Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 3 2025 09 22 171 179 Rahim Rostami Iran University of Medical Sciences Jamileh Jahanbakhsh Infertility Ward, Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran. Shirin Salehi Department of Pharmacy, Faculty of Pharmacy, Iran University of Medical Sciences, Tehran, Iran. Soudabeh Fallah Department of Clinical Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. 2025 09 22 2025 10 05 Objectives: Serum levels of complement proteins C3, C4, immunoglobulins (IgGs), and C-reactive protein (CRP) are crucial in understanding the pathophysiology of recurrent implantation failure (RIF). This study aims to quantify these biomarkers and explore their clinical significance. Methods: We conducted a cross-sectional study at Arash Hospital from December 2021 to December 2023, involving 50 women with a history of RIF after in vitro fertilization (IVF) and a control group of 50 healthy, fertile women. Serum levels of C3, C4, IgG, IgM, IgA, CRP, and hs-CRP were measured using immunoturbidimetric assays and ELISA. Results: Serum levels of complement components C3 and C4, IgG, IgA, CRP, and hs-CRP were significantly elevated in women with RIF compared to fertile controls. A positive correlation existed between C3 and C4 in the RIF group, but no significant correlations were found for IgG, IgA, or IgM. In contrast, significant associations between IgG, C3, C4, and CRP, with IgG levels also correlating with IgA were observed in fertile controls. ROC curve analysis indicated strong discriminatory power for IgG, IgA, C3, and C4. CRP AUC was 0.962, and hs-CRP AUC was 0.994, distinguishing RIF from fertile women, with CRP showing 94% sensitivity and 92% specificity at 5.3 mg/dL, and hs-CRP showing 98% sensitivity and specificity at 2.92 mg/L. Conclusion: The findings suggest that elevated serum levels of C3, C4, IgG, and IgA in the RIF group may be associated with the underlying mechanisms of RIF. https://abi.tums.ac.ir/index.php/abi/article/view/160 https://abi.tums.ac.ir/index.php/abi/article/download/160/117