Skip to main content

Advertisement

SpringerLink
Log in

Attempts to improve human ovarian transplantation outcomes of needle-immersed vitrification and slow-freezing by host and graft treatments

  • Fertility Preservation
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

An Erratum to this article was published on 08 April 2017

Abstract

Purpose

To investigate if needle-immersed vitrification or slow-freezing yields better implantation results for human ovarian tissue and which method benefits more when combined with the “improvement protocol” of host melatonin treatment and graft incubation with biological glue + vitamin E + vascular endothelial growth factor-A.

Methods

Human ovarian tissue was preserved by needle-immersed vitrification or slow-freezing and transplanted into immunodeficient mice, either untreated (groups A and C, respectively) or treated with the improvement protocol (groups B and D, respectively). Grafted and ungrafted slices were evaluated by follicle counts, apoptosis assay and immunohistochemistry for Ki67 and platelet endothelial cell adhesion molecule (PECAM).

Results

Follicle number in the recovered grafts was limited. The number of atretic follicles was significantly higher after vitrification with/without the improvement protocol and slow-freezing than that after slow-freezing + the improvement protocol. Stroma cell apoptosis was the lowest in the group D. PECAM staining showed a peripheral and diffuse pattern in the group D (mostly normal follicular morphology) and a diffuse pattern in all other groups (few follicles, mostly atretic), with significantly higher diffuse levels in the vitrification groups. Ki67 staining was identified in all normal follicles. Follicles did not survive transplantation in the vitrification groups.

Conclusions

Ovarian sample preparation with slow-freezing + the improvement protocol appears to yield better implantation outcomes than needle-immersed vitrification with/without the improvement protocol. The real quality of frozen tissue can be assessed only after grafting and not after thawing/warming.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Feigin E, Freud E, Fisch B, Orvieto R, Kravarusic D, Avrahami G, et al. Fertility preservation in female adolescents with malignancies. In: Moorland MT, editor. Cancer in female adolescents. Hauppauge: Nova; 2008. p. 103–38.

    Google Scholar 

  2. 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:10.1007/s10815-016-0843-9.

  3. 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;110:17474–4749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Suzuki N, Yoshioka N, Takae S, Sugishita Y, Tamura M, Hashimoto M, et al. Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency. Hum Reprod. 2015;30:608–15.

    Article  PubMed  Google Scholar 

  5. Amorim CA, Curaba M, Van Langendonckt A, Dolmans MM, Donnez J. Vitrification as an alternative means of cryopreserving ovarian tissue. Reprod Biomed Online. 2011;23:160–86.

    Article  PubMed  Google Scholar 

  6. Wang Y, Xiao Z, Li L, Fan W, Li SW. Novel needle immersed vitrification: a practical and convenient method with potential advantages in mouse and human ovarian tissue cryopreservation. Hum Reprod. 2008;23:2256–65.

    Article  CAS  PubMed  Google Scholar 

  7. Kagawa N, Silber S, Kuwayama M. Successful vitrification of bovine and human ovarian tissue. Reprod Biomed Online. 2009;18:568–77.

    Article  PubMed  Google Scholar 

  8. Keros V, Xella S, Hultenby K, Pettersson K, Sheikhi M, Volpe A, et al. Vitrification versus controlled-rate freezing in cryopreservation of human ovarian tissue. Hum Reprod. 2009;24:1670–83.

    Article  CAS  PubMed  Google Scholar 

  9. Xiao Z, Wang Y, Li L, Luo S, Li SW. Needle immersed vitrification can lower the concentration of cryoprotectant in human ovarian tissue cryopreservation. Fertil Steril. 2010;94:2323–8.

    Article  CAS  PubMed  Google Scholar 

  10. Amorim CA, Jacobs S, Devireddy RV, Van Langendonckt A, Vanacker J, Jaeger J, et al. Successful vitrification and autografting of baboon (Papio anubis) ovarian tissue. Hum Reprod. 2013;28:2146–56.

    Article  CAS  PubMed  Google Scholar 

  11. Dolmans MM, Binda JF, Jacobs S, Dehoux JP, Squifflet JL, Ambroise J, et al. Impact of cryopreservation technique and vascular bed on ovarian tissue transplantation in cynomolgus monkeys. J Assist Reprod Genet. 2015;32:1251–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Abir R, Fisch B, Jessel S, Felz C, Ben-Haroush A, Orvieto R. Improving posttransplantation survival of human ovarian tissue by treating the host and graft. Fertil Steril. 2011;95:1205–10.

    Article  PubMed  Google Scholar 

  13. Friedman O, Orvieto R, Fisch B, Felz C, Freud E, Ben-Haroush A, et al. Possible improvements in human ovarian grafting by various host and graft treatments. Hum Reprod. 2012;27:474–82.

    Article  CAS  PubMed  Google Scholar 

  14. Gavish Z, Peer G, Roness H, Cohen Y, Meriow D. Follicle activation and ‘burn-out’ contribute to post-transplantation follicle loss in ovarian tissue grafts: the effect of graft thickness. Hum Reprod. 2016;29:989–96.

    Article  Google Scholar 

  15. Lerer-Serfaty G, Samara N, Fisch B, Shachar M, Kossover O, Seliktar D, et al. Attempted application of bioengineered/biosynthetic supporting matrices with phosphatidylinositol-trisphosphate-enhancing substances to organ culture of human primordial follicles. J Assist Reprod Genet. 2013;30:1279–88.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Telfer EE, McLaughlin M, Ding C, Thong KJ. A two-step serum-free culture system supports development of human oocytes from primordial follicles in the presence of activin. Hum Reprod. 2008;23:1151–8.

    Article  CAS  PubMed  Google Scholar 

  17. Abir R, Biron-Shental T, Orvieto R, Garor R, Krissi H, Fisch B. Transplantation of frozen-thawed late-gestational-age human fetal ovaries into immunodeficient mice. Fertil Steril. 2009;92:770–7.

    Article  PubMed  Google Scholar 

  18. Gougeon A. Regulations of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17:121–54.

    Article  CAS  PubMed  Google Scholar 

  19. Gumina RJ, Kirschbaum NE, Rao PN, Kenny D, Warltier DC, Newman PJ, et al. The human PECAM1 gene maps to 17q23. Genomics. 1996;34:229–32.

    Article  CAS  PubMed  Google Scholar 

  20. Fraser HM. Regulation of the ovarian follicular vasculature. Reprod Biol Endocrinol. 2006;12:4–18.

    Google Scholar 

  21. Woodfin A, Voisin MB, Nourshargh S. PECAM-1: a multi-functional molecule in inflammation and vascular biology. Arterioscler Thromb Vasc Biol. 2007;27:2514–23.

    Article  CAS  PubMed  Google Scholar 

  22. Privratsky JR, Newman DK, Newman PJ. PECAM-1: conflicts of interest in inflammation. Life Sci. 2010;87:69–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rahimi G, Isachenko V, Kreienberg R, Sauer H, Todorov P, Tawadros S, et al. Re-vascularisation in human ovarian tissue after conventional freezing or vitrification and xenotransplantion. Eur J Obstet Gynecol Reprod Biol. 2010;149:63–7.

    Article  PubMed  Google Scholar 

  24. Isachenko V, Lapidus I, Isachenko E, Krivokharchenko A, Kreienberg R, Woriedh M, et al. Human ovarian tissue vitrification versus conventional freezing: morphological, endocrinological and molecular biological evaluation. Reproduction. 2009;138:319–27.

    Article  CAS  PubMed  Google Scholar 

  25. Hewitt SM, Baskin DG, Frevert CW, Stahl WL, Rosa-Molinar E. Controls for immunohistochemistry: the Histochemical Society’s standards of practice for validation of immunohistochemical assays. J Histochem Cytochem. 2014;62:693–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ehrbar M, Djonov VG, Schnell C, Tschanz SA, Martiny-Baron G, Schenk U, et al. Cell-demanded liberation of VEGF121 from fibrin implants induces local and controlled blood vessel growth. Circ Res. 2016;94:1124–32.

    Article  Google Scholar 

  27. Tang J, Hua Y, Su J, Zhang P, Zhu X, Wu L, et al. Expression of VEGF and neural repair after alprostadil treatment in a rat model of schiatic nerve crush injury. Neurol India (Serial: Online). 2009;57:387–94.

    Article  Google Scholar 

  28. Schmidt KL, Byskov AG, Nyboe-Andersen A, Müller J, Andersen Yding C. Density and distribution of primordial follicles in single pieces of cortex from 21 patients and in individual pieces of cortex from three entire human ovaries. Hum Reprod. 2003;18:1158–64.

    Article  CAS  PubMed  Google Scholar 

  29. Van Eyck A-S, Bouzin C, Feron O, Romeu L, Van Langendonckt A, Donnez J, et al. Both host and graft vessels contribute to revascularization of xenografted human ovarian tissue in a murine model. Fertil Steril. 2010;93:1676–85.

    Article  PubMed  Google Scholar 

  30. Demeestere I, Simon P, Dedeken L, Moffa F, Tsepelidis S, Branchet C, et al. Live birth after autograft of ovarian tissue cryopreserved during childhood. Hum Reprod. 2015;30:2107–9.

    Article  PubMed  Google Scholar 

  31. Anderson RA, McLaughlin M, Wallace WH, Albertini DF, Telfer EE. The immature human ovary shows loss of abnormal follicles and increasing follicle developmental competence through childhood and adolescence. Hum Reprod. 2014;29:97–106.

    Article  CAS  PubMed  Google Scholar 

  32. Lande Y, Fisch B, Tsur A, Farhi J, Prag-Rosenberg R, Ben-Haroush A, et al. Short term exposure of human ovarian follicles to cyclophosphamide metabolites seems to promote follicular activation in vitro. RBM Online. 2016;34:104–14.

    PubMed  Google Scholar 

  33. Li YB, Zhou CQ, Yang GF, Wang Q, Dong Y. Modified vitrification method for cryopreservation of human ovarian tissues. Chin Med J. 2007;120:110–4.

    CAS  PubMed  Google Scholar 

  34. Huang L, Mo Y, Wang W, Li Y, Zhang Q, Yang D. Cryopreservation of human ovarian tissue by solid-surface vitrification. Eur J Obstet Gynecol Reprod Biol. 2008;139:193–8.

    Article  CAS  PubMed  Google Scholar 

  35. Revel A, Laufer N, Ben Meir A, Lebovich M, Mitrani E. Micro-organ ovarian transplantation enables pregnancy: a case report. Hum Reprod. 2011;26:1097–103.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are indebted to Ms. G. Ganzach from the Editorial Board of Rabin Medical Center for the English editing. The authors are also grateful to our laboratory technician Carmela Felz for the histological sections.

Author information

Author notes

  1. Nivin Samara

    Present address: In Vitro Fertilization Unit, Lis Maternity and Women’s Hospital, Tel Aviv Sourasky Medical Center, 6423906, Tel Aviv, Israel

Authors and Affiliations

  1. Infertility and IVF Unit, Beilinson Women Hospital, Rabin Medical Center, Petach Tikva, 49100, Israel

    Ronit Abir, Benjamin Fisch, Noa Fisher, Nivin Samara, Galit Lerer-Serfaty, Roei Magen, Avi Ben-Haroush & Anat Stein

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

    Ronit Abir, Benjamin Fisch, Noa Fisher, Nivin Samara, Galit Lerer-Serfaty, Avi Ben-Haroush, Anat Stein & Raoul Orvieto

  3. Faculty of Health Sciences, Goldman Medical School, Ben Gurion University of the Negev, Beer Sheva, 8410501, Israel

    Roei Magen

  4. Department of Nephrology, Rabin Medical Center, Felsenstein Research Center 49100 and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel

    Michal Herman-Edelstein

  5. Infertility and IVF Unit, Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Ramat Gan, 52621, Israel

    Raoul Orvieto

Authors
  1. Ronit Abir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Benjamin Fisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noa Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nivin Samara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Galit Lerer-Serfaty
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roei Magen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michal Herman-Edelstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Avi Ben-Haroush
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Anat Stein
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Raoul Orvieto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ronit Abir.

Ethics declarations

The study was approved by the local institutional ethics committee. Informed consent to donate tissue for the present study was obtained from the patients or the parents of minors.

Additional information

Dr. Noa Fisher D.M.D. performed most of the experiments as a partial requirement for her M.Sc. degree at Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

An erratum to this article is available at http://dx.doi.org/10.1007/s10815-017-0918-2.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abir, R., Fisch, B., Fisher, N. et al. Attempts to improve human ovarian transplantation outcomes of needle-immersed vitrification and slow-freezing by host and graft treatments. J Assist Reprod Genet 34, 633–644 (2017). https://doi.org/10.1007/s10815-017-0884-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-017-0884-8

Keywords

Search

Navigation