Philosophiae Doctor - PhD / This study is located in the fourth-year obstetrics curriculum that undergraduate medical students at the University of Cape Town, South Africa, traverse, and in which they are initiated into the knowledge and skills of practical obstetrics practices in local birthing facilities. I investigate student learning and what contributes to students being rendered in/capable when they find themselves immersed in the high levels of prevailing injustices to women in labour. Disrespect during the intrapartum period is a local as well as global problem which has actually reached epidemic levels. Drawing on the theoretical frameworks of posthumanism and feminist new materialism, and using post-qualitative inquiry and non-representational methods, I put forward a novel perspective for interrogating responsibilities in terms of students’ ability to respond to unjust practices they observe, I discern what matters for student learning, exploring the troubled practices that emanate through/with/from the curriculum-student relationships in the past/present, and what it means for the future. Assemblage thinking provides a relational tool to understand the impact of the curriculum, assessment processes and other materialising forces that have agency as students are becoming-with human and more-than-human bodies. An initial survey was followed up with interviews and focus groups with students, midwives, educators and administrators. My study revealed hidden aspects of student engagement with their curriculum in obstetrics. What emerged was that students are entangled in a mesh of forces influencing their ability and capacity to respond to the injustices they witness. These forces arise from the discursive and material practices and the in-between relationships that are generated in the learning processes. The study also brought to the fore the intensive forces of affect that appeared to be obfuscated in terms of students’ response-abilities. My findings foreground how reciprocal relationships matter and that a relational ontology can provide helpful insights to engage with responsibility, response-ability and social justice. Students’ capacity to respond to the injustices they witness is limited by multiple forces that include the curriculum itself and other materialising forces generated, for instance by floors, beds, curtains and the student logbook. Time is also a crucial issue amidst the tensions emerging in the complex and risky process of birthing. What matters to students, such as their assessment needs, appears to undermine their efforts to offer care and to promote social justice. Affect plays a powerful part in shaping students’ actions, yet there are few opportunities for acknowledgement of affect. I used drawings as data-in-the making. The process of drawing contributed an extra material force to the study illuminating the power of an affective pedagogical approach for fostering students’ capability to respond to injustice. This socially just pedagogy as well as classroom performances and online collaborative engagement contributed to a collective effort to engage with obstetric disrespect in an innovative and empowering manner that gave voice to students’ experiences and the emerging forces. My study contributes to the field of medical education by opening up a relational perspective to issues of social justice and responsibility that moves beyond individualist and human-centred conceptions of student learning. Through a relational ontology, students’ clinical encounters can be conceived as enactments of the multiple prevailing forces. Each moment matters.

The primary aim of the present study was to compare mothers' reactions to obstetrical interventions and procedures and obstetricians' perceptions of these. The sample population consisted of one hundred and forty seven white, married, English-speaking mothers and a group of fifty three obstetricians practising in trie Johannesburg area. Questionnaires, developed for both groups, were administered postally to obstetricians and in hospital within the first post-partum week to mothers. Perceptions of interventions occurring in the ante-natal period and during the three stages of labour were explored. Reactions to psycho-social and hospital procedures were also obtained. Median and modal ratings of these events were calculated for both samples. The data were analysed using the Median test to compare the groups and Fisher's exact probability test to determine significant differences. Using a significance level of one per cent, several significant findings emerged. Results suggested that, in general, obstetricians rated mothers' experiences more negatively than did the mothers themselves, These findings were discussed in the light of available research and literature in the area

The purpose of this study was to ascertain the effects of music and relaxation techniques on pain and anxiety of gynecology patients undergoing colposcopy, punch biopsy, or cryosurgery. / Dependent variables measured for control and experimental subjects were pulse rate, respiratory rate, behavioral observations, and self reports of pain and anxiety during and twenty-four hours following the procedure. / Graphic analysis of the data revealed differences in scores between groups which were then statistically analyzed using a Mann-Whitney U test. / The results of the study showed a significantly higher respiratory rate (U = 1.5, n$\sb1$ = 3, n$\sb2$ = 5, $\alpha$ =.05) and behavioral observation score (U = 2.5, n$\sb1$ = 4, n$\sb2$ = 5, $\alpha$ =.05) for the control group during punch biopsy. Control subjects rated higher on pulse rate, respiratory rate, behavioral observations, and anxiety reports over all during the procedure, however these scores were not significantly higher than those of the experimental group. / Source: Masters Abstracts International, Volume: 29-04, page: 0655. / Adviser: Jayne M. Standley. / Thesis (M.M.)--The Florida State University, 1991.

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Insulin resistance and androgen excess are the cardinal phenotypic features of polycystic ovary syndrome (PCOS). The severity of hyperandrogenism and metabolic dysfunction in PCOS are closely correlated. Aldoketoreductase type 1C3 (AKR1C3) is an important source of androgen generation in human adipose tissue, and may represent a link between androgen metabolism and metabolic disease in PCOS. We performed integrated in vitro studies using a human preadipocyte cell line and primary cultures of human adipocytes, coupled with in vivo deep phenotyping of PCOS women and age- and BMI-matched controls. We have shown that insulin upregulates AKR1C3 activity in primary female subcutaneous adipocytes. AKR1C3 mRNA expression increased with obesity. Androgens were found to increase lipid accumulation in human adipocytes. In clinical studies, androgen exposure induced relative suppression of adipose lipolysis in PCOS women, supporting a role for androgens in lipid accumulation. Androgens were detectable in adipose fluid from PCOS women, and correlated with systemic markers of androgen metabolism. Using comprehensive in vivo, ex vivo, and in vitro techniques, we have shown regulation of adipose androgen generation through AKR1C3, with evidence of a vicious circle of hyperinsulinaemia, adipose androgen generation and lipid accumulation. These data identify AKR1C3 as a promising therapeutic target in PCOS.

Fetal chromosomes are examined conventionally by G-band karyotyping. More recently Prenatal Chromosomal Microarray (CMA) has been used to look for fetal chromosomal abnormalities. Advantages of CMA include its higher detection rate. Disadvantages include its detection of Variants of Unknown Significance (VOUS). I recruited a prospective cohort of 243 women with structural abnormalities on fetal ultrasound scan. A 1Mb targeted BAC array was performed in addition to G-band karyotyping. In 62 cases from this cohort an additional higher resolution 60K oligonucleotide array was used. A health economic analysis, by use of a decision tree, was performed. Finally qualitative work determined women’s feelings about testing. The 1Mb BAC cohort found a 4.1% increase in fetal chromosomal abnormalities over karyotyping, with a low detection rate of VOUS (0.4%). The 60K sub-cohort noted an extra 4.8% pathogenic chromosomal anomalies but, in addition, a 13% increase in VOUS. The health economic analysis indicated that when CMA is £360 (per test) and the Willingness To Pay (WTP) for a “positive diagnosis” is £9768; then CMA is cost effective over karyotyping. Qualitative analysis showed that couples were keen for as much information as possible. They struggled to recall and retain information conveyed at the time of the testing.

The ovarian follicle is the major site of sex steroid production in females, hormones that are crucially required for normal ovarian function and female reproduction. The biosynthesis and metabolism of androgens by individual follicles throughout development has been difficult to study because androgens and androgen precursors are structurally similar molecules present in low concentrations. Androgens have dual dose-dependent effects on folliculogenesis, with reduced or exaggerated levels of androgens being deleterious for follicle development. Few studies have shown the whole spectrum of androgen action using a single experimental model. Here we employed tandem mass spectrometry to measure sex steroid production by murine follicles, cultured in an alginate encapsulated, 3-dimensional model. We showed developmental stage-dependant FSH-stimulated androgen and oestrogen secretion. When follicles were cultured in the presence of non-aromatisable 5-dihydrotestosterone, endogenous androgen production decreased. Following exposure to the universal sex steroid precursor dehydroepiandrosterone, high androgen generation was achieved by immature follicles. We described androgen receptor-mediated growth-promoting effects of androgen supplementation in developing follicles. However, when androgen exposure was gradually increased, we first observed suppression of oocyte development, followed by stagnation of follicle growth. These data provide the rationale for androgen treatment in women with low ovarian reserve, but call for caution as over-replacement might cause harm to oocyte quality. Furthermore, this study describes mechanisms which might contribute to the follicular developmental arrest that is observed in androgen excess conditions such as polycystic ovary syndrome.

The aim of this PhD thesis was to produce research that could inform and benefit clinical practice by exploring the application of basic science and clinical research methodologies to disorders in obstetrics and gynaecology. Chapter 1’s investigation of endometriosis is the first to 1) report detailed genetic mapping of endometriosis-associated ovarian cancer, 2) report the existence of micro-LOH (loss of heterozygosity) in ovarian endometriosis through a SNP 100K DNA array. Chapter 2 explores the efficacy of interventions to treat menstrual abnormalities using clinical cohort studies. Furthermore, Chapter 2 highlights how negligence in female sterilization failure may be mathematically (Bayesian) modelled. Chapter 3 explores the value of systematic reviews for preventing preterm delivery and use of LNG-IUS (Mirena coil). The clinical guidelines published in Chapter 4 include: vaginal birth after previous caesarean, ectopic pregnancy, safe laparoscopic entry and minimising risk of sterilisation failure. The thesis concludes (Chapter 5) by suggesting strategies to augment the research methodological approaches evaluated in this thesis in order fulfill the aim of benefitting clinical practice. Work included in this PhD thesis has been orally presented at international conferences, published in peer-reviewed journals, and published as a national clinical guideline by the Royal College of Obstetricians and Gynaecologists, UK (RCOG).

Hypertension is one of the most common medical conditions complicating pregnancy, with significant implications on maternal and perinatal morbidity and mortality. Abnormalities in placentation have been implicated as the primary pathology responsible for the development of hypertension during pregnancy and its effects such as pre-eclampsia and eclampsia. With advancing research, the focus is now gradually shifting towards abnormalities in the maternal vasculature, including endothelial damage/dysfunction and impaired repair as a probable cause for this, with the latter also being implicated in the development of cardiovascular disorders in later life in these women. Hypertensive disorders occur in 6-8% of pregnancies. They also determine and influence the development of cardiovascular disease (CVD) in the mother in later life. Hypertension, obesity, metabolic syndrome and CVD are commoner in women with pre-eclampsia and preterm deliveries, whereas the risk of cerebrovascular disease is much higher in those with recurrent spontaneous abortions. This research thesis is a study of the various processes occurring in the maternal vasculature, including angiogenesis, apoptosis, endothelial damage and regeneration/repair, the extra-cellular matrix and the haem oxygenase systems, the abnormalities that occur in them and their associations with hypertensive disorders of pregnancy and their complications.

Thyroid hormones (THs) are important for fetoplacental development. Human intrauterine growth restriction (IUGR) is associated with malplacentation and reduced fetal circulating concentration of THs. The expression of the plasma membrane TH transporters MCT8, MCT10, LAT1, LAT2, OATP1A2 and OATP4A1 was characterised in human placental biopsies across gestation. The protein expression of MCT8 was increased in samples from severe IUGR compared with normal pregnancies. In vitro, triiodothyronine (T\(_3\)) decreased survival and increased apoptosis of IUGR compared with normal cytotrophoblasts, which was associated with increased MCT8 expression. In normal cytotrophoblasts, MCT8 upregulation decreased survival, whilst MCT8 silencing increased survival independently of T\(_3\). In the extravillous trophoblast-like cell line, SGHPL-4, T\(_3\) resulted in a significant increase in cell invasion when MCT8 was upregulated. Contrary to cytotrophoblasts, silencing MCT8 decreased apoptosis in SGHPL-4s independently of T\(_3\). In mice, fetal to placental weight ratio was decreased in male MCT8-null compared with wild-type embryos. These findings support the hypothesis that THs have an important role in fetoplacental development and that IUGR is associated with changes in TH transport and responsiveness of the placenta. Furthermore, they highlight the importance of MCT8, which impacts on placental cells via both T\(_3\)- dependent and independent mechanisms.