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• W4252460112 abstract "We thank the authors for their interest in our paper (1Schmidt K.L. Rosendahl M. Ernst E. Loft A. Andersen A.N. Dueholm M. et al.Autotransplantation of cryopreserved ovarian tissue in 12 women with chemotherapy-induced premature ovarian failure: the Danish experience.Fertil Steril. 2011; 95: 695-701Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar) and for raising the issues regarding the risk of reintroduction of a malignant disease after autotransplantation of cryopreserved ovarian tissue. We fully agree with the authors that patients with leukemia should presently not be offered autotransplantation because of the risk of the cortical tissue harboring residual malignant cells, as we and others have previously demonstrated (2Rosendahl M. Andersen M.T. Ralfkiaer E. Kjeldsen L. Andersen M.K. Andersen C.Y. Evidence of residual disease in cryopreserved ovarian cortex from female patients with leukemia.Fertil Steril. 2010; 94: 2186-2190Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar, 3Meirow D. Hardan I. Dor J. Fridman E. Elizur S. Ra’anani H. et al.Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients.Hum Reprod. 2008; 23: 1007-1013Crossref PubMed Scopus (260) Google Scholar, 4Dolmans M.M. Marinescu C. Saussoy P. Van Langendonckt A. Amorim C. Donnez J. Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe.Blood. 2010; 116: 2908-2914Crossref PubMed Scopus (295) Google Scholar). Indeed, none of the 12 patients in the present study had leukemia, and to the best of our knowledge, no women with leukemia have been transplanted worldwide. There is good evidence that the patients who are offered ovarian tissue cryopreservation (OTC) rarely have ovarian metastases, as the indication in itself requires low-stage disease. We have recently published a study on 51 patients with breast cancer whose ovarian cryopreserved cortical biopsy samples were examined by histologic and immunohistochemical analysis and showed no signs of metastases (5Rosendahl M, Wielenga VT, 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. Published online January 11, 2011.Google Scholar). This has also been demonstrated in a large series by another group (6Sánchez-Serrano M. Novella-Maestre E. Rosello-Sastre E. Camarasa N. Teruel J. Pellicer A. Malignant cells are not found in ovarian cortex from breast cancer patients undergoing ovarian cortex cryopreservation.Hum Reprod. 2009; 24: 2238-2243Crossref PubMed Scopus (75) Google Scholar). Ovarian cortical biopsies from at least 82 patients suffering from Hodgkin lymphoma undergoing OTC have been evaluated. One biopsy from a single patient with stage IIIB disease was suspicious for involvement of the malignancy, but no other biopsies showed any sign of malignant infiltration (7Bittinger S.E. Nazaretian S.P. Gook D.A. Parmar C. Harrup R.A. Stern C.J. Detection of Hodgkin lymphoma within ovarian tissue.Fertil Steril. 2011; 95: 803.e3-803.e6Abstract Full Text Full Text PDF Scopus (44) Google Scholar). Similarly, ovarian cortex from 21 patients with non-Hodgkin lymphoma showed no evidence of malignant cell infiltration (3Meirow D. Hardan I. Dor J. Fridman E. Elizur S. Ra’anani H. et al.Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients.Hum Reprod. 2008; 23: 1007-1013Crossref PubMed Scopus (260) Google Scholar, 8Kim S.S. Radford J. Harris M. Varley J. Rutherford A.J. Lieberman B. et al.Ovarian tissue harvested from lymphoma patients to preserve fertility may be safe for autotransplantation.Hum Reprod. 2001; 16: 2056-2060Crossref PubMed Scopus (187) Google Scholar). It is also reassuring that with approximately 30 published cases of ovarian tissue transplantation worldwide for malignant disease, no cases of relapse due to the graft have been reported. We always have approval from the patient’s oncologist or hematologist before any autotransplantation procedure is performed; if they have any reservations, we refrain from the procedure. The potential risks involved in the procedure are presented to the patient in detail and are discussed with her before any transplantation; the operation will not be performed without her informed consent. Additionally, we never offer OTC to patients with disseminated disease, so the risk of metastases to the ovary in patients with solid tumors is very low. We can, however, never be 100% sure that there are not a few malignant cells present in the particular cortical fragment that is autotransplanted, and a histologic or immunohistochemical examination of a neighboring cortical fragment from the same ovary cannot eliminate this risk. Notwithstanding, it is very reassuring that there have been no cases of reintroduction of the disease due to the transplanted tissue in any of our 12 patients with autotransplanted tissue after a minimum of 24 months and a maximum of 96 months of follow-up evaluations. We believe that if you decide to offer OTC as fertility preservation to cancer patients you should be willing to offer to transplant it in collaboration with the patient and her oncologist in cases, where neither the nature of her disease nor the literature provides any evidence of an increased risk of malignant cells in the ovarian tissue. Unknown risk of the reintroduction of malignant cells in a Danish cohort of women autotransplanted with ovarian tissueFertility and SterilityVol. 95Issue 7PreviewTo the Editor: Full-Text PDF" @default.
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• W4252460112 title "Reply of the Authors" @default.
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