Effect of endometriosis on oocyte quantity and quality of patients undergoing In vitro fertilisation (IVF)/ Intracytoplasmic sperm injection (ICSI)

Endometriosis is a disease that arises in females of reproductive age and has been investigated for more than 100 years. The natural cause of endometriosis is ill-defined because of the uncertainty regarding pathogenesis and the evolution of the condition. It is clearly challenging to diagnose, and it is indeed associated with low fecundity; as such, management of endometriosis-related infertility is not straightforward. Although widely researched, significant controversies surrounding the impact of the disease on the reproductive system remain unsolved. This thesis primarily aims to examine the influence of endometriomas, as well as endometriosis in general, on specific reproductive outcomes in women who have undergone fertility treatment. Moreover, the thesis further focuses on understanding how endometriosis may influence the microenvironment of the developing oocyte. Towards these aims, an initial systematic review and meta-analysis concluded that females suffering from endometriosis had fewer oocytes and mature oocytes collected during their fertility treatment cycle (in comparison to women receiving fertility treatment without endometriosis). A further retrospective database analysis of 841 patients who recently underwent fertility treatment in the local assisted conception unit (Jessop Fertility, Sheffield) supported the finding that women with endometriosis undertaking IVF/ICSI yielded fewer oocytes, but also revealed additional reductions in pregnancy outcomes including implantation rate and live birth rate. Following this, a prospective study was carried out to analyse the composition of the follicular fluid (FF) of women undergoing fertility treatment with or without endometriosis (n=15 and 22, respectively). Here, a highly specific and sensitive proteomics analysis approach (nano-flow LC–MS/MS) identified a panel of 45 proteins that were differentially expressed in FF of endometriosis patients, with 44 of these being upregulated (FDR<0.05). Most of these proteins were associated with complement cascade, blood coagulation cascade, binding, innate immunity and transport. Exploring the FF composition in patients with endometriomas (n=5) vs controls (n=10) in a sub-analysis revealed a panel of 8 differentially expressed proteins. Thus, it is clear that developing oocytes in women with endometriosis and endometriomas are exposed to a different FF microenvironment – which plausibly has an impact on the developmental potential of the oocytes. The proteomics analysis also provides a platform for further biomarker discovery and revealed distinctive proteins not yet defined in the current practice. The general conclusion is that endometriosis is a condition that is detrimental to the quality of the oocyte due to the inflammatory influences on the FF, meaning fewer are ovulated under natural circumstances. Fortunately, ovarian stimulation protocols can provide a mechanism to rescue sufficient numbers of oocytes in order to improve the chances of fertilisation. Therefore, the impact of endometriosis on fertility is complex and it is now more apparent that its influence does not only restrict the anatomical distortion. Until there is a treatment for endometriosis, rather than its symptoms, the best answer to this problematic condition depends on the early diagnosis and referring the patients to fertility treatment as early as possible to achieve better reproductive outcomes. Exploring the FF of endometriosis patients could potentially aid the development of treatments that target specific proteins with distinct roles in disease development. Whilst achieving these aims could take multiple years, this thesis provides some preliminary data for further investigation into targeted therapies for women with endometriosis.