Matrix metalloproteinases in serum and the follicular fluid of women treated by in vitro fertilization.

PURPOSE: To assess levels of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) in follicular fluids and sera of female patients undergoing in vitro fertilization (IVF) treatment, and discover the role of MMPs in IVF outcome prediction. METHODS: Sera and follicular fluids were obtained from 58 female patients treated for infertility by IVF. Twenty-nine of them became pregnant after the embryo-transfer; another 29 were not successful in IVF and did not conceive. Forty female non-pregnant blood donors and 38 healthy pregnant patients in the first trimester after the physiological conception were examined as control groups. MMP-2 and MMP-9 were quantitively assessed using enzyme-linked immunosorbent assay. RESULTS: IVF females successfully conceiving after the IVF have shown the highest MMP-9 concentrations in sera (833.5 {686.0;958.7} ng/mL) and follicular fluids (9.6 {6.0; 17.0} ng/mL) compared to all other examined cohorts. Different behavior of MMP-2 and MMP-9 during the artificial ovulation was confirmed, because only MMP-9 has shown a vast difference between serum and follicular concentrations. CONCLUSIONS: MMP-9 could be a good predictor of the successful IVF outcome (pregnancy), which was proven for serum as well as follicular MMP-9 levels.

Concentrations of sRAGE in serum and follicular fluid in assisted reproductive cycles--a preliminary study.

BACKGROUND: To investigate inflammatory processes during ovarian hyperstimulation, we have studied the soluble receptor for advanced glycation end products (sRAGE) levels in sera and follicular fluids of women undergoing in vitro fertilisation (IVF) cycle. METHODS: A total of thirty-three women undergoing IVF treatment were recruited, the number of follicles in investigated IVF cycles was 18 +/- 10 (mean +/- SD), oocytes 12 +/- 8, and the clinical pregnancy rate was 42% (14/33). The control group of serum samples was comprised of 35 healthy female blood donors. Sera and follicular fluids were examined for sRAGE levels by enzyme-linked immunosorbent assay (sRAGE ELISA, Quantikine, R&D Systems). RESULTS: Serum levels of sRAGE in women after ovarian hyperstimulation and induction of ovulation (1039 +/- 493 pg/mL) were significantly lower than in healthy blood donors (1535 +/- 438 pg/mL), p = 0.045. Follicular sRAGE levels (4355 +/- 1100 pg/mL) were significantly higher than serum levels (1039 +/- 493 pg/ml), p < 0.001. Serum sRAGE levels showed significant negative correlation with the number of stimulated follicles (r = -0.71, p = 0.01) and retrieved oocytes (r = -0.54, p = 0.048). Women who successfully conceived after the IVF showed significantly higher sRAGE levels in follicular fluid (4595 +/- 925 pg/mL) compared to women who did not conceive (3986 +/- 806 pg/mL), p = 0.031. CONCLUSIONS: Concentration of sRAGE in follicular fluid is several-fold higher compared to serum and most other biological fluids investigated until this time. It supports the hypothesis that mammalian ovulation can be compared to an inflammatory event. A significant negative correlation of serum sRAGE with the yield of follicles and oocytes, together with the high follicular sRAGE levels, in particular in women who conceive after the IVF, could be explained by the essential outflow of sRAGE to the follicular compartment.

Intracellular cytokine production in peripheral blood lymphocytes: a comparison of values in infertile and fertile women.

PROBLEM: To analyze the relation of the fertility and pregnancy of women of childbearing age to the intracellular (IC) production of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukins 2 and 4 (IL-2 and IL-4). METHOD OF STUDY: Intracellular cytokine production in peripheral blood CD3(+) CD4(+) lymphocytes was analyzed by flow cytometry in 185 women being treated for infertility and 50 fertile women of childbearing age. RESULTS: Infertile women have a significantly higher IC production of TNF-α, IFN-γ, IL-2, and IL-4 and higher ratios of TNF-α/IL-2, TNF-α/IL-4, and TNF-α/IFN-γ compared to the fertile women. CONCLUSION: Cytokines produced by Th lymphocytes are important in orchestrating the immune response during conception, and Th-cell dysregulation could be a reason for infertility.