Trajectory of ovarian morphology during the adolescent reproductive transition.

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PROJECT SUMMARY. Perturbations in reproductive maturation during female adolescence may have lasting consequences on future health and disease. Establishment of regular menstrual cycles is a key component of reproductive maturation and a recognized vital sign for health and well-being. Menstrual cyclicity can be unpredictable in the early gynecological years. Therefore, diagnosis and intervention of reproductive disturbances are commonly delayed for several years post-menarche. Limited data on the adolescent reproductive transition has hampered the ability to identify early markers that might predict underlying reproductive disorders. Ovarian morphology may represent a viable and convenient biomarker given its known ability to inform the diagnosis, evaluation and treatment of reproductive disorders in women in a relatively non- invasive manner. The improved image quality and analysis tools afforded by new transabdominal ultrasound (TAUS) technology may now enable the reliable and comprehensive characterization of ovarian characteristics across adolescence. A demonstration of distinct trajectories in ovarian morphology during the transition to regular menses versus sustained cycle irregularity may serve as a basis for identifying girls at risk for future reproductive disorders and its associated comorbidities. This project aims to establish the feasibility of a prospective longitudinal TAUS assessment of ovarian morphology in adolescents during the first 2 years post- menarche. Our approach involves the use of both two- (2D) and three-dimensional (3D) TAUS to contrast the trajectory of ovarian morphology in adolescents with regular and irregular menstrual cycles for 1 year. The main hypotheses to be tested are that ovarian morphology changes in association with the establishment of regular menstrual cycles and that there are distinct aspects of ovarian morphology that predict the likelihood of regular menses compared to persistent cycle irregularity. This proposal is consistent with prioritized areas of research outlined by the Fertility and Infertility Branch of the National Institute of Child Health and Human Development (NICHD) as it strives to develop innovative tools to non-invasively evaluate normal and abnormal morphologic characteristics of the adolescent reproductive transition. The findings of this research will immediately refine the utility of ultrasound in the clinical evaluation of ovarian morphology by identifying aspects of ovarian morphology that can be reliably assessed in adolescents using either 2D or 3D TAUS. Further, this project will serve as the basis for a larger longitudinal cohort study aimed at fully characterizing the progression of ovarian morphology during normal and abnormal reproductive development which is critical for identifying early sonographic biomarkers for future reproductive disturbance and disease.