Biomarker Panels in Follicular Fluid to Predict Oocyte Quality and IVF Outcomes

The assessment of oocyte quality and identification of the best oocytes in human in vitro fertilization (IVF) is critical to IVF outcomes. To date, non-invasive assessment of oocyte competence remains a critical unmet need in assisted reproduction. Follicular fluid (FF) contains small molecules, proteins, lipids, extracellular vesicles, and cell-free nucleic acids that reflect granulosa–oocyte crosstalk and oocyte health. Although many single-analyte candidates have been studied, reproducible panels that generalize across stimulation protocols, diseases (e.g., PCOS, endometriosis, diminished ovarian reserve), and laboratories are still lacking.

This Research Topic invites original research, methodological papers, and targeted reviews that (i) discover or validate multimodal biomarker panels in FF including metabolomic/lipidomic, proteomic, extracellular vesicle-cargo, cell-free DNA/epigenomic signals and (ii) link them to concrete clinical end points—mature (MII) oocyte yield, fertilization, blastulation, euploidy, implantation, clinical pregnancy, and live birth. We particularly welcome:

· Omics-driven panels with transparent pipelines (quality control, normalization, drift correction), pre-specified modeling (e.g., nested cross-validation), and external validation;

· Condition-specific signatures, such as PCOS lipid panels (e.g., ceramides/FFAs) or endometriosis-related amino-acid shifts, including pathway analyses that are biologically interpretable;

· Assay translation such as targeted LC-MS panels and multiplex immunoassays demonstrating robustness to collection timing, follicle size, and stimulation regimen;

· Integrative models fusing FF panels with clinical covariates, embryology metrics, or embryo-level genomics/AI imaging;

· Standards and reporting checklists such as pre-analytics, contamination control, follicle-level vs patient-level inference, multi-follicle clustering.

By curating methodologically rigorous, clinically anchored studies, this collection aims to move the field from exploratory ‘hit lists’ to validated, implementable FF biomarker panels that improve patient counseling, reduce unnecessary embryo manipulation, and enhance IVF efficiency.

Keywords: Biomarker, follicular fluid, IVF, ovary, oocyte quality

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.