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Background: Sperm 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.
Methods: Results for Sperm Chromatin Structure Assay (SCSA) tests performed for 70 European fertility clinics between January 1, 2008 and December 31, 2022 were examined. A small retrospective study included 406 couples receiving their first treatment with IVF or ICSI. These results were then used for a mathematical simulation to investigate the role of intra-individual variation. The large retrospective study included a total of 14,138 diagnostic tests and 637 tests from an IUI study. The distribution of DFI was assessed for the IUI cohort and cohorts of patients attending Sims IVF and Fertility Center Hamburg (FCH). Descriptive analysis of the data was performed regarding time of year, male age, and year.
Results: When 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 Conclusions: Ongoing 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.
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Source |
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http://dx.doi.org/10.1111/andr.13801 | DOI Listing |
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