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The diagnosis and related endometrial dysfunction of chronic endometritis in recurrent pregnancy loss
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Odendaal, Joshua (2022) The diagnosis and related endometrial dysfunction of chronic endometritis in recurrent pregnancy loss. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3903236
Abstract
Recurrent pregnancy loss is a common condition carrying stark physical and psychological morbidity. Chronic endometritis (CE) is a purported cause with an emerging body of literature demonstrating an association. Despite this the pathophysiology of this association is poorly understood. This thesis aims to understand further the pathophysiology of CE through understanding the biological significance of the diagnostic methodology of CE and profiling the effect of CE on the characteristics of the endometrium. A three-fold approach to this is taken. Firstly, through systematic review and meta-analysis, current CE diagnostic methodology was reviewed. This demonstrated a wide heterogeneity in methodology with under-reporting of key steps. A wide range in reported CE prevalence was seen. Diagnostic methodology was shown to affect the ability to predict clinical outcome. Secondly, given the variance in prevalence, the primary diagnostic methodology utilising the plasma cell marker CD138 was explored. Evaluation of the constitutive endometrial expression of CD138 was undertaken. Immunohistochemical and transcriptional profiling demonstrated proliferative phase constitutive stromal expression of CD138 which dissipated on transition into the secretory phase. This finding suggested that CD138+ CE may be related to disordered progression of the endometrium across the menstrual cycle. Two-distinct sub types of CE based on immunohistochemical staining pattern were identified. Thirdly, using both histological and molecular timing, this timing relationship was examined in a prospective clinical study. CD138+ endometrium was shown to be associated with impaired endometrial timing. This was also associated with alterations in the balance between decidualised and senescent endometrial cells. Nevertheless, a causal relationship with the endometrial microbiota was not seen. These findings are the first to demonstrate a relationship between impaired endometrial timing and CE further elucidating the likely pathophysiological mechanisms by which CE predisposes to miscarriage. Furthermore, two distinct sub-types of CE may provide a clinical triage platform for differing treatment approaches.
Item Type: | Thesis (PhD) | ||||
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Subjects: | R Medicine > RG Gynecology and obstetrics | ||||
Library of Congress Subject Headings (LCSH): | Endometriosis, Endometriosis -- Diagnosis, Immunohistochemistry, Miscarriage, Pregnancy -- Complications | ||||
Official Date: | September 2022 | ||||
Dates: |
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Institution: | University of Warwick | ||||
Theses Department: | Warwick Medical School | ||||
Thesis Type: | PhD | ||||
Publication Status: | Unpublished | ||||
Supervisor(s)/Advisor: | Quenby, Siobhan | ||||
Sponsors: | National Institute for Health Research (Great Britain) | ||||
Format of File: | |||||
Extent: | 198 pages | ||||
Language: | eng |
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