Hindawi Publishing Corporation Obstetrics and Gynecology International Volume 2012, Article ID 564794, 7 pages doi:10.1155/2012/564794 Review Article Reproductive Late Effects in Female Survivors of Childhood Cancer Shivany Gnaneswaran,1 Rebecca Deans,1, 2, 3 and Richard J. Cohn1, 3 1 University of New South Wales, Sydney, NSW 2052, Australia 2 Royal Hospital for Women, Barker Street, Randwick, NSW 2031, Australia 3 Centre for Children’s Cancer and Blood Disorders, Sydney Children’s Hospital, High Street, Randwick, NSW 2031, Australia Correspondence should be addressed to Richard J. Cohn, richard.cohn@sesiahs.health.nsw.gov.au Received 26 October 2011; Revised 27 December 2011; Accepted 25 January 2012 Academic Editor: Catherine Poirot Copyright © 2012 Shivany Gnaneswaran et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Childhood cancer treatments can cause female reproductive late eﬀects. Radiation to the hypothalamic-pituitary-ovarian axis is associated with altered menarche, miscarriage, and implantation failure. Patients who receive chemotherapy and/or ovarian radiation are at risk of premature ovarian failure; the risk increases with increasing radiation dose, alkylating agent score, combination therapy, and older age at treatment. Ovarian reserve may be assessed using antimullerian hormone assay and ultrasound measurements of ovarian volume and antral follicle count; however, their eﬃcacy is poorly established in this cohort. Fertility preservation options including cryopreservation, oophoropexy, and gonadotropin-releasing hormone analogues may be initiated prior to treatment, although most are still considered experimental. Uterine radiation has been linked to pregnancy complications including miscarriage, premature delivery, stillbirth, low-birth-weight and small-for-gestational-age infants. This paper summarises the literature on female reproductive late eﬀects. The information should facilitate counseling and management of female survivors throughout their reproductive lives. 1. Introduction Cancer is the second commonest cause of death in children in developed countries [1]. Common childhood cancers include leukaemia, lymphoma, rhabdomyosarcoma, neurob- lastoma, Wilms’ tumour, central nervous system tumours, and germ cell tumours [2, 3]. Most of these cancers are curable using chemotherapy, radiotherapy, or surgery, either alone or in combination [2, 4]. More aggressive or treatment- refractory cancers require intensive multimodal therapies involving multiagent chemotherapy [4]. As a result of advances in paediatric cancer treat- ment protocols, survival rates from childhood cancers have improved dramatically over the past 3 decades [2]. The expected 5-year survival rate for newly diagnosed patients is at least 70% [2, 5]. Despite being highly successful in treating cancers, therapies such as chemotherapy and radiotherapy have also produced complications referred to as late eﬀects [6]. Late eﬀects can either arise during treatment or shortly thereafter to persist as chronic conditions. They may also manifest years after the completion of therapy [4]. Late eﬀects encompass a range of clinical conditions including neurocognitive deﬁcits, skeletal deformities, cardiopulmonary, and renal and hepatic damage, as well as endocrine and reproductive dysfunction. It is estimated that 60–75% of survivors of childhood cancer will develop at least one late eﬀect as a direct result of their treatment [7]. The female reproductive system is especially vulnerable to late eﬀects of cancer therapy. Normal hypothalamic, pituitary, ovarian, and uterine functions as well as ade- quate ovarian reserve are required for pubertal progression, fertility and pregnancy [2]. Potential late eﬀects on the female reproductive system can therefore occur as a result of chemotherapy and/or radiation to the hypothalamic- pituitary-ovarian (HPO) axis, ovaries or uterus [2, 4]. Although the late eﬀects show individual variation, there is a strong relationship with the treatment received [2].