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

Several retrospective analyses of NF and oocyte donation programmes, perfor med to gain clinical knowledge of the factors implicated in the aetiology o f 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 cond itions induced during folliculogenesis in women with and without endometrio sis were investigated. The first approach was to study ovarian steroid secr etion in women undergoing IVF. Progesterone concentrations in follicular fl uid increased with the severity of the disease and an increase in progester one accumulation in vitro was observed in basal and hCG-stimulated granulos a 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, follicul ar fluid and granulosa cell cultures. IL-6 concentrations in serum were hig her in the natural cycles of women with endometriosis than in women in the control group, and were modulated by ovarian stimulation, decreasing signif icantly in serum from stimulated cycles. Zn addition, IL-6 concentrations w ere higher in the follicular fluid of women with endometriosis than in thos e 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. The se observations indicate that infertility in patients with endometriosis ma y be related to alterations within the follicle which, in turn, result in o ocytes and embryos of lower quality, as demonstrated in the IVF programme. In addition, these embryos have a reduced ability to implant, as observed i n 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.