Mean number of DNA breakpoints: illuminating sperm DNA integrity and in vitro fertilization outcomes

Abstract

ObjectiveTo verify the capacity of the mean number of DNA breakpoints (MDB) for evaluating sperm integrity and its relationship with in vitro fertilization (IVF) outcomes. DesignRetrospective cohort study. SettingReproductive center in a tertiary hospital.Patient(s): All men whose female partners underwent IVF from March to October 2022 in the reproductive center. Intervention(s)MDB and DNA fragmentation index (DFI) were used to assess sperm DNA integrity. The patients were stratified into two groups according to MDB and DFI cutoffs: sperm DNA-normal and sperm DNA-impaired. Main outcome measures(1) semen parameters: concentration, progressive motility (PR), MDB and the DFI; (2) IVF outcome measures: two pronuclei (2PN), fertilization rate, fertilization cleavage rate, high-quality embryo rate, biochemical pregnancy rate, clinical pregnancy rate, and implantation rate. ResultsSperm MDB had a higher negative correlation with PR compared to the DFI (r=-0.43, P<0.01; r=-0.37, P<0.01, respectively). Sperm MDB did not have a statistical correlation with sperm concentration, while the DFI correlated significantly with concentration (r=-0.17, P=0.07; r=-0.27, P<0.01, respectively). Logistic regression analysis controlling for age and semen concentration demonstrated that an increase in MDB increased the risk of asthenospermia (OR=1.018, 95% CI 1.003-1.034, P=0.02). An increasing DFI also increased the risk of asthenospermia (OR=1.044, 95% CI 1.002-1.087, P=0.04). MDB showed a stronger clinical relevance with sperm PR than the DFI, as indicated by the area under the curve (AUC) (0.754, 95% CI 0.649-0.859, P<0.01 vs. 0.691, 95% CI 0.556-0.825, P<0.01). A threshold of MDB over 0.37 nM was calculated to define sperm DNA-impaired. Comparison of IVF results showed that the high-quality embryo rate (χ2=13.00, P<0.01) was significantly lower in the DNA-impaired group than in the DNA-normal group stratified by MDB, while there were no significant differences in IVF outcomes in DFI-stratified groups. ConclusionMDB are verified to correlate closely with semen PR and may serve as a predictive parameter for IVF outcomes. Rigorous prospective studies are required to explore MDB performance and to further validate and reinforce the potential application of MDB as a parameter for male infertility.