Orientador: Izildinha Maestá / Coorientador: Marcos Consonni / Banca: Joelcio Francisco Abbade / Banca: Antonio Rodrigues Braga Neto / Resumo: Não disponível / Abstract: Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia (GTN). However, there is limited information on whether uterine artery Doppler flow velocimetry (DFV) can predict GTN following complete hydatidiform mole (CHM). The purpose of this study was: 1) to compare uterine blood flow before and after CHM evacuation between women who developed post-molar GTN and those who achieved spontaneous remission; 2) to assess the usefulness of uterine DFV parameters as predictors of post-CHM GTN, and to determine the best parameters and cutoff values for predicting post-CHM GTN. Methods. This prospective cohort study included246 CHM patients attending three trophoblastic diseases centers (Botucatu -Sao Paulo State University, Rio de Janeiro Federal University and Fluminense Federal University) between 2013 and 2014. Pulsatility index (PI), resistivity index (RI), and sistolic/dyastolic ratio (S/D) were measured by DVF before and 4-6 weeks post CHM evacuation. Statistical analysis was performed using Wilcoxon's test, logistic regression and ROC analysis. Results. No differences in pre- and postevacuation DVF measurements were observed in patients who developed post-CHM GTN. In those that achieved spontaneous remission, PI and SD were increased after evacuation. Pre- and post-evacuation PI was significantly lower in patients who developed GTN with estimates of odds ratio of 13.9-30.5. Pre-evacuation PI ≤1.38 (77% sensitivity, 82% specificity), and post-evacuation PI≤1.77 (79% sensitivity, 86% specificity) were significantly predictive of GTN. Conclusions. Uterine DFV measurements, particularly pre- and post-molar evacuation PI, can be useful for predicting post-CHM GTN / Mestre

Made available in DSpace on 2014-06-11T19:29:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-10-03Bitstream added on 2014-06-13T21:00:22Z : No. of bitstreams: 1 ferreira_egv_me_botfm.pdf: 578426 bytes, checksum: 965dd8dff1cdf74bb54609e4bbb1d19d (MD5) / Financiadora de Estudos e Projetos (FINEP) / Clicar acesso eletrônico abaixo. / Objective: to assess quality of life and psychological aspects in patients with gestational trophoblastic disease (GTD). Methods: This cross-sectional self-report study was carried out among 54 women treated at Botucatu Trophoblastic Diseases Center, São Paulo, Brazil. Validated questionnaires were used to assess quality of life (QoL) (WHOQOL-bref), symptoms of depression (Beck Depression Inventory-BDI) and anxiety (State-Trait Anxiety Inventory –STAI). Results: Most patients rated overall QoL as good (44.44%), and were satisfied with their health status (42.59%). However, these findings did not reach statistical significance. Mean QoL domain score was the highest for psychological health (53.86 ± 21.46), and the lowest for social relationships (65.74 ± 22.41). BDI mean was 15.81 ± 11.15, indicating dysphoria. STAI means were 46 ± 6.46 for trait-anxiety, and 43.72 ± 4.23 for state-anxiety, both evidencing medium-high anxiety. Among patients who were employed, the environment domain mean was the highest (p=0.024). The presence of children prior to disease onset resulted in the lowest means for physical health (p=0,041) and environment (p=0.045). The patients desiring to have children showed significantly higher means for physical health (p=0.004), psychological health (p=0.021) and environment (p=0.003). The need for chemotherapy to achieve complete response had no significant influence on QoL. Conclusion: This study evidenced the psychological impact on GTD patients. This information suggests that specialized care centers should provide psychological interventions during the treatment and follow-up of GTD patients... (Complete abstract click electronic access below)

Abstract Chlamydiae are obligatory intracellular gram-negative bacteria with a unique growth cycle. They are very successful pathogens and responsible for a wide variety infections in humans and different animal species. In addition, they have a tendency to cause recurrent, persistent or chronic infections with potentially severe sequelae years or decades later. The general purpose of this work was to study the possible serological associations between chronic chlamydial infection, systemic inflammation and reproductive health in a general population. The chlamydial heat shock proteins 60 and 10 (Hs10 and Hsp60) have been suggested to contribute to the pathogenesis of chronic chlamydial infections. Thus, the antibodies to chlamydial Hsp10 and Hsp60 were also investigated in complications of pregnancy. The present study was a longitudinal population-based birth cohort study, and all of the original papers of this dissertation are based on a nested case - control design. Our results confirmed the serological association between C. trachomatis infections and subfertility and the rather high incidence of undiagnosed C. trachomatis infections in the male partners of subfertile couples. We further demonstrated a serological association between previous C. trachomatis infections, immunity to chlamydial Hsps and female subfertility. We also showed that serological markers of chronic chlamydial infection present as early as the first trimester are associated with preterm delivery among nulliparous women. When elevated levels of C. trachomatis IgG and hsCRP were present, the estimated risk for preterm delivery was over 4-fold. According to our study, nulliparous women who subsequently developed preeclampsia leading to preterm delivery, which was used as a marker of more serious illness, had significantly more often serum IgG antibodies to C. pneumoniae during the first trimester of pregnancy compared to the preeclamptic women who delivered at term. In conclusion, chronic C. trachomatis infection was found to associate with subfertility both in men and in women. In addition, a subclinical chronic inflammatory process associated at least partly with chronic C. trachomatis infection and present in the first trimester already may be important in the development of preterm delivery. Chronic C. pneumoniae infection and systemic low-grade inflammation were found to associate with pregnancies that lead to preeclampsia and preterm delivery.

4 p. / The saying “you are what you eat” takes on a new meaning when a woman learns she is expecting a baby. For the next several months, her growing baby’s health is directly dependent upon what she eats, and what she chooses to avoid. What is more, a woman’s diet during pregnancy has been shown to affect her child’s health long after she is no longer eating for two.

Surrogate motherhood is considered one of the most disputed and controversial method of assisted reproduction available to childless couples. This contemporary topic assists rising numbers of couples with reproductive disorders. Professional and nonprofessional discourse on the topic of surrogacy has grown in the Czech Republic since 2009. This discussion has contributed to increasing destigmatisation of the parties that make use of the option of surrogate motherhood. As a result, we have first- hand accounts on how the Czech legal system in its current form responded. This diploma thesis presents an overview of the methods of assisted reproduction and their history as well as the legal basis for assisted reproduction in international, European and national law. Furthermore, the thesis touches upon the topic of surrogate motherhood with a view to identifying the risks and dangers of surrogate motherhood both in general and with a focus on the specific legal issues in the Czech Republic. In its conclusion it examines the politico-legal developments regarding surrogate motherhood both on the level of the European Union as well as the Council of Europe. The diploma thesis aims to map the legislation of surrogate motherhood in the Czech legal system including the first contact of the parties, the validity and...

Background: Diabetes is a growing chronic disease that affects more than 29 million adults in the United States and 422 million adults globally. Women with a history of gestational diabetes (GDM) are identified to be at higher risk for developing subsequent type 2 diabetes mellitus (T2DM). The prevalence of GDM varies based on the data collection method, response rate, and diagnostic criteria. The aim of this study is to examine the association between history of GDM diagnosis and current T2DM status and how the relationship differs based on the participant’s age, race, and BMI. Methods: Data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Surveys (NHANES) were analyzed to conduct a cross-sectional study of 4,006 U.S. non-pregnant women ages 20 years and older with a history of prior pregnancy. The race/ethnicity of the participants include non-Hispanic Whites, non-Hispanic Blacks, Mexican Americans, non-Hispanic Asians, and "Other" variables. Univariate and multivariate logistic regression analyses were used to determine the association between history of GDM and current T2DM status stratified by age, race, and BMI. Results: Three hundred and fifteen subjects from a sample size of 4006 were found to have a history of GDM. Of the 315 participants with GDM, 111 (35.2%) were found to develop T2DM. After controlling for age, race, and body mass index (BMI), women with a history of GDM were found to be at greater odds of T2DM (OR=4.71; 95% CI: 3.52-6.28) compared to women without a history of GDM. A multivariate analysis was performed adjusting for other covariates such as age, race, BMI, and cholesterol. When stratified by participant age, women between the ages of 20-44 years with a history of GDM were linked with an increased risk of T2DM (OR= 3.02; 95% CI: 1.88-4.85). Overweight and obese women with a history of GDM have a 2.5-fold risk of developing T2DM (OR=2.51; 95% CI: 1.49-4.23). Discussion: This study provides further understanding and awareness on the role of GDM during the subsequent risk for T2DM. Our study shows women between the ages of 20 and 44 years and with elevated BMIs (25 ≥ kg/m2) are at increased risk of developing subsequent T2DM. Findings suggest the need for health promotion and prevention efforts towards the populations at risk. Early intervention post-pregnancy and education may help prevent women with a history of GDM from developing T2DM.

Pendant la grossesse, les aquaporines (AQPs) exprimées au sein des membranes fœtales sont essentielles pour assurer l’homéostasie du volume de liquide amniotique (LA), mais leur régulation par l’insuline n’a jamais été explorée chez les femmes diabétiques.Le but de notre étude était de préciser le rôle des AQPs 1, 3, 8 et 9 au sein des membranes fœtales chez des parturientes diabétiques et d’étudier la régulation de leur expression par l’insuline.A partir des 129 membranes fœtales, réparties selon 4 populations (36 témoins, 35 diabètes de type 1 (DT1), 17 diabètes de type 2 (DT2) et 41 diabètes gestationnels (DG)), nous avons établi un profil d’expression qualitatif et quantitatif des gènes des AQPs. Dans un second temps, nous avons étudié la régulation par l’insuline de l’expression des AQPs 3 et 9 au sein d’explants d’amnion et de chorion. L’expression ARN et protéique des AQPs au sein de nos différents fragments de membranes fœtales a été étudiée par RT-PCR quantitative et ELISA. Des membranes fœtales issues de grossesses non pathologiques, séparées en ses 2 feuillets (amnion et chorion), ont été utilisées pour étudier la régulation de l’expression des gènes des AQPs 3 et 9 par l’insuline ainsi que la voie de signalisation de l’insuline au sein de l’amnion. Un test au glycérol tritié a permis l’étude fonctionnelle de l’insuline sur les AQPs. Un inhibiteur de la phosphatidyl-inositol 3-kinase (PI3K) est utilisé pour analyser le signal intracellulaire de l’insuline.L’expression du gène de l’AQP 3 est significativement plus faible dans les groupes DT2 et DG. Au sein d’explants de membranes fœtales non diabétiques, il a été observé au sein de l’amnion (mais pas du chorion), une répression significative par l’insuline de l’expression ARN et protéique des gènes AQPs 3 et 9 qui est bloquée par l’inhibiteur de PI3K. Au sein des membranes fœtales, la répression de l’AQP 3 observée in vivo, est permise par l’hyperinsulinisme connu des patientes atteintes de DT2 ou de DG. / During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling the homeostasis of the amniotic volume, but their regulation by insulin was never explored in diabetic women.The aim of our study was to investigate the involvement of AQP 1, 3, 8, and 9 expressed in fetal membranes in diabetic parturient women, and the control of their expression by insulin.From 129 fetal membranes in 4 populations, (controls, type 1 (T1D), type 2 (T2D) and gestational diabetes (GD)), we established an expression AQPs profile. In a 2nd step, the amnion was used to study control of the expression and functions of AQPs 3 and 9 by insulin.The expression of transcripts and proteins of AQPs was studied by qRT-PCR and ELISA. We analysed the regulation by insulin of the expression of AQPs 3 and 9 in the amnion. A tritiated glycerol test enabled us to measure the impact of insulin on the functional characteristics. Using an inhibitor of phosphatidylinositol 3-kinase (PI3K) we analysed the insulin intracellular signaling pathway.Expression of AQP3 protein was significantly weaker in groups T2D and GD. In non-diabetic fetal membranes, we showed for the amnion (not for the chorion) a significant repression by insulin of the ARN expression of AQPs 3 and 9, which was blocked by PI3K inhibitor.In fetal membranes, the repression of AQP3 protein expression and functions observed in vivo is allowed by the hyper-insulinism described in pregnant women with T2D or GD.

Background: The number of women considered overweight (OW) and obese (OB) in Canada has steadily increased over the past thirty years. In addition, there has also been a rise in the amount of weight women gain during pregnancy. Many adverse pregnancy outcomes are associated with maternal overweight, obesity and/or excessive gestational weight gain (GWG), which have been widely studied and reported. In 2009, the Institute of Medicine (IOM) developed healthy GWG guidelines, based on trial and observational evidence, that provide BMI-related weight gain targets. This evidence has shown that weight gain within the guidelines results in better health outcomes for the mother and baby, during pregnancy, as well as postpartum. Objectives: (1) To address diet quality and patterns using data collected from the Maternal Obesity Management (MOM) Intervention Trial, and (2) Develop and validate a comprehensive web-based questionnaire that can be used in a future study to examine women’s knowledge of the IOM GWG guidelines, dietary recommendations, physical activity (PA) practices, as well as other lifestyle habits. Methods: (1) Exploratory pooled analysis of dietary data from Maternal Obesity Management (MOM) trial - To identify diet quality of women who exceeded (EX) versus did not exceed (NEX) the 2009 IOM pregnancy weight gain targets. Participants (n=50) completed 7-day food records at 3 points during pregnancy (baseline (V1: 12-20 weeks), between 26-28 weeks (V2) and between, 36-40 weeks (V3). Data were analyzed in ESHA Food Processor Program and SPSS (version 13) to see if there was any difference found in diet between EX and NEX women. (2) Development and validation of a comprehensive maternal health questionnaire aimed to establish gaps in women’s behaviours and perceptions of the IOM GWG guidelines - An expert panel was consulted in the development of questionnaire constructs and items to gain content validity of the questionnaire. After multiple phases of questionnaire development and revisions, a 14-day test re-test validation pilot study was conducted to establish test re-test validity. Results: (1) In the EX and NEX analysis, significant decreases were found in total energy intake, including fat and protein, across pregnancy in the NEX GWG group. Significant group-by-time interaction was also found for energy intake and protein. (2) Most constructs included in the electronic maternal (EMat) Health questionnaire all proved to have sufficient test re-test validity via correlation analysis. Conclusion: In order to address the knowledge gaps regarding excess weight and changes in dietary habits during pregnancy, it is beneficial to explore pregnant women's knowledge and behaviours regarding these issues and collect information on what women report as barriers and facilitators to gestational weight management. The conclusions drawn from both of these studies may inform future interventions, as well as indicate where further education strategies are needed.

Pregnancies complicated with diabetes mellitus (DM) are associated with poor maternal and fetal outcomes, such as birth trauma, fetal overgrowth (macrosomia) and programming of the fetus to develop metabolic syndrome in adult life. Maternal hyperglycemia is thought to contribute to fetal macrosomia, however the role of the placenta in these pregnancies is incompletely understood, therefore we aimed to investigate the specific consequences of high glucose on placental metabolism. To achieve this aim an in vitro model of placental exposure to high glucose was developed. This model was used with the aim of analysing how high glucose alters the transcriptome and metabolome of these cells, using a systems biology approach to identify candidate functional pathways which may be altered in placenta as a result of hyperglycemia. These candidate functional pathways were validated in an ex vivo model of placenta exposed to high glucose and in placental tissue from pregnancies complicated by DM. A trophoblast cell line (BeWo) was cultured in low (5 mM) and high (12 mM or 25 mM) D-glucose conditions for 48 hours. Transcriptomic and metabolomic analysis of these cells was performed using microarrays, and gas- and liquid-chromatography-mass spectrometry, respectively. Transcript and metabolite changes were independently analysed and integrated, using network analysis. From the integrated analysis of the ‘omic datasets, β-fatty acid oxidation (β-FAO), purine metabolism, phosphatidylinositol/PI3K phosphate pathway and lipid metabolism, were identified as candidates for further study. Changes within the PI3K pathway and lipid metabolism/β-fatty acid oxidation were validated in an ex vivo placental explant model of high glucose and in placental tissue from women with DM, compared to uncomplicated pregnancies. mRNA, protein expression and protein activation of key molecules within the PI3K pathway were not significantly altered in placenta as a response of high glucose ex vivo or DM in vivo. The second candidate functional pathway, lipid metabolism, has previously been implicated in association with placental dysfunction in pregnancies complicated by DM. Placental fatty acid transporter and lipase protein expression, as well as, relative abundance of different fatty acids were unaltered in response to high glucose or DM. High glucose levels increased triglyceride levels within the placenta, indicating reduced rates of β-FAO. The effect of high glucose could be ameliorated using a PPARα agonist. This may provide a novel therapeutic intervention to prevent excess esterification of fatty acids to triglycerides in maternal diabetes, which may in turn influence fetal growth. This study illustrates how a systems biology approach can be used to identify novel candidate functional pathways that are altered within the trophoblast in response to high glucose. Thus, improving understanding of placental dysfunction in these pregnancies and providing novel candidate pathways for future study, which may represent potential therapeutic targets for intervention of fetal macrosomia in pregnancies complicated by DM.

Magister Pharmaceuticae - MPharm / Gestational diabetes mellitus (GDM) is a condition that affects pregnant women and is one of the most common complications related to pregnancy. According to the World health organisation (WHO), the usual window for diagnosing GDM is between 24 and 28 weeks of gestation and the primary aim of diagnosing gestational diabetes is to identify women and infants at risk of short- or longer-term adverse outcomes. Recent results from the hyperglycaemia and adverse pregnancy outcome (HAPO) study have suggested that even mild levels of hyperglycaemia can have adverse effects on foetal outcomes but there are uncertainties about the prevalence of these outcomes in GDM diagnosed according to the latest WHO 2013 guideline and/or IADPSG 2010 criteria in diverse populations. GDM prevalence has been studied by different researchers, but the prevalence of adverse foetal outcomes in GDM diagnosed based on the latest WHO 2013 guideline and/or IADPSG 2010 criteria have not yet been explored except for the data published by the HAPO study. Due to the lack of sufficient knowledge on foetal outcomes in GDM, this study was conducted to review the evidence on the prevalence of adverse foetal outcomes in GDM diagnosed according to WHO 2013 guideline and/or the IADPSG 2010 criteria. Different databases including PubMed, Science Direct, Google Scholar and CINAHL as well as bibliographic citations were searched using a well-formulated search strategy to find the relevant observational studies (prospective/retrospective cohort and case-control) using explicit inclusion and exclusion criteria. The following search terms were used, “gestational diabetes”, “pregnancy”, “adverse fetal outcomes” and “adverse foetal outcomes”. The findings of this study were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the obtained data analysed using MetaXL ® version 5.3. This review was registered online on PROSPERO, the International prospective register of systematic reviews (registration number: CRD42020155061). Fifteen studies with 88,831 pregnant women (range: 83-25,543 participants) from 12 countries around the world were identified, with a wide variation in the prevalence of foetal outcomes in GDM using the stipulated criteria. These studies were unevenly distributed geographically as six of them were conducted in Asia, four in Europe, four in North America, one in Australia and none in Africa, Antarctica and South America. A meta-analysis found that the overall prevalence of foetal outcomes ranged from 1% (perinatal mortality) to 11% ( large for gestational age). The finding is limited due to the paucity of data on the prevalence of foetal outcomes in GDM. However, more studies using these criteria in low- and middle- income countries (LMICs) are needed by health care providers, to inform practice and allocate resources for control of GDM and its adverse foetal outcomes in diverse settings and ethnic groups, especially in LMICs.