Uterine fibroids, endometriosis, and adenomyosis are gynecological disorders causing significant symptoms and have clinical struggles around diagnosis and treatment planning. The tissue changes associated with these disorders may support assessment via ultrasound shear wave elastography (SWE), an imaging method that estimates tissue stiffness. This dissertation examined the feasibility of gynecological SWE for the in vivo assessment of uterine tissues. Specifically, this thesis evaluated: 1) the validity and reliability of endoprobe SWE stiffness measured in tissue mimicking materials (TMMs), 2) the validity of indentation testing in TMMs, 3) the impact of indentation parameters on the agreement between indentation stiffness and stiffness parameters measured by SWE, and 4) the reliability of and confounders on in vivo SWE of the uterus. First, to establish the reliability and validity of gynecological endoprobe SWE stiffness measures, 31 homogenous TMM phantoms were manufactured with a range of elastic moduli. SWE stiffness was measured at 1cm, 3cm, and 5cm depths using a linear, curvilinear, and endo- SWE probes. Quasi-static ramp compression stiffness was the validity benchmark. Phantom moduli ranged from 17.10 kPa to 88.12 kPa. Endoprobe SWE stiffness reliability was excellent at all depths, however endoprobe SWE validity was poorer at 1cm depths than that of both the linear and curvilinear probe. The validity of endoprobe SWE stiffness was lower at the 3cm depth compared to the 1cm depth, and outcomes were not valid at the 5cm depth. Second, to establish the validity of indentation testing as a benchmark standard for SWE applications, indentation testing was conducted in TMM phantoms under a series of testing parameters with quasi-static ramp compression used as the benchmark. The best agreement between indentation and ramp compression outcomes was observed at low strain ranges with the lowest testing rate (0.01Hz). Higher strains required different material model and geometry parameters to improve validity. Regardless, indentation and ramp compression outcomes were highly correlated. It is recommended that researchers match testing parameters to in vivo loading conditions, while using this work to support material model and sample geometry selection. Third, to identify the optimal indentation testing parameters to maximize agreement between SWE and indentation stiffness, several loading strain, loading rate, sample geometry, and indentation models were evaluated in TMM phantoms. Findings showed strong relationships between indentation and SWE stiffness outcomes, regardless of testing conditions. It is recommended to match loading parameters to in vivo conditions. Small sample geometries and low indentation rates appeared to optimize agreement between indentation and SWE outcomes. The fourth and final study of this dissertation examined the in vivo reliability of uterine SWE. Institutional research ethics board approval was obtained (20170872-01H, H-08-18-790) and data were acquired from 32 participants with no active uterine disorders. SWE reliability was good to excellent, except in the anterior myometrium, where poor reliability was attributed to difficulty standardizing SWE sites between days. Phase in the menstrual cycle did not impact SWE outcomes. Site depth exhibited significant correlations with stiffness for multiple cases and heterogeneity in uterine stiffness was observed across sites. Anecdotal observations of confounding factors require further investigation. The findings of this thesis suggest that quasi-static flat-tip indentation testing is a suitable benchmark standard to validate SWE under a variety of parameters. However, endoprobe SWE of the uterus does not appear to be valid at target depths of 3cm and beyond. Even at depths less than 3cm, linear or curvilinear probe SWE outperformed endoprobe SWE. Results suggest that further development of endoprobe SWE for uterine applications is required prior to clinical investigation of gynecological SWE for diagnostic and treatment planning purposes.

Thesis (M. Biotech.)--Flinders University, Cardiovascular Medicine and Centre for Neuroscience, Cardiovascular Neuroscience Group. / Typescript bound. Includes bibliographical references: (leaves 117-125) Also available electronically.

Für eine Vielzahl der Frauen mit Blutungsstörungen steht das Erreichen einer „normalen Blutung“ als Therapieziel von Thermachoice® im Vordergrund und weniger ein völliger Blutungsstopp. Im telefonischen Gespräch mit den Studienteilnehmerinnen zeigte sich, dass viele Frauen die Menstruation als einen zyklisch wieder kehrenden Reinigungsprozess des Körpers ansehen, der nach einer inneren Uhr funktioniert, auf den sie ungern verzichten möchten. (Vgl. auch Bitzer et al., 2005, S. 282-287) Auch die Unversehrtheit des Körpers und die Vollkommenheit der Weiblichkeit sind Beweggründe für eine gebärmutter-erhaltende Therapie bei Hypermenorrhoe. Mit einer signifikanten Reduktion der Blutungsstärke, der Dysmenorrhoe und der seelischen Belastung in dieser Studie, stellt Thermachoice® eine effektive, sichere, kostengünstige und wenig in die körperliche Unversehrtheit eingreifende Option zur Behandlung von Hypermenorrhoe dar. Im Gegensatz zu hormonellen oder anderen medikamentösen Maßnahmen ist die fehlende systemische Wirkung auf den Organismus bei Thermachoice® ein erwähnenswerter Vorteil. Auch eine langfristige Anwendungsdauer ist bei einer Behandlung mit Thermachoice® hinfällig. Mit der Blutungsreduktion durch die Endometriumablation kann in vielen Fällen das Zeitfenster bis zum Erreichen der Menopause überbrückt werden. Im Vergleich mit invasiveren Operationsmethoden, wie der Hysterektomie, ist die Komplikationsrate von Thermachoice® geringer, ebenso das Risiko für Nachoperationen. Der Verlust der Fruchtbarkeit durch eine Hysterektomie kann zu einer emotionalen Belastung werden und zu Partnerschaftskonflikten führen. Auch wenn von einer Schwangerschaft nach Thermachoice® aus medizinischer Sicht abzuraten ist, so sind möglicherweise die Tatsache und das Wissen um die erhaltene Gebärmutter ausreichend, um das Auftreten affektiver Störungen zu mindern. Es ist nicht das Ziel dieser Arbeit festzulegen, ob Thermachoice® besser oder schlechter zur Behandlung von Blutungsstörungen geeignet ist als alternative Therapiemaßnahmen. Es lässt sich sagen, dass Thermachoice® im Rahmen der individuellen Entscheidung eine zufriedenstellende Option zur sanften Behandlung von Blutungsstörungen darstellt. Thermachoice® ist vor allem für diejenigen Frauen geeignet, die ihren Uterus behalten möchten und bei denen keine operationswürdige Senkung des Uterus und der Vagina besteht. Auch Patientinnen mit einem hohen Operationsrisiko und Frauen, bei denen Kontraindikationen für Alternativen bestehen, profitieren von dieser Methode. Vilos et al. hält fest, dass bei ausgewählten Kandidatinnen nach 10 Jahren klinischer Erfahrung TBEA die bevorzugte chirurgische Methode darstellt, um Menorrhagien zu behandeln. Für die individuellen Bedürfnisse der Frauen gibt es ein breites Spektrum an Behandlungsangeboten. Letztendlich kann ein ideales Therapieergebnis in Form maximaler Patientinnen-Zufriedenheit nur erzielt werden, indem im Vorfeld alle Vor- und Nachteile der einzelnen Therapieoptionen erörtert werden und gemeinsam mit der Frau eine Entscheidung getroffen wird. / The principal aim of the therapy with Thermachoice® for many women with bleeding disorders is in most cases is reaching the level of eumenorrhea, and not amenorrhea. As resulted from the telephone conversation the menstruation is considered as a cyclic, necessary purification by a lot of women. Furthermore the body´s integrity and the perfection of femaleness are reasons for privileging a medical procedure that conserves the uterus. The actual study shows a significant reduction of bleeding intensity, dysmenorrhea and mental pressure by Thermachoice®. It seems to be an effective, reliable, cost-efficient and little invasive option to treat bleeding disorders. As opposed to hormonal or drug therapy the loss of systemic effect of Thermachoice® is a mentionable advantage. In some cases the bleeding reduction by endometrial ablation can bridge the time frame until the menopause. The complication incidence and the risk for reoperations is lower by Thermachoice® in comparison to more invasive operation methods, like the hysterectomy. Loss of fertility in consequence of hysterectomy can lead to emotional distress and lead to partnership conflicts. Although it´s advised not to get pregnant after Thermachoice®, possibly the remained uterus is reason enough to reduce the incidence of affective distress. This paper doesn´t aim to determine if Thermachoice® is more or less appropriate to treat bleeding disorders than alternative methods. You can say that Thermachoice® presents a satisfactory outcome for an elected clientele. It´s especially convenient for women who want to keep their uterus, for patients with a high risk for operation and for women for whom alternative methods are contraindicated. According to Vilos et al. TBEA is the preferred surgical procedure to treat menorrhagia in pre-selected candidates after 10 years of clinical experience. There´s a great offer of options for the individual needs and expectances of each woman. Finally an ideal outcome with complete satisfaction can only be reached by discussing the pros and contras of each possible treatment and coming to a decision together with the patient.

Abstract not available

Ninety six women, average age 47, who had a hysterectomy between October 1997 and June 1999 were initially interviewed in hospital and followed up for four months after discharge. The findings of the study indicate that adequate support was needed in early recovery period and discharge programs should take into consideration the needs of women with small children and those who have no onsite home support. Strategies used by the women to assist convalescence included support from family and friends but little in the way of health professional or community support. The majority of women returned to normal activities by four months. Communication between women and health professionals was also considered by the women to be important following discharge, especially in terms of information and reassurance about their progress during recovery. / Master of Science (Hons) (Health)

Coordinated signals between the maternal endometrium and conceptus during the peri-implantation period are essential for the establishment and maintenance of pregnancy. In pigs, this involves estrogen secretion from conceptuses as the signal for maternal recognition of pregnancy. Pig conceptuses also secrete interferons (IFN) delta (IFND) and IFN gamma (IFNG). The uterine effects of pig IFNs are not known, although ruminant conceptuses secrete IFN tau (IFNT) for pregnancy recognition, and this increases the expression of IFN-stimulated genes (ISGs) in the endometrium. Therefore, studies were conducted to identify and characterize ISGs in the pig endometrium during pregnancy and to evaluate their regulation by estrogen and conceptus secretory proteins (CSPs) that contain IFNs. In the first study, four classical ISGs, including interferon regulatory factor 1 (IRF1) and signal transducer and activator of transcription 2 (STAT2), were detected in the pig endometrium and increased after Day 12 of pregnancy, specifically in stroma. IRF2, a transcriptional repressor of ISGs, increased in luminal epithelium (LE) by Day 12 of pregnancy. The increase of IRF2 was due to estrogen while the stromal increase of IRF1 was due to IFN-containing CSP infusion. In the second study, the ISG STAT1 increased in LE after Day 12 of pregnancy and estrogen resulted in a similar increase. After Day 15 of pregnancy, STAT1 increased in stroma. Infusion of IFN-containing CSPs resulted in a similar stromal increase. In the third study, the ISGs swine leukocyte antigen (SLA) class I and beta-2microglobulin (B2M) increased in LE between Days 5 and 9 of the estrous cycle and pregnancy and decreased between Days 15 and 20 of pregnancy. By Day 15 of pregnancy, SLAs and B2M increased in stroma where they remained through Day 40. Progesterone increased SLA and B2M in LE, and a progesterone receptor antagonist ablated the upregulation while infusion of IFN-containing CSP increased SLA and B2M in stroma. Collectively, these studies identify ISGs expressed in the pig endometrium during pregnancy. These genes may be involved in protecting the fetal semiallograft from immune rejection, limiting conceptus invasion through the uterine wall, and/or establishing a vascular supply to the conceptus. The interactions of estrogen, progesterone and IFNs to regulate cell-type specific expression of ISGs highlight the complex interplay between endometrium and conceptus for pregnancy recognition and implantation.

Endogenous retroviruses (ERVs) account for a substantial portion of the genetic pool of every animal species (e.g. ~ 8% of the human genome). Despite their overwhelming abundance in nature, many questions on the basic biology of ERVs are unanswered. Sheep harbor approximately 20 copies of endogenous betaretroviruses (enJSRVs), which are related to an exogenous oncogenic virus, Jaagsiekte sheep retrovirus (JSRV). Therefore, they are an attractive model for investigation of the potential beneficial roles of ERVs in reproductive biology. Studies were conducted to determine: 1) expression of enJSRVs envelope (env) and HYAL2 mRNAs in the ovine uterus and conceptus (embryo/fetus and extraembryonic membranes) throughout gestation; 2) regulation of enJSRVs expression by progesterone; and 3) the role of enJSRVs in regulating peri-implantation placental growth and differentiation. Study One determined the localization of enJSRVs env and HYAL2 mRNAs throughout gestation. Results demonstrate that alterations in expression of enJSRVs and HYAL2 in the sheep uterus and placenta suggest the probability of a variety of physiological roles in implantation and placentation. Partial sequencing of the transcriptionally active enJSRVs from ovine uteroplacental tissues revealed expression of multiple enJSRV loci. Study Two assessed the influence of progesterone, interferon tau, and pregnancy stage on enJSRVs expression, as an effort to understand factors that may regulate enJSRVs. Results of this study support the hypothesis that expression of enJSRVs is modulated by progesterone, but not IFNτ in vivo. Study Three provides for enJSRVs regulating trophectoderm growth and differentiation in the peri-implantation conceptus. Blocking conceptus enJSRVs Env expression compromised pregnancy by retarding trophoblast outgrowth and differentiation. Inhibition of enJSRVs Env in vitro also reduced proliferation of mononuclear trophectoderm cells. Consequently, these results demonstrate that enJSRVs Env regulates trophectoderm growth and differentiation in the ovine conceptus, strongly supporting the biological significance of ERVs in placental evolution and animal reproduction Collectively, these studies illustrate that enJSRVs play an integral role in success of pregnancy. While the definitive roles of the enJSRVs have not yet been elucidated, it is evident that enJSRVs are an important component of the ovine genome and that they influence recognition and maintenance of pregnancy and placental formation.

Recurrent early pregnancy loss in the ovine uterine gland knockout (UGKO) ewe model manifests on Day 14 of pregnancy, indicating that endometrial secretions are critical for peri-implantation conceptus development. Therefore, the following studies were conducted with fertile ewes and infertile UGKO ewes to identify candidate endometrial factors essential for normal conceptus survival, utilizing both genomics and proteomics approaches. The first study used transcriptional profiling of endometrium from Day 14 cyclic, pregnant, and bred UGKO ewes, as well as ewes treated with interferon tau (IFN??) and progesterone, to identify genes important for conceptus development. A number of novel and previously known IFN??-stimulated genes, as well as progesterone-stimulated genes were identified that are higher in fertile ewes, such as galectin-15. Interactive effects of progesterone and IFN?? regulate endometrial gene expression in a temporal and cell-type specific manner. The second study characterized the endometrial expression and hormonal regulation of galectin-15, a member of the galectin family of secreted ??-galactoside lectins. Galectin-15 was secreted into the uterine lumen by the lumenal (LE) and superficial glandular epithelium (sGE), where it may promote adhesion during implantation, as well as was phagocytosed by the trophectoderm and formed intracellular crystals. The third study determined the endometrial expression of galectin-15 throughout gestation. Galectin-15 was secreted into the uterine lumen, where it was phagocytosed by the trophectoderm/chorion, transferred through placental vasculature to the fetus, and cleared through the fetal kidney to be stored in allantoic fluid. The fourth study utilized proteomic analysis of uterine flushes and endometrial explant cultures from Day 14 cyclic, pregnant and UGKO ewes to identify differences in uterine secretions. Analyses identified several genes that were expressed by the LE and sGE and may be involved in prostaglandin production and/or pH regulation. Collectively, results of these studies suggest that transcriptional profiling and analysis of uterine secretions are effective tools to determine genes important for early pregnancy. Further, identified genes are expected to reveal novel endometrial factors and metabolic pathways for support of conceptus survival and implantation, as well as provide improvements for embryo culture methods and diagnose endometrial dysfunctions leading to infertility.

Thesis--Auburn University, 2010. / Abstract. Vita. Includes bibliographic references (p.98-114).

Thesis (M. Phil.)--University of Hong Kong, 1984.