Follicular fluid biomarkers for prediction of human IVF outcome in women with poor ovarian response

Background: The aim of controlled ovarian stimulation is to achieve an optimal number of mature oocytes to obtain good-quality embryos. High follicular fluid (FF) concentrations of FSH, hCG, and LH promote oocyte maturation and are associated with a higher probability of fertilization. LH concentrations in FF are consistently higher in follicles that will lead to a successful IVF outcome. The levels of some of these FF biomarkers may vary among different ovarian stimulation schemes; however, the effects of corifollitropin alfa, recombinant FSH (rFSH), LH (rLH), and highly purified urinary menotropins uhMG on these biomarkers are still unknown. The objective of this study was to characterize the profile of FF biomarkers (leptin, vascular endothelial growth factor (VEGF), metalloproteinases (MMPs), and NO2−/NO3−) according to three different protocols of controlled ovarian stimulation (COS) in poor ovarian responders (POR) and to evaluate the association between these profiles and clinical outcomes. Three groups of POR patients were examined according to the protocols used. Results: Group C showed significant higher levels in all biomarkers (p < 0001). FF samples from Group B had the lowest levels of VEGF and Pro-MMP-9. Group A showed the lowest concentration of pro-MMP-2. The VEGF level and number of captured oocytes were positively correlated in Group C (r = 0.534, p = 0.01). MMP-9 and fertilization rate were negatively correlated in Group C (r = −0.476, p = 0.02). We found negative correlations between proMMP-2 and serum estradiol levels on the day of rhCG administration. Conclusion: We found significant variations in the biomarker concentrations between the different controlled ovarian stimulation schemes used in POR patients. These differences can be potentially explained by the nature and composition of the gonadotropins. Our results support the hypothesis that some of these molecules should be thoroughly investigated as noninvasive predictors of egg quality.