Serum Protein Dynamics in Early Pregnancy Loss Management: Findings from the PreFaiR Trial

Medical management of early pregnancy loss (EPL) achieves ~90% efficacy with mifepristone-misoprostol combination versus ~70% with misoprostol alone, yet biomarkers predicting individual treatment response remain unknown. We performed proteomic analysis of serum samples from 59 participants in the PreFaiR trial, comparing pre- and post-treatment protein expression between responders and non-responders. Combination therapy showed 5 baseline predictors (LAP-TGF-β1, IL17RB, MYOC, CDH1, CD97) with higher expression in responders, while misoprostol monotherapy demonstrated 10 predictors with bidirectional patterns. Treatment-induced changes differed markedly: combination therapy showed significant alterations in 4 proteins, while misoprostol triggered changes in 30 proteins. TNNI3 emerged as a molecular efficiency marker, which showed almost no change between pre- and post-treatment levels in successful combination therapy but substantially declining post-treatment with misoprostol monotherapy. DPP7 showed opposite regulation between treatments among responders. These distinct molecular signatures provide evidence for treatment-specific mechanisms and offer potential biomarkers for personalized EPL management.