Skip to main content

Advertisement

SpringerLink
Log in

Cryopreservation of euploid blastocysts obtained after fertilization of in vitro matured ovarian tissue oocytes: a case report

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

Abstract

With the increased rate of stable remission after gonadotoxic cancer treatment, new methods of fertility preservation are required in order to provide the best possible care for oncological patients. Here, we report an original case of euploid blastocyst cryopreservation after in vitro maturation of ovarian tissue oocytes (OTO IVM). Thirty-three oocytes were obtained from the ovarian tissue after ovariectomy in the breast cancer patient. Six out of 12 matured oocytes fertilized successfully and 3 blastocysts were formed. Genetic investigation for mutations associated with this type of malignancy found that the patient is not a carrier. Preimplantation genetic testing was performed only for aneuploidies and found all 3 blastocysts to be euploid and suitable for embryo transfer. Our study showed that the ovarian tissue oocytes matured in vitro have the potential for euploid blastocyst formation after ICSI which could be screened for aneuploidies and inherited mutations and then be vitrified in order to provide the best fertility preservation strategy for women with cancer.

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

Similar content being viewed by others

References

  1. Shah NM, Scott DM, Kandagatla P, Moravek MB, Cobain EF, Burness ML, et al. Young women with breast cancer: fertility preservation options and management of pregnancy-associated breast cancer. Ann Surg Oncol. 2019 [Internet]. [cited 2019 Feb 13]; Available from: http://link.springer.com/10.1245/s10434-019-07156-7;26:1214–24.

    PubMed  Google Scholar 

  2. Ruddy KJ, Gelber S, Ginsburg ES, Schapira L, Abusief ME, Meyer ME, et al. Menopausal symptoms and fertility concerns in premenopausal breast cancer survivors: a comparison to age- and gravidity-matched controls. Menopause. 2011;18:105–8.

    PubMed  Google Scholar 

  3. Christinat A, Pagani O. Fertility after breast cancer. Maturitas. 2012;73:191–6.

    PubMed  Google Scholar 

  4. Medrano JV, Andrés MDM, García S, Herraiz S, Vilanova-Pérez T, Goossens E, et al. Basic and clinical approaches for fertility preservation and restoration in cancer patients. Trends Biotechnol. 2018;36:199–215.

    CAS  PubMed  Google Scholar 

  5. The Endogenous Hormones and Breast Cancer Collaborative Group. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. Cancer Spectrum Knowledge Environment. 2002;94:606–16.

    Google Scholar 

  6. Sonmezer M. Fertility preservation in female patients. Hum Reprod Update. 2004;10:251–66.

    PubMed  Google Scholar 

  7. Pacheco F, Oktay K. Current success and efficiency of autologous ovarian transplantation: a meta-analysis. Reprod Sci. 2017;24:1111–20.

    PubMed  Google Scholar 

  8. Yin H, Jiang H, Kristensen SG, Andersen CY. Vitrification of in vitro matured oocytes collected from surplus ovarian medulla tissue resulting from fertility preservation of ovarian cortex tissue. J Assist Reprod Genet. 2016;33:741–6.

    PubMed  PubMed Central  Google Scholar 

  9. Revel A. Oocyte collection during cryopreservation of the ovarian cortex. Fertil Steril. 2003;79:1237–9.

    PubMed  Google Scholar 

  10. Fasano G, Moffa F, Dechène J, Englert Y, Demeestere I. Vitrification of in vitro matured oocytes collected from antral follicles at the time of ovarian tissue cryopreservation. Reprod Biol Endocrinol. 2011;9:150.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hourvitz A, Yerushalmi GM, Maman E, Raanani H, Elizur S, Brengauz M, et al. Combination of ovarian tissue harvesting and immature oocyte collection for fertility preservation increases preservation yield. Reprod BioMed Online. 2015;31:497–505.

    CAS  PubMed  Google Scholar 

  12. Segers I, Mateizel I, Van Moer E, Smitz J, Tournaye H, Verheyen G, et al. In vitro maturation (IVM) of oocytes recovered from ovariectomy specimens in the laboratory: a promising “ex vivo” method of oocyte cryopreservation resulting in the first report of an ongoing pregnancy in Europe. J Assist Reprod Genet. 2015;32:1221–31.

    PubMed  PubMed Central  Google Scholar 

  13. Park CW, Lee SH, Yang KM, Lee IH, Lim KT, Lee KH, et al. Cryopreservation of in vitro matured oocytes after ex vivo oocyte retrieval from gynecologic cancer patients undergoing radical surgery. Clin Exp Reprod Med. 2016;43:119.

    PubMed  PubMed Central  Google Scholar 

  14. Fadini R, Dal Canto M, Mignini Renzini M, Milani R, Fruscio R, Cantù MG, et al. Embryo transfer following in vitro maturation and cryopreservation of oocytes recovered from antral follicles during conservative surgery for ovarian cancer. J Assist Reprod Genet. 2012;29:779–81.

    PubMed  PubMed Central  Google Scholar 

  15. Prasath EB, Chan MLH, Wong WHW, Lim CJW, Tharmalingam MD, Hendricks M, et al. First pregnancy and live birth resulting from cryopreserved embryos obtained from in vitro matured oocytes after oophorectomy in an ovarian cancer patient. Hum Reprod. 2014;29:276–8.

    CAS  PubMed  Google Scholar 

  16. Uzelac PS, Delaney AA, Christensen GL, Bohler HCL, Nakajima ST. Live birth following in vitro maturation of oocytes retrieved from extracorporeal ovarian tissue aspiration and embryo cryopreservation for 5 years. Fertil Steril. 2015;104:1258–60.

    PubMed  Google Scholar 

  17. Schmidt KLT. 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.

    CAS  PubMed  Google Scholar 

  18. Escribá M-J, Grau N, Escrich L, Novella-Maestre E, Sánchez-Serrano M. Spontaneous in vitro maturation of oocytes prior to ovarian tissue cryopreservation in natural cycles of oncologic patients. J Assist Reprod Genet. 2012;29:1261–5.

    PubMed  PubMed Central  Google Scholar 

  19. Isachenko E, Rahimi G, Isachenko V, Nawroth F. In-vitro maturation of germinal-vesicle oocytes and cryopreservation in metaphase I/II: a possible additional option to preserve fertility during ovarian tissue cryopreservation. Reprod BioMed Online. 2004;8:553–7.

    PubMed  Google Scholar 

  20. Kedem A, Yerushalmi GM, Brengauz M, Raanani H, Orvieto R, Hourvitz A, et al. Outcome of immature oocytes collection of 119 cancer patients during ovarian tissue harvesting for fertility preservation. J Assist Reprod Genet. 2018;35:851–6.

    PubMed  PubMed Central  Google Scholar 

  21. Huang JYJ, Tulandi T, Holzer H, Tan SL, Chian R-C. Combining ovarian tissue cryobanking with retrieval of immature oocytes followed by in vitro maturation and vitrification: an additional strategy of fertility preservation. Fertil Steril. 2008;89:567–72.

    PubMed  Google Scholar 

  22. The Vienna consensus: report of an expert meeting on the development of ART laboratory performance indicators. Reprod BioMed Online. 2017;35:494–510.

  23. Shirasawa H, Terada Y. In vitro maturation of human immature oocytes for fertility preservation and research material. Reprod Med Biol. 2017;16:258–67.

    PubMed  PubMed Central  Google Scholar 

  24. Masciangelo R, Bosisio C, Donnez J, Amorim CA, Dolmans M-M. Safety of ovarian tissue transplantation in patients with borderline ovarian tumors. Hum Reprod. 2018;33:212–9.

    CAS  PubMed  Google Scholar 

  25. Soares M, Saussoy P, Maskens M, Reul H, Amorim CA, Donnez J, et al. Eliminating malignant cells from cryopreserved ovarian tissue is possible in leukaemia patients. Br J Haematol. 2017;178:231–9.

    CAS  PubMed  Google Scholar 

  26. Gronier H, Terriou L, Robin G, Wacrenier A, Leroy-Martin B, Lefebvre C, et al. Detection of non-Hodgkin’s lymphoma in ovarian cortex pieces during the process of cryopreservation. J Assist Reprod Genet. 2014;31:1251–5.

    PubMed  PubMed Central  Google Scholar 

  27. Bittinger SE, Nazaretian SP, Gook DA, Parmar C, Harrup RA, Stern CJ. Detection of Hodgkin lymphoma within ovarian tissue. Fertil Steril. 2011;95:803.e3–6.

    Google Scholar 

  28. Stern CJ, Gook D, Hale LG, Agresta F, Oldham J, Rozen G, et al. Delivery of twins following heterotopic grafting of frozen-thawed ovarian tissue. Hum Reprod. 2014;29:1828.

    CAS  PubMed  Google Scholar 

  29. 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.

    CAS  PubMed  Google Scholar 

  30. Ernst EH, Offersen BV, Andersen CY, Ernst E. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue due to cancer recurrence. J Assist Reprod Genet. 2013;30:975–8.

    PubMed  PubMed Central  Google Scholar 

  31. Rosendahl M, Timmermans Wielenga V, Nedergaard L, Kristensen SG, Ernst E, Rasmussen PE, et al. Cryopreservation of ovarian tissue for fertility preservation: no evidence of malignant cell contamination in ovarian tissue from patients with breast cancer. Fertil Steril. 2011;95:2158–61.

    PubMed  Google Scholar 

  32. 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.

    PubMed  Google Scholar 

  33. Luyckx V, Durant JF, Camboni A, Gilliaux S, Amorim CA, Van Langendonckt A, et al. Is transplantation of cryopreserved ovarian tissue from patients with advanced-stage breast cancer safe? A pilot study. J Assist Reprod Genet. 2013;30:1289–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Coll L, Parriego M, Boada M, Devesa M, Arroyo G, Rodríguez I, et al. Transition from blastomere to trophectoderm biopsy: comparing two preimplantation genetic testing for aneuploidies strategies. Zygote. 2018;26:191–8.

    CAS  PubMed  Google Scholar 

  35. Liñán A, Lawrenz B, El Khatib I, Bayram A, Arnanz A, Rubio C, et al. Clinical reassessment of human embryo ploidy status between cleavage and blastocyst stage by Next Generation Sequencing. PLoS ONE. 2018;13:e0201652 Yu Y, editor.

    PubMed  PubMed Central  Google Scholar 

  36. Adler A, Lee H-L, McCulloh DH, Ampeloquio E, Clarke-Williams M, Wertz BH, et al. Blastocyst culture selects for euploid embryos: comparison of blastomere and trophectoderm biopsies. Reprod BioMed Online. 2014;28:485–91.

    PubMed  Google Scholar 

  37. Whitney JB, Balloch K, Anderson RE, Nugent N, Schiewe MC. Day 7 blastocyst euploidy supports routine implementation for cycles using preimplantation genetic testing. JBRA Assist Reprod. 2019;23:45–50.

    PubMed  PubMed Central  Google Scholar 

  38. Zhang XY, Ata B, Son W-Y, Buckett WM, Tan S-L, Ao A. Chromosome abnormality rates in human embryos obtained from in-vitro maturation and IVF treatment cycles. Reprod BioMed Online. 2010;21:552–9.

    PubMed  Google Scholar 

  39. Spits C, Guzman L, Mertzanidou A, Jacobs K, Ortega-Hrepich C, Gilchrist RB, et al. Chromosome constitution of human embryos generated after in vitro maturation including 3-isobutyl-1-methylxanthine in the oocyte collection medium. Hum Reprod. 2015;30:653–63.

    CAS  PubMed  Google Scholar 

  40. Fesahat F, Kalantar SM, Sheikhha MH, Saeedi H, Montazeri F, Firouzabadi RD, et al. Developmental and cytogenetic assessments of preimplantation embryos derived from in-vivo or in-vitro matured human oocytes. Eur J Med Genet. 2018;61:235–41.

    PubMed  Google Scholar 

  41. Abir R, Ben-Aharon I, Garor R, Yaniv I, Ash S, Stemmer SM, et al. Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy. Hum Reprod. 2016;31:750–62.

    CAS  PubMed  Google Scholar 

  42. Child TJ, Abdul-Jalil AK, Gulekli B, Lin TS. In vitro maturation and fertilization of oocytes from unstimulated normal ovaries, polycystic ovaries, and women with polycystic ovary syndrome. Fertil Steril. 2001;76:936–42.

    CAS  PubMed  Google Scholar 

  43. Pongsuthirak P, Songveeratham S, Vutyavanich T. Comparison of blastocyst and Sage Media for in vitro maturation of human immature oocytes. Reprod Sci. 2015;22:343–6.

    PubMed  PubMed Central  Google Scholar 

  44. Cha K-Y. Maturation in vitro of immature human oocytes for clinical use. Hum Reprod Update. 1998;4:103–20.

    CAS  PubMed  Google Scholar 

  45. Gruhn JR, Kristensen SG, Andersen CY, Hoffmann ER. In Vitro Maturation and Culture of Human Oocytes. In: Verlhac M-H, Terret M-E, editors. Mouse Oocyte Development. New York: Springer; 2018. p. 23–30. [Internet]. [cited 2020 Jan 15]. Available from: http://link.springer.com/10.1007/978-1-4939-8603-3_3.

    Google Scholar 

  46. Revel A. In vitro maturation and fertilization of oocytes from an intact ovary of a surgically treated patient with endometrial carcinoma: case report. Hum Reprod. 2004;19:1608–11.

    CAS  PubMed  Google Scholar 

  47. Albuz FK, Sasseville M, Lane M, Armstrong DT, Thompson JG, Gilchrist RB. Simulated physiological oocyte maturation (SPOM): a novel in vitro maturation system that substantially improves embryo yield and pregnancy outcomes. Hum Reprod. 2010;25:2999–3011.

    CAS  PubMed  Google Scholar 

  48. Saenz-de-Juano MD, Ivanova E, Romero S, Lolicato F, Sánchez F, Van Ranst H, et al. DNA methylation and mRNA expression of imprinted genes in blastocysts derived from an improved in vitro maturation method for oocytes from small antral follicles in polycystic ovary syndrome patients. Hum Reprod. 2019;34:1640–9.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Zohrab Makiyan for performing the ovariectomy surgery. We also thank Dr. Muminat Ibragimova for providing postoperative care. We are grateful to the personnel of the 1st gynecological department, National Medical Research Center for Obstetrics, Gynecology and Perinatology. We finally want to thank Cerridwen E. Aker for her critical reading of the manuscript.

Author’s roles

AK, TN and GT developed the IVM procedure. AA supervised the IVM procedures. NM, TN and EB were responsible for the diagnostic evaluation and clinical management of the couple. AK and EK were responsible for the laboratory procedures. AE performed preimplantation genetic screening. OB performed testing for mutations associated with breast cancer. MG created the custom panel of the genes. AK wrote the paper. OB and TN edited the paper.

Funding

AK and EB were supported by the Grant of the President of the Russian Federation - for state support of young.

Russian scientists - К-3244.2019.7.

Author information

Authors and Affiliations

  1. National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov, of the Ministry of Healthcare of Russian Federation, Moscow, Russia

    Anastasia Kirillova, Evgeniya Kovalskaya, Aleksey Ekimov, Ekaterina Bunyaeva, Nona Mishieva, Tatiana Nazarenko, Aydar Abubakirov & Gennady Sukikh

  2. Federal Research and Clinical Center, FMBA of Russia, Moscow, Russia

    Olga Brovkina

  3. National BioService LLC, St. Petersburg, Russia

    Marat Gordiev

Authors
  1. Anastasia Kirillova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Evgeniya Kovalskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Olga Brovkina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aleksey Ekimov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ekaterina Bunyaeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marat Gordiev
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nona Mishieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tatiana Nazarenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Aydar Abubakirov
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Gennady Sukikh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anastasia Kirillova.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Informed consent

A written informed consent was obtained from the patient.

Ethical approval

This study was approved by the Ethics Committee of our institution (protocol №11 from 13.12.2018).

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Table S1

(DOCX 45 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kirillova, A., Kovalskaya, E., Brovkina, O. et al. Cryopreservation of euploid blastocysts obtained after fertilization of in vitro matured ovarian tissue oocytes: a case report. J Assist Reprod Genet 37, 905–911 (2020). https://doi.org/10.1007/s10815-020-01729-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-020-01729-2

Keywords

Search

Navigation