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Polycystic ovary syndrome (PCOS) is a heterogenous endocrine disorder that impacts up to 13% of women of reproductive age worldwide as the leading cause of anovulatory infertility. Most women with PCOS present enlarged ovaries with an excess of small antral follicles which are abnormalities consistent with follicle arrest, anovulation, and stromal hypertrophy. As such, polycystic ovarian morphology (PCOM) has long been considered a cardinal feature of PCOS with its inclusion recently reaffirmed by the first ever International Evidence-Based Guideline for the Assessment and Management of PCOS. The current recommendations for PCOM are limited to clinical consensus and necessitate further validation using evidence-based approaches. Presentation of ovarian morphology on ultrasonography is known to be influenced by differences in technology and certain biological factors, such as age. However, the current definition for PCOM remains a “one-size-fits all” criterion and does not incorporate elements that may underlie the heterogeneity in ovarian ultrasound features observed across patients and clinical settings. An understanding of how methodological and biological factors impact the diagnostic performance of PCOM is critical for a more accurate evaluation of the severity and pathophysiology of PCOS. The central objective of this dissertation was to evaluate the current evidence on the diagnostic accuracy of ovarian ultrasound markers and subsequent opportunities to refine their performance in detecting PCOS. In Chapter 1, we conduct a systematic review and meta-analysis to determine the most accurate ovarian ultrasound markers in the diagnosis of PCOS. We found that follicle number per ovary (FNPO) is the most accurate marker of PCOS followed by ovarian volume (OV) and follicle number per single cross-sectional image (FNPS). Subgroup analysis indicated that the heterogeneity in diagnostic accuracy observed between studies is partially due to differences in PCOS diagnostic criteria and geography. In Chapter 2, we test the diagnostic performance of ovarian ultrasound markers evaluated using three-dimensional (3D) methods compared to two-dimensional (2D) methods and assess any impact of serum anti-Müllerian hormone (AMH) levels to serve as a surrogate or adjuvant marker to detect PCOS. We showed that 3D ovarian ultrasound measures outperform their 2D counterparts, with 3D follicle counts being the most accurate markers to diagnose PCOS. In comparison with 3D and 2D ovarian ultrasound markers, AMH was superior to ovarian size but inferior to follicle counts in diagnostic accuracy. The combination of AMH and ovarian size offered improved diagnostic performance compared to the markers alone and supports their utility as a robust alternative if poor image quality prevents accurate follicle counts. In Chapter 3, we test whether age-specific diagnostic criteria for PCOM can improve the ability to discriminate women with and without PCOS. We showed that age-specific thresholds for follicle counts and ovarian size for women in late reproductive age (≥34 years old) outperformed thresholds for the overall group. There was also a shift in the most accurate diagnostic marker across age groups, from ovarian size in mid reproductive age to follicle counts in late reproductive age. Collectively, this dissertation establishes our current knowledge on ovarian ultrasound markers in PCOS diagnosis and integrates methodological and physiological factors in refining the definition of PCOM. These findings offer opportunities to better inform on the pathophysiology of PCOS in research settings and translate to more accurate evaluation and management of this prevalent condition in clinical settings.

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181 pages


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Lujan, Marla

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Place, Ned
O'Brien, Kimberly
Cheong, Soon Hon

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Biomedical and Biological Sciences

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Ph. D., Biomedical and Biological Sciences

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Doctor of Philosophy

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dissertation or thesis

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