Altered circulating levels of matrix metalloproteinases 2 and 9 and their inhibitors and effect of progesterone supplementation in women with endometriosis undergoing in vitro fertilization

OBJECTIVE: To investigate differences in the activity of matrix metalloproteinases (MMPs) 2 and 9 and their respective tissue inhibitors (TIMPs) in follicular fluid of women with endometriosis, to correlate the findings with IVF outcome, and to examine the therapeutic potential of progesterone supplementation in restoring the fine balance between MMPs and TIMPs. DESIGN: Prospective case-control clinical study. SETTING: Infertility clinic and reproductive health research unit. PATIENT(S): A total of 340 infertile women undergoing IVF. INTERVENTION(S): Natural micronized progesterone capsules were administered for luteal support. MAIN OUTCOME MEASURE(S): Association of MMPs 2 and 9 and TIMP-1 with oocyte maturity and embryo development. RESULT(S): An abnormal expression of MMP-2, MMP-9, and TIMP-1 with extensive MMP-9/TIMP-1 imbalance in women with endometriosis undergoing IVF was observed. Transforming growth factor β1 plays an important role in these women with possible involvement of Smad-2 and -3 proteins. Progesterone supplementation improves the imbalance in MMP-9/TIMP-1 ratio significantly in women with endometriosis who conceive after IVF. CONCLUSION(S): Increase in MMP-2 and -9 and decrease in TIMP-1 expression was associated with poor oocyte and embryo development in women with endometriosis undergoing IVF. MMP-9/TIMP-1 balance was highly affected in these women, and progesterone supplementation appeared to restore this imbalance to a considerable degree.