COTS provided the necessary information for planning a definitive trial investigating the clinical effectiveness of monofilament non-braided suture materials in reducing pregnancy loss rate following cervical cerclage compared to the traditional multifilament braided sutures. COTS study was a stepwise process, which initially involved retrospective data analysis and later was supported by the evidence from national survey and systematic review. Evidence from retrospective analysis and systematic review confirmed that the research question about the suitability of multifilament/braided sutures in cervical cerclage; and that they may be associated with poor obstetric outcome. The Systematic review confirmed that at the time of writing there were no RCTs addressing this issue. Our national survey proved that this scientific question is of significant interest to the Obstetrical community and that the practice with cerclage varies across the country. Based on the findings of COTS trial, funding was sought from the NIHR HTA programme, and we were successful in being awarded £1.2 million (co-applicant) to conduct a multi-centre randomised controlled trial (RCT): The C-STICH trial Cerclage Suture Type for an Insufficient Cervix and its effect on Health outcomes Trial.

Research presented in this thesis was driven by the need to identify risk factors that predict local recurrence (LVR) in patients with vulval cancer (VSCC), and the need for more effective treatments for women with vulvar intraepithelial neoplasia (VIN). To identify the risk factors that predispose women to LVR, a multivariate analysis was performed on a well-characterized cohort of women treated for VSCC. This analysis revealed that the only independent predictor of LVR was the presence of Lichen Sclerosis (LS). These women were five times more likely to recur than those without LS. VIN is a recognised precursor lesion of HPV-positive VSCC. Topical application of Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, has been shown to be an effective treatment for genital warts; a condition caused by HPV. Although the mechanism(s) by which EGCG influences the growth of HPV-associated proliferative disorders are unknown, I demonstrate that EGCG inhibits cell proliferation and promotes apoptosis, an effect that was accompanied by down-regulation of the E6 and E7 proteins and the induction of p53, p21 and pRb. Biochemical analysis revealed that EGCG did not stimulate E6 degradation by enhancing poly-ubiquitination and proteasome-mediated degradation, suggesting that EGCG-mediated E6 proteolysis occurred through other mechanisms.

Background: Vulnerability is universally present but experienced biopsychosocially on an individual level. Stigma develops when populations are labelled vulnerable. Individual vulnerability can be lessened by resources accessed to assist in developing resilience. A deeper analysis of vulnerability and resilience is required to inform policy, ethics, law and social life. Design: Qualitative, quantitative and mixed method approaches were used. Sample: Five papers represented the perspectives of 102 women, 21 clinicians and 13 student midwives. A further paper presented a concept analysis which included the perspectives of 10,067 women and 325 clinicians (total sample size women n=10,169; clinicians n=346; student midwives n=13). Methods: Gadamer’s ontological perspective of time, place and culture and was seen through Engel’s biopsychosocial lens. Epistemologically, truth originated from multiple realities. Methodologically, women’s experiences were captured via mixed methods. 7 Analysis: Thematic analysis and descriptive statistics were synthesised via framework analysis. Findings: A coherent theme of vulnerability in maternity care was apparent. Women’s concerns were trivialised. The professional’s style of communication determined the women’s experience of maternity care. Clinician control of care provision undermined women’s ability to choose. Women developed resilience in adverse circumstances via: accessing other supportive members of society, identifying their need for information, talking to others and developing accommodative coping strategies. Conclusion: The new conceptual model, in this thesis, should be evaluated via mixed methods. A biopsychosocial approach should underpin informed choice. Clinicians need raised awareness about how interaction can lower women’s self-esteem and build resilience in others. Higher education needs to challenge preconceived biases in safe environments via reflective processes. Research should explore women’s influential circle in decision making during maternity care. Women should be involved in the design of research to inform how best to capture their complex lived experience. Funders of research and ethics committees should request information about how implementation of evidence may be influenced by the current clinical environment. Impact should be measured post implementation. Social policy should be informed by a deeper, conceptual analysis of vulnerability and resilience.

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Background: The prevalence of obesity is increasing in the US population, especially among pregnant women extending before, during and after pregnancy. This is a cause for concern, as it poses significant health risks for both mother and infant. Given the urgency of this problem, it is important to examine not only the pathways to obesity in this group but the correlated risks. One significant risk factor for obesity in the general population is childhood maltreatment. This early, varied, and often chronic form of maltreatment, has been associated with long-term adverse physiological and psychological health outcomes across the general population, often conferring heightened risk for health disparities or increasing the burden of already existing disparities. Only two studies have examined childhood maltreatment as a risk factor for maternal obesity and none have examined this relationship in an urban sample of young adult Latina nulliparas. This exploratory study examines relationships between and among a history of early maltreatment, maternal obesity, and key psychosocial risk indices in urban, nulliparous minority adolescents to better understand associations with this risk factor in the context of pregnancy. The Life Course Health Development Framework as outlined by Halfon and Hochstein is the theoretical framework guiding this study. Methods: This descriptive exploratory study performed a retrospective analysis of a subset of interview-collected data from a larger NIH funded prospective cohort study (1R01MH077144-01A2, Monk, PI). Study participants were pregnant, ranging from 14-19 years of age, and recruited from obstetrical practices affiliated with a large academic medical center in New York City. The sample was primarily Hispanic. An exploratory correlational design employed bivariate as well as multivariate analyses to examine associations among maternal childhood maltreatment (MCM), depression, PTSD, perceived stress, social support and maternal obesity as measured by pre-pregnancy BMI. An association between pre-pregnancy BMI and infant birth weight was also explored. Results: Forty-three percent of this study sample experienced at least one form of childhood maltreatment with more than half experiencing multiple forms. A similarly high percentage (40 %) of pre-pregnancy overweight and obesity (BMI ≥ 25 and BMI ≥ 30 respectively) was also evidenced. Of these, eighteen percent were obese. Maternal childhood maltreatment was significantly associated with depression, PTSD, elevated stress levels and low levels of social support. Clinically important finding, though not statistically significant, was the finding that mothers with MCM were more than twice as likely to have a pre-pregnancy BMI ≥ 30 than mothers without MCM. Both of these public health concerns confer a heightened risk for additional short and long-term adverse health outcomes for mothers and infants, especially those already compromised by health disparities. Conclusions & Implications: This study provides further evidence that childhood maltreatment and pre-pregnancy obesity are significant health priorities requiring attention. It has characterized, for the first time, the high occurrence of both of these health issues in young adult Latina nulliparas. The study presents a preliminary risk profile of significant psychosocial indices associated with childhood maltreatment and pre-pregnancy obesity that can serve to inform the development and implementation of systematic prenatal screening programs for populations at psychosocial risk Finally, the study finding that a history of childhood maltreatment more than doubled the risk of pre-pregnancy obesity, while not statistically significant, may be clinically meaningful in that it presents the possibility of early childhood trauma conferring pregnancy-related vulnerability for future adverse health outcomes for both the mothers and their offspring in this group. Next steps in this critical but neglected area of research are to focus on larger population-based studies which will further examine the complex nature of the relationship between MCM and pre-pregnancy obesity as well as correlated risk factors.

<p> The American Academy of Pediatrics (2012); the American College of Obstetricians and Gynecologists (2016); and the Association of Women&rsquo;s Health, Obstetric, and Neonatal Nurses (2015) endorses breastfeeding exclusively for six months, followed by continuation with complementary foods through age one year to achieve the most personal and public health benefits. However, while most mothers initiate breastfeeding, the majority do not meet their goals due to lack of support (CDC, 2016). </p><p> The Affordable Care Act mandates coverage for breastfeeding support, but federal, state, and insurance policies are not conducive to making such benefits accessible. </p><p> Electronic registration and medical record documentation allow for improved tracking and decreased risk to the facility. </p><p> This paper outlines the development and implementation of administrative practices in an existing Registered Nurse/Internationally Board-Certified Lactation Consultant (RN-IBCLC) led outpatient lactation clinic at a Baby Friendly (2012) designated facility with goals of increasing access to lactation support postpartum, improving patient outcomes, and realization of financial viability. Expected outcomes included identification of best practices and implementation strategies for the following: a. provider collaboration including outreach efforts to trigger referrals. b. number of dedicated hours per week to offer services. c. cost/benefit analysis. d. registration and documentation process. e. model of care. f. funding source. </p><p> Tests of change through plan-do-study-act (PDSA) cycles were based on the outcome of a gap analysis. Modifications to implementation were made dependent on PDSA cycle findings until optimized RN-IBCLC-led outpatient lactation clinic administrative practices for the facility and processes became streamlined. </p><p> Despite limited literature to guide administrative practices, the project met the aims of patient registration and electronic health record (EHR) documentation. However, extensive policy and systems barriers existed that prevented success in identifying a workable revenue stream despite the efforts of this investigator in collaboration with parent system-level managed care, finance, and compliance departments. </p><p> The solution agreed upon to provide sustainability to the program was to utilize outpatient lactation visits as a community benefit to quantify lost revenue of services provided and aid the hospital. Even though the lack of revenue equaled lack of department growth, the community benefit option added a layer of stability to the program as it stands. </p><p> This project provides a model for other organizations examining best practices in administrative and funding options for IBCLC-led outpatient lactation clinics. Thereby; creating sustainable breastfeeding support leading to improved health of mothers, babies, and the community.</p><p>

Introduction: Pelvic organ prolapse is present in up to 50% of women. It is commoner in older women, often above 50 years of age and associated with hormonal e.g. oestrogen decline, and stiffer vaginal tissue. Pregnancy, on the contrary is a physiologic condition with higher oestrogen level and exhibits reversible structural and mechanical changes in pelvic tissues. Advanced glycation products, the ageing markers, stiffen connective tissues. There has been no previous systematic study on the relationship and action mechanisms of oestrogen, glycation level and mechanical property of vaginal tissues. Aim: The aim of this project was to study the ultrastructural and mechanical properties of vaginal tissues, and understand the relationship and possible mechanisms of accumulation of glycation (pentosidine), vaginal wall mechanics and oestrogen receptor (ER-a) expression in the vaginal tissues in both pregnancy and prolapse. It was hypothesised that prolapse is a disease of accelerated ageing and that mechanical and ultrastructural changes in prolapsed tissues and oestrogen decline are related to the elevation of glycation content in the tissues. Methods: Following ethical approval, vaginal tissues from 49 women with prolapse and 16 controls were obtained and proformas containing information on known and suspected prolapse associations were completed for each participant. Female Sprague Dawley rats‘ vaginal tissues were used for the pregnancy study. Nano-scale, micro-scale and tissue level mechanical characterizations of the tissues were performed using ball indentation technique, scanning electron microscopy, peakforce nanomechanical property mapping atomic force microscopy, and optical coherence elastography, which was applied for the first time to the study of vaginal tissues. The glycation contents of vaginal tissues in pregnancy and prolapse were quantified by high performance liquid chromatography and values obtained were analysed in comparison to medical comorbidities. Tissues were qualified by histological and immunological staining for structure (haematoxylin &eosin, trichrome and picrosirus red stainings), glyoxalase I, ER-a, elastin and neural stain. A sulphated glycosaminoglycan (sGAG)-collagen model was used to study the role of sGAG in collagen fibrillogenesis. Results: Rat vaginal tissues in pregnancy contained significantly lower amounts of pentosidine, higher oestrogen receptor-a and glyoxalase I (antioxidant enzyme) expression with larger creep, lower elastic modulus, larger fibril diameter and higher sGAG content than their non-pregnant counterparts. Observed morphological changes of the collagen fibrils in pregnancy were attributed to sGAG, which was noted to influence collagen fibril aggregation and bundling. Skin pentosidine content was reflective of vaginal tissue pentosidine in the same subjects. Pentosidine was significantly higher in prolapsed tissues and increased with age; with more age-dependent increase observed in the prolapse population and also significantly different between the 6th and 7th decades. Glyoxalase I and ER-a were poorly expressed in the prolapsed tissues in comparison to controls. Prolapsed tissues had notably disorganized ultrastructure and higher collagen fibril modulus. At all levels of tissue organization, prolapsed tissues were stiffer than controls, with increased stiffening at the more superficial layers of the tissue. Hypertension and smoking were associated with higher glycation and prolapse. In both pregnancy and prolapse, higher expression of glyoxalase I and ER-a were associated with lower glycation content of the vaginal tissues and lower modulus. These observations have led to the suggestions that oestrogen plays an important role in increase or reduction of glycation through an oestrogen-gluthathione-glyoxalase (antioxdant) pathway, which directly affects vaginal tissues‘ mechanics. Future implications: These findings have implications to the current understanding of how prolapse may occur and can inspire future translational research on improved treatment of women with prolapse. Oestrogen may significantly influence the temporary and permanent mechanics of pelvic tissues such as the vaginal wall through its modulation of glycation accumulation within the tissues. Oestrogen thus shows promise of a potential future medical treatment for early stages of prolapse. The knowledge of new prolapse comorbidities can aid the early detection and possible prevention of prolapse through a high index of suspicion.

No description available.

Preterm birth is a major clinical problem, worldwide 15000000 babies are born prematurely each year. Inappropriate myometrial function is a major cause of preterm labour. Preterm labour is the result of multiple pathological processes involving several underlying mechanisms. In all cases, a quiescent uterus in pregnancy changes to one that can produce coordinated, forceful contractions, following an increase in uterine conductivity and contractility, and cervical remodelling to facilitate cervical dilatation. Currently there are several biochemical and clinical tests available to assist in the prediction of preterm birth. Many of these have a very high negative predictive value but their positive predictive value remains low. One in five women in the UK requires induction of labour. The outcomes of this process are again difficult to predict. Both of these areas of obstetrics would benefit from improvements in prediction of clinical outcomes. Previously, phospholipase C like 1 (PLCL1) was identified as a novel intracellular protein found to be significantly downregulated in both the myometrium with the onset of spontaneous labour using sequencing techniques (Chan et al., 2014). It acts as an IP3 chelator, uncoupling phospholipase C from myometrial contractions, maintaining myometrial quiescence and therefore regulating a common pathway to inflammatory, oxytocin or prostaglandin mediated labour. We aimed to develop a clinical test utilising PLCL1 as a quiescence or susceptibility marker to other stimuli to premature labour and to determine if this marker could determine sensitivity to prostaglandins and syntocinon during the induction of labour process. During a prospective observational cohort study, patients were recruited from a preterm prevention clinic throughout mid-pregnancy, and from the antenatal ward when attending for induction of labour at term. Cervical cytobrush samples were taken to obtain cervical epithelial cells. A novel assay was developed to quantify PLCL1 from these samples. There have been various challenges in the process, including the small and varying number of cells obtained, problems with interference from cervical mucus with protein quantification and difficulty adequately lysing our cells to release the protein. We have demonstrated the presence of PLCL1 in cervical cytobrush samples using immunocytochemistry, SDS-PAGE, and western blotting and ELISAs. We have developed a method to isolate our cervical cells from the cervical mucus, lyse these cells and quantify PLCL1 using an ELISA. Our findings demonstrate that PLCL1 is a promising novel protein which could be utilised in the prediction of preterm birth and outcomes of induction of labour. As a susceptibility marker, PLCL1 could be used in conjunction with other markers.

Embryo donation (ED) and double donation (DD) are fertility treatments whereby resulting children are raised by parents to whom they are genetically unrelated. The main similarity between ED/DD and adoption is the lack of genetic parent-­child relationships, and the main difference is the presence of the gestational link in ED/DD families, which provides an option of concealing genetic origins. This thesis consists of one large study followed by three subsidiary studies, with the overall aim of exploring the disclosure of genetic origins in the UK and Brazil, and the support available to assist parents with this process. In Study I, 36 ED/DD parents, and 27 adoptive parents were interviewed to determine if and how they disclosed to their children, and identify the support that they received to manage this process. In Study II, 30 UK-­based infertility counsellors completed an online survey to ascertain how they engage in disclosure-­related issues with patients seeking embryo donation/double donation treatment. In Study III, 19 Brazilian parents, who conceived a child using donated sperm or eggs, completed an online survey to explore if and how they disclosed to their children, and whether they felt supported with this process. In Study IV, 24 Brazilian fertility professionals completed an online survey to determine how they engage with parents seeking treatment with donated gametes. Overall, adopters were more confident in the process of adoption revelation, and received more support in order to achieve this, compared to ED/DD parents. Findings highlight the complex nature of disclosing donor conception, and identified that Brazilian parents experience similar challenges compared to those in the UK. Disparities were found in the disclosure-­related support provided both across and within these two country contexts. From these results, recommendations for how parents could be better supported with disclosure-­related issues are given.