Maternal homocysteine and chorionic vascularization in recurrent early pregnancy loss

Abstract
Defective chorionic villous vascularization has been suggested to be associated with embryonic death. There are no reports, however, describing ch1orionic vascular profiles in spontaneous miscarriage tissue. Therefore, we investigated chorionic villous vascularization by both histopathology and an image analysis system combined with CD34 immunohistochemistry in spontaneous miscarriage tissue of 19 women with recurrent early pregnancy loss (REPL). Subsequently, we studied the vascular profile parameters (median vascular area, perimeter, number of vascular elements per measured chorionic area, and the median area, perimeter and diameter per vascular element) in relation to the maternal plasma total homocysteine concentrations (an independent risk factor for REPL). The histopathological scores and the measured number of vascular elements per mm2 chorionic tissue were not significantly different between women with elevated and those with normal total homocysteine concentrations. However, women with elevated total homocysteine concentrations (fasting >18.3 μmol/l and/or 6 h after methionine load >61.5 μmol/l) showed (per measured chorionic area) significant smaller median vascular areas and perimeters. The single chorionic vascular elements in these women had significant smaller median areas, perimeters and diameters. Furthermore, the fasting total homocysteine was negatively correlated with the perimeter of the vascular element (r = –0.54: P <0.05). In conclusion, in REPL, elevated maternal total homocysteine concentrations are associated with defective chorionic villous vascularization.