| Table 1. Biomarkers analyzed in follicular fluid: a summary review results for oocyte evaluation in assisted reproductive technologies. | |||||
| Study | Study design | Oocyte quality predictor | Samples size | Main outcomes | p-value |
|---|---|---|---|---|---|
| Carpintero et al. (2014) |
Prospective cohort | Estradiol, progesterone, testosterone, DHEAS | FF from ICSI patients (n=31) | In FF with MII oocytes, testosterone positively correlated with progesterone (r=0.794 for normal fertilization; r=0.829 for failed fertilization) | <0.0001 both |
| Santonocito et al. (2014) | Crosssectional | miRNAs | FF from ICSI patients (n=15) | 37 upregulated in FF compared to plasma, with 32 in microvesicles expressing CD63 and CD81, impacting key follicle growth and oocyte maturation pathways | NA |
| Bastu et al. (2015) | Retrospective cohort | Cathepsin B | FF from IVF patients (n=79) | Cathepsin B levels, total oocytes, MII oocytes, and MII rate were higher in pregnant compared to nonpregnant patients | <0.05 all |
| Meijide et al. (2017) | Prospective case-control | PONs | FF from patients (n=155) | PONs activities were higher in larger follicles (diameter ≥18 mm) than in smaller ones (diameter <12mm); | <0.001 |
| In donors, PON1 arylesterase and paraoxonase activities showed positive correlations (R2=0.078 and R =0.073, resp.) | <0.05 both | ||||
| Fu et al. (2018) | Case-control | miRNAs | FF from ICSI patients (n=91) | MIR-663B was negatively expressed in FF of oocytes that yielded viable blastocysts compared to those that did not | 0.019 |
| Bouet et al. (2020) | Cross-sectional | Cytokine Profile | FF from IVF/ICSI patients (n=57) | PDGF-BB and RANTES was lower in DOR than NOR; | 0.05, 0.023, |
| MCP-1 and IL-1RA was elevated in DOR; | 0.030, 0.041 | ||||
| Fewer oocytes in DOR than NOR | 0.003 | ||||
| Karabulut et al. (2020) |
Prospective cohort | TAS; TOS | FF from ICSI patients (n=166) | Mature oocyte rates were decreased in the HOS group | 0.002 |
| Latif Khan et al. (2020) |
Prospective cohort | cfDNA; melatonin | FF (n=895) from IVF patients (n=325) | Intra-follicular cfDNA negatively correlated with elevated melatonin levels in FF samples of mature oocytes | <0.001 |
| Uppangala et al. (2020) |
Prospective cohort | E2; MDA | FF from ART patients (n=30) | Patients with poor ovarian response and serum E2 <2000pg/mL had elevated MDA levels, with an inverse relationship observed between serum E2 and follicular MDA levels | <0.01 both |
| Yi et al. (2020) | Prospective cohort | Prdx4 | FF from IVF/ICSI patients (n=138) | Pdx4 was positively correlated with the oocyte fertilization rate and showed a hight accuracy for clinical pregnancy prediction (AUC= 0.754) | 0.011,<0.01, resp. |
| Wyse et al. (2021) | Retrospective | Adiponectin; chemerin; Creactive protein; IL-6; IL-10; IL-18; insulin; leptin; prolactin; resistin; TNF-α; BMP- 15 | FF from IVF patients (n=44) | TNF-α and leptin were positive predictors of oocyte maturation (OR=10.2 and 1.2, resp., AUC=0.8); | 0.01, 0.04, resp. |
| IL-10 was predictive of oocyte maturation after controlling for BMI (OR 1.3x1012; AUC=0.98) | 0.02 | ||||
| Ekapatria et al. (2022) |
Cros-ssectional | Vitamin D | FF (n=77) from IVF patients (n=77) | Vitamin D level in FF was positively correlated with oocyte quality (r=0.32) | 0.01 |
| Molka et al. (2022) | Prospective and longitudinal |
IGF1; GH; IL-6; IL-7 | FF from IVF/ICSI patients (n=140) | GH, IGF1, and IL-6 values were higher in group of patients aged ≥ 35 or with development failure or RIF antecedent; | 0.001, 0.001, <0.05, resp. |
| ROC curve between IL-6 and implantation rate of ongoing pregnancy found an IL-6 cutoff >9.85pg/ml (AUC+0.6) | 0.04 | ||||
| Yu et al. 2022) | Prospective cohort | LH; FSH; cortisone | FF (n=136) from IVF/ICSI patients (n=138) | FF levels of 17-OHP, testosterone and cortisone level were lower in oocytes of top-quality blastocysts on D5 than the unfertilized group FF DHT concentrations were lower in fertilized follicles after ICSI than in follicles with unfertilized oocytes | <0.05 |
ART: assisted reproductive technology; BMP-15: bone morphogenetic protein 15; cfDNA: cell-free 913 DNA; DOR: diminished ovarian reserve; E2: estradiol; FF: follicular fluid; FSH: follicle-stimulating hormone; GH: growth hormone; HOS: high oxidative stress; ICSI: intracytoplasmic sperm injection; IGF1: insulin-like growth factor 1; IL: interleukin; IVF: in vitro fertilization; LH: luteinize ng hormone; MDA: malondialdehyde; MII: metaphase II oocyte; MCP-1: CCL2; miRNAs: microRNAs; NA: not applicable; NOR: normal ovarian reserve; PONs: paraoxonases; Prdx4: peroxiredoxin 4; RANTES: CCL5; 918 TAS: Total Antioxidant Status; TOS: Total Oxidant Status; TNF-α: tumor necrosis factor-alpha; DHEAS: dehydroepiandrosterone sulfate; DHT: dihydrotestosterone; 17-OHP: 17-hydroxy pregnenolone; D5: day 5; IL-1RA: IL-1 receptor antagonist; PDGF-BB: platelet-derived growth factor-BB.