P-036 Female age affects the combined impact of DNA fragmentation and high DNA stainability on embryo development in intracytoplasmic sperm injection cycles

Abstract

Abstract Study question To investigate the role of female age in regulating the co-effect of DNA fragmentation index (DFI) and high DNA stainability (HDS) on ICSI embryological outcomes. Summary answer When female age exceeded 35, co-exposure high DFI and middle HDS might delay embryonic development after ICSI treatment. What is known already Sperm DNA damage had a negative influence on embryonic development. Oocytes and embryos have adopted specific response and repair mechanisms to repair sperm DNA damage. However, the DNA repair capacity in the oocyte is limited and likely decline with increasing age. Study design, size, duration This historical cohort study was included 1334 couples underwent ICSI from January 2017 to December 2022. An unsupervised K-means clustering method was used to divide participants into three clusters base on DFI value and HDS value, as follow: cluster 1 with low DFI values and low HDS values (lDFI-lHDS group), cluster 2 with middle DFI values and high HDS values (mDFI-hHDS group), and cluster 3 with high DFI values and middle HDS values (hDFI-mHDS group). Participants/materials, setting, methods All participants were further stratified into female age<35 subgroup and female age≥35 subgroup. The univariate and multivariate linear regression model was used for statistical analysis. Multivariate model was adjusted for female factor (including age, AMH, basal FSH and the numbers of retrieved oocyte) and male age which were significantly correlated with embryo development in univariate models. The main outcome measure was D5 blastocyst development rate and D6 blastocyst development rate. Main results and the role of chance In the female age<35 subgroup, D5 blastocyst development rate in the mDFI-hHDS group (48.53% [25.00%, 66.67%] and the hDFI-mHDS group (50.00% [28.57%, 71.07%]) was significantly higher than that in the lDFI-lHDS group (40.00% [0.00%, 63.96%]). No significant differences were observed between the three groups regarding D6 blastocyst development rate. And univariate model and multivariate model showed that the mDFI-hHDS group (adjusted B value=0.36, 95% CI: 0.08∼0.64, P=0.010) and hDFI-mHDS group (adjusted B value=0.41, 95% CI: 0.12∼0.70, P=0.006) had higher D5 blastocyst development rate compared with lDFI-lHDS group. In the female age≥35 subgroup, D5 blastocyst development rate in the hDFI-mHDS (20.00% [0.00%, 50.00%]) group was significantly lower than that in the lDFI-lHDS group (36.93% [0.00%, 66.67%]) and the mDFI-hHDS group (41.43% [0.00%, 63.54%]). Accordingly, D6 blastocyst development rate in the hDFI-mHDS group (66.67% [33.33%, 100.00%]) was significantly higher than that in the lDFI-lHDS group (50.00% [16.67%, 80.00%]) and the mDFI-hHDS group (50.00% [33.33%, 66.67%]). And both model showed that hDFI-mHDS group (adjusted B value=0.73, 95% CI: 0.36∼1.11, P<0.001) had higher D6 blastocyst development rate compared with the lDFI-lHDS group. Although not statistically significant, hDFI-mHDS had negative correlation with D5 blastocyst development rate. Limitations, reasons for caution The main weakness of this study was the participants were not randomized. Wider implications of the findings hDFI-mHDS group were negatively associated with D5 blastocyst development rate and positively related with D6 blastocyst development rate in female age≥35 subgroup. These results suggested that co-exposure high DFI and middle HDS might be recommended as a predictor for the detection of delayed embryo development when female age exceeded 35. Trial registration number not applicable