google Scholar
  48. 48.
    Nakamura Y, Obata R, Okuyama N, Aono N, Hashimoto T, Kyono K. Residual ethylene glycol (EG) and dimethyl sulfoxide (DMSO) concentration in ovarian tissue during warming steps of vitrification protocol. Reprod Biomed Online. Online publication complete: 20-JUN-2017. DOI:
  49. 49.
    Iwatani M, Ikegami K, Kremenska Y, Hattori N, Tanaka S, Yagi S, et al. Dimethyl sulfoxide has an impact on epigenetic profile in mouse embryoid body. Stem Cells. 2006;24:2549–56.CrossRefPubMedGoogle Scholar
  50. 50.
    Larman MG, Katz-Jaffe MG, McCallie B, Filipovits JA, Gardner DK. Analysis of global gene expression following mouse blastocyst cryopreservation. Hum Reprod. 2011;26:2672–80.CrossRefPubMedGoogle Scholar
  51. 51.
    Cordeiro RM, Stirling S, Fahy GM, de Magalhaes JP. Insights on cryoprotectant toxicity from gene expression profiling of endothelial cells exposed to ethylene glycol. Cryobiology. 2015;71:405–12.CrossRefPubMedGoogle Scholar
  52. 52.
    Dolmans MM, Jadoul P, Gilliaux S, Amorim CA, Luyckx V, Squifflet J, et al. A review of 15 years of ovarian tissue bank activities. J Assist Reprod Genet. 2013;30:305–14.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Brigham KB, Cadier B, Chevreul K. The diversity of regulation and public financing of IVF in Europe and its impact on utilization. Hum Reprod. 2013;28:666–75.CrossRefGoogle Scholar
  54. 54.
    Directive 2011/24 EU of the European Parliament and of the Council of 9 March 2011 on the application of patents’ rights in cross-border healthcare.European Court of Human Rights. Case of S.H. and others v. Austria, 2011. (26 November 2012, date last accessed).
  55. 55.
    Shenfeld F, de Mouzon J, Pennings G, Ferraretti AP, Nyboe Andersen A, de Wert G, et al. The ESHRE taskforce on cross border reproductive care. Cross border reproductive care in six European countries. Hum Reprod. 2010;25:1361–8.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • K Kyono
    • 1
    • 2
    Email author
  • T Hashimoto
    • 1
    • 2
  • M Toya
    • 1
    • 2
  • M Koizumi
    • 1
    • 2
  • C Sasaki
    • 1
    • 2
  • S Shibasaki
    • 1
    • 2
  • N Aono
    • 1
    • 2
  • Y Nakamura
    • 1
    • 2
  • R Obata
    • 1
    • 2
  • N Okuyama
    • 1
    • 2
  • Y Ogura
    • 1
    • 2
  • H Igarashi
    • 1
    • 2
  1. 1.Kyono ART Clinic TakanawaTokyoJapan
  2. 2.Kyono ART ClinicSendaiJapan

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