Factors influencing the timing of ovarian tissue cryopreservation in young girls

Abstract

The aim of this study was to identify pitfalls in ovarian tissue cryopreservation protocol from referral to surgical procedures and to analyze factors associated with chemotherapy exposure of the cryopreserved tissue and decreased ovarian function in a cohort of young girls at high risk of infertility. The study population comprised 200 girls eligible for ovarian tissue cryopreservation between 2002 and 2020 at the Children's Hospital of the University Central Hospital of Helsinki (Finland). Analyses included the evaluation of the proportion of patients who underwent ovarian tissue cryopreservation, factors associated with patient selection and timing of ovarian tissue cryopreservation, and ovarian function during long-term follow-up in relation to oncological treatments. Lack of counseling was identified as the major reason for not receiving ovarian tissue cryopreservation. A longer interval from scheduling gonadotoxic therapy to cryopreservation correlated with a higher exposure to alkylating agents of the ovarian tissue. The long-term ovarian function was mainly influenced by age at the time of gonadotoxic treatment. Current selection criteria for ovarian tissue cryopreservation should be implemented in order to stratify patients at risk of infertility and timely identify those at higher risk, especially in relation to age and pubertal stage. Efforts to increase healthcare providers’ awareness and facilitate guided timing in relation to the treatment protocols are needed to guarantee early access to ovarian tissue cryopreservation for all patients at high risk of infertility. Lay summary Girls affected by cancer may undergo aggressive treatments to cure the disease, such as chemotherapy and radiotherapy, which can harm the ovaries. These treatments often result in the destruction of the ovaries and infertility. Nowadays, an option exists to help these girls recover their fertility after the cancer has been successfully treated. A fragment or an entire ovary can be removed by surgery and frozen before the treatments begin. When the girls are well and wish as adults to start a family, this fragment can be reimplanted back into the remaining ovary to restore fertility. This technique is called ovarian tissue cryopreservation. In this article, we report on the experience of ovarian tissue cryopreservation at the Children’s Hospital in Finland for 200 girls undergoing cancer treatment with a high risk of subsequent infertility. We analyzed the proportion of girls who had ovarian tissue cryopreservation performed among those exposed to aggressive treatments and investigated the reasons why some of them did not undergo the procedure. We also examined the time passing before the procedure was done to identify potential avoidable sources of delay. Finally, we explored how the ovaries of all the girls functioned during the time after the cancer diagnosis and looked at this in relation to their cancer treatments and ovarian tissue freezing.

Keywords

• children
• fertility preservation
• gonadotoxic treatment
• ovarian tissue cryopreservation