The pathophysiology of endometriosis-associated infertility: follicular environment and embryo quality.

Several retrospective analyses of IVF and oocyte donation programmes, performed to gain clinical knowledge of the factors implicated in the aetiology of endometriosis-associated infertility, have demonstrated that the quality of the embryo is affected in patients with endometriosis. To understand the mechanisms of this alteration, the endocrine, paracrine and autocrine conditions induced during folliculogenesis in women with and without endometriosis were investigated. The first approach was to study ovarian steroid secretion in women undergoing IVF. Progesterone concentrations in follicular fluid increased with the severity of the disease and an increase in progesterone accumulation in vitro was observed in basal and hCG-stimulated granulosa cell cultures. It is proposed that the pattern of progesterone secretion may be related to changes in the release of cytokines by ovarian and white blood cells. Hence, a second trial measured interleukin 1 (IL-1), IL-6 and vascular endothelial growth factor (VEGF) concentrations in serum, follicular fluid and granulosa cell cultures. IL-6 concentrations in serum were higher in the natural cycles of women with endometriosis than in women in the control group, and were modulated by ovarian stimulation, decreasing significantly in serum from stimulated cycles. In addition, IL-6 concentrations were higher in the follicular fluid of women with endometriosis than in those in the control group and IL-6 was released in higher amounts by granulosa luteal cells of patients with endometriosis. VEGF was accumulated in lower concentrations in the follicular fluid of patients with endometriosis. These observations indicate that infertility in patients with endometriosis may be related to alterations within the follicle which, in turn, result in oocytes and embryos of lower quality, as demonstrated in the IVF programme. In addition, these embryos have a reduced ability to implant, as observed in the oocyte donation model. These alterations may be induced by functional changes in the process of folliculogenesis that affect steroid synthesis, as well as by cytokine release by ovarian and blood cells.