Efficient Metabolic Fingerprinting of Follicular Fluid Encodes Ovarian Reserve and Fertility

Ovarian reserve (OR) and fertility are critical in women's healthcare. Clinical methods for encoding OR and fertility rely on the combination of tests, which cannot serve as a multi-functional platform with limited information from specific biofluids. Herein, metabolic fingerprinting of follicular fluid (MFFF) from follicles is performed, using particle-assisted laser desorption/ionization mass spectrometry (PALDI-MS) to encode OR and fertility. PALDI-MS allows efficient MFFF, showing fast speed (≈30 s), high sensitivity (≈60 fmol), and desirable reproducibility (coefficients of variation <15%). Further, machine learning of MFFF is applied to diagnose diminished OR (area under the curve of 0.929) and identify high-quality oocytes/embryos ( p < 0.05) by a single PALDI-MS test. Meanwhile, metabolic biomarkers from MFFF are identified, which also determine oocyte/embryo quality ( p < 0.05) from the sampling follicles toward fertility prediction in clinics. This approach offers a powerful platform in women's healthcare, not limited to OR and fertility.