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

Objective: To verify the capacity of the mean number of DNA breakpoints (MDB) for evaluating sperm integrity and its relationship with in vitro fertilization (IVF) outcomes.

Design: Retrospective cohort study.

Setting: Reproductive 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): The 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: Semen parameters: concentration, progressive motility (PR), MDB, and the DFI; IVF outcome measures: two pronuclei (2-PN), fertilization rate, fertilization cleavage rate, high-quality embryo rate, biochemical pregnancy rate, clinical pregnancy rate, and implantation rate.

Results: Sperm MDB had a higher negative correlation with PR compared with the DFI (r = -0.43; r = -0.37, respectively). Sperm MDB did not have a statistical correlation with sperm concentration, whereas the DFI correlated significantly with concentration (r = -0.17; r = -0.27, respectively). Logistic regression analysis controlling for age and semen concentration demonstrated that an increase in MDB increased the risk of asthenospermia (odds ratio = 1.018, 95% confidence interval [CI] 1.003-1.034). An increasing DFI also increased the risk of asthenospermia (odds ratio = 1.044, 95% CI 1.002-1.087). The MDB showed a stronger clinical relevance with sperm PR than the DFI, as indicated using the area under the curve values (0.754, 95% CI 0.649-0.859 vs. 0.691, 95% CI 0.556-0.825). A threshold of the MDB >0.37 nM was calculated to define sperm DNA-impaired. Comparison of IVF results showed that the high-quality embryo rate (χ = 13.00) was significantly lower in the DNA-impaired group than in the DNA-normal group stratified using the MDB, although there were no significant differences in IVF outcomes in DFI-stratified groups.

Conclusion: The MDB has been 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.