www.thelancet.com/diabetes-endocrinology Published online April 12, 2015 http://dx.doi.org/10.1016/S2213-8587(15)00039-X 1 Series Lancet Diabetes Endocrinol 2015 Published Online April 12, 2015 http://dx.doi.org/10.1016/ S2213-8587(15)00039-X See Online/Series http://dx.doi.org/10.1016/ S2213-8587(15)00008-X This is second in a Series of three papers about endocrine late-effects of cancer treatment *Joint first authorship MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK (Prof R A Anderson MD, R T Mitchell MD); School of Computer Science, University of St Andrews, St Andrews, UK (T W Kelsey PhD); Centre for Integrative Physiology, Hugh Robson Building, University of Edinburgh, Edinburgh, UK (Prof N Spears PhD, Prof E E Telfer PhD); and Department of Paediatric Oncology, Royal Hospital for Sick Children, Edinburgh, UK (Prof W H B Wallace MD) Correspondence to: Prof R A Anderson, MRC Centre for Reproductive Health, Queen’s Medical Research Institute, The University of Edinburgh, Edinburgh EH16 4TJ, UK richard.anderson@ed.ac.uk Endocrine late-effects of cancer treatment 2 Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults Richard A Anderson*, Rod T Mitchell*, Thomas W Kelsey, Norah Spears, Evelyn E Telfer, W Hamish B Wallace Preservation of gonadal function is an important priority for the long-term health of cancer survivors of both sexes and all ages at treatment. Loss of opportunity for fertility is a prime concern in both male and female cancer survivors, but endocrine effects of gonadal damage are likewise central to long-term health and wellbeing. Some fertility preservation techniques, such as semen and embryo cryopreservation, are established and successful in adults, and development of oocyte vitrification has greatly improved the potential to cryopreserve unfertilised oocytes. Despite being recommended for all pubertal male patients, sperm banking is not universally practised in paediatric oncology centres, and very few adolescent-friendly facilities exist. All approaches to fertility preservation have specific challenges in children and teenagers, including ethical, practical, and scientific issues. For young women, cryopreservation of ovarian cortical tissue with later replacement has resulted in at least 40 livebirths, but is still regarded as experimental in most countries. For prepubertal boys, testicular biopsy cryopreservation is offered in some centres, but how that tissue might be used in the future is unclear, and so far no evidence suggests that fertility can be restored. For both sexes, these approaches involve an invasive procedure and have an uncertain risk of tissue contamination in haematological and other malignancies. Decision making for all these approaches needs assessment of the individual’s risk of fertility loss, and is made at a time of emotional distress. Development of this specialty needs better provision of information for patients and their medical teams, and improvements in service provision, to match technical and scientific advances. Introduction Treatment for cancer can affect reproductive and endocrine function in both men and women, and loss of fertility is a major concern for patients. 1 Although survival rates in young people with cancer were low in the 1960s, major advances in treatment—especially use of multiagent chemotherapy—and in supportive care have resulted in substantially increased numbers of patients being cured during the past 5 decades. Cancer affects one in 800 children: data suggest that around 80% will be alive 5 years from diagnosis and 70% will become long-term survivors. With increasing numbers of long- term survivors, gonadal function and fertility have become important concerns for these young men and women. If the planned treatment is deemed to put gonadal function and future fertility at risk, fertility preservation options should be considered and discussed with the patient before treatment commences. Although evidence suggests that the greater awareness, knowledge, and willingness needed by oncologists to discuss fertility issues is increasing, 2,3 many patients receive little information. 4,5 Discussion of fertility prognosis at the time of diagnosis is an additional burden for the treatment team, but can have a positive psychological effect on the patient and their family, and can be acceptable even if no realistic fertility preservation options are available. 6,7 New approaches for fertility preservation have been developed, with rapid translation of some into clinical practice. Discussion about whether approaches are experimental (which should therefore be offered only in the context of an approved clinical trial) is especially important when counselling patients who are about to commence cancer treatment. In this Series paper, we discuss assessment of risk to fertility and possible mechanisms of gonadal damage, and propose a schema-based approach to counselling for individual patients. Which patients are at risk? Consideration of the extent of risk to gonadal function in both male and female patients is crucial for provision of the most accurate information to patients, and enables investigation of potential fertility preservation strategies, which can be time consuming, invasive, and in some cases experimental. 8 Risk of infertility for some young men and women is low, whereas other patients will almost certainly lose gonadal function. Consideration of this risk can be usefully structured into intrinsic and extrinsic factors (panel 1). 9 Extrinsic factors centre on the proposed treatment, which depends on diagnosis and stage of disease. Treatments known to have the most clinically significant risk to gonadal function in both male and female patients include total body irradiation and chemotherapy conditioning before bone marrow transplantation, radiotherapy to a field that includes the gonads, and some chemotherapy agents (eg, alkylating agents). 10–14