Objective:

To provide a comprehensive overview of non-invasive biomarkers in IVF and ART, focusing on their biological significance, clinical applications, and future directions.

Approach:

• Literature Review: A literature search was conducted using PubMed and Scopus databases to identify relevant articles on non-invasive biomarkers in ART, focusing on their biological rationale, clinical applicability, validation status, and translational potential.

Key Findings:

• Current embryo selection and endometrial evaluation methods rely heavily on morphological criteria, which do not provide direct insight into biological competence.
• Non-invasive biomarkers, including those derived from embryo culture media, follicular fluid, and uterine secretions, show potential in predicting embryo viability and implantation success.
• Emerging technologies such as metabolomics, proteomics, and artificial intelligence are improving the analysis of complex datasets for enhanced predictive modeling.

Interpretation:

While non-invasive biomarkers show associations with embryo viability and implantation potential, evidence linking them to live birth rates is limited. Their clinical application is challenged by methodological variability and standardization issues.

Limitations:

• Limited validation of non-invasive biomarkers in clinical settings.
• Methodological variability across studies.
• Challenges in standardizing biomarker assessment.

Conclusion:

Integrative multi-parameter approaches are likely to improve predictive accuracy in ART. Ongoing efforts toward data harmonization, large-scale validation, and clinically relevant model development are crucial for the successful integration of non-invasive biomarkers into routine IVF practice.