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Sperm DNA fragmentation testing as a general marker for pregnancy outcome in IVF patients. Marron K, Harrity C, Walsh D, Walsh APH. Sims IVF Clinic, Dublin.

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Presentation on theme: "Sperm DNA fragmentation testing as a general marker for pregnancy outcome in IVF patients. Marron K, Harrity C, Walsh D, Walsh APH. Sims IVF Clinic, Dublin."— Presentation transcript:

1 Sperm DNA fragmentation testing as a general marker for pregnancy outcome in IVF patients. Marron K, Harrity C, Walsh D, Walsh APH. Sims IVF Clinic, Dublin 14, Ireland. STUDY QUESTION Can sperm DNA fragmentation testing be used as a useful tool to predict ART outcome independent of female factors? INTRODUCTION Sperm DNA is packaged by nature in a different way compared to that of other cells due to the decreased size of a spermatozoa The DNA is arranged in very tight organised loops so that it can be carried safely and efficiently to the oocyte. Many obstacles must be overcome before successful fertilisation, not least of which is oxidative stress. Certain reactive oxygen species can “nick” the sperm DNA and cause DNA fragmentation in susceptible individuals. If such a sperm is accepted for fertilisation, errors in DNA transcription and synthesis can occur when maternal and paternal DNA join. The outcome is a negative cycle. We employed an in-house flow cytometer based DNA fragmentation test (SDA,) based on the technique developed by Evenson et al to retrospectively assess the contribution of male sperm integrity to pregnancy outcomes. SUMMARY ANSWER Sperm DNA fragmentation analysis (SDA) was retrospectively shown to be potentially an important independent variable in ART and thereby proves its inherent value as a useful laboratory test. WHAT IS KNOWN ALREADY Reactive oxygen species generated within sperm from IVF or indeed natural conception can have singularly destructive effects on susceptible sperm DNA and thus have knock on effects on fertilisation, embryo formation and pregnancy rate. Many techniques are available to determine this susceptibility but to-date none have shown a clear correlation between the technique used, the use of IVF or ICSI and the clinical pregnancy rate (CPR). STUDY DESIGN, SIZE, DURATION From January to August 2014, 231 SDA tests were performed on male partners of couples undergoing ART. The SDA outcomes were then retrospectively matched with the ART procedure employed and the clinical outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS An in-house sperm DNA fragmentation test (SDA) was developed based on the technique described by Evenson. Following validation versus commercially available SCSA the test was offered commercially within Sims IVF Clinic, Dublin. MAIN RESULTS AND THE ROLE OF CHANCE 231 sperm samples were analysed using this technique and centile charts of the distribution were calculated. At the time of analysis 137 cycles were performed in 104 of these couples, and the observed fragmentation rates were correlated with outcomes. Mean DFI was 21.4, with a standard deviation of 11.3. A DFI less than 21.4% was associated with a CPR with ICSI of 31.0% and IVF of 33.3% (p=0.84). In the group with “borderline” DNA fragmentation (21.4 to 32.7%) CPR was higher with ICSI than IVF, 31.3% vs. 16.7%. However, due to low patient numbers this difference was not statistically significant (p=0.44). No patients with a DFI above 31.4% had IVF used as the method of fertilisation. LIMITATIONS, REASONS FOR CAUTION There are a limited number of observations, giving insufficient statistical power to draw firm conclusions in the borderline DFI group. Although not described, clinical decisions were made based on many factors and so may have influenced the ongoing CPR independent of SDA values or assessment. WIDER IMPLICATIONS OF THE FINDINGS Sperm DNA fragmentation analysis is an unbiased laboratory technique with merit as part of a male evaluation in preparation for ART. Further research is needed to assess if couples with DFI between ~20 and 30% would truly benefit from ICSI rather than IVF. A power calculation demonstrates that 294 cycles would be needed to identify if the difference in pregnancy rates in this group of patients is statistically significant. A prospective RCT to assess this further would be beneficial to clarify the answer to this question.


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