Ceruloplasmin and complement C3 are markers of diminished ovarian reserve in premenopausal women

Aim. To establish cut-off values for the concentrations of complement C3 and ceruloplasmin, diagnostic markers of reduced antral follicle count (AFC) and anti-Müllerian hormone (AMH) which both indicate diminished ovarian reserve, in women of reproductive age.
Materials and Methods. Here we enrolled 864 women (18-40 years of age, average age 31.70 ± 5.14 years) who underwent an annual medical examination in 2017–2019 in the Irkutsk Region and the Republic of Buryatia. Reduced AFC was defined as ≤ 5 antral follicles in each ovary at pelvic ultrasound examination whilst reduced AMH was defined as < 1.2 ng/mL. In total, 112 women had reduced ovarian reserve and 752 were included into the control group. In addition to AMH, we also measured serum prolactin, gonadotropins, inhibin B, estradiol, complement C3, and ceruloplasmin using enzyme-linked immunosorbent assay. The cut-off values were determined by plotting a receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC).
Results. The cut-off level of complement C3 was 894 (867; 1355.5) mg/mL [AUC: 0.769 (0.635; 0.904)] in women with reduced AFC (≤ 5) and 981.5 (916.5; 1467.5) mg/mL [AUC: 0.62 (0.493; 0.746)] in women with reduced AMH (< 1.2 ng/mL). The cut-off level of ceruloplasmin was 1.745 (1.625; 1.975) mg/mL [AUC: 0.859 (0.759; 0.96)] in women with reduced AFC (≤ 5) and 1.975 (1.665; 2.15) mg/mL, [AUC: 0.662 (0.542; 0.782)] in women with reduced AMH (< 1.2 ng/mL).
Conclusion. We have established the cut-off values for the serum complement C3 and ceruloplasmin in women with reduced AFC and AMH, indicators defining diminished ovarian reserve in women of reproductive age.

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