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Fertility preservation for people with cancer

Ovarian tissue cryopreservation

Clinical Question

Does the use of ovarian tissue cryopreserved before cancer treatment transplanted in women with a history of cancer result in pregnancy and live birth? What are the risks of the harvesting procedure?

Ovarian tissue cryopreservation is the main option for pre-pubertal girls and young women with a history of cancer when other options (including oocyte cryopreservation) are contraindicated or not possible because of time constraints.[1] Ovarian stimulation with oocyte cryopreservation has been performed in pre-pubertal[2] and peri-pubertal girls,[3] however these were investigational case reports and the procedure is not recommended in routine care.

Recent advances, including birth after grafting of ovarian tissue taken from pre-pubertal girls, have demonstrated the clinical usefulness of this technique as a safe form of fertility preservation that may result in restoration of ovarian function, pregnancy and live birth.[4][5][6] However, even after optimal cryopreservation and grafting, ovarian function is somewhat fragile, with some follicular atresia of the tissue and a finite duration of ovarian activity. While some reported pregnancies are spontaneous, the follicular dynamics and oocyte quality are variable and IVF may be required.[7] This technique is no longer considered experimental.[8]

Tissue cryopreservation requires technical expertise and therefore is best performed in centres with experience to ensure the best possible chance of tissue viability after grafting.[9] Improvements in tissue handling will expand the opportunities for pregnancy from this technique. The recent creation of international registries for fertility preservation and for ovarian tissue cryopreservation will allow better data evaluation to inform best practice.[10]

The best summary of evidence regarding complications of tissue retrieval surgery and grafting technique comes from three systematic reviews[7][11][12] and a meta-analysis.[4] Corkum et al found that three studies noted bleeding as a complication of ovarian tissue cryopreservation, although this was rare. The same publication also noted tubal pregnancy and graft failure as a complication of ovarian tissue auto-transplantion.[7]

Despite concerns of malignant cells being in grafted tissue, one systematic review found that recurrence of cancer due to ovarian tissue transplantation is unlikely.[11] Histological and molecular examination of the tissue for malignant cells before transplantation is recommended as is close monitoring of transplant patients for recurrence. Malignant cell contamination has been demonstrated in patients with acute leukemia and non-Hodgkin's lymphoma prior to chemotherapy or remission[6][13][14]. Various strategies are in development to reduce the risk, including in vitro maturation, purging, the artificial ovary and xenografting.[15][16][17]

Evidence Summary

Evidence summaryLevelReferences
Ovarian tissue cryopreservation and transplantation for post-pubertal females is no longer considered experimental, with increasing numbers of births after both spontaneous pregnancies and IVF. For pre-pubertal girls, ovarian tissue cryopreservation remains the main option for future fertility and reported births suggest the future success of this technique. Risk of malignant spread is considered high in leukemia and may be relevant in other cancers. Currently experimental models are evaluating techniques to optimise safe pregnancy for these patients.IV[7], [11], [12], [4]


Recommendation

Evidence-based recommendationGrade
Ovarian tissue cryopreservation should be considered for pre-pubertal girls, and for young women at significant risk of premature ovarian insufficiency from gonadotoxic cancer treatments. Referral to a fertility service and laboratory with experience in tissue cryopreservation is recommended. The safety of grafting in leukemia patients has not been demonstrated.C

References

  1. Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, et al. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol 2018 Jul 1;36(19):1994-2001 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29620997.
  2. Azem F, Brener A, Malinger G, Reches A, Many A, Yogev Y, et al. Bypassing physiological puberty, a novel procedure of oocyte cryopreservation at age 7: a case report and review of the literature. Fertil Steril 2020 Aug;114(2):374-378 Available from: http://www.ncbi.nlm.nih.gov/pubmed/32386868.
  3. Reichman DE, Davis OK, Zaninovic N, Rosenwaks Z, Goldschlag DE. Fertility preservation using controlled ovarian hyperstimulation and oocyte cryopreservation in a premenarcheal female with myelodysplastic syndrome. Fertil Steril 2012 Nov;98(5):1225-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22884018.
  4. Pacheco F, Oktay K. Current Success and Efficiency of Autologous Ovarian Transplantation: A Meta-Analysis. Reprod Sci 2017 Aug;24(8):1111-1120 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28701069.
  5. Demeestere I, Simon P, Dedeken L, Moffa F, Tsépélidis S, Brachet C, et al. Live birth after autograft of ovarian tissue cryopreserved during childhood. Hum Reprod 2015 Sep;30(9):2107-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26062556.
  6. 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 Mar;30(3):305-14 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23417329.
  7. Corkum KS, Rhee DS, Wafford QE, Demeestere I, Dasgupta R, Baertschiger R, et al. Fertility and hormone preservation and restoration for female children and adolescents receiving gonadotoxic cancer treatments: A systematic review. J Pediatr Surg 2019 Jan 22 Available from: http://www.ncbi.nlm.nih.gov/pubmed/30773394.
  8. Meirow D, Ra'anani H, Shapira M, Brenghausen M, Derech Chaim S, 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 Aug;106(2):467-74 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27181924.
  9. Andersen CY, Bollerup AC, Kristensen SG. Defining quality assurance and quality control measures in connection with ovarian tissue cryopreservation and transplantation: a call to action. Hum Reprod 2018 Jul 1;33(7):1201-1204 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29718400.
  10. Anazodo AC, Stern CJ, McLachlan RI, Gerstl B, Agresta F, Cohn RJ, et al. A Study Protocol for the Australasian Oncofertility Registry: Monitoring Referral Patterns and the Uptake, Quality, and Complications of Fertility Preservation Strategies in Australia and New Zealand. J Adolesc Young Adult Oncol 2016 Sep;5(3):215-25 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26981848.
  11. Gellert SE, Pors SE, Kristensen SG, Bay-Bjørn AM, Ernst E, Yding Andersen C. Transplantation of frozen-thawed ovarian tissue: an update on worldwide activity published in peer-reviewed papers and on the Danish cohort. J Assist Reprod Genet 2018 Apr;35(4):561-570 Available from: http://www.ncbi.nlm.nih.gov/pubmed/29497953.
  12. Ladanyi C, Mor A, Christianson MS, Dhillon N, Segars JH. Recent advances in the field of ovarian tissue cryopreservation and opportunities for research. J Assist Reprod Genet 2017 Jun;34(6):709-722 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28365839.
  13. Greve T, Ernst E, Markholt S, Schmidt KT, Andersen CY. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue. Acta Obstet Gynecol Scand 2010 Dec;89(12):1589-91 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21050152.
  14. Rosendahl M, Greve T, Andersen CY. The safety of transplanting cryopreserved ovarian tissue in cancer patients: a review of the literature. J Assist Reprod Genet 2013 Jan;30(1):11-24 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23263841.
  15. Soares M, Sahrari K, Amorim CA, Saussoy P, Donnez J, Dolmans MM. Evaluation of a human ovarian follicle isolation technique to obtain disease-free follicle suspensions before safely grafting to cancer patients. Fertil Steril 2015 Sep;104(3):672-80.e2 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26095134.
  16. Prasath EB, Chan ML, Wong WH, Lim CJ, 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 Feb;29(2):276-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24327539.
  17. Bedaiwy MA, Falcone T. Ovarian tissue banking for cancer patients: reduction of post-transplantation ischaemic injury: intact ovary freezing and transplantation. Hum Reprod 2004 Jun;19(6):1242-4 Available from: http://www.ncbi.nlm.nih.gov/pubmed/15117897.

Body of evidence

In female cancer patients does ovarian tissue cryopreservation result in pregnancy and livebirth? Is there any reduction in the quality of oocytes/follicles? Can transplantation restore pubertal development? Are there any risks involved?

CitationLevel of EvidenceQuality of EvidenceSize of EffectNumber of PatientsRelevance of Evidence
Corkum KS, Rhee DS, Wafford QE, Demeestere I, Dasgupta R, Baertschiger R, et al. Fertility and hormone preservation and restoration for female children and adolescents receiving gonadotoxic cancer treatments: A systematic review. J Pediatr Surg 2019 Jan 22 Available from:http://www.ncbi.nlm.nih.gov/pubmed/30773394 IVHigh5181
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 Mar;30(3):305-14 Available from:http://www.ncbi.nlm.nih.gov/pubmed/23417329 IVLow5111
Gellert SE, Pors SE, Kristensen SG, Bay-Bjørn AM, Ernst E, Yding Andersen C. Transplantation of frozen-thawed ovarian tissue: an update on worldwide activity published in peer-reviewed papers and on the Danish cohort. J Assist Reprod Genet 2018 Apr;35(4):561-570 Available from:http://www.ncbi.nlm.nih.gov/pubmed/29497953 IVHigh53601
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 Oct;31(4):497-505 Available from:http://www.ncbi.nlm.nih.gov/pubmed/26278808 IVHigh52442
Imbert R, Moffa F, Tsepelidis S, Simon P, Delbaere A, Devreker F, et al. Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis. Hum Reprod 2014 Sep;29(9):1931-40 Available from:http://www.ncbi.nlm.nih.gov/pubmed/24958067 IVHigh581
Ladanyi C, Mor A, Christianson MS, Dhillon N, Segars JH. Recent advances in the field of ovarian tissue cryopreservation and opportunities for research. J Assist Reprod Genet 2017 Jun;34(6):709-722 Available from:http://www.ncbi.nlm.nih.gov/pubmed/28365839 IVHigh5801
Tanbo T, Greggains G, Storeng R, Busund B, Langebrekke A, Fedorcsak P. Autotransplantation of cryopreserved ovarian tissue after treatment for malignant disease - the first Norwegian results. Acta Obstet Gynecol Scand 2015 Sep;94(9):937-41 Available from:http://www.ncbi.nlm.nih.gov/pubmed/26095872 IVHigh521
Wallace WH, 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 Sep;15(10):1129-36 Available from:http://www.ncbi.nlm.nih.gov/pubmed/25130994 IVMediumN/A4105
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Cancer Council Australia