Evaluation of quantitative polymerase chain reaction markers for the detection of breast cancer cells in ovarian tissue stored for fertility preservation.

OBJECTIVE: To develop molecular tools increasing the sensitivity of breast cancer micrometastases detection within ovarian tissue cryopreserved for fertility preservation. DESIGN: Expression of breast markers was evaluated by quantitative polymerase chain reaction in ovarian tissue from patients with benign or cancerous diseases. Suspected tissues were long-term xenografted into mice. SETTING: Academic research institute. PATIENT(S): Patients undergoing a fertility preservation procedure. INTERVENTION(S): Ovarian tissue was processed for RNA extraction and quantitative polymerase chain reaction analysis. Cryopreserved ovarian cortex from patients with breast cancer or benign disease was grafted for 6 months into severe combined immunodeficiency mice. MAIN OUTCOMES MEASURE(S): Predictive values of mammaglobin 1 (MGB-1), gross cystic disease fluid protein-15 (GCDFP-15), small breast epithelial mucine (SBEM), and mammaglobin 2 (MGB-2) to detect breast cancer cells in ovarian tissue, and the potential development of cancerous disease after xenograft of ovarian cortex from breast cancer patients. RESULT(S): MGB-1 and GCDFP-15 presented the highest predictive values to detect breast cancer micrometastases in the ovarian cortex, with an efficiency reaching 100% and 77%, respectively. The MGB-2 assay resulted in a high false-positive rate (47%) in the ovarian cortex but could be used to detect breast cancer cells in ovarian medulla. MGB-1 was detected in three of five ovarian cortex samples from early-stage breast cancer patients but not in the ovarian tissue from advanced breast cancer patients (none of 10). None of the mice grafted with ovarian tissue expressing these markers developed cancerous disease. CONCLUSION(S): MGB-1, GCDFP-15, and MGB-2 can serve as molecular markers for the detection of breast cancer micrometastases within the ovarian tissue of breast cancer patients. However, the clinical relevance of such a highly sensitive assay must be further investigated.

Live birth after autograft of ovarian tissue cryopreserved during childhood.

Ovarian insufficiency is a major long-term adverse event, following the administration of a myeloablative conditioning regimen, and occurring in >80% of children and adolescents receiving such treatment for malignant or non-malignant disease. Cryopreservation of ovarian tissue is currently offered to preserve the fertility of these young patients. At least 35 live births have been reported after transplantation of cryopreserved ovarian tissue in adult patients, but the procedure remains unproven for ovarian tissue harvested at a prepubertal or pubertal age. We report here the first live birth after autograft of cryopreserved ovarian tissue in a woman with primary ovarian failure after a myeloablative conditioning regimen as part of a hematopoietic stem cell transplantation performed for homozygous sickle-cell anemia at age 14 years. This first report of successful fertility restoration after the graft of ovarian tissue cryopreserved before menarche offers reassuring evidence for the feasibility of the procedure when performed during childhood.

Safety of ovarian tissue autotransplantation for cancer patients.

Cancer treatments can induce premature ovarian failure in almost half of young women suffering from invasive neoplasia. Cryopreservation of ovarian cortex and subsequent autotransplantation of frozen-thawed tissue have emerged as promising alternatives to conventional fertility preservation technologies. However, human ovarian tissue is generally harvested before the administration of gonadotoxic treatment and could be contaminated with malignant cells. The safety of autotransplantation of ovarian cortex remains a major concern for fertility preservation units worldwide. This paper discusses the main tools for detecting disseminated cancer cells currently available, their limitations, and clinical relevance.