Table 3. Biomarkers encompassing miRNAs, morphology parameters, DNA methylation, and patient characteristics: a summary of review results for oocyte evaluation in assisted reproductive technologies.
Study Study design Oocyte quality predictor Samples size Main outcomes p-value
Wirleitneret al. (2018) Prospective cohort Follicle size Follicles from IVF patients (n=118) Oocyte recovery was lower in small follicles (63.8%) versus medium (76.6%) and large (81.3%); Estradiol and progesterone levels were higher in large compared to medium and small follicles 0.001, 0.01, 0.05, resp.
Martinez et al. (2019) Cross-sectional Phenols and phthalates; EVmiRNAs FF EV-miRNA from IVF patients (n=130) Select urinary phenol and phthalate biomarkers are associated with altered expression of eight FF EV-miRNAs <0.05
McCulloh et al. (2020) Prospective cohort Follicle size Follicles from oocyte donors (n=22) The incidence of MII oocytes was significantly associated with larger follicle size (mm) (ROC’s AUC=0.87) <0.0001
Yuan et al. (2021) Prospective experimental LINE, LTRs, and methylation alterations in PBI promoter PBIs and sibling MII oocytes (n=74) from donors (n=6) PBI methylome aligns closely with sibling MII oocyte (r=0.92); elevated LINE & LTR methylation noted in PBIs not progressing to blastocyst <0.05 both
Zhang et al. (2021a) Prospective observational EV-miRNAs; BDNF FF EV-miRNA from ART patients (n=56) BDNF mRNA and protein levels were higher in FF from mature follicles; <0.01, <0.05, resp.
miR-103a-3p and miR-10a-5p expressions had negative correlations with BDNF mRNA levels in FF <0.01 both
Bartolacciet al. (2022) Systematic review Oocyte dismorphisms Systematic Review (study size=76) Negative outcomes were associated with COC Morphology, SER, vacuoles, and granulometry with an OLS 8.33,7.78, 7.14, and 6.25, resp. NA
Tepla et al. (2022) Prospective observacional cohort MS visibility and relative position to the PB on oocyte maturity IVF patients (n=679) Patients >35 years: 32% PR 58/182) with and 24% PR (47/195) without MS visualization <0.1 both
Machtingeret al. (2023) Prospective cohort r-hCG, GnRH-a, EV-miRNA FF EV-miRNA from IVF patients (n=91) r-hCG stimulation protocol group had fewer oocytes retrieved and fewer mature oocytes than the GnRH-a group; 0.02 both
41 EV-miRNAs expression levels significantly differed between the two protocols <0.05

ART: assisted reproductive technology; BDNF: brain-derived neurotrophic factor; COC: cumulus-oocyte complex; EV miRNA: extracellular vesicle microRNA; FF: follicular fluid; GnRH-a: gonadotropin-releasing hormone agonist; IVF: in vitro fertilization; LINE: hypermethylated long interspersed nuclear element; LTRs: long terminal repeats; MII: metaphase II; microRNA: micro RNA; MS: meiotic spindle; NA: not applicable; OLS: oocyte literature score; PB: polar body; PR: pregnancy rate; r-hCG: recombinant human chorionic gonadotropin; ROC: receiver operating characteristic; SER: smooth endoplasmic reticulum aggregates.