| Table 4. Oocyte quality biomarkers in embryo assessment: a summary of review results for oocyte evaluation in assisted reproductive technologies. | ||||||
| Study | Study design | Time of |
Developmental quality predictor | Developmental stage grading | Main outcomes | p-value |
|---|---|---|---|---|---|---|
| Carpintero |
Prospective cohort | D3 | Estradiol; progesterone; testosterone | Ardoy et al. (2008) | Embryo qualities A and C, and B and C, differed in the estradiol/progesterone ratio; | 0.003, 0.0009 |
| Embryo qualities B and C differed in the estradiol/testosterone ratio | 0.001 | |||||
| Wirleitner |
Prospective cohort | D5 | Follicle size | Gardner et al. (2000) | Blastocyst rates were lower in small than in medium follicles, both per aspirated follicle (15.3% vs 27.9%) and Per COC (24.0% vs 36.4%); | <0.05 Both |
| The rate of top-quality blastocysts was 12.1% in small, 19.4% in medium and 14.3% in large follicles | NS | |||||
| Fu et al. (2018) | Case-control | D5 | MIR-663B | Top-scoring: blastocysts with good ICM and TE assessed as A or B (≥3BB); poor-scoring: blastocysts with few and large cells for ICM or TE assessed as C (<3BB) | Expression levels of FF MIR-663B for top-scoring embryos were lower than that of poor scoring | 0.003 |
| Latif Khan |
Prospective cohort | D3 | cfDNA; melatonin | Morphological criteria: i) cleavage rate and the number of blastomeres, ii) cytoplasmic appearance, iii) extent of fragmentation, iv) regularity in the symmetry of blastomeres | cfDNA was lower in FF related to oocytes that produced topquality embryos compared to low quality embryos | <0.001, |
| In non-pregnant women, oocytes from FF with lower melatonin levels resulted in embryos with higher fragmentation rates | < 0.001 | |||||
| McCulloh |
Prospective cohort | D5; D6 | Follicle size | Gardner et al. (2000) | Quality blastocysts were found to have an association with larger follicles | 0.01 |
| Scarica et al. (2019) | Prospective exploratory | Before TE biopsy | PTGS2; CAMK1D; HAS2 | Gardner & Schoolcraft (1999) | CAMK1D, PTGS2, and HAS2 were more highly expressed in GC of oocytes that resulted in embryos reaching the blastocyst stage than in those that experienced developmental arrest | 0.01, 0.05, 0.03, resp. |
| Shen et al. (2020) | Prospective observational | D3 | VCAN | Gardner & Sakkas (2003) | VCAN was positively correlated to embryo grade | 0.024 |
| Uppangala et al. (2020) | Prospective cohort | D3 | E2; MDA | Morphological criteria: grade I corresponded to stage-specific cell number, uniform blastomere size, without multinucleation, and no or <10%fragmentation | Patients with normal ovarian response and serum E2 between 2000-3000 pg/mL had |
<0.01 both |
| Patients with lower and higher levels had 40.74% and 51.88% compared to normal, resp. | < 0.01 | |||||
| Yi et al. (2020) | Prospective cohort | D3 | Prdx4; SOD | Good quality embryos contained at least 7 cells and with ≤ 10% of fragmentation | Prdx4 and SOD levels were positively correlated with good quality embryo rate | 0.013, 0.021 |
| Yuan et al. (2021) | Prospective experimental | T2; t4; t8; D5; D6 | LINE; LTRs | Not specified | DNA methylation in LINE (including L1, L2) and LTR was higher in PBIs of embryos that could not reach the blastocyst stage | <0.05 |
| Zhang et al. (2021a) | Prospective observational | D3; D5 | miR-103a-3p; miR-10a-5p | Good quality embryos developed from normal fertilized eggs with no or ≤ 1/3 fragmentation | miR-103a-3p and miR-10a-5p expression levels were increased in the subgroups in which oocytes did not develop into high-quality embryos on D3 or D5 | D3: 0.05, 0.01, resp. |
| Yu et al. (2022) | Prospective cohort | D3;D5 | LH;FSH; cortisone | High-quality embryos had 8 symmetrical, non-fragmented blastomeres on D3, and showed the development of ICM, the appearance of the TE, and the expansion of the blastocyst on D5 | FF LH, FSH, and cortisone were strong predictors of top-quality embryos on D5 | 0.037, 0.014, 0.04, |
| Machtinger |
Prospective cohort | D3 | r-hCG; GnRH-a | Top-quality embryo contained 7-8 equal blastomeres and ≤10% of fragmentation | There was no significant difference in the number of top-quality embryos between the r-hCG and GnRH-a stimulation protocol groups | NS |
CAMK1D: calcium/calmodulin-dependent protein kinase ID; cfDNA: cell-free DNA; COC: cumulus-oocyte complex; D2: day 2; D3: day 3; D5: day 5; D6: day 6; E2: estradiol; FF: follicular fluid; FSH: follicle stimulating hormone; GC: granulosa cells; GnRH-a: gonadotropin-releasing hormone GnRH agonist; HAS2: hyaluronan synthase 2; ICM: inner cell mass; LH: luteinizing hormone; LINE: long interspersed nuclear element; L1: LINEI; L2: LINE2; LTR: long terminal repeats; MDA: malondialdehyde; MIR-663b: microRNA-663B; NS: not significant; PBI: polar body I; Prdx4: peroxiredoxin 4; PTGS2: prostaglandin-endoperoxide synthase 2; r-hCG: recombinant human chorionic gonadotropin; SOD: superoxide dismutase; TE: trophectoderm; t2: two-cell stage; t4: four-cell stage; t8: eight-cell stage; VCAN: versican.