Skip to main content
SpringerLink
Log in

Vitrification of embryos and oocytes for fertility preservation in cancer patients

  • Review Article
  • Published:
Reproductive Medicine and Biology

Abstract

As survival rates and the life expectancy of those with malignancy have increased, more women in their reproductive years are referred for fertility preservation. Chemotherapy and radiotherapy can severely affect ovarian function, and the effect is irreversible. Therefore, it is optimal to attempt fertility preservation before chemotherapy and radiotherapy are initiated. Oocyte and embryo cryopreservation is the most common option for fertility preservation in women. Several reports have proven that embryo and oocyte cryopreservation can achieve a successful pregnancy. This review discusses the impact of chemotherapy and radiotherapy on ovarian function, and the importance of oocyte and embryo cryopreservation for fertility preservation. In addition, the current status of pregnancy outcomes and potential for cryopreserved oocytes to result in live births in cancer patients was reviewed. This may provide useful information for decision-making in cancer patients regarding oocyte and embryo cryopreservation and fertility preservation.

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

Similar content being viewed by others

References

  1. Johnson MD, Cooper AR, Jungheim ES, Lanzendorf SE, Odem RR, Ratts VS. Sperm banking for fertility preservation: a 20-year experience. Eur J Obstet Gynecol Reprod Biol. 2013;170:177–82.

    Article  PubMed  Google Scholar 

  2. Tournaye H, Dohle GR, Barratt CL. Fertility preservation in men with cancer. Lancet. 2014;384:1295–301.

    Article  PubMed  Google Scholar 

  3. Sokmensuer LK, Bozdag G, Esinler I, Sever A, Gunalp S. Live birth after transfer of vitrified-warmed blastocyst derived from ICSI with frozen-thawed sperm: case report. Clin Exp Obstet Gynecol. 2015;42:251–2.

    PubMed  Google Scholar 

  4. Demirtas E, Elizur SE, Holzer H, Gidoni Y, Son WY, Chian RC, et al. Immature oocyte retrieval in the luteal phase to preserve fertility in cancer patients. Reprod Biomed Online. 2008;17:520–3.

    Article  PubMed  Google Scholar 

  5. Grifo JA, Noyes N. Delivery rate using cryopreserved oocytes is comparable to conventional in vitro fertilization using fresh oocytes: potential fertility preservation for female cancer patients. Fertil Steril. 2010;93:391–6.

    Article  CAS  PubMed  Google Scholar 

  6. Huang JY, Chian RC, Gilbert L, Fleiszer D, Holzer H, Dermitas E, et al. Retrieval of immature oocytes from unstimulated ovaries followed by in vitro maturation and vitrification: a novel strategy of fertility preservation for breast cancer patients. Am J Surg. 2010;200:177–83.

    Article  PubMed  Google Scholar 

  7. Maman E, Meirow D, Brengauz M, Raanani H, Dor J, Hourvitz A. Luteal phase oocyte retrieval and in vitro maturation is an optional procedure for urgent fertility preservation. Fertil Steril. 2011;95:64–7.

    Article  PubMed  Google Scholar 

  8. Shalom-Paz E, Holzer HE. Fertility preservation for cancer patients. Current options. Minerva Ginecol. 2011;63:517–30.

    CAS  PubMed  Google Scholar 

  9. Moria A, Das M, Shehata F, Holzer H, Son WY, Tulandi T. Ovarian reserve and oocyte maturity in women with malignancy undergoing in vitro maturation treatment. Fertil Steril. 2011;95:1621–3.

    Article  PubMed  Google Scholar 

  10. Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in cancer patients. Fertil Steril. 2005;83:1622–8.

    Article  Google Scholar 

  11. de Mouzon J, Goossens V, Bhattacharya S, Castilla JA, Ferraretti AP, Korsak V, et al. Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE. Hum Reprod. 2010;25:1851–62.

    Article  PubMed  Google Scholar 

  12. Konc J, Kanyo K, Kriston R, Somoskoi B, Cseh S. Cryopreservation of embryos and oocytes in human assisted reproduction. Biomed Res Int. 2014;2014:307268.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Herrero L, Martinez M, Garcia-Velasco JA. Current status of human oocyte and embryo cryopreservation. Curr Opin Obstet Gynecol. 2011;23:245–50.

    PubMed  Google Scholar 

  14. Shalom-Paz E, Almog B, Shehata F, Huang J, Holzer H, Chian RC, et al. Fertility preservation for breast-cancer patients using IVM followed by oocyte or embryo vitrification. Reprod Biomed Online. 2010;21:566–71.

    Article  PubMed  Google Scholar 

  15. Mori C, Yabuuchi A, Ezoe K, Murata N, Takayama Y, Okimura T, et al. Hydroxypropyl cellulose as an option for supplementation of cryoprotectant solutions for embryo vitrification in human assisted reproductive technologies. Reprod Biomed Online. 2015;30:613–21.

    Article  CAS  PubMed  Google Scholar 

  16. 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;30:608–15.

    Article  PubMed  Google Scholar 

  17. Oktay K. Spontaneous conceptions and live birth after heterotopic ovarian transplantation: is there a germline stem cell connection? Hum Reprod. 2006;21:1345–8.

    Article  PubMed  Google Scholar 

  18. Oktay K, Oktem O. Ovarian cryopreservation and transplantation for fertility preservation for medical indications: report of an ongoing experience. Fertil Steril. 2010;93:762–8.

    Article  PubMed  Google Scholar 

  19. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, et al. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet. 2004;364:1405–10.

    Article  CAS  PubMed  Google Scholar 

  20. Donnez J, Martinez-Madrid B, Jadoul P, Van Langendonckt A, Demylle D, Dolmans MM. Ovarian tissue cryopreservation and transplantation: a review. Hum Reprod Update. 2006;12:519–35.

    Article  PubMed  Google Scholar 

  21. Silber SJ, DeRosa M, Pineda J, Lenahan K, Grenia D, Gorman K, et al. A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation. Hum Reprod. 2008;23:1531–7.

    Article  CAS  PubMed  Google Scholar 

  22. Peek R, Bastings L, Westphal JR, Massuger LF, Braat DD, Beerendonk CC. A preliminary study on a new model system to evaluate tumour-detection and tumour-purging protocols in ovarian cortex tissue intended for fertility preservation. Hum Reprod. 2015;30:870–6.

    Article  CAS  PubMed  Google Scholar 

  23. Dolmans MM, Marinescu C, Saussoy P, Van Langendonckt A, Amorim C, Donnez J. Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood. 2010;116:2908–14.

    Article  CAS  PubMed  Google Scholar 

  24. Meirow D, Hardan I, Dor J, Fridman E, Elizur S, Ra’anani H, et al. Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Hum Reprod. 2008;23:1007–13.

    Article  PubMed  Google Scholar 

  25. Thomson AB, Critchley HO, Kelnar CJ, Wallace WH. Late reproductive sequelae following treatment of childhood cancer and options for fertility preservation. Best Pract Res Clin Endocrinol Metab. 2002;16:311–34.

    Article  PubMed  Google Scholar 

  26. Critchley HO, Bath LE, Wallace WH. Radiation damage to the uterus—review of the effects of treatment of childhood cancer. Hum Fertil (Camb). 2002;5:61–6.

    Article  Google Scholar 

  27. Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol. 2006;24:2917–31.

    Article  PubMed  Google Scholar 

  28. Bar-Joseph H, Ben-Aharon I, Rizel S, Stemmer SM, Tzabari M, Shalgi R. Doxorubicin-induced apoptosis in germinal vesicle (GV) oocytes. Reprod Toxicol. 2010;30:566–72.

    Article  CAS  PubMed  Google Scholar 

  29. Meirow D, Biederman H, Anderson RA, Wallace WH. Toxicity of chemotherapy and radiation on female reproduction. Clin Obstet Gynecol. 2010;53:727–39.

    Article  PubMed  Google Scholar 

  30. Ezoe K, Murata N, Yabuuchi A, Okuno T, Kobayashi T, Kato O, et al. Long-term adverse effects of cyclophosphamide on follicular growth and angiogenesis in mouse ovaries. Reprod Biol. 2014;14:238–42.

    Article  PubMed  Google Scholar 

  31. Yucebilgin MS, Terek MC, Ozsaran A, Akercan F, Zekioglu O, Isik E, et al. Effect of chemotherapy on primordial follicular reserve of rat: an animal model of premature ovarian failure and infertility. Aust N Z J Obstet Gynaecol. 2004;44:6–9.

    Article  PubMed  Google Scholar 

  32. Tarumi W, Suzuki N, Takahashi N, Kobayashi Y, Kiguchi K, Sato K, et al. Ovarian toxicity of paclitaxel and effect on fertility in the rat. J Obstet Gynaecol Res. 2009;35:414–20.

    Article  CAS  PubMed  Google Scholar 

  33. Schultheis B, Nijmeijer BA, Yin H, Gosden RG, Melo JV. Imatinib mesylate at therapeutic doses has no impact on folliculogenesis or spermatogenesis in a leukaemic mouse model. Leuk Res. 2012;36:271–4.

    Article  CAS  PubMed  Google Scholar 

  34. Carlsson IB, Laitinen MP, Scott JE, Louhio H, Velentzis L, Tuuri T, et al. Kit ligand and c-Kit are expressed during early human ovarian follicular development and their interaction is required for the survival of follicles in long-term culture. Reproduction. 2006;131:641–9.

    Article  CAS  PubMed  Google Scholar 

  35. Abusief ME, Missmer SA, Ginsburg ES, Weeks JC, Partridge AH. The effects of paclitaxel, dose density, and trastuzumab on treatment-related amenorrhea in premenopausal women with breast cancer. Cancer. 2010;116:791–8.

    Article  CAS  PubMed  Google Scholar 

  36. Larsen EC, Muller J, Rechnitzer C, Schmiegelow K, Andersen AN. Diminished ovarian reserve in female childhood cancer survivors with regular menstrual cycles and basal FSH <10 IU/l. Hum Reprod. 2003;18:417–22.

    Article  CAS  PubMed  Google Scholar 

  37. Bath LE, Wallace WH, Shaw MP, Fitzpatrick C, Anderson RA. Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Mullerian hormone, inhibin B and ovarian ultrasound. Hum Reprod. 2003;18:2368–74.

    Article  CAS  PubMed  Google Scholar 

  38. Sklar CA, Mertens AC, Mitby P, Whitton J, Stovall M, Kasper C, et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J Natl Cancer Inst. 2006;98:890–6.

    Article  PubMed  Google Scholar 

  39. Green DM, Sklar CA, Boice JD Jr, Mulvihill JJ, Whitton JA, Stovall M, et al. Ovarian failure and reproductive outcomes after childhood cancer treatment: results from the Childhood Cancer Survivor Study. J Clin Oncol. 2009;27:2374–81.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Schover LR, Brey K, Lichtin A, Lipshultz LI, Jeha S. Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors. J Clin Oncol. 2002;20:1880–9.

    Article  PubMed  Google Scholar 

  41. Baysal O, Bastings L, Beerendonk CC, Postma SA, IntHout J, Verhaak CM, et al. Decision-making in female fertility preservation is balancing the expected burden of fertility preservation treatment and the wish to conceive. Hum Reprod. 2015;30:1625–34.

    Article  CAS  PubMed  Google Scholar 

  42. Practice Committee of American Society for Reproductive Medicine; Practice Committee of Society for Assisted Reproductive Technology. Ovarian tissue and oocyte cryopreservation. Fertil Steril. 2008;90:S241–6.

    Google Scholar 

  43. Practice Committees of American Society for Reproductive Medicine; Society for Assisted Reproductive Technology. Mature oocyte cryopreservation: a guideline. Fertil Steril. 2013;99:37–43.

    Article  Google Scholar 

  44. Cobo A, Kuwayama M, Perez S, Ruiz A, Pellicer A, Remohi J. Comparison of concomitant outcome achieved with fresh and cryopreserved donor oocytes vitrified by the Cryotop method. Fertil Steril. 2008;89:1657–64.

    Article  PubMed  Google Scholar 

  45. Cobo A, Meseguer M, Remohi J, Pellicer A. Use of cryo-banked oocytes in an ovum donation programme: a prospective, randomized, controlled, clinical trial. Hum Reprod. 2010;25:2239–46.

    Article  PubMed  Google Scholar 

  46. Rienzi L, Romano S, Albricci L, Maggiulli R, Capalbo A, Baroni E, et al. Embryo development of fresh ‘versus’ vitrified metaphase II oocytes after ICSI: a prospective randomized sibling-oocyte study. Hum Reprod. 2010;25:66–73.

    Article  PubMed  Google Scholar 

  47. Parmegiani L, Cognigni GE, Bernardi S, Cuomo S, Ciampaglia W, Infante FE, et al. Efficiency of aseptic open vitrification and hermetical cryostorage of human oocytes. Reprod Biomed Online. 2011;23:505–12.

    Article  CAS  PubMed  Google Scholar 

  48. Cutting R, Barlow S, Anderson R. Human oocyte cryopreservation: evidence for practice. Hum Fertil (Camb). 2009;12:125–36.

    Article  CAS  Google Scholar 

  49. Cobo A, Serra V, Garrido N, Olmo I, Pellicer A, Remohi J. Obstetric and perinatal outcome of babies born from vitrified oocytes. Fertil Steril. 2014;102(1006–15):e4.

    PubMed  Google Scholar 

  50. Pickering SJ, Braude PR, Johnson MH, Cant A, Currie J. Transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in the human oocyte. Fertil Steril. 1990;54:102–8.

    Article  CAS  PubMed  Google Scholar 

  51. Mullen SF, Agca Y, Broermann DC, Jenkins CL, Johnson CA, Critser JK. The effect of osmotic stress on the metaphase II spindle of human oocytes, and the relevance to cryopreservation. Hum Reprod. 2004;19:1148–54.

    Article  CAS  PubMed  Google Scholar 

  52. Mullen SF, Rosenbaum M, Critser JK. The effect of osmotic stress on the cell volume, metaphase II spindle and developmental potential of in vitro matured porcine oocytes. Cryobiology. 2007;54:281–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Larman MG, Minasi MG, Rienzi L, Gardner DK. Maintenance of the meiotic spindle during vitrification in human and mouse oocytes. Reprod Biomed Online. 2007;15:692–700.

    Article  CAS  PubMed  Google Scholar 

  54. Coticchio G, Bromfield JJ, Sciajno R, Gambardella A, Scaravelli G, Borini A, et al. Vitrification may increase the rate of chromosome misalignment in the metaphase II spindle of human mature oocytes. Reprod Biomed Online. 2009;19(Suppl 3):29–34.

    Article  PubMed  Google Scholar 

  55. Huang JY, Chen HY, Tan SL, Chian RC. Effect of choline-supplemented sodium-depleted slow freezing versus vitrification on mouse oocyte meiotic spindles and chromosome abnormalities. Fertil Steril. 2007;88:1093–100.

    Article  PubMed  Google Scholar 

  56. Cao YX, Xing Q, Li L, Cong L, Zhang ZG, Wei ZL, et al. Comparison of survival and embryonic development in human oocytes cryopreserved by slow-freezing and vitrification. Fertil Steril. 2009;92:1306–11.

    Article  PubMed  Google Scholar 

  57. Martinez-Burgos M, Herrero L, Megias D, Salvanes R, Montoya MC, Cobo AC, et al. Vitrification versus slow freezing of oocytes: effects on morphologic appearance, meiotic spindle configuration, and DNA damage. Fertil Steril. 2011;95:374–7.

    Article  PubMed  Google Scholar 

  58. Meirow D, Raanani H, Maman E, Paluch-Shimon S, Shapira M, Cohen Y, et al. Tamoxifen co-administration during controlled ovarian hyperstimulation for in vitro fertilization in breast cancer patients increases the safety of fertility-preservation treatment strategies. Fertil Steril. 2014;102(488–95):e3.

    PubMed  Google Scholar 

  59. Turan V, Bedoschi G, Moy F, Oktay K. Safety and feasibility of performing two consecutive ovarian stimulation cycles with the use of letrozole–gonadotropin protocol for fertility preservation in breast cancer patients. Fertil Steril. 2013;100(1681–5):e1.

    PubMed  Google Scholar 

  60. Revelli A, Porcu E, Levi Setti PE, Delle Piane L, Merlo DF, Anserini P. Is letrozole needed for controlled ovarian stimulation in patients with estrogen receptor-positive breast cancer? Gynecol Endocrinol. 2013;29:993–6.

    Article  CAS  PubMed  Google Scholar 

  61. Reddy J, Oktay K. Ovarian stimulation and fertility preservation with the use of aromatase inhibitors in women with breast cancer. Fertil Steril. 2012;98:1363–9.

    Article  CAS  PubMed  Google Scholar 

  62. Yang D, Brown SE, Nguyen K, Reddy V, Brubaker C, Winslow KL. Live birth after the transfer of human embryos developed from cryopreserved oocytes harvested before cancer treatment. Fertil Steril. 2007;87(1469):e1–4.

    PubMed  Google Scholar 

  63. Porcu E, Venturoli S, Damiano G, Ciotti PM, Notarangelo L, Paradisi R, et al. Healthy twins delivered after oocyte cryopreservation and bilateral ovariectomy for ovarian cancer. Reprod Biomed Online. 2008;17:265–7.

    Article  CAS  PubMed  Google Scholar 

  64. Tsai YY, Chen SU, Shieh CJ, Yao YL, Yang YS, Chen CD. Live birth after single embryo transfer of autologous cryopreserved oocytes from a patient with myelodysplastic syndrome who underwent allogenic peripheral blood stem cell transplantation. J Formos Med Assoc. 2014;113(12):966–9.

    Article  PubMed  Google Scholar 

  65. Kim MK, Lee DR, Han JE, Kim YS, Lee WS, Won HJ, et al. Live birth with vitrified-warmed oocytes of a chronic myeloid leukemia patient nine years after allogenic bone marrow transplantation. J Assist Reprod Genet. 2011;28:1167–70.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Doshida M, Nakajo Y, Toya M, Kyono K. A live birth from vitrified-warmed oocytes in a Philadelphia chromosome-positive acute lymphoid leukemia patient 5 years following allogenic bone marrow transplantation and after a magnitude 9.0 earthquake in Japan. Reprod Med Biol. 2013;12:187–91.

    Article  Google Scholar 

  67. Garcia-Velasco JA, Domingo J, Cobo A, Martinez M, Carmona L, Pellicer A. Five years’ experience using oocyte vitrification to preserve fertility for medical and nonmedical indications. Fertil Steril. 2013;99:1994–9.

    Article  PubMed  Google Scholar 

  68. Martinez M, Rabadan S, Domingo J, Cobo A, Pellicer A, Garcia-Velasco JA. Obstetric outcome after oocyte vitrification and warming for fertility preservation in women with cancer. Reprod Biomed Online. 2014;29:722–8.

    Article  PubMed  Google Scholar 

  69. da Motta EL, Bonavita M, Alegretti JR, Chehin M, Serafini P. Live birth after 6 years of oocyte vitrification in a survivor with breast cancer. J Assist Reprod Genet. 2014;31(10):1397–400.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Alvarez M, Sole M, Devesa M, Fabregas R, Boada M, Tur R, Coroleu B, Veiga A, Barri PN. Live birth using vitrified—warmed oocytes in invasive ovarian cancer: case report and literature review. Reprod Biomed Online. 2014;28(6):663–8.

    Article  PubMed  Google Scholar 

  71. Oktay K, Cil AP, Bang H. Efficiency of oocyte cryopreservation: a meta-analysis. Fertil Steril. 2006;86:70–80.

    Article  PubMed  Google Scholar 

  72. Cancer Statistics in Japan. 2014. Division of Cancer Information Service, National Cancer Center. http://ganjoho.jp/reg_stat/statistics/brochure/backnumber/2014_jp.html.

  73. Platet N, Cathiard AM, Gleizes M, Garcia M. Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion. Crit Rev Oncol Hematol. 2004;51:55–67.

    Article  PubMed  Google Scholar 

  74. Azim AA, Costantini-Ferrando M, Oktay K. Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: a prospective controlled study. J Clin Oncol. 2008;26(16):2630–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

Keiichi Kato declares that he has no conflict of interest.

Human rights statement and informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from all patients for inclusion in the study.

Animal studies

No studies with animal subjects were performed by the author in preparation of this paper.

Author information

Authors and Affiliations

  1. Kato Ladies’ Clinic, 7-20-3 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan

    Keiichi Kato

Authors
  1. Keiichi Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Keiichi Kato.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kato, K. Vitrification of embryos and oocytes for fertility preservation in cancer patients. Reprod Med Biol 15, 227–233 (2016). https://doi.org/10.1007/s12522-016-0239-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12522-016-0239-7

Keywords

Search

Navigation