Angiogenic Role of Histidine-Rich Glycoprotein and Vascular Endothelial Growth Factor in Idiopathic Recurrent Miscarriage

Background: Recurrent miscarriage (RM) is defined by the European Society of Human Reproduction and Embryology (ESHRE) as the loss of two or more pregnancies, irrespective of their sequence. Angiogenesis is essential for implantation and placentation, and impaired angiogenic regulation has been implicated in RM. Moreover, various factors have been identified as participating in the angiogenesis process, including histidine-rich glycoprotein (HRG) and vascular endothelial growth factor (VEGF). Objective: This study aimed to evaluate serum HRG and VEGF levels and their relationship in women with idiopathic recurrent miscarriage. Methods: A case-control study was performed involving 70 women with first trimester idiopathic RM and 70 first trimester pregnant controls who had two or more live birth. Both patients and controls were matched for ages (18-35) years, their husbands were aged (20-40) years, and BMI ranged (18.5-29.9) kg/m². Blood samples (10 ml) were obtained from participants. For patient group; blood samples were collected after confirmation of first trimester miscarriage and before any medical or surgical intervention. Laboratory testing were employed to exclude probable causes of RM by confirming that they were within normal limits. Serum stored at -80°C was used to examine HRG and VEGF concentrations by ELISA technique. Results: Women with idiopathic recurrent miscarriages had significantly lower levels of histidine rich glycoprotein (P <0.001) and lower levels of vascular endothelial growth factor (P <0.001) than controls. Moreover, a positive correlation (p <0.001; r=0.497) between these two parameters was noted among patient group. The area under curve for HRG was (75.9%), while sensitivity and specificity values were (75.7%), (61.4%) respectively. The area under curve for VEGF was (92.8%), while sensitivity and specificity values were (91.4%), (77.1%) respectively. Conclusion: The positive correlation between HRG and VEGF, together with their reduced serum levels in individuals with idiopathic recurrent miscarriage, suggests a potential association between these angiogenic factors and idiopathic RM. These findings may reflect an imbalance in angiogenic regulation that may be associated with first trimester pregnancy failure.