Cumulus Cell DNA Damage as an Index of Human Oocyte Competence

Abstract

The determination of oocyte quality is crucial for achieving effective syngamy post-sperm injection and embryonic development. Cumulus cells (CCs) have been proposed as biomarkers of oocyte quality because of their close bio-dynamic relationship with the oocyte. To determine the quality of the oocyte, CCs were sampled during oocyte preparation for ICSI to determine a CC DNA fragmentation index (CCDFI) of each individual oocyte using a variant of the chromatin dispersion test. One hundred and thirty oocytes were selected and studied from two Spanish fertility clinics, 90 of which were fertilized and developed to embryos. Significant differences were found between the CCDFI of unfertilized and fertilized oocytes (p < .001) and between the CCDFI of embryos that were discarded and those that developed suitable for transfer or cryopreservation (p < .001). Oocyte quality was negatively correlated with CCDFI (Spearman's rho = - 0.45; p < .001). Receiver operator characteristics curves (ROC) suggested that a cut-off value of 24% CCDFI was able to discriminate the capacity of the gametes to result in syngamy with a sensitivity and specificity of 75.6% and 65%, respectively. This cut-off supports the application of CCDFI as potential index for the evaluation of the reproductive potential of oocytes prior to fertilization.

Keywords: Biomarker; Cumulus cells (CCs); DNA fragmentation; Embryo quality; IVF/ICSI; Oocyte quality.

Fig. 1

Visualization of DNA fragmentation in CCs using the chromatin dispersion assay

Fig. 2

Box-Whisker plots of the CCDFI with respective to (A) increasing levels of oocyte quality (B) embryos rejected by the embryologist (REJ) and those incubated for 3–5 days (EMB) before transfer and (C) grade quality of the embryos produced based in morphological parameters

Fig. 3

Green line ROC curve shows the ability of CCDFI to predict fertilized oocytes (FEO) and those that were not fertilized (NOI + UFO; AUC, .769; 95% CI [0.68–0.86]; SE, 0.046; p < .001). Blue line ROC shows the ability of CCDFI to predict embryos that were rejected by the embryologist (REJ) and those that were suitable for transfer and/or cryopreservation (AUC, .775; 95% CI [0.68–0.87]; SE, 0.048; p = .001). Red line ROC shows the ability of CCDFI to predict embryos reaching 3–5 days of development (AUC, 0.808; 95% CI [0.74–0.88]; SE, 0.037; p < .001)