The Reproductive Window in Young Adult Cancer Survivors

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DESCRIPTION (provided by applicant): Infertility and premature ovarian senescence are life-changing consequences of cancer in young women. Yet, the reproductive window after cancer treatment in young adult cancer survivors (YA survivors) is not known. In light of growing numbers of YA survivors and emergence of promising interventions on fertility after cancer treatment, there is a clear need to identify and categorize patterns of ovarian aging after cancer and the clinical profiles associated with them to assist in patient counseling and decision making. 1000 female YA survivors who are between ages 18-35 will be enrolled at varying durations after cancer treatment and followed for 18 months. First, the study will test the hypothesis that patterns of anti-mullerian hormone (AMH), follicle stimulating hormone (FSH) and estradiol (E2) after cancer treatment will differ among three broad treatment toxicity groups. Ovarian function biomarker levels will be measured from serial self-collected dried blood spot (DBS) samples in each participant. Data from the entire cohort will then be modeled by time after cancer treatment, and patterns (including time to peak, duration at peak and time to decline of ovarian function) will be compared among minimal, moderate and severe treatment toxicity groups. The aim will demonstrate that these biomarkers can depict differential durations of the reproductive window. Second, spurred by exciting preliminary data, the study will test the hypothesis that disproportionate psychological distress experienced by this population is associated with hypothalamic suppression of ovarian function. The aim will determine the association between distress (measured by patient-reported symptoms and salivary cortisol) and luteinizing hormone (LH), FSH, E2 and AMH. Hypothalamic-pituitary-ovarian axis suppression has never been studied in the context of cancer, and discovery of an association between distress and ovarian function would be critical to future intervention studies on distress to modify reproductive health outcomes. Third, the study will generate clinical risk profiles for te window of ovarian function for the moderate toxicity group, which encompasses the majority of YA survivors. Due to heterogeneity, there are no data on predicting variability in the course of ovarian aging within this group. This aim will identify subpopulations in patterns of ovarian function within the moderate toxicity group, followed by the clinical factors that are associated with them. Building on the PI's K23 data, this proposal directly responds to priorities of the NICHD Fertility Preservation Program to develop biomarkers and clinical parameters to better predict gonadal reserve, and optimize and expand options for fertility preservation. The significance lies in estimating the reproductive lifespan in the context of cancer in order to guid patient counseling, individualize risks and preserve opportunities for biologic parenthood. Through innovative use of social media for recruitment and non-clinic- based, minimally invasive DBS and saliva collection for biosample accrual, the proposal overcomes longstanding, critical barriers to studying young adults with cancer. 1