Evaluation of the Gonadotoxicity of Cancer Therapies to Improve Counseling of Patients About Fertility and Fertility Preservation Measures: Protocol for a Retrospective Systematic Data Analysis and a Prospective Cohort Study.

Background: Cytotoxic treatments such as chemo- and radiotherapy and immune therapies are required in cancer diseases. These therapies have the potential to cure patients but may also have an impact on gonadal function and, therefore, on fertility. Consequently, fertility preservation treatments such as freezing of gametes and gonadal tissue might be required. However, as detailed data about the necessity to perform fertility preservation treatment are very limited, this study was designed to fill this data gap.

Objective: Primary objective of this study is to analyze the impact of cancer therapies and chemotherapies on the ovarian reserve and sperm quality. Secondary objectives are to analyze the (1) impact of cancer therapies and chemotherapies on other fertility parameters and (2) probability of undergoing fertility preservation treatments in relation to specific cancer diseases and treatment protocols and the probability to use the frozen gametes and gonadal tissue to achieve pregnancies.

Methods: First, previously published studies on the gonadotoxicity of chemo- and radiotherapies among patients with cancer will be systematically analyzed. Second, a prospective cohort study set up by approximately 70 centers in Germany, Switzerland, and Austria will collect the following data: ovarian function by analyzing anti-Müllerian hormone (AMH) concentrations and testicular function by analyzing sperm parameters and total testosterone immediately before and around 1 year after gonadotoxic therapies (short-term fertility). A follow-up of these fertility parameters, including history of conceptions, will be performed 5 and 10 years after gonadotoxic therapies (long-term fertility). Additionally, the proportion of patients undergoing fertility-preserving procedures, their satisfaction with these procedures, and the amount of gametes and gonadal tissue and the children achieved by using the frozen material will be analyzed. Third, the data will be merged to create the internet-based data platform FertiTOX. The platform will be structured in accordance with the ICD (International Classification of Diseases) classification of cancer diseases and will be easily be accessible using a specific App.

Results: Several funding bodies have funded this study. Ten systematic reviews are in progress and the first one has been accepted for publication. All Swiss and many German and Austrian ethics committees have provided their approval for the prospective cohort study. The study registry has been set up, and a study website has been created. In total, 50 infertility centers have already been prepared for data collection, which started on December 1, 2023.

Conclusions: The study can be expected to bridge the data gap regarding the gonadotoxicity of cancer therapies to better counsel patients about their infertility risk and their need to undergo fertility preservation procedures. Initial data are expected to be uploaded on the FertiTOX platform in 2026.

Trial Registration: ClinicalTrials.gov NCT05885048; https://clinicaltrials.gov/study/NCT05885048.

International Registered Report Identifier (irrid): DERR1-10.2196/51145.