Plasma Proteomics Analysis of Early Biomarkers for Predicting Female Fecundability: A Nested Case-Control Study

Abstract

The present study aimed to identify and verify new plasma protein markers to predict the female fecundability level. A nested case-control study was conducted involving couples who participated in the Chinese National Free Preconception Check-up Project. Women who successfully conceive within one year were defined as the high fecundability group, and those unable to conceive were defined as the low fecundability group. In the training cohort, potential protein biomarkers were identified using proteomics technology and were further tested in a validation cohort by the Western blotting assay, enzyme-linked immunosorbent assay, and biochemical tests. Meanwhile, receiver operating characteristic curve analysis were used to evaluate the predictive value. Cox proportional hazard regression analyses were conducted to calculate hazard ratios; restricted cubic spline analysis was used to assess the linear relationship between the the protein level and hazard ratios for fecundability. Pyruvate, a key product of glycolysis, was significantly increased in the high fecundability group (P < 0.01) compared to the low fecundability group, and its area under the curve value was 0.68 (P < 0.05). There was a linear positive dose–response association between the pyruvate level and fecundability possibility (hazard ratios = 1.66, 95% CI: 1.07–2.59, p for trend = 0.025, nonlinearity, p-value = 0.2927).