The purpose of this study is to develop ultrasound criteria for polycystic ovaries for women with PCOS across early, mid and late adulthood and to assess the impact of body composition on these ultrasound criteria.. The study will also compare ultrasound features of the ovary against or in combination with AMH (a hormonal biomarker) in predicting PCOS. This research will help improve the diagnosis of PCOS by considering multiple markers (i.e., ultrasound features and AMH levels) and multiple modifiers of those markers (i.e., age and adiposity).~As the name implies, the primary ultrasound feature used to diagnose PCOS is polycystic ovaries (PCO). However, PCO have frequently been observed in healthy women, calling into question the specificity of PCO to the condition of PCOS, as well as its ability to inform progression of the disease and/or response to treatment. The Lujan laboratory recently showed that the most widely accepted ultrasound criteria for PCO overlap with features of the normal ovary, and their laboratory proposed new thresholds to redefine PCO. These new criteria represented a significant change in the definition of PCO owing to the improved resolution of new technology. That said, these new criteria are still limited. They do not account for factors known or suspected to influence ovarian morphology. For example, follicle counts and ovarian size increase at puberty and decrease with age. Additional results from the Lujan laboratory showed that follicle number per ovary (FNPO) thresholds for women in later adulthood (35-38y) were substantially lower than those in early (18-25y) and mid-adulthood (26-34y). Furthermore, the new criteria for PCO do not account for a potential impact of adiposity on ovarian morphology. In the same study, conducted by the Lujan laboratory, overweight women exhibited more 6-9mm follicles than lean women, irrespective of androgen status.~Lastly, there is significant interest in determining whether AMH can serve as a surrogate to sonographic measures to define PCO. AMH is a peptide hormone produced by the granulosa cells of growing follicles and circulating levels represent secretions by antral follicles ≤8mm. Accordingly, serum AMH is increased in women with PCOS, reflecting the accumulation of 2-5mm antral follicles and greater production by granulosa cells of PCO compared to normal ovaries. Excess AMH is thought to inhibit follicle growth and selection. Unlike discrete aspects of ovarian morphology (i.e. follicle number or size),85 AMH levels remain largely constant throughout the normal menstrual cycle.Such stability may make AMH a more advantageous functional and surrogate morphological indicator of ovarian status compared to morphologic features. Further, some have argued that the variability in ultrasound assessments, and unsuitability of transvaginal approaches in certain clinical populations, justify the pursuit of a less onerous biomarker of PCO. However, there is significant bias across AMH assays and a consensual threshold for AMH to define PCO has not been determined. Proposed thresholds were hindered by heterogeneity in assay performance and in the clinical cohorts assessed. Ultimately, the ability of AMH to serve as a surrogate marker for PCO remains unknown and should be evaluated against sonographic measures in well-defined cohorts with improved assays. In this study, the researchers plan to refine the sonographic definition of PCO by establishing age-specific criteria that maintain sensitivity and specificity for PCOS in both lean and overweight populations. They will also clarify any ability of anti-Müllerian hormone (AMH) to better inform the diagnosis of PCOS.~To accomplish these objectives, the investigators plan to recruit 120 women with regular ovulatory cycles and 120 women with PCOS. Within each of these categories, the investigators plan to recruit 20 lean and 20 overweight women in each age group: 18-24y (early), 25-34y (mid), ≥35y (later adulthood). Ultrasound scans of the ovaries will be assessed for the total number, size, and distribution of follicles using both two- and three-dimensional imaging techniques. Additionally, participants will have blood samples collected to determine serum concentrations of AMH. Because features of the ovaries are expected to be different in lean and overweight women, the researchers hope to develop ultrasound criteria that will help healthcare providers to diagnosis specific ovulation problems in women across all body sizes and ages. This project addresses the need to improve methods and criteria used to define PCO across clinical populations.
The investigators would like to determine how aspects of adiposity and age influence ultrasound features of the ovaries which are used to diagnose polycystic ovarian syndrome (PCOS). The study will also compare anti-Müllerian hormone (AMH) levels against ultrasound features of the ovary to predict PCOS.