Follicular hormonal environment and embryo quality in women with endometriosis

The use of in-vitro fertilization (IVF) as a therapeutic tool in patients with endometriosis has provided information about the disease and, in particular, aspects of the reproductive process in humans, particularly folliculogenesis, fertilization, embryo development and implantation. Retrospective analyses of IVF and oocyte donation programmes showed impaired implantation in patients with endometriosis. Otherwise, the observation that embryo development was blocked more frequently in cases of endometriosis, suggested that impaired embryo quality may be responsible for the reduced implantation rates. Similarly, women with the disease undergoing oocyte donation had the same chance of implantation as patients without endometriosis, suggesting that the endometrial milieu is not affected in patients with endometriosis. The quality of the oocyte may, therefore, be altered in patients with endometriosis. To investigate this, we studied 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 human chorionic gonadotrophin (HCG)-induced granulosa cell cultures. We postulated that the pattern of progesterone secretion may be related to the release of cytokines by ovarian and/or immune cells. To test this, we measured interleukin (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 increased in natural cycles in women with endometriosis and showed a significant decrease in stimulated cycles in IVF. Also, IL-6 concentrations were increased in the follicular fluid of women with endometriosis and released in higher amounts by granulosa-luteal cells from patients with endometriosis. VEGF was accumulated in lower concentrations in the follicular fluid of endometriosis patients. These observations show that the follicular environment is different in cases with endometriosis and suggest that infertility in patients with endometriosis may be related to alterations within the oocyte which, in turn, result in embryos of lower quality, and with a reduced ability to implant.