The use of ultrasound in the prediction of endometrial cancer in women with postmenopausal bleeding

The aim of the work presented in this thesis was to identify the ultrasound methods and ultrasound features that are most useful for the prediction of endometrial cancer in patients with postmenopausal bleeding and sonographic endometrial thickness 4.5 mm or more. The grey-scale ultrasound variable that best predicted malignancy was heterogeneous endometrial echogenicity (area under the receiver operating characteristics curve, AUC, 0.83), and the power Doppler ultrasound variable that best predicted malignancy was irregular branching of endometrial blood vessels (AUC 0.77). Mathematical models for evaluation of the individual risk of endometrial malignancy were constructed using clinical data, sonographic endometrial thickness, grey-scale ultrasound morphology of the endometrium, and power Doppler ultrasound findings. The model with the largest AUC (0.91) and the highest specificity at 90% sensitivity included the variables endometrial thickness, Vascularity index (reflecting the vascularization of the endometrium when using power Doppler ultrasound), age, and use of hormone replacement therapy. The endometrial volume as measured by three-dimensional (3D) ultrasound was larger and the 3D power Doppler flow indices (reflecting endometrial vascularization) were higher in both the endometrium and in the subendometrium in women with malignant endometrium than in those with benign endometrium, but there was substantial overlap between the two categories. The saline contrast sonohysterography (SCSH) variable that best discriminated between benignity and malignancy for both two-dimensional (2D) and 3D SCSH was the presence of at least one focal lesion with an irregular surface (for 2D SCSH the AUC was 0.84, for 3D SCSH the AUC was 0.70). The mathematical models to estimate the individual risk of endometrial malignancy constructed in this thesis are likely to be useful for individualizing the management of women with postmenopausal bleeding and sonographic endometrial thickness 4.5 mm or more, but they need to be prospectively validated before they can be introduced into clinical practice

Ultrasonographic assessment of reproductive diseases in gorillas and other captive great apes

Dissertação de Mestrado Integrado em Medicina VeterináriaThe present work focused on the analysis of ultrasound examinations from 29 male and female captive great apes performed since 1995 by the Leibniz-Institut für Zoo-und Wildtierforschung, IZW (Berlin, Germany), reproduction management group. The ultrasonographic appearance of the normal and abnormal reproductive tract was described. Out of 22 female captive subjects, 18 were detected to have reproductive tract lesions. The altered ultrasound scans led to several suggested diagnoses, namely uterine leiomyomas, adenomyosis, nabothian cysts, functional ovarian cysts, paraovarian cyst, polycystic ovaries, endometrioma and hydrosalpinges in gorillas; cervical tumour and hydrosalpinx, in chimpanzees; and mostly functional ovarian cysts, in orangutans. Two cases of pyosalpinx with involvement of the intestinal tract occurred, and the suspected causes were: acute pelvic inflammatory disease, in a gorilla, and diverticulitis in an orangutan. Regarding the 7 male captive subjects, 3 gorillas were detected with testicular lesions. Suspicion of malignancy existed on the 3 cases, but only 1 was confirmed to be a Leydig cell tumour. The collected data compared with the reproductive outcome of the subjects showed that (a) the absence of ultrasonographic alterations did not guarantee the production of offspring; (b) ultrasound examinations were efficient in identifying reproductively incompetent animals, since all the subjects whose suggested diagnosis was associated with a prognosis of “fertility most likely compromised” produced no offspring.RESUMO - Avaliação Ecográfica de Doenças Reprodutivas em Gorilas e outros Grandes Símios em Cativeiro - O presente trabalho centrou-se na análise de ecografias ao trato reprodutivo de 29 grandes símios de ambos os sexos, obtidas desde 1995 pelo grupo de gestão de reprodução do Leibniz-Institut für Zoo-und Wildtierforschung, IZW (Berlim, Alemanha). Descreveu-se a aparência ecográfica do trato reprodutivo normal e anormal. De entre 22 fêmeas cativas, detectaram-se lesões reprodutivas em 18 e as suas respectivas alterações ecográficas levaram a várias sugestões de diagnóstico, nomeadamente leiomiomas uterinos, adenomiose, quistos nabotianos, quistos ováricos funcionais, ovários poliquísticos, endometrioma e hidrosalpinges, em gorilas; tumor no cérvix e quisto paraovárico, em chimpanzés; e, maioritariamente, quistos ováricos funcionais, em orangotangos. Encontraram-se 2 casos de piossalpinge com envolvimento do trato digestivo, sendo as causas sugeridas: doença inflamatória pélvica aguda, em uma gorila, e diverticulíte, em uma orangotango. Relativamente aos 7 machos deste estudo, detectaram-se lesões testiculares em 3 gorilas. Houve suspeita de malignidade nos 3 casos, mas apenas em 1 se confirmou ser um tumor das células de Leydig. A comparação dos dados obtidos com o desfecho reprodutivo dos pacientes mostrou que: (a) a ausência de lesões ecográficas não garantiu a produção de descendência; (b) os exames ecográficos foram eficientes na identificação dos animais reprodutivamente incompetentes, uma vez que todos os indivíduos cuja sugestão de diagnóstico estava associada a um prognóstico de “fertilidade muito provavelmente comprometida” não produziram descendência

Image analysis of dominant ovarian follicles and ovarian follicular development during continuous and conventional oral contraceptive dosing schemes

The objective of this research was to assess ultrasound image attributes of human dominant ovarian follicles in the final stages of development during natural and oral contraceptive (OC) cycles, as well as characterize ovarian follicular and endometrial development during and after continuous versus conventional dosing schemes. We utilized sophisticated computer algorithms to elucidate an association between image attributes and physiologic status of follicles in their final stage of development. We used transvaginal ultrasonography to quantify changes in the numbers and diameters of ovarian follicles and changes in endometrial thickness and pattern during and following discontinuation of two different regimens of OC. Developmental changes in ovarian follicles and corpora lutea were correlated with serum estradiol-17â and progesterone, respectively to provide a comprehensive approach to examining ovarian and uterine function. We reported for the first time that follicles which develop during natural and OC cycles have similar image attributes, which provides preliminary evidence that image attributes of human follicles are associated with physiologic status during the growth phase. Further research should be performed to elucidate the exact correlation between image attributes during all stages of follicular development throughout the menstrual cycle, prediction of dysfunctional follicular development (i.e., hemorrhagic anovulatory follicles) and the effects of different OC formulations on follicle development. Once the association between image attributes and various scenarios of follicular development are determined, a computer program could be developed to assess follicular health with a single ultrasound examination, obviating many ethical constraints that currently prevent large scale progress in ovarian follicular research. We further documented that continuous OC administration schemes provide greater follicular suppression than conventional dosing schemes. No dominant follicles developed during three consecutive 28 day cycles of continuous OC use, whereas eight dominant follicles developed during the same time period of conventional OC use. We interpreted these findings to mean that continuous OC dosing schemes provide a more effective contraceptive with a decreased risk of “escape” ovulation compared to conventional dosing schemes. Most follicles ovulated in the immediate cycle following discontinuation of OC. We suggest that the delay to fertility following cessation of OC is not due to anovulation but other yet, unknown, biological factors

Study of endometrial histopathology in women with abnormal uterine bleeding

Background: Abnormal uterine bleeding is a major gynaecological problem accounting for 33% of Gynaec outpatients. The cause of the bleeding is established in only 50-60% of the cases. The aim of this study was to evaluate the various histopathological patterns in the endometrial biopsy of patients presenting with abnormal uterine bleeding and to determine the specific pathology in the different age groups.Methods: This was a prospective study done in a tertiary care teaching hospital for a period of 2 years. Total of 905 patients with abnormal uterine bleeding were included in the study and they were subjected to a Dilatation and Curettage. Histopathological examination of the endometrial biopsy was done and the various histopathological patterns identified and classified.Results: The age of patients ranged from 24-74 years. 54.7% were in the age group 40-49 years followed by 23.4% in the age group 30-39 years. The most frequent findings were proliferative findings in 47.3% followed by secretory endometrium in 16.1 % patients. Proliferative endometrium was more common in the age group 40-49 years as also disordered proliferation, secretory endometrium, cystoglandular hyperplasia and endometrial hyperplasia.Conclusions: Endometrial curettings and biopsy is an important diagnostic procedure for assessing all cases of abnormal uterine bleeding and to plan for successful management

Computer-Assisted Image Analysis of Human Ovarian Follicles: Imaging Physiologic Selection

Antral ovarian folliculogenesis involves recruitment of a cohort of small follicles, physiological selection of a dominant follicle, and ovulation. The mechanism of selection has not been precisely determined. Identification of the timing of preovulatory selection is a key component in understanding natural and peri-menopausal ovarian function, ovarian suppression for contraception, and improvement of ovarian stimulation protocols. Morphologic characteristics obtained by ultrasonography cannot be precisely quantitated by the human eye. Computer-assisted image analysis overcomes subjective human evaluation of ultrasonographic images. The objectives of this research were to assess ultrasound image attributes of human dominant (DF) and 1st subordinate (SF1) ovarian follicles during natural menstrual cycles and following discontinuation of conventional and continuous oral contraceptives (OC). We utilized sophisticated computer algorithms to elucidate an association between image attributes and physiologic status of follicles. Transvaginal ultrasonographic images obtained in 2 previous studies were used to quantify changes that occur in ovarian follicles. We detected quantitative differences between the dominant and largest subordinate follicles of ovulatory and major anovulatory follicular waves, as well as during the first wave following OC discontinuation. Differences in ultrasonographic image attributes were associated with the physiological status of follicles. Evidence of follicular dominance in follicles which develop during major ovulatory waves or following OC discontinuation can be detected prior to the time of selection manifest by differences in dominant and subordinate follicle diameters. In addition, differences in quantitative image attributes were detected between ovulatory and anovulatory DF. Follicles that develop following conventional and continuous OC administration schemes exhibit the same image characteristics. Further research is necessary to elucidate the exact correlation of follicle image attributes during all stages of development with histological characteristics, prediction of the timing of DF selection and the effects of different OC formulations on follicle development during and following OC cessation. Computer-assisted image analysis of ultrasound images has the potential to develop into a diagnostic, prognostic, and research tool for the in vivo evaluation of ovarian physiology and pathology and elucidate biologically important times such as physiologic selection, ovulation of DF and characterization of abnormal follicles (i.e., follicular cysts, luteinized unovulated follicles)

Investigation and management of women presenting with postmenopausal vaginal bleeding

Postmenopausal vaginal bleeding (PMB) is a common gynaecological symptom that requires investigation to exclude an underlying malignant cause. Endometrial cancer is the most common malignancy diagnosed in women investigated for PMB. The risk of a patient being diagnosed with endometrial cancer varies depending on the presence or absence of certain clinical and demographic characteristics. Although all women presenting with PMB are referred urgently for investigation, the majority of the patients will be diagnosed with a benign pathology. The main aim of the work included in this thesis is to present the development of diagnostic models that predict the risk of endometrial cancer in patients presenting with PMB. In addition, I attempted to quantify the risk of endometrial cancer in particular subgroups of women undergoing investigation for PMB. I developed the idea for this project during my clinical training in Obstetrics and Gynaecology. Following literature review, I identified the need for new predictive models in patients presenting with PMB. The work presented in this thesis is based on prospective data collection of consecutive patients referred to a hospital clinic for investigation of PMB. In collaboration with my colleagues, I developed and internally validated two diagnostic predictive models, one based on clinical characteristics only and a second model incorporating clinical characteristics and the results of endometrial thickness measurement using transvaginal ultrasonography. Implementation of the predictive models in clinical practice will allow stratification of patients into risk groups and, subsequently, better prioritisation of the diagnostic tests. However, several other stages in the model development process such external validation and impact analysis are required prior to implementation of the models in clinical practice. In other manuscripts included in this thesis, I evaluated the causes of PMB and quantified the risk of endometrial cancer for young postmenopausal women, women using hormone therapy and those with inadequate assessment of the endometrium on ultrasonography. The results of these studies help to improve our understanding of different steps of the investigation pathways for women with PMB

Ultrasound Imaging

This book provides an overview of ultrafast ultrasound imaging, 3D high-quality ultrasonic imaging, correction of phase aberrations in medical ultrasound images, etc. Several interesting medical and clinical applications areas are also discussed in the book, like the use of three dimensional ultrasound imaging in evaluation of Asherman's syndrome, the role of 3D ultrasound in assessment of endometrial receptivity and follicular vascularity to predict the quality oocyte, ultrasound imaging in vascular diseases and the fetal palate, clinical application of ultrasound molecular imaging, Doppler abdominal ultrasound in small animals and so on