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Hum. Reprod. Advance Access published online on March 15, 2008
Human Reproduction, doi:10.1093/humrep/den055
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients

Dror Meirow1,5, Izhar Hardan2, Jehoshua Dor1, Eduard Fridman3, Shai Elizur1, Hila Ra'anani1, Elena Slyusarevsky4, Ninette Amariglio2, Eyal Schiff1, Gideon Rechavi2, Arnon Nagler2 and Dina Ben Yehuda4

1 IVF Unit, Division of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Israel 2 Hematology Division, Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel 3 Pathology Department, Chaim Sheba Medical Center, Tel Hashomer, Israel 4 Hematology Division, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

5 Correspondence address. Tel: +972 3 5302882; Fax: +972 3 5341589; E-mail: meirow{at}post.tau.ac.il

BACKGROUND: Storing ovarian tissue for fertility preservation in cancer patients carries the risk of the presence of malignant cells that could lead to recurrence of cancer after reimplantation. Methods to exclude presence of cancer cells were used to improve the safety of cryopreservation–reimplantation procedures.

METHODS: Fifty-eight patients with hematological malignancies were referred for the storage of ovarian tissue for fertility preservation. Investigation included preoperative imaging and histological evaluation of fresh ovarian tissue. After thawing markers to detect minimal residual disease (MRD) were used and compared with patient's disease used as positive control (five patients).

RESULTS: Preoperative imaging detected disease in the ovaries (two patients). Conventional histology post-tissue harvesting did not disclose malignant cells (56 patients). MRD results post-thawing were negative in Hodgkin's disease (CD30 immunohistochemical staining), in T- and B-cell lymphoma (PCR for T-cell receptor and Ig clones, respectively) and in two chronic myelogenous leukemia patients (RT–PCR for BCR–ABL gene expression). However, highly sensitive real-time RT–PCR was positive in one CML patient and, this alarming result avoided tissue transplantation.

CONCLUSIONS: Preoperative imaging prevented operations and storage of tissue with cancer. Evaluation of stored ovarian tissue for MRD using sensitive markers is essential to increase safety and to prevent reimplantation of tissue with malignant cells.

Key words: fertility preservation/ovarian tissue/minimal residual disease/cancer/lymphoma/leukemia

Submitted on December 25, 2007; resubmitted on January 30, 2008; accepted on February 4, 2008.


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