Much has been written in recent years of a ‘crisis’ in the recruitment and retention of midwives in the NHS. The crisis has been attributed variously to burnout, a lack of professional autonomy, a bullying culture, and an ideological conflict between the way in which midwives wish to practise and the way they are required to practise within large bureaucratic institutions, such as NHS Trusts. Negotiating these experiences requires a significant amount of emotional labour by midwives, which they may find intolerable. This thesis explores the strategies NHS midwives deploy in order to continue working in NHS maternity services when many of their colleagues are leaving. It examines the extent to which working in a midwife-led service rather than a consultant-led service helps or hinders midwives’ capacity to manage the emotional and ideological demands of their practice. Ethnographic fieldwork was carried out in a consultant unit and an Alongside Midwife-led Unit (AMU) in two NHS Trusts in England. The findings from negotiated interactive observation and in-depth unstructured interviews with eighteen midwives were analysed using inductive ethnographic principles. In order to ameliorate the emotional distress they experienced, the midwives used coping strategies to organise the people and spaces around them. These strategies of organisation and control were part of a personal and professional project which they found almost impossible to articulate because it ran contrary to the ideals of the midwifery discourse. Midwives explained these coping strategies as firstly, necessary in order to deal with institutional constraints and regulations; secondly, out of their control and thirdly, destructive and bad for midwifery. In practice it appeared that the midwives played a role in sustaining these strategies because they formed part of a wider professional project to promote their personal and professional autonomy. These coping strategies were very similar in the Consultant Unit and the Midwifery Unit. A midwife-led service provided the midwives with a space within which to nurture their philosophy of practice. This provided some significant benefits for their emotional wellbeing, but it also polarised them against the neighbouring Delivery Suite. The resulting poor relationships profoundly affected their capacity to provide a service congruent with their professional ideals. This suggests that whilst Alongside Midwife-led Units may attempt to promote a midwifery model of care and a good working environment for midwives, their proximity to consultant-led services compounds the ideological conflict the midwives experience. The strength of their philosophy may have the unintended consequence of silencing open discussion about the negative influence on women of the strategies the midwives use to compensate for ideological conflict and a lack of institutional and professional support.

This thesis examines to what extent women were involved in their own healthcare and that of others, in the late medieval period. It starts from the observation that modem text editing practices often exclude from discussion other widely disseminated texts that formed the 'travelling companions' of a manuscript - in this case particularly the ensemble known as the Trotula. By focusing on one specific text within the manuscript compilations, the diverse and widespread dissemination of women's knowledge of healthcare and the use of vernacular texts have been marginalised. The thesis argues that the consideration of these 'travelling companions' can offer an alternative view of women's involvement in healthcare, despite the seeming female exclusion from the culture of book-learning and the development of professional licensing in the later Middle Ages. The corpus of manuscripts examined is taken from a range of vernacular compilations produced in England, Flanders and Italy, with some discussion of ownership and transmission of these into the Early Modem period. A number of transcriptions and close readings of the contents are used to identify the discrete characteristics of each copy and to track changes that took place during the transmission process. Detailed comparisons demonstrate that conscious, active choices were made in both the adaptation and interpretation of the material being copied. Analysis of these manipulations reveals that the production of vernacular texts enabled easier consultation and use. The manuscripts point to women's continuing engagement with both the texts and the practice of self-care and that, despite the increase in the number of professional male practitioners over the period, women continued to offer advice to others well into the sixteenth century.

The research within this thesis concerns the monitoring of the fetus during labour, using the fetal electrocardiogram (FECG). A versatile FECG analysis system was developed for the Microsoft Windows environment, to allow various FECG parameters to be extracted. Algorithms, currently used in other FECG analysis systems, were implemented using Object Oriented Programming, thus allowing new algorithms to be easily added at a later stage. Although these current algorithms have been demonstrated by several authors, it was felt that they had been used with only partial investigation of their limitations, and with failure to fully determine their accuracy in controlled conditions. These factors are fully addressed within this thesis. By developing a FECG simulator, in which heart-rate, morphology, and noise levels could be varied, the ability of the analysis algorithms to extract the parameters, and the accuracy of these parameters under different noise conditions, were thoroughly checked. Both ability and accuracy were shown to be very good in ideal noiseless conditions; but, with the addition of noise, there exists a compromise between parameter accuracy when the morphology is static, and parameter accuracy when the morphology is changing. The accuracies of the most common indices in this field (the Conduction Index, and the T/QRS ratio) were determined for different levels of simulated noise, and their values demonstrated for data previously recorded from the fetal scalp. Errors as large as 0.3 in the CI and 0.05 in the T/QRS suggested that in the clinical environment, an indication of the accuracy of each index ought to be displayed, and this may be estimated from the measured level of noise. Furthermore, this analysis system allows the direct comparison of both indices. Finally, in order to design a more effective front-end filter, it is important to be aware of the frequency content of the underlying FECG. The Integral Pulse Frequency Modulation (IPFM) model, combined with Pulse Amplitude Modulation (PAM), was used to estimate realistic frequency components within the FECG signal. The effects of filtering could then easily be modelled to show the distortion of both the FECG and any parameters taken from it. For a FECG frontend filter, distortion was found to be insignificant provided that, above 1 Hz, both the gain remained constant and there was no phase-distortion.

Computational and mathematical models have become increasingly important and have contributed to significant advances in our understanding of complex biological systems. We developed a mathematical model to characterise the expression profile of transmembrane electrogenic proteins of excitable cells. The cell of interest is the myometrium smooth muscle cell, which is the principal unit of electrical activity in the uterus. These cells remain quiescent throughout most of gestation, whereas just prior to and during labour they are able to generate spontaneous action potentials. A more detailed and comprehensive characterisation of these cells, in comparison to previous models, would furnish an appropriate tool for the development of therapeutics to manage preterm birth and other perinatal problems associated with uterine contractility, such as postpartum haemorrhage. The "conductome" can be defined as the totality of ion channels and ion transporters expressed by an electrically active cell, i.e., a list specifying the cell surface density and oligomeric composition of each of these species. Gene expression techniques can accurately survey the complete set of all mRNA species encoding electrogenic proteins (e.g., subunits of channels). The conductome is constrained by this transcriptome, but the link between the two is complicated by the facts that (i) presence of an mRNA species does not necessarily imply the presence at the transmembrane proteomics level; and (ii) subunits can combine in various ways to give rise to conducting channels with different properties. Every individual potential oligomeric channel complex was represented as a mathematical model on the basis of biophysical data taken from the literature; these data were obtained mainly using heterologous expression systems. We investigate the possibility of combining the behavioural information of the action potential with the detailed molecular data of the transcriptome. The general problem is that electrical behaviour does not necessarily lead to a unique solution. The question addressed here is to what extent the additional information provided by transcriptomics helps to constrain the solution space. We develop and apply a method to characterise the functional redundancy of electrically active cells. We use mRNA sequencing to determine which electrogenic species the cell is capable of expressing, combined with a least-squares parameter estimation procedure to determine the conductome from electrophysiological data. Moreover, we estimate the parameters associated with the gating kinetics from published data, so that the only remaining free parameters are the surface densities of the species on the list defined by the transcriptomics analysis.

Introduction: The human endometrium undergoes cyclical changes of proliferation, differentiation and shedding. This cyclical process has been described as an inflammatory process. Menstrual abnormalities account for the morbidity of a large population of females in their reproductive age. Aberration in endometrial angiogenesis has been implicated in the mechanism of heavy menstrual bleeding (HMB). Although the precise mechanism for control the endometrial neoangionesis is not fully understood, vascular endothelial growth factor and other cytokines such as cyclooxygenases, prostaglandins, interleukin -8 and leukocytes have been implicated in both endometrial pathologies and angiogenesis dysregulation. In addition, heavy menstrual bleeding results from upregulation of the expression/synthesis of these local markers. Uterine fibroids are the most common benign tumor affecting the female reproductive tract. Heavy menstrual bleeding is the main presenting complaint of women with uterine fibroids. However, the mechanism by which uterine fibroids cause heavy menstrual bleeding has not been elicited yet. Therefore, the mechanism of action of different available treatments for this condition, including uterine artery embolisation is unclear. This thesis is based on the hypothesis that a) uterine fibroid changes the physiology of endometrium and we aimed to find out whether these markers work in a different way in heavy menstrual bleeding in those with uterine fibroids and those without., In addition I we wished to study whether uterine fibroid upregulate these local markers in heavy menstrual bleeding, whereas uterine artery emolisation down-regulates them. Methods: This thesis describes the use of endometrial samples, taken with a Pipelle sampler, collected from women with heavy menstrual bleeding both with uterine fibroids and also with normal uteri, to estimate the difference in the endometrial expression of the factors likely to be involved in the control of menstrual bleeding between the two groups. Results: The study found no differences between the expression of both either proteins or mRNA for the cytokines under investigation By using endometrium, myometrium and different types of fibroid tissue collected from women who had hysterectomies with the complaint of heavy menstrual bleeding, there was higher expression of VEGF, COX-2, PGE2 and IL8 proteins in fibroid than myometrial tissue. However, the level mRNA of expression for VEGF, COX-1, COX-2, IL8 and EP2 showed no differences between myometrial and fibroid tissue. In the same group, endometrial expression of these markers for women who had no hormonal therapy before operation compared with that for women who received gonadotropin releasing hormone agonists (GnRH), higher expression of VEGF mRNA in women who had GnRH agonists than those who had no any hormones. In fibroid tissue, GnRHdownregulated the expression of VEGF protein and other cytokines compared with those not on any hormonal therapy. In addition, the estimated serum levels of these factors, indicating a higher level of IL8 in the GnRH group than in the other group. Conclusion: It seems that theses markers play a role in HMB mechanism in both uterine fibroid and normal uteri group in same manner. In addition, they have a fundamental role in the growth of uterine fibroids as well.

Background: Young women with Polycystic Ovary Syndrome (PCOS) may have increased measures of cardiovascular risk. It is difficult to determine how much of this risk is due to PCOS itself and how much is due to obesity and insulin resistance,which are common in PCOS and are themselves associated with greater cardiovascular risk. Aims and Methods: The study aimed to determine if arterial stiffness, carotid intima-media thickness and diastolic dysfunction were increased in young women with PCOS independently of the effects of obesity. A cross-sectional study of women with PCOS and healthy volunteers aged 16-45 years was undertaken. Subjects had a comprehensive assessment of body composition (including computed tomography assessment of visceral fat), measurements of arterial stiffness (aortic pulse wave velocity; aPWV), common carotid intima-media thickness (ccIMT), diastolic function (longitudinal tissue velocity; e’:a’) and metabolic measures including an oral glucose tolerance test to assess insulin area under the curve (IAUC), a marker of insulin resistance. Results: After adjustment for age and body mass index, PCOS subjects had greater insulin response (IAUC) following glucose challenge (adjusted difference [AD] 35900 pmol min/l, P<0.001), higher testosterone (AD 0.57 nmol/l, P<0.001) and high molecular weight adiponectin (AD 3.01μg/ml, P=0.02) than controls. There were no significant differences in aPWV (AD -0.13m/s, P=0.33), ccIMT (AD - 0.01mm, P=0.13) or e’:a’ (AD -0.01, P=0.86). After adjustment for age, height and central pulse pressure, aPWV and e’:a’ were associated with log visceral fat and IAUC. After adjusting for log visceral fat, the relationships between aPWV or e’:a’ and IAUC were only party attenuated. There was no relationship between cardiovascular measures and adiponectin or testosterone. Conclusions: Insulin resistance and central obesity are associated with subclinical dysfunction in young women, but a diagnosis of PCOS does not appear to confer additional risk at this age.

The study investigated the cost-effectiveness of caesarean section (CS) as the major component of Emergency Obstetric Care (EMOC) in a humanitarian context. Research was conducted from December 2007 until June 2008 in Bunia, in the north-east of the Democratic Republic of Congo. Methods A case-control study explored the factors determining whether a woman had a CS or a vaginal delivery. Cases (n=178) were randomly selected from women who had delivered by CS. Controls (n=180) were women who had delivered vaginally within two weeks of a case and were matched by place of residency. Face-to face interviews in the local language used a structured questionnaire about obstetric and socio-economic factors. Obstetric care was assessed during repeat visits to health structures using checklists. Provider cost of CS was calculated for four hospitals, of which one provided free emergency healthcare. Information about cost allocation to CS was collected from hospital managers, maternity staff, and administrators. Costs were verified with local entrepreneurs, international organisations and UN agencies. The social cost of maternal death was discussed in focus groups, which also obtained user cost information additional to the data from the case-control study. Results CS constituted 9.7% of expected deliveries in the Bunia Health Zone. During the study period, the humanitarian hospital performed 75% of all CS. There were no elective CSs in the study sample. The study found no evidence of obstetric surgery for non-medical reasons. Previous CS and prolonged labour during this delivery were the strongest predictive factors for CS. The risk increased with age of the mother and decreased with the number of children alive. Fifteen obstetric deaths were reported to the research team, three among them were women who had a CS. After adjusting the observed number for missed pregnancy-related and late post-partum deaths, the estimated number of maternal deaths avoided by humanitarian EMOC, compared to expected mortality without additional services, ranged from 20 to 228. Compared to recent estimates for the DRC, perinatal deaths avoided ranged from 237 to 453. Cost-effectiveness was expressed as cost per year of healthy life expectancy (HALE) gained. The estimated cost of adding one year of HALE by providing CSs in a humanitarian context ranged from 3.77 USD to 9.17 USD. Comparison of the cost of EMOC and the social cost of maternal death was complicated by the existence of local customs such as “sororate”. The user capacity to pay for health insurance was found to be low. Conclusion Caesarean sections as part of humanitarian assistance were cost-effective. To keep EMOC accessible during and following the transition from emergency relief to development, a change in the national financing policy for health services is advisable.

Recurrent miscarriage (RM) is stressful. One reason for this is because no causes can be found for the pregnancy loss in the majority of cases. Focus has been on the endometrium which undergoes decidualisation in preparation for implantation. Any problems in the finely organised interactions between the endometrium and invading trophoblast cells may contribute towards a miscarriage. Immunological mechanisms are thought to be one of the pathways involved as there is the need of maternal adaptation of her immune response to the semi-allogenic developing embryo. Uterine natural killer (uNK) cells are the most abundant in the endometrium during the window of implantation. They interact with trophoblast cells, and are involved in vascular remodelling, an important step in implantation. Hence, they have a biological plausibility of playing a major role in RM. Both peripheral NK (pNK) and uNK cells tests have been developed as assessments of immunological causes of RM. A systematic review performed showed inadequate evidence for both pNK and uNK cells tests as markers for adverse pregnancy outcomes. There were only twelve studies, with 446 patients reporting pregnancy outcomes. There was no accepted consensus of normality and methodology for analysing NK cells. The conclusion was the need for well-designed studies to assess the role of NK cell tests as a clinically useful marker for screening. This led to the conduct of the pilot phase of a RCT of prednisolone in early pregnancy in women with idiopathic RM and raised uNK cells density. The main aim of this trial was to assess feasibility of recruitment and tolerability of prednisolone. Secondary clinical outcomes included live birth, types of miscarriage, miscarriage karyotype, gestational age at delivery, birthweight and pregnancy complications (eg: pre-eclampsia, gestational diabetes, fetal abnormality, stillbirth, IUGR). 160 women were screened for uNK cells density and 40 were randomised, despite the majority (85%) desiring prednisolone if given a choice. There was a trend towards improved live birth rate with prednisolone treatment but this was not significant. There were equal numbers of biochemical, sac and fetal pregnancy losses in both groups. All completed treatment with main reported side effects in the prednisolone group of insomnia. There were no pregnancy complications. The analysis of uNK cells was found to be very time consuming. To accommodate potentially large numbers who will be screened in the definitive trial, an alternative, quicker and equally accurate method of analysing uNK cells was developed using the colour deconvolution and area measurement plug-ins of a public domain image analysis package, Image J. Women supported this trial. Randomisation was acceptable. The prednisolone was safe. UNK cell density is a valid biomarker of severe outcomes. There was a trend towards improvement in live birth rates. This trial paves the way for the development of an endometrial based test to screen for the subgroup of women with RM that could potentially benefit from individualised treatment.

The extensive assessment of bull’s reproductive potential prior to breeding is highly important and includes examination of general physical soundness, external and internal genitalia and semen quality. Breeding success depends on the efficient use of bulls with high breeding value but simultaneously semen quality imposes restrictions on the use of these bulls in AI. Several techniques have been devised to assess quality of either fresh or frozen-thawed semen. Among a variety of traditional parameters sperm concentration, sperm raw and post-thaw motility and sperm morphology are commonly used for routine semen assessment in the laboratory. In this study, we investigated differences in sperm metabolic activity relative to their motility that may reflect better the fertility of bulls from their non-return rates (NRRs). To investigate the relationship between mid-piece length and fertility of bovine spermatozoa, sperm biometry was performed on ejaculates obtained from 34 bulls representing six breeds: Holstein (yearlings and mature), Friesian, Belgian Blue, Aberdeen Angus, Charolais and Limousin. Significant differences (P<0.01) between ejaculates were found in 9/34 bulls, as well as differences (P<0.001) between individual bulls within the same breed. The average mid-piece length for Aberdeen Angus was 13.35μm, for Belgian Blues and Limousin around 13.8μm, and for Charolais 13.68μm: for dairy breeds (Holstein and Friesian) it was about 13.4μm. The mean value of mid-piece length for breed was compared with their 49 day non-return rate; a negative correlation was found in the dairy breeds, while in bulls from beef breeds this correlation was positive but very low: the small numbers of bulls involved prevented meaningful statistical relationships being established. To differentiate live and dead sperm and non-sperm-specific particles, a flow cytometry method was developed by labelling sperm with JC-1 and propidium iodide (PI) dyes and to determine maximum mitochondrial membrane potential (ΔΨm) at minimum incubation. This method entailed setting regional and logical gates to exclude dead sperm and other non-cellular components from live sperm present within an ejaculate. It was confirmed that spermatozoa of both fresh and frozen-thawed semen exhibited maximum high:low ΔΨm ratio after 40 min incubation. Flow cytometric dot plots of analyses of fresh and frozen-thawed spermatozoa incubated with JC-1 could identify a unified sperm population of membrane-intact cells, each population characterised by both low and high ΔΨm but to varying degrees suggesting that this flow cytometric method simplifies the determination of mitochondrial membrane potential using JC-1. This method serves two purposes: using this method, one could able to evaluate sperm ΔΨm as well as the proportion of live:dead. Changes in mitochondrial structure and integrity appear to be an important component associated with sperm motility and reduced fertility. The ΔΨm was assessed using JC-1 and PI in the presence of glycolytic and respiratory inhibitors. Mean high ΔΨm was significantly greater for control compared to the treatments in fresh and frozen-thawed semen. In samples treated with valinomycin (VAL) and iodoacetamide (IAM) ΔΨm was lowered significantly. The proportion of sperm with a high ratio of high:low ΔΨm was higher in control and 2-deoxy-D-glucose (DOG) treated samples representing more active mitochondria: in samples treated with VAL and IAM the ratio was reduced, representing loss in activity of mitochondria. Cryopreservation significantly decreases high:low ΔΨm ratio in control suggesting that lower mitochondrial activity may be associated with oxidative stress produced by reduced antioxidant levels due to the freeze/thaw cycle. The relationship between ZO2 (µl oxygen consumed /108 spermatozoa/hr) and mitochondrial function was assessed in fresh and frozen-thawed semen. Sperm oxygen consumption was greater in fresh compared to frozen-thawed semen. Insignificant positive correlations existed between ZO2 and ratio of high:low ΔΨm in fresh (r=0.82) and frozen-thawed (r= 0.49) semen suggesting that the ΔΨm measured in this way by flow cytometry can be used as an indicator of ZO2. Finally, the metabolic pathways by which spermatozoa produce energy to support their motility were investigated in fresh and frozen-thawed semen diluted in media containing glycolytic and respiratory inhibitors. Total and progressive motilities were not significantly different in sperm incubated with DOG and VAL but decreased significantly with IAM compared to control. This indicates that sperm can maintain a similar degree of motility when generating their energy exclusively from either glycolysis or mitochondrial activity. IAM significantly lowered sperm motility as well as mitochondrial activity (as described above) and was found to be an inhibitor of both glycolysis and respiration possibly linked with either modification of mitochondrial cysteine and/or glutathione levels. Sperm are considered in a state of hyperactivation/capacitation when their amplitude of lateral head displacement (ALH) increases and path straightness (STR) and linearity (LIN) decrease. In the present study higher ALH and lower STR and LIN were observed when spermatozoa were dependent on mitochondrial energy (DOG), whereas these estimates were reversed when they were on glycolytic energy (VAL) indicating that sperm hyperactivation and capacitation are associated with mitochondrial function. There was a positive correlation of sperm progressive motility, ZO2 and high:low ΔΨm ratio with bull NNRs suggesting that these sperm characteristics may be useful for predicting bull fertility. Furthermore sperm mid-piece length was significantly correlated with sperm average curvilinear velocity and amplitude of lateral head displacement. Since the mitochondria are localized on the sperm mid-piece, it is likely that its energy may contribute in high sperm velocity and also hyperactivation that helps sperm disengagement from oviduct epithelium and positioning at the site of fertilization.

Over 5 million babies have been born as a result of IVF procedures. Worldwide, over 1 million cycles of IVF are performed annually. The IVF procedure involves ovarian stimulation with the purpose of developing multiple follicles and maximising the potential oocyte yield. As a consequence of high oestradiol levels produced during treatment and the use of GnRH agonists or antagonists, a luteal phase deficiency results. This phenomenon is associated with reduced implantation potential and suboptimal conditions for maintenance of early pregnancy. Luteal support in the form of progesterone or HCG has been demonstrated to improve pregnancy rates after IVF. A number of luteal support protocols have been investigated with progesterone the most commonly used drug. The optimum duration of luteal support has yet to be defined. With no agreement in clinical practice evident, the reported use of progesterone ranges from withdrawing luteal support at confirmation of biochemical pregnancy to continuation beyond 12 weeks gestation. Whilst luteal support is considered a very important aspect of IVF treatment, there is very little evidence to support an optimum duration of use. The DOLS trial is a prospective randomised double blind placebo controlled trial investigating the effect of additional luteal support beyond confirmation of pregnancy test after assisted conception. Four hundred and sixty seven patients were randomised after confirmation of biochemical pregnancy to receive a further 8 weeks of vaginal progesterone or 8 weeks of placebo. Summary results were to include a primary outcome defined as viable pregnancy at 12 weeks gestation, whilst secondary outcomes were to report on live birth rates, pregnancy associated complications, neonatal outcomes, effect on first trimester serum screening and effect on uterine artery Doppler velocity. The DOLS trial reported no difference in pregnancy outcome at 12 weeks gestation, with 167/228 (73.3%) women randomised to the extended luteal support treatment arm having a confirmed viable intrauterine pregnancy compared with 167/233 (71.7%) women randomised to the placebo arm of the trial; adjusted risk ratio 0.97 (95%CI 0.87 to 1.09). Similarly live birth rates were not different between the treatment groups; 71.1% versus 70.4% respectively. No effect of extending luteal support beyond positive pregnancy test was observed in reference to complications of pregnancy, neonatal outcome, uterine artery Doppler velocity or antenatal screening outcome. In conclusion, we have confirmed that continuing luteal support using progesterone beyond confirmation of biochemical pregnancy offers no benefit in terms of pregnancy outcomes. However the extended use of progesterone until 12 weeks gestation does not confer harm. We suggest that all clinics worldwide should consider offering luteal support no further than positive pregnancy test, at which point it can be safely withdrawn without compromising live birth rates and reducing treatment burden.