Paper III reprinted with kind permission of Elsevier, sciencedirect.com

Paper III reprinted with kind permission of Elsevier, sciencedirect.com

Polycystic ovary syndrome (PCOS) is an endocrine abnormality with multiple diagnostic criteria due to its heterogenic manifestations. One of the diagnostic criterion includes analysis of ultrasound images of ovaries for the detection of number, size, and distribution of follicles within the ovary. This involves manual tracing of follicles on the ultrasound images to determine the presence of a polycystic ovary (PCO). A novel method that automates PCO morphology detection is described. Our algorithm involves automatic segmentation of follicles from ultrasound images, quantifying the attributes of the segmented follicles using stereology, storing follicle attributes as feature vectors, and finally classification of the feature vector into two categories. The classification categories are PCO morphology present and PCO morphology absent. An automatic PCO diagnostic tool would save considerable time spent on manual tracing of follicles and measuring the length and width of every follicle. Our procedure was able to achieve classification accuracy of 92.86% using a linear discriminant classifier. Our classifier will improve the rapidity and accuracy of PCOS diagnosis, and reduce the chance of the severe health implications that can arise from delayed diagnosis.

Polycystic ovary syndrome (PCOS) is an endocrine abnormality with multiple diagnostic criteria due to its heterogenic manifestations. One of the diagnostic criterion includes analysis of ultrasound images of ovaries for the detection of number, size, and distribution of follicles within the ovary. This involves manual tracing of follicles on the ultrasound images to determine the presence of a polycystic ovary (PCO). A novel method that automates PCO morphology detection is described. Our algorithm involves automatic segmentation of follicles from ultrasound images, quantifying the attributes of the segmented follicles using stereology, storing follicle attributes as feature vectors, and finally classification of the feature vector into two categories. The classification categories are PCO morphology present and PCO morphology absent. An automatic PCO diagnostic tool would save considerable time spent on manual tracing of follicles and measuring the length and width of every follicle. Our procedure was able to achieve classification accuracy of 92.86% using a linear discriminant classifier. Our classifier will improve the rapidity and accuracy of PCOS diagnosis, and reduce the chance of the severe health implications that can arise from delayed diagnosis.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2000. / Restricted until November 2001. Bibliography: leaves 82-97.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Thesis (M.S.)--University of Missouri-Columbia, 2008. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Includes bibliographical references.

Thesis (Ph. D.)--Marshall University, 2004. / Title from document title page. Document formatted into pages; contains p. viii, 210 p. Includes abstract. Includes bibliographical references (p. 179-204).

Polycystic ovary syndrome (PCOS) is a common and complex endocrine condition with reproductive and metabolic complications, affecting up to 10% of reproductive-age women. Hyperandrogenemia, ovulatory dysfunction, and luteinising hormone hypersecretion are characteristic traits of PCOS however, it seems that the most concerning long-term key issues are metabolic problems associated with the syndrome, such as hyperinsulinemia, insulin resistance, obesity, dyslipidaemia and non-alcoholic liver disease. Despite the numerous studies on PCOS, its origin and pathophysiology are still not fully understood. However, there is increasing evidence that the adult PCOS phenotype is programmed in fetal life by androgen excess. Exposure to increased levels of testosterone in utero in rodents, sheep and monkeys result in adult reproductive and metabolic pathologies that parallel those seen in PCOS women. Since hyperandrogenemia is a hallmark of PCOS and daughters of PCOS mothers have elevated levels of androgens at birth, it is likely that prenatal androgenisation during early life predispose to the future development of PCOS. Animal models of PCOS provide an opportunity to examine the developmental aetiology and molecular mechanisms underlying the pathogenesis of this condition. Over last 10 years our lab has successfully utilised a well-established ovine model of PCOS, where pregnant ewes were treated with testosterone propionate (TP) through mid-gestation. From this model, we had a large sample bank of fixed and frozen tissues from the fetal, lamb and adolescent prenatally androgenised animals that allowed to carry a broad range of experiments. In addition, a new cohort of prenatally androgenised adult sheep enabled additional in vivo analysis. Past research documented that prenatal androgenisation result in hyperinsulinemia with altered pancreas structure and function, and early fatty liver without difference in body weight in adolescent sheep. This thesis examines the effects and consequences of increased in utero androgen exposure on metabolic dysregulation in adolescent and adult female sheep. During puberty, but not fetal or early life, there was decreased adipogenesis in subcutaneous adipose tissue (SAT), but not visceral adipose tissue (VAT), accompanied by decreased circulating concentrations of fibroblast growth factor 21 (FGF21), leptin and adiponectin, and increased concentrations of fasting free fatty acids (FFA) in prenatally androgenised sheep. This was countered by upregulated expression of FFA transporters in liver. As adults, TP-exposed animals had increased body weight, elevated fasting insulin and FFA concentrations but normal FGF21, leptin and adiponectin levels. Histological analysis revealed that adult TP-exposed animals had SAT hypertrophy, which was associated with increased expression of inflammatory markers and correlated with increased fasting FFA. Therefore, it is likely that impaired preadipocyte differentiation in SAT during adolescence resulted in hypertrophy and inflammation of adult SAT. This consequently lowered capacity of SAT to safely store fat and potentially explains metabolic perturbations observed in PCOS-like female sheep. To further investigate potential causes of obesity in adult PCOS-like sheep postprandial thermogenesis (PPT), an important constituent of energy expenditure, was measured through implantation of datalogger thermometers into interscapular adipose tissue. Adult prenatally androgenised sheep had decreased amplitude of PPT, without difference in basal body temperature, despite receiving the same caloric intake, and independent of obesity. These findings indicate that adult PCOS-like sheep have reduced capacity for energy expenditure, which is mirrored in women with PCOS. This reduced capacity for postprandial thermogenesis was correlated with hyperinsulinemia decreased noradrenaline levels and reduced thermogenic potential of brown and/or beige adipose tissue. This suggests that women with PCOS might be prenatally programmed to become obese. In summary, findings documented in this thesis provide better understanding into the pathophysiology of PCOS from puberty to adulthood and give opportunities for early clinical intervention to ameliorate the metabolic phenotype of PCOS.

【目的】从整体上把握多囊卵巢综合征的发生、发展及其规律, 为临床进一步诊断治疗提供整体思路和文献学基础。【方法】收集整理近10 年与多囊卵巢综合征研究相关的中、英文献，归纳和总结该病的病因病机、诊断、治疗，找出存在问题，提出发展方向。【结果】①多囊卵巢综合征主要病因为：肾虚、脾虚、肝郁、痰湿、痕血，并与饮食、环境、精神、遗传具有相尖性；②多囊卵巢综合征基本病机：本虚标实，肾虚、脾虚为本’肝郁、气滞、血痕、痰浊、痰湿为标；③PCOS 的分型大致有：肾虚血脐型、肾虚血痕痰浊型；脾肾阳虚型；痕血内阻型；肝气郁结型；脾肾阳虚型；痰湿阻滞型；④PCOS 的治疗以辨证分型论治为主，参考名老中医经验、专方专药、针灸、周期疗法、辨体质进行诊治，重视中西医结合在治疗中的应用。⑤PCOS 仍存在病因、病机认识不一，诊断存在争议’辨证分型众说纷纭等问题。⑥PCOS 发展方向：找出与PCOS 相尖性最强的病因，明确中西医发病机制，规范PCOS 诊断’研发有效药物，加强临床及实验研究，注重基础治疗和健康宣敦。【结论】多囊卵巢综合征的病因、病机、诊断及治疗研究已取得可喜的成绩，形成了完整的体系。但仍存在具体病因不明’发病机制不清，缺乏有效治疗方法等问题。今后应加强高级别基础和临床研究’尽快明确病因病机’找出有效治疗方案。关键词：多囊卵巢综合征；中医；病因病机；证治规律；药物