Originally published as JCO Early Release 10.1200/JCO.2008.20.1541 on April 13 2009

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Fertility of Female Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

From the Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, Memphis, TN; Clinical Statistics and Cancer Prevention Programs, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Pediatrics, Emory University, Atlanta, GA; Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA and Boyne Research Foundation, Washington, DC.

Corresponding author: Daniel M. Green, MD, Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 735, Memphis, TN 38105-2794; e-mail: daniel.green{at}stjude.org.

Purpose This study was undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on fertility.

Patients and Methods We reviewed the fertility of female participants in the Childhood Cancer Survivor Study (CCSS), which consisted of 5-year survivors, and a cohort of randomly selected siblings who responded to a questionnaire. Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered; the cumulative dose of drug administered for several drugs of interest; and the doses, volumes, and dates of administration of all radiation therapy.

Results There were 5,149 female CCSS participants, and there were 1,441 female siblings of CCSS participants who were age 15 to 44 years. The relative risk (RR) for survivors of ever being pregnant was 0.81 (95% CI, 0.73 to 0.90; P < .001) compared with female siblings. In multivariate models among survivors only, those who received a hypothalamic/pituitary radiation dose 30 Gy (RR, 0.61; 95% CI, 0.44 to 0.83) or an ovarian/uterine radiation dose greater than 5 Gy were less likely to have ever been pregnant (RR, 0.56 for 5 to 10 Gy; 95% CI, 0.37 to 0.85; RR, 0.18 for > 10 Gy; 95% CI, 0.13 to 0.26). Those with a summed alkylating agent dose (AAD) score of three or four or who were treated with lomustine or cyclophosphamide were less likely to have ever been pregnant.

Conclusion This large study demonstrated that fertility is decreased among female CCSS participants. The risk factors identified may be utilized for pretreatment counseling of patients and their parents.

Supported by the National Institutes of Health, National Cancer Institute Grant No. U24 CA55727 (L.L.R.); by the Children's Cancer Research Fund to the University of Minnesota Cancer Center; and by the American Lebanese Syrian Associated Charities.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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