ESPE Abstracts (2015) 84 WG5.1

Impact of Malignancies and Their Treatment on Reproductive Function in Girls

Charles A Sklar

Memorial Sloan Kettering Cancer Center, New York, New York, USA

Background: A 5-year survival rates for children/adolescents diagnosed with cancer are currently ~80%, with survival rates ~90% for those with acute leukaemia, the most common type of cancer in this population. It is estimated that there will be some 500 000 survivors of childhood cancer in the USA by the year 2020. These impressive survival rates are due, in large part, to the use of multi-modality therapy (i.e., surgery, multiagent chemotherapy, and surgery) in a large proportion of children with cancer. Moreover, a smaller percent require very intensive therapy such as stem cell transplantation (SCT). Ovarian dysfunction, including premature ovarian insufficiency (POI) and impaired fertility, is a known complication of certain cancer therapies, less commonly due to the cancer itself.

Objective and hypotheses: Review prevalence and risk factors for POI and impaired fertility in survivors of childhood cancer.

Results: Primary ovarian damage has most often been associated with exposure to alkylating agents (dose–response) and radiation (RT) that includes the ovary (dose–response). Early onset POI occurs commonly in girls exposed to ovarian RT at doses >10 Gy and following high-dose alkylating agents as is given for SCT. Late onset POI may be seen following modest doses of alkylating agents and low doses, <10 Gy, of ovarian RT. Recent data indicate that overall, female survivors have a modestly decreased risk a pregnancy (RR 0.8) 0.80 compared to population norms. Greatest risk of infertility observed after pelvic RT >5 Gy and/or exposure to high-dose alkylating agents. Pelvic RT also associated with adverse pregnancy outcomes, including SGA and preterm births as well as neonatal deaths. Because women are born with a finite number of primordial oocytes that decline over time, older age at treatment is associated with a greater risk for POI and impaired fertility

Conclusion: Survivors of childhood cancer exposed to pelvic RT and high-dose alkylating agents are at high risk of developing POI and impaired fertility, especially if treated at an older age. Such individuals may benefit from fertility preservation techniques such as ovarian tissue cryopreservation and oocyte retrieval, ideally prior to start of cancer therapy.

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