Context: Clinical assessment of cervical maturity is mainly based on anatomical criteria and often fails to detect early functional changes that precede spontaneous preterm birth.

Objective: To develop and validate a comprehensive approach for assessing cervical remodeling according to the degree of cervical maturity at different stages of gestation.

Methods: This late-breaking analysis was conducted within a prospective observational cohort of 346 pregnant women with pregnancy outcomes finalized after October 28, 2025. A total of 577 cervical ultrasound examinations were performed using E-Cervix elastography. Cluster analysis of quantitative parameters—cervical length (CL), hardness ratio (HR), elasticity contrast index (ECI), internal os strain (IOS), and external os strain (EOS)—was used to identify cervical remodeling phenotypes. Three-dimensional power Doppler angiography with VOCAL™ software was performed in 223 examinations. In a nested cohort of 81 women, venous blood and cervical fluid samples were analyzed for systemic and local biomarkers, including relaxin-1, relaxin-2, elastin, PAMG-1 (Actim PARTUS), inflammatory mRNA expression (ImmunoQuantEx), and vaginal microbiota composition assessed by real-time PCR (Femoflor).

Main Outcome Measures: Cervical remodeling phenotype, time to delivery, spontaneous preterm birth.

Results: Three distinct and reproducible cervical remodeling phenotypes were identified: immature, maturing, and mature. Progression toward the mature phenotype was associated with a gradual decrease in HR and cervical length, together with an increase in ECI, IOS, and EOS. Compared with the immature phenotype, the risk of spontaneous labor within 14 days was 3.86 times higher in the maturing phenotype (95% CI 1.87–7.98; p < 0.001) and 10.08 times higher in the mature phenotype (95% CI 5.02–20.25; p < 0.001). Vascular indices (VI, FI, VFI) increased consistently across phenotypes and correlated with elastographic parameters. Systemic and local levels of relaxin-1, relaxin-2, and elastin differed significantly between phenotypesIntegration of elastography, 3D angiography, and biochemical markers improved early identification of women at risk for spontaneous preterm remodeling cervix uteri compared with cervical length alone. A validated multiparametric software-based calculator was developed to automatically classify cervical phenotypes based on elastographic data (https://www.celasto.com).

Conclusions: Cervical remodeling is a multidimensional biophysical and molecular process that precedes anatomical shortening. This late-breaking integrated approach enables objective digital phenotyping of cervical maturity and provides a clinically actionable tool for early prediction and personalized prevention of spontaneous preterm birth

Vladislava Khalenko is an obstetrician-gynecologist and reproductive medicine specialist, PhD candidate, and young clinical researcher at the D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductive Medicine (Saint Petersburg, Russia). Her clinical and scientific work focuses on reproductive endocrinology, infertility management, assisted reproductive technologies (ART), and translational obstetrics. She combines daily clinical practice in IVF programs with research aimed at improving prediction, prevention, and treatment strategies for adverse reproductive outcomes. Her PhD research is dedicated to cervical remodeling during pregnancy and the development of innovative diagnostic tools for preterm birth prediction. She leads projects integrating ultrasound elastography (E-Cervix), biochemical biomarkers (relaxin, elastin), immune and microbiome profiling, and advanced statistical modeling to create personalized risk-assessment algorithms. She is also involved in translational studies on endometrial pathology, chronic endometritis, implantation failure, and novel therapeutic approaches, including growth factor-based and cell-derived treatments. She is an author and co-author of multiple peer-reviewed publications and regularly presents her work at international congresses in reproductive medicine and obstetrics. Her research aims to bridge fundamental science and clinical decision-making, contributing to precision medicine in fertility and pregnancy care. She is committed to advancing evidence-based reproductive healthcare and developing practical tools that directly improve patient outcomes.