Role of intra-individual variation in the detection of thresholds for DFI and for misclassification rates: A retrospective analysis of 14,775 SCSA

backgroundSperm DNA damage is associated with reduced male fertility after natural conception and intrauterine insemination. However, the impact on in vitro fertilization (IVF) and especially intracytoplasmic sperm injection (ICSI) treatments is still unclear. Few studies have focused on the intra-individual variation in DFI even though it may have an important role to play in terms of detection of thresholds and for misclassification rates.

methodsResults for Sperm Chromatin Structure Assay (SCSA

resultsWhen DFI was above the thresholds of 15 and 25, a significant reduction in ongoing pregnancies after 12 weeks of gestation was observed for IVF and ICSI treatments, respectively. For IVF treatments, the pregnancy rate was reduced from 45.1% to 24.6%, odds ratio = 2.58 (p = 0.004). For ICSI treatments, the pregnancy rate was reduced from 48.6% to 29.6%, odds ratio = 2.00 (p = 0.032). Intra-individual variation was significantly related to the misclassification rate and the sample size required to identify a threshold. The percentage of patients with a DFI below 15 was 64.8% for the IUI cohort and 51.7% and 41.6% for cohorts of patients attending Sims IVF and FCH, respectively. The median DFI for these cohorts differed significantly and was 11.6, 15.0 and 17.2, respectively. DFI shows a seasonal variation, and increases with male age. During the past 15 years, the median DFI has increased by 0.05% per year (p = 0.02). DISCUSSION AND

conclusionsOngoing pregnancy rates are reduced significantly for both IVF and ICSI treatments when DFI is above the thresholds of 15 and 25, respectively. The misclassification rate and the required sample size increase with increasing intra-individual variation. Couples with a DFI above 15 are more likely to experience failed assisted reproductive technology (ART) cycles. DFI appears to have increased during the past 15 years.