Livebirth after cryopreserved ovarian tissue autotransplantation
Authors: Kutluk Oktay, Jonathan Tilly
Journal: The Lancet (2004)

Although autotransplantation of frozen-banked ovarian tissue is accepted as a promising technology for fertility restoration, the findings of J Donnez and colleagues (Oct 16, p 1405)1Donnez J Dolmans MM Demylle D et al.Livebirth after orthotopic transplantation of cryopreserved ovarian tissue..Lancet. 2004; 364: 1405-1410Summary Full Text Full Text PDF PubMed Scopus (1439) Google Scholar, 2Oktay K Karlikaya G Ovarian function after autologous transplantation of frozen-banked human ovarian tissue..N Engl J Med. 2000; 342: 1919Crossref PubMed Scopus (497) Google Scholar, 3Oktay KH Yih M Preliminary experience with orthotopic and heterotopic transplantation of ovarian cortical strips..Semin Reprod Med. 2002; 20: 63-74Crossref PubMed Scopus (49) Google Scholar fall short of providing conclusive evidence for the first pregnancy after this procedure for various reasons. First, the risk of ovarian failure in patients with lymphoma aged 25 years or younger who receive chlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine with or without radiation is 20% or less, with half of patients conceiving spontaneously.4Schilsky RL Sherins RJ Hubbard SM Wesley MN Young RC DeVita VT Long-term follow up of ovarian function in women treated with MOPP chemotherapy for Hodgkin's disease..Am J Med. 1981; 71: 552-556Summary Full Text PDF PubMed Scopus (174) Google Scholar Even when receiving chemotherapy regimens with low potential to cause premature menopause, most patients will go through a temporary or pseudomenopausal state, which can last more than 6 months, due to damage of developing follicles. Thus, raised concentrations of follicle stimulating hormone 3 months after chemotherapy do not necessarily indicate permanent ovarian failure. Indeed, the patient in the latest report1Donnez J Dolmans MM Demylle D et al.Livebirth after orthotopic transplantation of cryopreserved ovarian tissue..Lancet. 2004; 364: 1405-1410Summary Full Text Full Text PDF PubMed Scopus (1439) Google Scholar had three ovulations from her intact left ovary, despite the fact that she was presumed to be in menopause. Second, the woman was not monitored daily during the cycle that led to her pregnancy. A clear understanding of the history of this patient is further complicated by the fact that she was placed on hormone replacement therapy (HRT) 3 months after chemotherapy, which prevented assessment of her endocrine profile. HRT was discontinued 2·5 years later and the patient attempted a pregnancy on her own for a year, during which time she ovulated at least once from her left ovary. Since the frequency of monitoring is not provided, we cannot assess how many other ovulations from either ovary might have been missed. Third, Donnez and colleagues grafted ovarian tissue fragments contiguous with the pre-existing right ovary. The oocyte fertilised could therefore have ovulated from the pre-existing tissue rather than the graft. Although the authors state the occurrence of monthly follicle development in the graft 5–9 months post-transplantation, the timing, frequency, and values of such measurements are not provided. For example, data on peak oestradiol concentrations or whether a gonadotropin surge occurred are missing. Fourth, Donnez and colleagues report a gonadotropin surge followed 3-weeks later by the appearance of a 26-mm follicle on the site of transplant, before ovulation. From figure 2, the day of this ovulation roughly corresponds to a β human chorionic gonadotropin measurement of 2000 mIU/mL, indicating that the 26-mm structure was a corpus luteum and the conception occurred in the previous cycle. Finally, no mention is made of whether the patient had menses between the surge at 9·5 months post-transplantation and the positive pregnancy test. The day of ovulation, as determined by basal body temperature, in reference to when the 26-mm structure was seen, was also not specified. The findings of Donnez and colleagues,1Donnez J Dolmans MM Demylle D et al.Livebirth after orthotopic transplantation of cryopreserved ovarian tissue..Lancet. 2004; 364: 1405-1410Summary Full Text Full Text PDF PubMed Scopus (1439) Google Scholar coupled with an earlier report of a four-cell embryo derived from an oocyte of heterotopically transplanted ovarian tissue in a menopausal patient,5Oktay K Buyuk E Veeck L et al.Embryo development after heterotopic transplantation of cryopreserved ovarian tissue..Lancet. 2004; 363: 837-840Summary Full Text Full Text PDF PubMed Scopus (499) Google Scholar raise optimism that autotransplantation of frozen-banked ovarian tissue will ultimately prove useful as a fertility option for cancer survivors. However, definitive evidence for the feasibility of pregnancy resulting from such procedures is, in our opinion, still lacking. This technique cannot yet, therefore, be recommended for routine use. Livebirth after cryopreserved ovarian tissue autotransplantationAuthors' reply Full-Text PDF