Dissertations / Theses on the topic 'R Medicine (General) : RG Gynecology and obstetrics'

Time-lapse system(s) (TLS) have, potentially, two benefits over standard incubation systems; an undisturbed culture environment and an enormous volume of images of the embryos within them. The current research aimed to determine if a TLS could provide a comparably stable culture environment compared to a standard incubator measured as pH, osmolality and treatment success rates. Second, the hypothesis that patient, treatment and environment specific embryo selection algorithms (ESAs) are required to improve the efficacy of a TLS as an embryo assessment tool was tested. A TLS was shown to provide a comparably stable environment when compared to a standard incubator in terms of pH and osmolality. In addition, using a strict matched-pair design, embryos cultured in a TLS resulted in a significantly higher implantation, clinical pregnancy and live birth rates. It was also concluded that, of six published ESAs, none performed with clinically relevant predictive capabilities when applied to the same cohort of known implantation embryos. Owing to this, the identification of five abnormal division events as significantly reducing an embryos implantation potential was performed providing an easily adopted, clinically relevant means to deselect embryos cultured in a TLS. A regression analysis found a number of treatment and patient parameters having a significant effect on crucial morphokinetic parameters, although no systemic effect was observed. Finally, an interim analysis of a sibling oocyte study of three, commercially available culture media revealed significant differences in the time of embryo compaction as well as embryo quality and utilisation. Together, these results highlight that a TLS provides a stable culture environment and leads to increased implantation, clinical pregnancy and live birth rates. It is also likely that the patient, treatment type and environment can significantly alter an embryos morphokinetic profile and specific ESAs are required to unlock the true potential of time-lapse technology.

This thesis examines the diffusion of obstetric ultrasound technology in Scotland, from the early 1960s through to the end of the 1980s. Although the origins of obstetric ultrasound can be traced to 1955, and the pioneering work undertaken by Professor Ian Donald and his colleagues in Glasgow on the gynaecological applications of ultrasound, it was not until the early 1960s that the pathologies associated with pregnancy were directly investigated. Over the next thirty years, the technology underwent a number of significant transformations - in technical design, application and use, and organisation. The main focus of this thesis is on the uptake and implementation of obstetric ultrasound in new locations across Scotland, and on the dynamics of change associated with its use in clinical practice. U sing a case-study approach which centres on four individual Scottish hospitals, this thesis traces the complexity and heterogeneity evident in the diffusion of this technology. The definition of 'technology' employed in this thesis is three-dimensional - comprising of technical, cognitive and interactive/performative dimensions. Here it is argued that all three of these dimensions compose a technology, and that all three are open to adaptation and change, thus essentially changing the nature of the technology itself. This is highlighted through a comparative account, focussing on site-specific differences in the development, organisation and use of the technology. The evidence presented here has been drawn from a variety of historical sources. The recollections of a number of actors involved in the introduction, use and development of obstetric ultrasound in Scotland, as well as of women who experienced ultrasound during their pregnancies, have been collected using semi-structured interviews. To this oral history has been added information from a variety of archival sources held at the British Medical Ultrasound Society's Historical Collection (housed at The Queen Mother's Hospital, Glasgow). These include specialist professional journals, correspondence relating to ultrasound, manufacturers' literature, draft versions of key published papers, transcripts of interviews with prominent actors in the field and material donated by ultrasound workers across Scotland. Furthermore, the Collection also boasts a wide array of visual information (including pictures of various types of ultrasound equipment and images generated from them) and artifacts (ultrasound machines dating from the 1950s through to the 1980s). These, less conventional, historical sources are also employed in this thesisIn this comparative study of the diffusion of ultrasound, three related arguments are presented. Firstly, it is argued that innovation and diffusion are not mutually exclusive terms or periodising concepts, but are interwoven processes and forms of activity. The diffusion of obstetric ultrasound did not signal the 'end' of innovation, but merely the point at which new actors in new locations undertook it. Innovation is a crucial component in adapting a technology to new circumstances, users or contexts and thus it is argued that innovation and diffusion are inter-related, mutually dependent forms of interested human action. Secondly, obstetric ultrasound is characterised in this thesis as an emergent phenomenon, shaped by both technical and social factors. When the development of this technology is examined in a variety of historical and spatial contexts, it is evident that the form it takes is determined by the interplay of social factors (professional relationships and interests, actors interpretations of technology, etc.) and more technical or material factors (the way a machine responds to new demands or itself requires certain types of human or social response). Thus a complete account of the diffusion of obstetric ultrasound necessitates an approach that considers both social and material influences on technological change. Finally, this thesis explores the significance of site-specific local arrangements for the shaping of obstetric ultrasound. Interactions with technology take place within specific historical and locational settings. The specific character of each setting can affect the nature of inter-professional relationships, the organisation and administration of the technology, the characteristics of the patient population, and so on. Thus, the diffusion of obstetric ultrasound and the form that it takes in each new location are partly shaped by the way in which the technology interacts with new environments

Objective To undertake Health Technology Assessment (HTA) in maternal and perinatal medicine for tests and treatment in the areas of pre eclampsia, preterm labour, epilepsy and congenital heart disease (CHD) in newborn. Methods The work undertaken in the thesis is divided into 4 sections: Delphi survey of practice; Systematic review of reviews; Systematic reviews of therapeutic effectiveness; Systematic reviews of test accuracy Results The Delphi survey identified blood pressure to be the best predictor of complications. A significant benefit of progestational agents was observed in reducing preterm delivery before 37 weeks (OR 0.42, 95% CI 0.31 to 0.57). The combined rate of seizure deterioration was 0.40 (95% CI 0.26 to 0.55) in pregnant women with epilepsy on lamotrigine dosage based on serum levels compared to 0.73 (95% CI 0.56 to 0.86) in those managed by clinical features only. The abstracts of 19,500 citations were reviewed to identify the studies of accuracy of tests in pre eclampsia including proteinuria, uric acid, liver function tests, symptoms and blood pressure. The sensitivity and specificity were 0.63 (95% CI 0.39, 83) and 0.998% (95% CI, 0.99, 100) respectively for detecting CHD in the newborn by pulse oximetry. Conclusion Through the HTA of tests and treatment in priority areas of maternal and perinatal medicine, the thesis has led to the generation of clinical recommendation where there was clear evidence of benefit and for further research where there were gaps in evidence.

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).

Restriction of fetal growth and compromise of its wellbeing remain significant causes of perinatal death and childhood disability. There is a lack of scientific consensus about the best strategies for predicting these conditions before birth and thus there is uncertainty about the best management of pregnant women who might have a growth-restricted baby. This health technology assessment thesis used state of the art methods to review 337 studies including 472,544 women. It determined : 1. The accuracy of available tests for predicting small for gestational age infants (SGA) and 2. Compromise of fetal wellbeing and 3. Summarised the effectiveness of available treatments for these conditions. To allow translation of these results into patient care, the diagnostic and therapeutic information was integrated in a model based economic evaluation. This thesis has demonstrated that the tests reviewed have a limited use in screening/diagnosis for SGA/compromise of fetal and neonatal wellbeing when used in isolation. The quality of primary research was variable with recommendations being made particularly for the use of standardised and relevant outcome measures. The decision model and economic analysis identified that an effective, affordable and safe intervention applied to all mothers without prior testing is likely to be the most cost-effective strategy in the prevention of these conditions.

Cervical human papillomavirus (HPV) infection is a very common sexually transmitted disease which is now considered to be a necessary, but not sufficient, cause of cervical cancer. It has been suggested that the association between HPV infection and cervical neoplasia can be exploited to improve the efficiency and effectiveness of primary- and secondary-prevention programmes for cervical cancer. However, whether this aspiration can be realized in practice requires a greater understanding of the natural history of early cervical HPV infection and its role in the acquisition of epithelial abnormalities of the cervix. In this thesis, a longitudinal study of young women who had recently embarked on sexual activity has provided sequential observations on the natural history of cervical HPV infection. This thesis addresses four aspects of this natural history: the association between HPV infection and the proximity of first sexual intercourse to menarche; the association between smoking, cervical HPV infection and high-grade cervical disease; the validation of a neutralising antibody assay and its use in defining the kinetics of the humoral immune response to cervical HPV16 and HPV18 infections; and the analysis of measurements of the viral load of HPV16 and HPV18, and their association with epithelial abnormalities of the cervix

Ovarian cancer is one of the most lethal malignancies and often presents at an advanced stage, resulting in a poor prognostic outlook. Platinum chemotherapy leads to an initial clinical response, however most patients will ultimately relapse and there remains a sub-group who are intrinsically resistant to platinum. I focussed on high grade serous ovarian cancer (HGSOC), the most common subtype of ovarian cancer. The ID8 CRISPR-generated models represented a novel and simple tool to investigate the biology of HGSOC. By using this in vivo model, I aimed to further the understanding of platinum sensitivity in HGSOC by investigating the homologous recombination pathway and the tumour microenvironment. In vitro work showed that sensitivity to PARP inhibitors was clearly correlated with defective homologous recombination but the relationship with platinum sensitivity was more complicated. Using the ID8 derivatives, in vivo cisplatin experiments identified Pten and Nf1 loss to be associated with the worst prognosis with the knockout of Brca1 or Brca2 prolonging survival. A Brca1 mutation in the PALB2 domain compared to the BRCT2 domain was found to be associated with a greater sensitivity to cisplatin. The tumour microenvironment was shown to differ between genotypes and altered with the addition of platinum chemotherapy. Specifically, the loss of Pten was associated with an immunosuppressive microenvironment with increased levels of myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs). The chemokines, Ccl2 and Ccl7 were shown to be significantly increased in the Trp53-/-;Pten-/- genotype. I targeted both the cytokine/chemokine response directly by using a transgenic mouse model (CCR1, 2, 3, 5 receptors knockout) and the PI3K/AKT pathway by using a PI3K inhibitor (p110β) (AZD8186) to attempt to reverse the effect of Pten loss. The transgenic mouse model (GGTACKO) showed encouraging early results with a reduction in MDSCs and TAMs in the knockout mice injected with the Trp53-/-;Pten-/- genotype but a repeat experiment is required before valid conclusions can be made. The AZD8186 in vivo experiment showed a significant reduction in MDSC levels in the ascites following AZD8186 treatment in mice injected with the Trp53-/; Pten-/- genotype and a non-significant decrease in the tumour samples. There was also a reversal in the anaemia previously shown with the loss of Pten and a decrease in Ccl2 and Ccl7 expression. I have used a transplantable in vivo model for HGSOC to investigate potential mechanisms of platinum sensitivity and identified poor prognostic genotypes (Pten, Nf1). I have found Pten loss to be associated with an immunosuppressive microenvironment and highlighted potential therapeutic targets. By targeting the PI3K/AKT pathway I have shown that the effect of Pten loss can be reversed. The next step will be to determine whether this reversal results in a prolonged survival.

The postnatal period is an important and extremely vulnerable time for new mothers and their infants. Research has outlined the considerable extent of maternal physiological and psychological morbidity following childbirth. The underreporting and undiagnosed aspect of this morbidity has also been highlighted. Newborn infants are totally dependent on their needs being met and are also at risk of newborn conditions particularly if they are undiagnosed, for example neonatal jaundice. There is however, mounting evidence regarding the lack of postnatal support from health professionals, with women continuing to report their dissatisfaction with postnatal care. Research into postnatal care is pre-dominantly quantitative and clinically focused. Few empirical studies have examined the meaning women give to their postnatal care experiences. This research aims to generate a deeper understanding of the meanings, and lived experiences of postnatal care. In addition, it aims to reveal future possibilities to enhance women’s postnatal care experiences. Initially, an in-depth examination of relevant literature is undertaken followed by a presentation of the process and findings from a qualitative meta-synthesis. An in-depth exploration of Martin Heidegger’s biography and explication of his philosophy is then outlined. This research is a Heideggerian hermeneutical phenomenological study of Irish women’s aspirations for, and experiences of, postnatal care. Purposive sampling is utilised in this research, which was undertaken in two phases. Phase one involved group interviews over three different time periods (between 28-38 weeks gestation, 2-8 weeks and 3-4 months postnatally), with a cohort of primigravid women and a cohort of multigravid women. The second phase involved recruiting two further cohorts of primigravid and multigravid women who participated in individual in-depth interviews over the same longitudinal period. In total nineteen women completed the study. Thirty-three interviews were held in total. The data analysis is guided by Crist and Tanner’s (2003) interpretative hermeneutic framework. The women’s aspirations/expectations for their postnatal care are represented through three interpretive themes: ‘Presencing’, ‘Breastfeeding help and support’ and ‘Dispirited perception of postnatal care’. In addition, five main themes emerged from the data and capture the meanings the women gave to their lived experiences of postnatal care: ‘Becoming Family’, ‘Seen or not seen’, ‘Saying what matters’, ‘Checked in but not always checked out’ and ‘The struggle of postnatal fatigue’. The original insights from this research clearly illuminate the vulnerability women face in the days following birth. A further in-depth interpretation and synthesis of the findings was undertaken. This philosophical-based discussion drew from the work of Heidegger (1962) and Arendt (1998). Engaging with these theoretical perspectives contributed to a new understanding about why some women within a similar context, have positive experiences of postnatal care while others do not. As such, the very nature that midwives and other postnatal carers are human beings has an influence on a woman’s experience of her care. These carers, in their exposition of ‘being’ have the ability to demonstrate ‘inauthentic’ or ‘authentic’ caring practices. It is those who choose to be ‘the sparkling gems’ that are the postnatal carers who make a difference and stand out from the others. For the women in this study, their postnatal care experiences mattered. While some new mothers reported positive and meaningful experiences others revealed experiences which impacted unnecessarily. The relevance of these findings, recommendations and suggestions for future research are offered.

Regular breastfeeding surveillance is essential to determine to what extent national breastfeeding targets are being met and how breastfeeding practices change over time. There have been irregular infant feeding studies or national surveys carried out in Kuwait so it is difficult to assess secular trends in breastfeeding practices. The objective of the Kuwait Infant Feeding Study (KIFS) was to identify the incidence and prevalence of breastfeeding up to 26 weeks postpartum among a population of women living in Kuwait and to identify the factors associated with the initiation and duration of breastfeeding. A sample of 373 women recruited shortly after delivery from four hospitals in Kuwait completed a structured, interviewer-administered questionnaire and follow-up telephone interview at 6, 12, 18 and 26 weeks postpartum. Multivariate logistic regression analysis was used to identify those factors independently associated with the initiation of breastfeeding and survival analysis was used to examine the duration of breastfeeding. In total, 92.5% of mothers initiated breastfeeding and at discharge from hospital the majority of mothers were partially breastfeeding (55%), with only 30% of mothers fully breastfeeding. Prelacteal feeding was the norm (81.8%) and less than 1 in 5 infants (18.2%) received colostrum as their first feed. Only 10.5% of infants had been exclusively breastfed prior to hospital discharge, the remainder of breastfed infants having received either prelacteal or supplementary infant formula feeds at some time during their hospital stay. At six months of age, 39% of mothers were still breastfeeding but none of the women were fully or exclusively breastfeeding. The median duration of any breastfeeding duration was 13.9 weeks. 2 Breastfeeding at discharge from hospital was independently positively associated with paternal support for breastfeeding and negatively associated with delivery by caesarean section and with the infant having spent time in the Special Care Nursery. Mothers originally from other Arab countries were more likely to initiate breastfeeding in hospital than Kuwaiti mothers. Women whose husbands worked in sales or clerical occupations and Kuwaiti national mothers were at higher risk of early breastfeeding termination. Women whose husband or own mother preferred breastfeeding, breastfed for longer than those women whose husbands or mothers preferred formula feeding or were ambivalent about how they fed the infant. Hospital-related factors including time of first feeds, type of first feed, age of introducing a pacifier and feeding on demand were significantly associated with breastfeeding duration. The results of this study indicate that while breastfeeding is almost universally initiated, very few women achieve the WHO recommendations of exclusive breastfeeding to 6 months of age. The reasons for the high use of prelacteal and supplementary formula feeding warrant further investigation. Data collected in this study will contribute to the limited breastfeeding surveillance data available for Kuwait and inform future public health policy. Hospital policies and staff training are needed to promote the early initiation of breastfeeding and to discourage the unnecessary use of infant formula in hospital, in order to support the establishment of exclusive breastfeeding among mothers in Kuwait.

Extra-welfarist measures are recommended, by decision-makers, for use in economic evaluations. Hence they are commonly used to value outcomes in chronic conditions with episodic symptoms, such as menorrhagia. In menorrhagia, a woman’s perceived change in quality-of-life (QoL) is the measure of treatment success and consequently, the primary clinical and economic outcome is change in QoL. This thesis presents findings of a comparison between welfarist and extra-welfarist approaches to valuing outcomes in menorrhagia, and aims to determine the value of levonorgestrel-releasing intrauterine system (LNG-IUS) compared to usual medical treatment for menorrhagia. Findings from the systematic review demonstrated concerns that extra-welfarist measures may be unsuitable in menorrhagia due to their narrow health-related focus and that results depend on the timing of assessment, given the condition’s episodic nature. The economic evaluation alongside the ECLIPSE trial showed that the extra-welfarist measures, EQ-5D and SF-6D, provide contrasting cost-effectiveness decisions. The welfarist willingness-to-pay (WTP) was shown to capture important aspects of wellbeing that are not captured by these extra-welfarist measures. Similar to SF-6D, the economic evaluation using WTP presented evidence against the use of the decision-maker recommended EQ-5D. It is argued that each measure provides information that should be considered by decision-makers when allocating healthcare resources.

The use of antiretroviral therapy (ART) during pregnancy and lactation has significantly reduced the rate of mother-to-child transmission (MTCT) of HIV. However, pregnancy is known to affect the pharmacokinetics of many drugs, including key antiretroviral (ARV) drugs. In addition, ARV use during lactation raises questions about unintended exposure of breastfed infants to maternal drugs through breast milk. For drugs with significant genetic contribution to observed pharmacokinetic variability, we hypothesised that polymorphisms in drug disposition genes may accentuate or attenuate pregnancy-induced changes and/or breastfed infants’ exposure. HIV positive pregnant women and nursing mothers taking efavirenz (EFV)- or nevirapine (NVP)-based ART were recruited from three hospitals in Benue State, Nigeria. A novel strategy involving a preliminary pharmacogenetic association study was used to investigate the magnitude of pregnancy-induced changes in EFV and NVP pharmacokinetics in women stratified by single nucleotide polymorphisms (SNPs) in disposition genes. EFV apparent clearance (CL/F) was higher and AUC0-24, Cmax and Cmin were significantly lower in pregnant compared with postpartum women. When stratified based on the SNP with the highest predictive power, pregnant women with CYP2B6 516GG genotype were especially at risk. In the NVP cohort, exposure was also significantly lower in pregnant compared with postpartum women. When stratified based on composite CYP2B6 516G > T and 983T > C genotypes, Cmin was below target in most patients with combined CYP2B6 516GG and 983TT during pregnancy and postpartum. Cmin was below target in at least 50% of pregnant women with one or two variant alleles, compared with 0% in postpartum women. The intensive pharmacokinetics of EFV and NVP in breast milk and pharmacogenetic predictors were described for the first time. Breast milk pharmacokinetic parameters of EFV in breast milk differed significantly between patient groups stratified by CYP2B6 516G > T. The median time averaged milk-to-plasma concentration (M/P) ratio was 1.10 (range: 0.57-1.71) and the paediatric dose weight-adjusted exposure index was 4.05% (1.08-13.8). The resulting infant plasma concentration was influenced by CYP2B6 516G > T, highest up to 8 days of age at 1590 ng/mL (190-4631) and decreased by about 90% in the age stratum 9 days to 3 months. NVP AUC0-12, Cmax and Cmin in breast milk were significantly lower in patients with composite CYP2B6 516GG/983TT than those with at least one variant allele. The M/P ratio was 0.88 (0.74-1.2) and paediatric dose weight-adjusted exposure index was 3.64% (1.99-9.88). Infant plasma concentration differed significantly based on CYP2B6 516G > T/983T > C and CYP3A4 20230G > A (*1G), highest in those exposed through both breast milk and post-exposure prophylaxis compared with either alone. A breastfeeding physiologically-based pharmacokinetic (PBPK) model to predict infant exposure to maternal drugs through breast milk was developed and validated, with over 90% of all individual observed data points within the predictive interval. This thesis presents details about five different studies where these findings were observed. Their clinical implications in the context of current knowledge and practice were also explored.

The main aim of this research was to explore the experience of known egg donation in order to identify the psychosocial issues involved. Previous research into known egg donation remains sparse, with the majority of studies focusing on the psychological aspects of treatment, providing largely quantitative information about the practice. In addition to the purely psychological, the current research acknowledges the importance of social factors, highlighting the psychosocial implications of known egg donation for those involved. The study took a hermeneutic phenomenological approach in an effort to understand and interpret participants’ experience of known egg donation through the use of language during interviews. The research was conducted in two distinct phases. During Phase One, semi-structured interviews were conducted with counsellors in UK licensed treatment centres and analysed using a version of thematic analysis. During Phase Two, known egg donors, recipients and the partners of recipients were interviewed in-depth and analysed using a voice-centred relational approach. Following the identification of a number of key themes, the data collected during both phases were synthesized to enable the identification of the psychosocial implications of known egg donation. The main findings highlighted the importance of negotiating relationships before, during and after the donation. Key psychosocial issues identified are: the existence of pressure (both overt and covert) within the donor-recipient relationship, defining and maintaining clear relationship boundaries, involvement of male partners, relationship changes, and a continued renegotiation of relationships in the longer-term. The psychosocial implications identified emphasise the need for counsellors to: adopt a relationally-focused approach within their work, promote the best interests of the families involved, work with all those involved in the donation throughout the donation process and beyond, encourage ongoing discussion surrounding the implications of secrecy and disclosure, and ensure consistency of psychosocial care.

This thesis is a discussion of the ethical issues surrounding the allocation of donated sperm and eggs to patients at fe1iility clinics. It adopts an empirical bioethics approach in which traditional philosophical analysis is combined with the collection and analysis of empirical data in order to ensure that the views of those involved in the field are represented. Following the preliminary philosophical analysis, the second section of this thesis presents the results of a qualitative study, which was undertaken with fertility clinic staff and other relevant professionals such as academics and representatives of patient organisations. The views and ideas that emerged from these data were considered in light of the earlier philosophical analysis, and where relevant, initial conclusions were revised to account for these considerations. The results suggest that the prioritisation of patients based on age, violent history, and health and health behaviours is justified, that allowing conditional and known donations may benefit all patients by increasing the number of donors, and that a national system of allocation may confer similar benefits, as well as being fairer than current, local allocation.