Diagnostic Value of HIF-2α, VEGF-A, and IL-13 Expression in Iraqi Women with Primary Infertility.

BackgroundCooperation among hypoxia signalling, immune modulation and angiogenesis plays an important part in determining the receptivity of the endometrium, the lining of the uterus, to implantation. How Hypoxia-Inducible Factor-2 alpha (HIF-2α), IL-13 and Vascular Endothelial Growth Factor A (VEGF-A) contribute to female infertility in Middle Eastern populations is not well understood.Objectives: Quantifying HIF-2α and IL-13 gene expression and VEGF-A serum levels in women with primary infertility, along with evaluating their diagnostic value and how they relate to each other.MethodsCase-control study of 70 women with primary infertility and 30 age-matched fertile controls (age range 18-35 years). Gene expression in peripheral blood was measured by RT-qPCR (SYBR Green) using GAPDH normalization (2-ΔΔCt). Serum VEGF-A was measured by ELISA. Statistical analyses included independent t-tests, Pearson correlation and ROC curve analysis. P≤0.05 was considered significant.ResultsInfertile women were found to have a significantly lower level of HIF-2α (mean fold change of 0.189; p=0.038*). A non-significant decrease in IL-13 levels (mean fold change of 0.69; p=0.458) was also observed. A statistically significantly lower level of the serum level of VEGF-A was noted (310 ± 60 pg/ml; p=0.006*) in patients compared to controls (480 ± 44 pg/ml; p=0.006*). ROC analysis of the use of HIF-2α and IL-13 for the diagnosis of infertility showed high sensitivity but low specificity (r=0.468; p≤0.001).ConclusionsThe association of HIF-2α expression and change in VEGF-A serum levels indicate the potential diagnostic utility of a multi-marker test for the diagnosis of infertility in this population.