Ovarian Function After Removal of an Entire Ovary for Cryopreservation of Pieces of Cortex Before Gonadotoxic Treatment: A Follow-Up Study

Abstract

Cryopreservation of ovarian cortex tissue before gonadotoxic treatment may preserve fertility in premenopausal women with certain types of cancer. The effect of removal of ovarian tissue and gonadotoxic treatment on residual ovarian function is poorly understood. This study assessed residual ovarian function in premenopausal women who had an ovary removed for cryopreservation of cortex tissue before gonadotoxic therapy, and evaluated patient experience with the procedure. The study subjects were 92 Danish women who had 1 ovary removed for cryopreservation 18 to 75 months before administration of chemo and/or radiation therapy. Patients were grouped into 4 categories: (1) breast cancer (n = 31, 34%), (2) Hodgkin lymphoma (n = 23, 25%), (3) bone marrow transplantation (BMT) (n = 19, 21%), and (4) others (n = 19, 21%). Mean age of the patients at time of diagnosis and follow-up was 25.4 years (range, 9–37) and 28.7 years (range, 18–41), respectively. Thirty-eight age-matched women with cancer (n = 38) served as the reference group. Patients completed a questionnaire that provided opinions about the cryopreservation procedure and complications. The serum levels of 2 markers of ovarian reserve, follicle stimulating hormone, and antiMüllerian hormone, were determined in 73 women. The antral follicle count, also a marker of ovarian reserve, was measured by transvaginal ultrasonography. After cryopreservation and treatment, only 11% of the BMT patients reported regular monthly bleeding, whereas 60% of breast cancer and Hodgkin disease patients (who had received regimens more gonadotoxic than ABVD) (doxorubicin, bleomycin, vinblastine, and dacarbazine) reported regular monthly bleeding. Regular menstruation after cryopreservation of ovarian tissue was a good indicator of residual ovarian function. The patients’ report on bleeding regularity correlated well with the serum levels of follicle stimulating hormone, antiMüllerian hormone, and with antral follicle counts. The vast majority of patients was pleased with the procedure, had few complications, and was comforted during treatment by the potential to preserve their fertility. The cryopreservation procedure rarely interfered with cancer treatment. The investigators believe that patients receiving BMT with expected long-term survival and young women with Hodgkin lymphoma receiving more aggressive treatment than ABVD should be considered for ovarian cryopreservation. They suggest that asking a patient whether she has regular bleeding without hormone replacement therapy is a noninvasive, inexpensive and rapid way to assess residual ovarian function after treatment.