Serum PAPP-A as a potential biomarker for early detection of ectopic pregnancy: an exploratory case-control study

In this exploratory case-control study, we investigated the potential associations of pregnancy-associated plasma protein-A (PAPP-A), β-human chorionic gonadotrophin (β-HCG), vascular endothelial growth factor (VEGF), and leukemia inhibitory factor (LIF) with ectopic pregnancy (EP), using logistic regression to describe unadjusted associations and receiver operating characteristic (ROC) curve analysis to characterise exploratory biomarker performance.

We conducted a case-control study including 48 patients with EP and 46 patients with normal intrauterine pregnancy as controls, recruited between October 2022 and May 2024 at a single center. Logistic regression was applied to describe associations between each biomarker and EP. ROC curves were derived from these models to explore discrimination, and an exploratory threshold was identified using the Youden index.

The area under the curve (AUC) for β-HCG and PAPP-A were the highest (0.85 and 0.84, respectively), compared with VEGF (0.73) and LIF (0.54). PAPP-A showed the strongest association among the candidate markers (OR = 0.774), with an exploratory sensitivity of 0.77. VEGF had the highest specificity (0.96). The combined exploratory AUC of PAPP-A and β-HCG (0.89) was similar to that of PAPP-A and VEGF (0.88).

This exploratory study suggests that PAPP-A may be a promising candidate biomarker for early EP detection in the context of an exploratory case-control comparison with normal intrauterine pregnancy, with performance comparable to β-HCG. Further prospective studies with external validation in clinically relevant populations are needed to confirm these preliminary findings and assess clinical potential.