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

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).