Abnormal expression of MMP‐9 and imbalance of MMP‐9/TIMP‐1 is associated with prolonged uterine bleeding after a medical abortion with mifepristone and misoprostol

Abstract

To investigate the expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitory of metalloproteinase-1 (TIMP-1) in women who had undergone a medical abortion and explore their possible role in the mechanism of prolonged uterine bleeding after a mifepristone-misoprostol abortion. Cross-sectional study. Tertiary referral university hospital. Forty women were recruited following a medical abortion with mifepristone and misoprostol, 20 with duration of bleeding >14 days and 20 with duration of bleeding <or= 14 days. Endometrial specimens were stained with hematoxylin and eosin for histological examination. The expression of MMP-9 and TIMP-1 was evaluated by immunohistochemistry. Histology was analyzed by light microscope and expression of MMP-9 and TIMP-1 was semi-quantitatively evaluated. Histological examination showed residual villi and trophoblasts with inflammatory cell infiltration in women with duration of bleeding >14 days after a medical abortion (bleeding group), whereas each sample of women with duration of bleeding <or= 14 days after a medical abortion (control group) showed normal endometrial changes. Immunohistochemistry and semi-quantitative scoring showed a significantly decreased expression level of MMP-9 in the bleeding group, compared with the control group. There was no significant difference of TIMP-1 expression between the bleeding group and the control group. The MMP-9/TIMP-1 ratio value was significantly lower in the bleeding group than in the control group. This study documents that prolonged bleeding after a medical abortion with mifepristone and misoprostol is associated with retained products of conception with inflammatory cell infiltration, abnormal expression of MMP-9 and imbalance of MMP-9/TIMP-1.