Cancer cell contamination and decontamination methods for ovaries and testes: special focus on prepubertal gonads with a view to safe fertility restoration

Abstract

Fertility restoration in patients that survived a hematological cancer during childhood is a core part of their care pathway. Nonetheless, there might be a risk of contamination of the gonads by cancer cells, especially in patients presenting with leukemia and lymphoma. When only a few cancer cells have reached the gonad, they may not be detected by routine histological examination, and therefore more sensitive techniques are required before being confident of the safety of transplanting cryostored testicular and ovarian tissues or cells back to the patient after recovery. Furthermore, if neoplastic cells are identified in the gonadal tissue, methods to eliminate such cells are urgently awaited as the presence of only a few cancer cells may induce disease relapse in these patients. In this review, contamination rates of human gonadal tissue in the case of leukemia or lymphoma as well as decontamination methods applied to both adult and prepubertal testicular and ovarian tissues are presented. Prepubertal gonads will be the main focus as we aim to show how far we have come in establishing safe approaches to fertility restoration. Advances have been made using animal tissue that is usually artificially contaminated by the addition of cancer cell lines to the gonadal cells or tissue, but these techniques need to be improved and still await development in the case of in vivo cancer cell invasion of tissue.

Evaluating the safety and efficacy of cryopreserved ovarian tissue transplantation in leukemia patients with different bone marrow remission status using xenotransplantation

“…Using molecular biology techniques such as RQ-PCR, fluorescence in situ hybridization (FISH), NGS, and MFC to search for evidence of MRD in ovarian tissue is a current focus in the safety studies of OTT ( 11 , 27 , 30 ). Nevertheless, the outcomes of MRD detection are constrained by the sensitivity of the detection method.…”

“…The autopsy in leukemia patients indicates the ovarian metastasis rate is 8.4% ( 10 ), but when the ovarian tissue is harvested for fertility preservation, the contamination rate with malignant cells reaches 24% ( 11 ). At the same time, OTC remains the primary fertility preservation strategy of female leukemia patients ( 12 ).…”

A 20-year overview of fertility preservation in boys: new insights gained through a comprehensive international survey

“…However, cryopreservation in the context of malignant haematological diseases raises the issue of potential malignant contamination of testicular tissue through haematological spread, and the associated future concern of potential re-transplantation of contaminated tissue. A recent comprehensive review found overall malignant contamination rates of 37% in the pre-pubertal testis and 12% in the pre-pubertal ovary, in cases of leukaemia and lymphoma ( Kourta et al , 2023 ). This concern of malignant contamination, however, is not limited to patients with haematological malignancies; in our survey, we had one centre reporting histological evidence of metastatic neuroblastoma in otherwise normal testicular tissue cryopreserved from a pre-pubertal boy.…”

Innovative Strategies for Fertility Preservation in Female Cancer Survivors: New Hope from Artificial Ovary Construction and Stem Cell-Derived Neo-Folliculogenesis

“…After thawing and subsequent transplantation of the OT, these micrometastases have shown the capacity to develop into recurrent tumors in the mouse model, indicating that the autotransplantation of frozen-thawed ovarian tissue could lead to the reintroduction of the malignancy [45]. With the rising number of OTT, the urgency to develop strategies directed at the elimination of malignant cells or to offer alternatives to autotransplantation has become even more evident [46]. A safe fertility restoration program based on OT cryopreservation and transplantation should necessarily take into account the contamination of malignant cells potentially leading to cancer recurrence after allografting.…”