Preservation of fertility in young women treated for cancer W Hamish Wallace a , Richard Anderson b , and David Baird c Advances in assisted reproduction , such as in vitro maturation of spermatozoa and oocytes, have renewed interest in the preservation of gonadal tissue from women scheduled to receive chemotherapy or radiotherapy. Recent reports describing human embryo development after heterotopic transplantation of cryopreserved ovarian tissue 1 and the birth of a Rhesus monkey after transplantation of ovarian tissue 2 have shown that it may soon be realistic to restore ovarian function after the sterilising effects of cancer treatment. The only successful strategy available for preservation of female fertility is cryopreservation of embryos after in vitro fertilisation. This technique, however, requires patients to have either a partner prepared to make a long-term commitment, or a sperm donor available. In addition, the number of resultant cryopreserved embryos is limited, and superovulation inevitably delays cancer therapy. Cryopreservation of oocytes after vitrification is an alternative, and is suitable for women without a partner. Although less successful at present, it is a rapidly advancing technology. 3 Cryopreservation of ovarian cortical tissue and subsequent restoration of ovarian function and fertility was first reported by Gosden and colleagues 4 in sheep. Frozen, and subsequently thawed, cortical strips were autotransplanted onto the ovarian pedicle of oophorectomised sheep. Ovulation was restored within 4 months of transplantation, and a resultant pregnancy yielded healthy offspring. It is important to note, however, that the number of follicles is reduced during the freezing and thawing process, occurring mostly during revascularisation, 5 and the limited life span of ovarian grafts suggests that transplantation should be delayed until fertility is desired rather than for the purpose of restoring hormone production. Laparoscopic collection and cryopreservation of ovarian cortical tissue from girls and young women before gonadotoxic chemotherapy is now available in some centres. Because of the age-dependent decline in the number of primordial oocytes, younger patients at risk of ovarian damage should be given priority, although the number of oocytes necessary to establish normal ovarian function after gonadal sterilisation is not known. At least 20 000 primordial oocytes were present in the grafts used to restore fertility in sheep. 5 And in our own unpublished data, based on a group of 14 young women, the number of follicles stored and available for transplantation ranged from 0 to 10 835. 6 The cryopreservation and subsequent use of ovarian tissue presents several practical and ethical issues that should be addressed before embarking on any clinical programme. These include the difficulties of predicting the risk of permanent sterility resulting from the anticancer treatment and the safety issues surrounding the harvesting of the tissue, its subsequent use, and the effect on any resultant progeny. The removal of ovarian tissue is an invasive procedure that carries an element of risk—a risk that is increased in individuals whose health is already compromised by their disease. Of major concern is the potential for ovarian tissue to harbour malignant cells capable of inducing a relapse of the disease on reimplantation. 7 Valid consent is therefore essential when proposing the possibility of future transplantation of cryopreserved ovarian tissue. Such consent must be both informed and voluntarily obtained from a competent person. In practice, it can be difficult to satisfy these criteria, especially in children and young women with cancer. 8 It is equally debatable as to whether their parents are competent to consent on their behalf for an experimental technique, and whether the sometimes limited time available for informed discussion invalidates consent. Some of these difficulties could be alleviated if obtaining consent was considered in two stages: part one at the time of tissue harvesting and cryopreservation, and part two when the tissue is intended to be used. By adopting this process, the timing of the second stage of consent would allow for the successful completion of the patient's anticancer treatment and for any developments in autotransplantation, or in vitro follicle and gamete maturation. Preservation of fertility before cancer treatment should be considered in all young patients at high risk of infertility, and it is important that appropriate counselling is included in their routine care, taking into account the uncertainties surrounding the current options. The Royal College of Obstetricians and Gynaecologists in the UK and the British Fertility Society have published reports on the storage of ovarian and pre-pubertal testicular tissue that aim to set standards for best practice in the cryopreservation of gonadal tissue. 9,10 Although unrealistic expectations should not be placed on the rapid advances seen in the experimental techniques for harvesting ovarian tissue, the recent reports in The Lancet 1 and Nature 2 indicate that successful preservation of fertility in girls and young women treated for cancer is likely to be realised within the next few years. References 1 Oktay K, Buyuk E, Veeck L, et al. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet 2004; 363: 837-40. [ PubMed] 2 Lee DM, Yeoman R, Battaglia D, et al. Live birth after ovarian tissue transfer. Nature 2004; 428: 137-38. [ PubMed] 3 Porcu E, Fabbri R, Damiano G, et al. Oocyte cryopreservation in oncological patients. Eur J Obstet Gynecol Reprod Biol 2004; 113 (suppl): S14–16. 4 Gosden RG, Baird DT, Wade JC, Webb R. Restoration of fertility to opherectomized sheep by ovarian autografts stored at −196°C. Hum Reprod 1994; 9: 597-603. [ PubMed] 5 Baird DT, Webb R, Campbell BK, et al. Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at −196°C. Endocrinology 1999; 140: 462-71. [ PubMed] 6 Bertolino MV, Anderson RA, Wallace WH, Baird DT. Follicle density in cryopreserved ovarian biopsies collected from young women prior to treatment for cancer. Proceedings of the XVII FIGO World Congress of Gynecology and Obstetrics, Santiago, Chile, 2003: 83 (abstr ThP31). 7 Shaw JM, Bowles J, Koopman P, et al. Fresh and cryopreserved ovarian tissue samples from donors with lymphoma transmit the cancer to graft recipients. Hum Reprod 1996; 11: 1668-73. [ PubMed] 8 Grundy R, Larcher V, Gosden RG, et al. Personal practice: fertility preservation for children treated for cancer (2): ethics of consent for gamete storage and experimentation. Arch Dis Child 2001; 84: 360-62. [ PubMed] 9 Royal College of Obstetricians and Gynaecologists. Storage of ovarian and prepubertal testicular tissue: report of a working party. London, Royal College of Obstetricians and Gynaecologists, 2000. 10 Multidisciplinary working group convened by the BFS. A strategy for fertility services for survivors of childhood cancer. Hum Fertil 2003; 6: A1–40. Affiliations: a Division of Child Life and Health, University of Edinburgh Centre for Reproductive Biology, Edinburgh, Scotland, UK. b MRC Human Reproductive Sciences Unit, University of Edinburgh Centre for Reproductive Biology, Edinburgh, Scotland, UK. c Department of Reproductive and Developmental Sciences, University of Edinburgh Centre for Reproductive Biology, Edinburgh, Scotland, UK. The Lancet, Vol 5, Number 5, 5/01/04 Abstract # 5130 ASCO, 2004 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.