Endometriosis is a chronic inflammatory disease that responds to steroidal manipulation. The gonadotrophin-releasing hormone (GnRH) agonist is the gold standard for the treatment of endometriosis. The levonorgestrel-relasing intrauterine system (LNG-IUS) has been shown in small pilot studies to be an acceptable and effective symptomatic treatment option. The studies in this thesis were in two parts. The first was investigating the mechanisms by which the LNG-IUS was effective in the symptomatic treatment of endometriosis. The symptoms were improved by significant down regulation of estrogen (ER) and progesterone (PR) receptors as well as the reduction in mast cells number present in the ectopic endometrium (P<0.05). The second was a comparative randomized study comparing the efficacy of the LNG-IUS and the GnRH agonist. This was via the ER and PR and the clinical outcome of the patients. The ER and PR were down-regulated by the GnRH agonist (P<0.05) in the ectopic endometrium while the ER, PR-A and the stromal compartment of PR-B were down-regulated (P<0.05) by the LNG-IUS. These were also improvement in the clinical symptoms as seen in the visual analogue scale (VAS) score in both treatment groups (P<0.05). When the concentration levels of Interleukin-6 (IL-6) and Soluble Intracellular Adhesion molecule-I (sICAM-I) in the peritoneal fluid (PF) were compared before and after treatment with the LNG-IUS and the GnRH agonist there was significance difference in IL-6 levels (P<0.05) with the LNG-IUS but not with the GnRH agonist and no differences in the sICAM-1 levels with the use of either medication. In conclusion the LNG-IUS improves symptoms of endometriosis via the down regulation of ER, PR and reduction in mast cells number. The efficacy of the LNG-IUS was comparable to that of the GnRH agonist as evidence by the patients‘ clinical outcome and their effects on ER and PR.

The aim of this research is to examine the abnormal features of uterine growth and development associated with tamoxifen use, to determine if this is due to its failure to replicate all the effects of oestradiol; either inducing or repressing the expression of key paracrine acting regulators of uterine cellular populations or their gene expression profiles, and to examine if such abnormal features could be prevented by the administration of a progestagen-containing levonorgestrel intrauterine device (LNG-IUS) from the onset of tamoxifen treatment for breast cancer. Postmenopausal women were assessed by hysteroscope and ultrasound scanning for uterine volume, endometrial thickness and the presence of endometrial polyps or submucous fibroids before insertion of the LNG-IUS system and after 1 year. The same was done on a control group that were not treated with LNG-IUS. Benign changes in the uterus were histologically related to, (1) steroid receptor isoform, (2) proliferation and apoptosis markers, (3) mesenchymal marker expression and (4), gene expression and pathway profiles, when compared to the oestrogen induced changes of the proliferative phase uterus and the oestrogen deficient, atrophic, postmenopausal uterus. The uterotrophic effects and benign changes induced by tamoxifen were confirmed; LNG-IUS prevented both the uterotrophic effects and formation of endometrial polyps. Additionally, ERα, PRA and PRB expression were increased in tamoxifen endometrium similar to that of the proliferative phase endometrium; ERβ expression was also up regulated in the tamoxifen uterus linking it with tamoxifen associated proliferation. Increased Ki67 and Bcl2, but low BAX expression, in the tamoxifen uteri signified increased proliferation and apoptosis failure, coupled with the unique mesenchymal positivity associated with large endometrial cystic glands, suggested a transitional state tissue, undergoing remodelling with significant gene modulation. This was confirmed with microarray analysis where tamoxifen induced not only “oestrogen genes” but also “tamoxifen only genes” and pathways, revealing some of the mechanism(s) whereby tamoxifen causes uterine growth; some of these changes are oestrogen-like and others are brought out through the direct action of tamoxifen itself.

No description available.

Cryopreservation of unfertilised oocytes for banking or oocyte donation would be a valuable adjunct to reproductive technology. As the mature oocyte contains a temperature-sensitive meiotic spindle, cryopreservation of immature germinal vesicle (GV) stage oocytes, which do not contain the spindle, may be a practical alternative. However, one of the major obstacles to the application of immature oocyte cryopreservation is the difficulty associated with in vitro maturation (IVM) of the thawed oocytes prior to in vitro fertilisation. The cumulus cells surrounding the oocyte are essential to oocyte maturation. Thus the aim was to assess survival and function of both oocyte and cumulus cells post-cryopreservation. Initially, culture conditions during IVM of murine GV stage cumulus-oocyte complexes (COCs) were modified. In the second part of the study, survival (morphological appearance and membrane integrity) and function (ability, in vitro, to mature, be fertilised and develop into blastocysts) of the oocytes and their associated cumulus cells was assessed following cryopreservation. An attempt was made to determine the stage of the protocol at which damage was incurred. Alterations to culture conditions had little impact on the ability of fresh GV stage oocytes to develop to blastocysts, although IVM in the presence of mixed ovarian cells was found to be detrimental. Treatment with 1.5M dimethyl sulphoxide (Me2SO) without freezing had little effect on the parameters investigated, unlike exposure to a 6M Me2SO solution. Slow-cooled/thawed or cumulus-denuded oocytes had decreased developmental potential when compared with control oocytes. Development was not improved by co-culture with fresh cumulus cells. Much of the damage caused to the cumulus cells occurred during plunging from -60 &deg;C to -196 &deg;C. Damage was reduced by cooling at 10 &deg;C/min from -60 &deg;C to -150 &deg;C prior to plunging to -196 &deg;C. However, embryo development was not improved. Vitrification of COCs led to substantial cumulus cell damage and very poor embryo development.

Estimates of the cost-effectiveness of chlamydia control interventions are highly sensitive to the risk of progression from genital chlamydia infection to pelvic inflammatory disease (PID). There is no consensus for the risk of PID following asymptomatic chlamydia infections detected through population-based testing. The aim of this thesis is to generate improved estimates of this risk of PID that can be used to parameterise mathematical models and inform chlamydia control policy. We have determined the risk of PID following a positive chlamydia test in three cohorts: a small historic prospective clinical cohort of sex workers (Praed Street Project (PSP)); a large population-based retrospective cohort from Manitoba, Canada established for this research; and a large nationally representative retrospective cohort from Denmark. The risk of PID was higher in women with a positive chlamydia test compared to women who tested negative (PSP: adjusted hazard ratio (AHR) 2.03 (95%CI 0.75-5.49); Manitoba: 1.55 (95%CI 1.43-1.70); Denmark: 1.42 (95%CI 1.32-1.53)). There was heterogeneity in this risk: 13-23% higher following a repeat infection; up to four-fold higher in younger women (Manitoba: AHR 4.55 (95%CI 3.59-5.78) in 12-15 compared to 30-40 years); two-fold higher following previous gonorrhoea (PSP: 2.28 (95%CI 1.14-4.56)). The increased risk following a positive test lasted considerably longer than the likely duration of infection and fewer than 10% of PID diagnoses within 12 months of a test could be attributed to a positive result. This suggests that there are other important causes of PID. Individual-based risks of progression that capture this heterogeneity may improve the accuracy of estimates from mathematical models and therefore their utility to policy makers. Further research is needed to fully characterise the aetiology of PID to inform the design of chlamydia control interventions. In the meantime, interventions should focus on young women and those at risk of repeat chlamydia infection.

No description available.

No description available.

No description available.

Female genital mutilation (FGM) or female circumcision is the term given to traditional practices involving the intentional cutting or partial or total removal of the external female genitalia (WHO, 1999). This two part study used both qualitative and quantitative methods. The first part of the study aimed to explore the views and experiences of FGM amongst women who had undergone the practice. It also explored their views about what clinical psychologists needed to know and do in order to provide appropriate services. In this part of the study six participants were interviewed using a semi-structured interview. The data was analysed using interpretative phenomenological analysis (IPA). Findings indicated that participants felt that despite there being many reasons given for FGM none of them justified the continuation of the practice. Further findings suggested that participants felt that clinical psychologists needed to; understand how FGM is accounted for (e.g. reasons and contexts); acknowledge the different views towards the practice; have knowledge of the many consequences of the procedure (e.g. on physical health, psychological health and relationships) and talk about FGM in a sensitive and non-judgemental manner during consultations. Part two of the study explored the experiences, knowledge and training needs related to FGM amongst qualified clinical psychologists. A survey was completed by 74 clinical psychologists working in a range of specialities. The findings indicated that there was minimal experience of working with FGM related difficulties amongst participants. Knowledge about FGM and the consequences of it were also limited. Furthermore, clinical psychologists had received little training about FGM and many did not feel confident in working with issues related to the practice. Implications for clinical practice and recommendations for further research are suggested including; training opportunities specifically regarding FGM and further research that explores the connections between the physical and psychological consequences of the practice.

No description available.