Background: Reproductive health needs of females ages 15 to 55 with cancer are poorly understood and overlooked, despite their importance to patients. Uncertainties regarding fertility and pregnancy are intricate and challenging for a patient and a cancer care team. The goals of reproductive health care may come in conflict with the primary objective of cancer care. However, with appropriate counseling and preventive measures, this conflict can be absolved to unify objectives. The primary objective of this trial is to evaluate the success of the implementation of reproductive health programming among reproductive aged females with cancer. To expand knowledge on this subject, the NCI approved the ECOG-ACRIN EROS trial: Engendering Reproductive Health within Cancer Survivorship, with two ancillary studies: Endocrine Disruption in Cancer Care and Sexuality in the first 5 years after Cancer Diagnosis. Methods: The primary study is a multicenter, cluster randomized control trial, with NCI Community Oncology Research Programs randomized to either the non-intervention arm (usual standard practice related to reproductive health) or the intervention arm (using study-specific training and tools). The accrual goal is 668 patients based on the expectation that the intervention can increase the adoption of appropriate reproductive health management within 3 months from the baseline visit from 50% to 80%, with the first 200 to consent to the endocrine disruption substudy. All patients participate in the sexuality part. Pre-menopausal female patients ages 15 to 55 with an initial diagnosis of any type of cancer who have not initiated treatment of any type are eligible to participate. Patients are asked to complete 2 questionnaires at 8 timepoints regarding their reproductive health interests. Providers are also asked to complete questionnaires regarding their healthcare practice in general as well as specific to patients enrolled in this study. The reproductive health management rate at each time point will be summarized, by arm, with frequency and percentage along with its 95% confidence interval. The comparison between the two arms, using a GEE model, can evaluate the intervention effect. EROS was activated in September 2015. To date, 264 patients have been enrolled to the main study and half of these patients are participating in the endocrine disruption correlative. Outcomes pertaining to management and treatment implementation and modification are the cornerstones of this study. It should inform organizations in cancer care to improve guidelines and to include a reproductive health assessment for all young females with cancer. Clinical trial information: NCT01806129