{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:20:41Z","timestamp":1780604441567,"version":"3.54.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"Background<\/jats:title>Angiogenesis in folliculogenesis contributes to oocyte developmental competence in natural and in vitro<\/jats:italic> fertilization (IVF) cycles. Therefore, the identification of key angiogenic factors in follicular fluid (FF) during folliculogenesis is clinically significant and important for in vitro<\/jats:italic> fertilization. This study aims to identify the key angiogenic factors in FF for predicting oocyte maturity during in vitro<\/jats:italic> fertilization.<\/jats:p><\/jats:sec>Materials and methods<\/jats:title>Forty participants who received ovarian stimulation using a GnRH antagonist protocol in their first in vitro<\/jats:italic> fertilization treatment were recruited. From each patient, two follicular samples (one preovulatory follicle, &gt; 18\u00a0mm; one mid-antral follicle, &lt; 14\u00a0mm) were collected without flushing during oocyte retrieval. In total, 80 FF samples were collected from 40 patients. The expression profiles of angiogenesis-related proteins in FF were analyzed via<\/jats:italic> Luminex high-performance assays. Recorded patient data included antral follicle count, anti-m\u00fcllerian hormone, age, and BMI. Serum samples were collected on menstrual cycle day 2, the trigger day, and the day of oocyte retrieval. Hormone concentrations including day 2 FSH\/LH\/E2\/P4, trigger day E2\/LH\/P4, and retrieval day E2\/LH\/P4 were measured by chemiluminescence assay.<\/jats:p><\/jats:sec>Results<\/jats:title>Ten angiogenic factors were highly expressed in FF: eotaxin, Gro-\u03b1, IL-8, IP-10, MCP-1, MIG, PAI-1 (Serpin), VEGF-A, CXCL-6, and HGF. The concentrations of eotaxin, IL-8, MCP1, PAI-1, and VEGF-A were significantly higher in preovulatory follicles than those in mid-antral follicles, while the Gro-\u03b1 and CXCL-6 expressional levels were lower in preovulatory than in mid-antral follicles (p<\/jats:italic> &lt; 0.05). Logistic regression and receiver operating characteristic (ROC) analysis revealed that VEGF-A, eotaxin, and CXCL-6 were the three strongest predictors of oocyte maturity. The combination of VEGF-A and CXCL-6 predicted oocyte maturity with a higher sensitivity (91.7%) and specificity (72.7%) than other combinations.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings suggest that VEGF-A, eotaxin, and CXCL-6 concentrations in FF strongly correlate with oocyte maturity from the mid-antral to preovulatory stage. The combination of VEGF-A and CXCL-6 exhibits a relatively good prediction rate of oocyte maturity during in vitro<\/jats:italic> fertilization.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1173079","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T11:35:30Z","timestamp":1691667330000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of potential angiogenic biomarkers in human follicular fluid for predicting oocyte 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