BACKGROUND: Despite a significant number of studies on female fertility following childhood, adolescent, and young adult (CAYA) cancer, studies establishing precise (dose-related) estimates of treatment-related risks are still scarce. Previous studies have been underpowered, did not include detailed treatment information, or were based on self-report only without any hormonal assessments. More precise assessments of who is at risk for sub- or infertility are needed. OBJECTIVE: The objective of our study is to describe the design and methods of 2 studies on female fertility (a cohort study and a nested case-control study) among female survivors of CAYA cancer performed within the European PanCareLIFE project. METHODS: For the cohort study, which aims to evaluate the overall risk of fertility impairment, as well as the risk for specific subgroups of female CAYA cancer survivors, 13 institutions from 9 countries provide data on fertility impairment. Survivors are defined as being fertility impaired if they meet at least one of 8 different criteria based on self-reported and hormonal data. For the nested case-control study, which aims to identify specific treatment-related risk factors associated with fertility impairment in addition to possible dose-response relationships, cases (fertility impaired survivors) are selected from the cohort study and matched to controls (survivors without fertility impairment) on a 1:2 basis. RESULTS: Of the 10,964 survivors invited for the cohort study, data are available from 6619 survivors, either questionnaire-based only (n=4979), hormonal-based only (n=72), or both (n=1568). For the nested case-control study, a total of 450 cases and 882 controls are identified. CONCLUSIONS: Results of both PanCareLIFE fertility studies will provide detailed insight into the risk of fertility impairment following CAYA cancer and diagnostic- or treatment-related factors associated with an increased risk. This will help clinicians to adequately counsel both girls and young women, who are about to start anticancer treatment, as well as adult female CAYA cancer survivors, concerning future parenthood and to timely refer them for fertility preservation. Ultimately, we aim to empower patients and survivors and improve their quality of life. REGISTERED REPORT IDENTIFIER: RR1-10.2196/10824.

Boyne Research Institute Drogheda Ireland

Centre Hospitalier Universitaire de Saint Étienne Saint Étienne France

Danish Cancer Society Research Center Copenhagen Denmark

Department of Clinical Medicine Faculty of Health Aarhus University Hospital Aarhus Denmark

Department of Obstetrics and Gynaecology Amsterdam UMC Vrije Universiteit Amsterdam Netherlands

Department of Pediatrics Amsterdam UMC University of Amsterdam Amsterdam Netherlands

Department of Pediatrics Amsterdam UMC Vrije Universiteit Amsterdam Netherlands

Division of Oncology and Hematology Department of Pediatrics Charité Universitätsmedizin Berlin Berlin Germany

Edmond and Lily Safra Children's Hospital Chaim Sheba Medical Center Tel Aviv Israel

Erasmus MC University Medical Center Rotterdam Netherlands

Gaslini Children Hospital Genova Italy

German Childhood Cancer Registry Institute for Medical Biometry Epidemiology and Informatics University Medical Center Mainz Mainz Germany

Great Ormond Street Children's Hospital London United Kingdom

International Clinical Research Center of St Anne's University Hospital Brno Brno Czech Republic

Motol Teaching Hospital Prague Czech Republic

Netherlands Cancer Institute Amsterdam Netherlands

Oslo University Hospital Oslo Norway

Pediatrics 3 University Hospital Essen Essen Germany

Princess Máxima Center for Pediatric Oncology Utrecht Netherlands

Swiss Childhood Cancer Registry University of Bern Bern Switzerland

The Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

University Children's Hospital Bonn University of Bonn Medical School Bonn Germany

University College London Hospital London United Kingdom

West German Cancer Centre German Cancer Research Centre Essen Germany

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