The use of in-vitro fertilization (IVF) as a therapeutic tool in patients w
ith endometriosis has provided information about the disease and, in partic
ular, aspects of the reproductive process in humans, particularly folliculo
genesis, 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 dev
elopment was blocked more frequently in cases of endometriosis, suggested t
hat impaired embryo quality may be responsible for the reduced implantation
rates. Similarly, women with the disease undergoing oocyte donation had th
e 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 end
ometriosis. To investigate this, we studied steroid secretion in women unde
rgoing 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 se
cretion 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 end
othelial growth factor (VEGF) concentrations in serum, follicular fluid and
granulosa cell cultures. IL-6 concentrations in serum were increased in na
tural cycles in women with endometriosis and showed a significant decrease
in stimulated cycles in IVF. Also, IL-6 concentrations mere increased in th
e follicular fluid of women with endometriosis and released in higher amoun
ts by granulosa-luteal cells from patients with endometriosis. VEGF was acc
umulated in lower concentrations in the follicular fluid of endometriosis p
atients. These observations show that the follicular environment is differe
nt in cases with endometriosis and suggest that infertility in patients wit
h endometriosis may be related to alterations within the oocyte which, in t
urn, result in embryos of lower quality, and with a reduced ability to impl
ant.