Integrative follicular fluid biomarkers for oocyte competence and IVF outcomes: from molecular networks to multianalyte panels
- 1Department of Obstetrics and Gynecology, China Medical University Hospital
- 2Department of Medicine, School of Medicine, China Medical University
Abstract
Accurate assessment of oocyte developmental competence remains a major challenge in assisted reproductive technology because conventional morphological grading and ovarian-reserve markers provide limited information about the molecular state of individual follicles. Follicular fluid offers a minimally invasive window into this microenvironment, integrating systemic endocrine inputs with bidirectional oocyte–somatic cell communication, steroidogenesis, metabolic coupling, extracellular-matrix remodeling, periovulatory inflammation, redox homeostasis, mitochondrial function, and angiogenesis. This narrative review synthesizes mechanistic and clinical evidence concerning follicular-fluid biomarkers associated with oocyte maturity, fertilization, embryo development, blastocyst formation, implantation, and live birth. Particular attention is given to granulosa cell-associated signaling networks involving epidermal growth factor-like ligands, pentraxin 3, transforming growth factor-β and bone morphogenetic protein family members, activins and follistatin, glial cell line-derived neurotrophic factor, cytokines, steroid hormones, metabolic intermediates, lipids, oxidative-damage markers, and extracellular-matrix components. Available evidence indicates that individual analytes generally lack sufficient reproducibility, discrimination, and calibration for routine clinical prediction because their concentrations are influenced by patient phenotype, ovarian-stimulation regimen, follicular stage, sampling strategy, preanalytical handling, analytical platform, and outcome definition. Follicular heterogeneity and the statistical non-independence of multiple oocytes obtained from the same patient further complicate biomarker evaluation. We therefore propose a transition from single-analyte measurements toward mechanism-informed, outcome-specific multianalyte panels integrating follicular-fluid measurements with cumulus- or granulosa-cell transcriptomic, proteomic, metabolomic, and lipidomic features. Phenotype-specific models, particularly for polycystic ovary syndrome, may further improve biological interpretation. Clinical translation will require standardized individual-follicle sampling, one-to-one linkage between biomarkers and oocyte or embryo outcomes, targeted assay development, multilevel statistical modeling, independent prospective validation, and demonstration of incremental clinical utility beyond established patient and embryological variables. The ultimate goal is a parsimonious and reproducible biomarker panel that complements, rather than replaces, conventional embryological assessment and supports more individualized IVF decision-making.
Related
- A practical approach to follicular-patterned thyroid neoplasms: Diagnostic criteria, molecular genetics, and patient management
- The PancreaSure Multianalyte Blood Test Performs Well at Distinguishing Early-Stage Pancreatic Ductal Adenocarcinoma from High-Risk Controls: A Retrospective Secondary Analysis
- Integrative transcriptomics and metabolomics reveal Cry1-associated hepatic alterations and plasma essential fatty acids as biomarkers of residual circadian disruption post-sepsis
- Integrative proteomic and machine learning strategies identify key biomarkers associated with response to JAK inhibitor in rheumatoid arthritis.
- Single-Cell RNA Sequencing Reveals Molecular Differences Underlying Meiotic Competence of Brilliant Cresyl Blue (BCB) Selected Alpaca Oocytes.
BibTeX
@article{chen2026integrative,
title = {{Integrative follicular fluid biomarkers for oocyte competence and IVF outcomes: from molecular networks to multianalyte panels}},
author = {Chih-Ying Chen and Yu-Ting Lu and Po-Han Chang and Hsuan-Ju Chen and Ya-Wen Hsueh and Chia-Wei Chang and Hsi-Chen Hsu and Tung-Chuan Yang and Yin-Yi Chang and Hsun-Ming Chang},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1962631},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1962631/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative follicular fluid biomarkers for oocyte competence and IVF outcomes: from molecular networks to multianalyte panels
AU - Chih-Ying Chen
AU - Yu-Ting Lu
AU - Po-Han Chang
AU - Hsuan-Ju Chen
AU - Ya-Wen Hsueh
AU - Chia-Wei Chang
AU - Hsi-Chen Hsu
AU - Tung-Chuan Yang
AU - Yin-Yi Chang
AU - Hsun-Ming Chang
PY - 2026
DA - 2026/10/19
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1962631
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1962631/full
AB - Accurate assessment of oocyte developmental competence remains a major challenge in assisted reproductive technology because conventional morphological grading and ovarian-reserve markers provide limited information about the molecular state of individual follicles. Follicular fluid offers a minimally invasive window into this microenvironment, integrating systemic endocrine inputs with bidirectional oocyte–somatic cell communication, steroidogenesis, metabolic coupling, extracellular-matrix remodeling, periovulatory inflammation, redox homeostasis, mitochondrial function, and angiogenesis. This narrative review synthesizes mechanistic and clinical evidence concerning follicular-fluid biomarkers associated with oocyte maturity, fertilization, embryo development, blastocyst formation, implantation, and live birth. Particular attention is given to granulosa cell-associated signaling networks involving epidermal growth factor-like ligands, pentraxin 3, transforming growth factor-β and bone morphogenetic protein family members, activins and follistatin, glial cell line-derived neurotrophic factor, cytokines, steroid hormones, metabolic intermediates, lipids, oxidative-damage markers, and extracellular-matrix components. Available evidence indicates that individual analytes generally lack sufficient reproducibility, discrimination, and calibration for routine clinical prediction because their concentrations are influenced by patient phenotype, ovarian-stimulation regimen, follicular stage, sampling strategy, preanalytical handling, analytical platform, and outcome definition. Follicular heterogeneity and the statistical non-independence of multiple oocytes obtained from the same patient further complicate biomarker evaluation. We therefore propose a transition from single-analyte measurements toward mechanism-informed, outcome-specific multianalyte panels integrating follicular-fluid measurements with cumulus- or granulosa-cell transcriptomic, proteomic, metabolomic, and lipidomic features. Phenotype-specific models, particularly for polycystic ovary syndrome, may further improve biological interpretation. Clinical translation will require standardized individual-follicle sampling, one-to-one linkage between biomarkers and oocyte or embryo outcomes, targeted assay development, multilevel statistical modeling, independent prospective validation, and demonstration of incremental clinical utility beyond established patient and embryological variables. The ultimate goal is a parsimonious and reproducible biomarker panel that complements, rather than replaces, conventional embryological assessment and supports more individualized IVF decision-making.
SN - 1664-2392
ER -