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Ovarian Tissue Transplantation as an Option for Fertility Preservation
implantation (autotransplantation) to culture and mature the Many studies have indicated that autotransplantation of whole
follicles in vitro. ovaries of cryopreserved sheep and other animals have been
surgically successful.
17,38–44
The autotransplantation of fresh ovaries
Several autotransplantation studies conducted using animal to the deep inferior epigastric vessels provides good short-term
models have been successful and resulted in the return of ovarian results.
39,40
The main concern with avascular transplantation is that
function, pregnancies and live births.
17,22,23
Human studies have the success of the graft is entirely dependent on the establishment
followed and used two separate techniques: heterotopic and of neovascularisation.
45,46
orthotopic transplantation. Heterotopic transplantation involves
surgical re-implantation of ovarian tissue to a site outside of the Arav et al. reported progesterone activity 36 months after the
pelvis such as the forearm,
21,24,25
which allows for accessible vascular transplantation of frozen–thawed sheep ovaries. This led
follicular retrieval after stimulation. Re-implantation of tissue to the to successful retrieval of oocytes and embryo development.
44
forearm is a standard method of parathyroid autotransplantation.
26
Bedaiwy et al. also reported restoration of ovarian function in
Autotransplantation of cryopreserved ovarian cortex has resulted frozen–thawed sheep ovaries after microvascular anastamosis.
in the first viable embryo and a live birth in a Rhesus monkey.
25,27
However, eight of 11 ovaries failed due to thrombosis at the pedicle
Worldwide, there has been a total of five children born as a result site.
47
In another study, Imhof et al. showed that autotransplantation
of autotransplanted frozen–thawed ovarian tissue.
28–30
Anderson et of whole sheep ovaries with subsequent microvascular
al. recently reported two live births that were the result of anastamosis to the ovarian pedicle could lead to pregnancy
frozen–thawed tissue that had been placed on ice for four to five and delivery.
41
hours prior to cryopreservation.
31
This suggests that the procedure
may even be offered in hospitals without the necessary local The relatively short duration of successful ovarian function is thought
expertise in performing cryopreservation provided that the tissue to be caused by ischaemia and thrombosis.
48
Recent improvements in
can immediately be sent to a cryopreservation unit.
31
Another microvascular surgery and techniques have led to improved graft
option, orthotopic transplantation, is performed by transplanting survival.
39,40,49,50
With careful preservation of vasculature pedicles
ovarian tissue near the infundibulo-pelvic ligament, which allows during surgical dissection and improved preservation with
for the possibility of a spontaneous pregnancy. This technique has cryoprotectants and freeze–thaw techniques there has been
been more successful. Since 2004, eight live births or ongoing improved tissue survival and improved follicular viability.
40,47
pregnancies have been reported from the orthotopic
transplantation of ovarian tissue.
28–33
Currently, research is being conducted on whole human ovaries with
vasculature canalisation and the efficacy of different freeze–thaw
There are two main concerns for those considering these techniques to minimise tissue damage. It has been proposed that
experimental fertility-preserving procedures. For patients pursuing whole-ovary cryopreservation must be considered the vital direction
treatment due to malignancy, there is a legitimate concern that in ongoing research to make the transplantation of an entire ovary a
autotransplantation may re-seed the patient with metastatic cancer feasible option for fertility preservation.
45
cells.
34
After the removal of tissue, it is necessary to analyse the
cortical tissue for follicles and malignant cells prior to freezing.
4,35
In Conclusion
addition, the success of all transplanted tissue depends on Increasing success in the treatment of childhood cancers and fertility
revascularisation to prevent ischaemia. While follicular function awareness among oncologists has facilitated rapid advances in
appears normal after transplantation, the follicular reserve is fertility-preservation research. Currently, ovarian cortical tissue and
significantly compromised by ischaemia during the long period of whole-ovary cryopreservation are still considered to be an
time required for full neovasularisation to occur.
23,33,36,37
experimental protocol and can be offered only in selected settings.
Research and continued development in cryoprotectants and surgical
Cryopreservation of Whole Ovaries techniques will allow for enhancement of vascularisation of
The transplantation of whole ovaries has been successfully transplanted tissues to minimise post-transfusion ischaemia, which is
accomplished in animal models, but is still considered experimental critical for the viability of ovarian tissue, and therefore improved
in humans. reproductive success. ■
1. Ries LAG, et al., SEER Cancer Statistics Review, 1975–2004, 15. Newton H, et al., Hum Reprod, 1996;11(7):1487–91. 33. Silber SJ, et al., Hum Reprod, 2008;23(7):1531–7.
National Cancer Institute, Bethesda, MD. 16. Oktay K, et al., Fertil Steril, 1997;67(3):481–6. 34. Bromer JG, Patrizio P, Placenta, 2008;29(Suppl. B):200–205.
2. Chatterjee R, Goldstone AH, Bone Marrow Transplant, 17. Gosden RG,et al., Hum Reprod, 1994;9(4):597–603. 35. Blumenfeld Z, Curr Opin Obstet Gynecol, 2003;15(5):359–70.
1996;17(1):5–11. 18. Nugent D, et al., Hum Reprod Update, 1997;3(3):267–80. 36. Liu J, et al., Hum Reprod, 2002;17(3):605–11.
3. Barlow DH, Baillieres Clin Obstet Gynaecol, 1996;10(3):361–84. 19. Donnez J, Bassil S, Hum Reprod Update, 1998;4(3):248–59. 37. Nisolle M, et al., Fertil Steril, 2000;74(1):122–9.
4. Sonmezer M, Oktay K, Hum Reprod Update, 2004;10(3): 20. Donnez J, et al., Curr Opin Obstet Gynecol, 2000;12(1):1–9. 38. Falcone T, et al., Fertil Steril, 2004;81(2):243–57.
251–66. 21. Oktay K, et al., Fertil Steril, 2003;80(1):193–8. 39. Jeremias E, et al., Fertil Steril, 2002;77(6):1278–82.
5. Stillman RJ, et al., Am J Obstet Gynecol, 1981;139(1):62–6. 22. Sztein J, et al., Biol Reprod, 1998;58(4):1071–4. 40. Bedaiwy MA, et al., Fertil Steril, 2003;79(3):594–602.
6. Sklar C, Med Pediatr Oncol, 1999;33(1):2–8. 23. Baird DT, et al., Endocrinology, 1999;140(1):462–71. 41. Imhof M, et al., Fertil Steril, 2006;85(Suppl. 1):1208–15.
7. Byrne J, Med Pediatr Oncol, 1999;33(1):24–8. 24. Oktay K, et al., JAMA, 2001;286(12):1490–93. 42. Goding JR, et al., J Endocrinol, 1967;39(1):37–52.
8. Bakker B, et al., Bone Marrow Transplant, 2004;33(10): 25. Oktay K, et al., Lancet, 2004;363(9412):837–40. 43. Revel A, et al., Fertil Steril, 2004;82(6):1714–5.
1049–56. 26. Wells SA Jr, et al., N Engl J Med, 1976;295(2):57–62. 44. Arav A, et al., Hum Reprod, 2005;20(12):3554–9.
9. Afify Z, et al., Bone Marrow Transplant, 2000;25(10):1087–92. 27. Lee DM, et al., Nature, 2004;428(6979):137–8. 45. Donnez J, et al., Hum Reprod Update, 2006;12(5):519–35.
10. Wallace WH, et al., Clin Oncol, 1989;1(2):75–6. 28. Donnez J, et al., Lancet, 2004;364(9443):1405–10. 46. Tao T, Del Valle A, J Assist Reprod Genet, 2008;25(7):287–96.
11. Martin JR, et al., Fertil Steril, 2007;87(1):189. 29. Meirow D, et al., N Engl J Med, 2005;353(3):318–21. 47. Bedaiwy MA, et al., Hum Reprod, 2006;21(12):3258–69.
12. Oktay K, et al., Fertil Steril, 1998;69(1):1–7. 30. Demeestere I, et al., Oncologist, 2007;12(12):1437–42. 48. Yin H, et al.,Hum Reprod, 2003;18(6):1165–72.
13. Green SH, et al., J Endocrinol, 1956;13(3):330–34. 31. Andersen CY, et al., Hum Reprod, 2008;23(10):2266–72. 49. Jeremias E, et al., Fertil Steril, 2003;79(3):651–3.
14. Hovatta O, et al., Hum Reprod, 1996;11(6):1268–72. 32. Donnez J, et al., Fertil Steril, 2005;84(4):1018. 50. Wang X, et al., Nature, 2002;415(6870):385.
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