Unexplained infertility (UI) remains a diagnostic challenge affecting a significant proportion of women of reproductive age. Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis and inflammation, has been implicated in reproductive and immune processes. This prospective observational study evaluated serum VEGF levels and allergen sensitization (via ALEX² macroarray) in 70 women—51 with UI and 19 fertile controls—to assess VEGF’s potential as a biomarker in UI. Median VEGF concentrations were higher in women with UI compared to fertile controls (128.6 pg/mL vs. 82.5 pg/mL), though not statistically significantly. However, sensitized women showed significantly elevated VEGF levels compared to non-sensitized peers (115.9 pg/mL vs. 85.7 pg/mL, p = 0.028), and a stepwise increase in VEGF was observed with rising allergy severity (p = 0.045). Sensitization to pet allergens, particularly cat allergen Fel d 1, was associated with the highest VEGF levels. A literature review confirmed wide variability in VEGF concentrations and the lack of standardized norms. While VEGF alone may not serve as a definitive biomarker for infertility, elevated levels may reflect an underlying inflammatory state. Our findings suggest VEGF testing could support broader clinical evaluation in women with UI, especially in the presence of allergic sensitization.

Unexplained infertility (UI) remains a diagnostic challenge affecting a significant proportion of women of reproductive age. Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis and inflammation, has been implicated in reproductive and immune processes. This prospective observational study evaluated serum VEGF levels and allergen sensitization (via ALEX² macroarray) in 70 women—51 with UI and 19 fertile controls—to assess VEGF’s potential as a biomarker in UI. Median VEGF concentrations were higher in women with UI compared to fertile controls (128.6 pg/mL vs 82.5 pg/mL), though not statistically significant. However, sensitized women showed significantly elevated VEGF levels compared to non-sensitized peers (115.9 pg/mL vs 85.7 pg/mL, p = 0.028), and a stepwise increase in VEGF was observed with rising allergy severity (p = 0.045). Sensitization to pet allergens, particularly cat allergen Fel d 1, was associated with the highest VEGF levels. Literature review confirmed wide variability in VEGF concentrations and the lack of standardized norms. While VEGF alone may not serve as a definitive biomarker for infertility, elevated levels may reflect an underlying inflammatory state. Our findings suggest VEGF testing could support broader clinical evaluation in women with UI, especially in the presence of allergic sensitization.