Clinical utility of sperm DNA fragmentation tests Aboubakr Elnashar Benha University Hospital, Egypt

Clinical utility of sperm DNA fragmentation tests Aboubakr Elnashar Benha University Hospital, Egypt

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  Clinical utility ofsperm DNA fragmentation tests Aboubakr Elnashar Benha University Hospital, Egypt Aboubakr Elnashar
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  CONTENTS 1. Origin ofSDF 2. Etiology of SDF 3. Assessment of SDF 4. Correlation between semen parameters & SDF 5. Correlation between clinical parameters & SDF 6. Clinical utility of SDF tests 2013 2014 2015  Conclusion 6Aboubakr Elnashar
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  1. ORIGIN OFSDF (Marin et al, 2012)  First line: Spermiogenesis/or spermatogenesis A breakdown in keys of cell system: -Apoptosis -DNA repair -Chromatin remodelin  Second line: • Increase radical oxygen species • Failure of antioxidant defense system during transport through male reproductive tractAboubakr Elnashar
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  2. ETIOLOGY OFSDF (Evgini et al, 2014) I. Primary Testicular Factors 1. Abnormal germ cell apoptosis 2. Advanced paternal age 3. Exposure to gonadotoxins 4. Sperm protamine deficiency 5. High level of ROS II. Extratesticular Factors 1. Smoking 2. Radiation 3. Chemotherapy 4. Genital tract inflammation 5. Testicular hyperthermia 6. Varicocele Aboubakr Elnashar
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  3. ASSESSMENT OFSDF TestPrincipleMethod TUNEL ISNT Incorporation of probes at the site of damage Direct SCSA SCD Comet Susceptibility of DBs to denature in acid solution Indirect Aniline blue Toluidine blue Incorporation of probes to nuclear proteins Chromatin incorporation (Feijo and Esteves, 2014) Aboubakr Elnashar
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  Aboubakr Elnashar
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  Normal= 10 Fragmented= 4 DFI=4X100/10+4 =28.5% normal normal normal normal normal normal normal normal normal fragmented fragmented fragmented fragmented normal ≥30: male infertility 15-30: RM. ≤15: Excellent to Good fertility potential Aboubakr Elnashar
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  4. CORRELATION BETWEENSEMEN PARAMETERS & SDF Majority of the studies: an inverse correlation between SDF rate and sperm quality (sperm concentration, motility, vitality and morphology), irrespective of the age of the subjects (Lo´pez et al, 2013; Evgini et al, 2014) A significant negative correlation between % of morphologically normal spermatozoa and SDF Aboubakr Elnashar
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  5. CORRELATION BETWEEN CLINICALPARAMETERS & SDF SDF showing correlations with 1. Fertilization rates 2. Embryonic development 3. Implantation 4. Pregnancy 5. Abortion rates 6. Congenital anomalies of the offspring (Evgini et al, 2014) Aboubakr Elnashar
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  6. CLINICAL UTILITYOF SDF TESTS ASRM, 2013 5 questions 1. Does SDF test predict male fertility with natural conception?  There is an association with increased SDF and reduced fertility in men (Simon, Lewis; 2011) Insufficient evidence (Level C) to use the test as a predictor of fertility {cut-points have not been clearly established and validated} Aboubakr Elnashar
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  2. Does SDFtest predict pregnancy with IUI? Conflicting A Level II-1study showed a positive predictive value of the SCSA test with DFI ≥30% associated with a lower PR and LBR. (Bungum et al, 2007) Other studies did not confirm the cutoff  Another study found no association with DNA integrity and pregnancy with IUI. Insufficient evidence (Level C) to recommend the use of SDF tests to predict pregnancy with IUI. Aboubakr Elnashar
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  3. Is SDFpredictive of pregnancy with in IVF? Meta-analysis (Zini et al, 2011) SDF was associated with a modest but significant. reduction in IVF. PR Insufficient evidence (Level C) to recommend routine use of SDF testing for patients undergoing IVF. Aboubakr Elnashar
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  4. Is SDFpredictive of pregnancy with IVF and ICSI? A meta-analysis (Collins et al, 2008) SDF was significantly associated with PR in IVF/ICSI cycles. Association was mild Predictive ability was weak. Test cut-offs were not clearly established. Aboubakr Elnashar
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  Meta-analysis [Zini etal, 2011] No consistent relationship between SDF and embryo quality and/or development. The influence of SDF on embryo quality/development may be more significant in ICSI compared to IVF cycles. Insufficient evidence (Level C) to recommend routine DNA integrity testing for patients undergoing IVF/ICSI. Aboubakr Elnashar
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  5. Is SDFpredictive of pregnancy loss?  A meta-analysis (Zini, 2008) significant association between SDF and pregnancy loss after IVF or ICSI  Insufficient evidence (Level C) to recommend routine DNA integrity testing to predict pregnancy loss. For diagnostic test 1. Results must be reproducible 2. Applicable to a given patient 3. Change management of patient Aboubakr Elnashar
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  II. British FertilitySociety, 2013 Testing of SDF shows much promise both as diagnostic test for male infertility and prognostic test for ART outcomes. SDF closely associated with fertility outcomes including Negative relationships with: fertilization, embryo quality, implantation Positive relationships with: miscarriage and childhood diseases. Aboubakr Elnashar
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  III. Evgni etal, 2014: Clinical indications for SDF tests 1.Prolonged idiopathic infertility 2.Low fertilization rate or bad quality embryos in IVF 3.Implantation failure following IVF 4.Repeated abortions 5.Prolonged exposure to toxic environmental conditions affecting fertility 6.Conventional seminal parameters found below the reference range 7.Advanced male partner age 8.Varicocele patients 9.Cancer patients Aboubakr Elnashar
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  Semen analysis Abnormal SDF T DFI≤30 ICSI DFI≥30 Lifestyle,antioxidant SDF T after 3 months Normal+ Female factor ICSIFailed Due to its strong correlation with several aspects of ART procedures and further consequences for the offspring: SDF T should be integrated in routine clinical practice (Evgni et al, 2014) Aboubakr Elnashar
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  Aboubakr Elnashar Osman etal, 2015: SR and MA LBR increased significantly in couples with low SDF compared with those with high SDF After IVF and ICSI, men with low SDF had significantly higher LBR A sensitivity analysis: no statistically significant difference in LBR between low and high SDF when ICSI was used
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  Aboubakr Elnashar Conclusion There isinsufficient evidence to recommend the routine use of SDF testing in evaluation and treatment of infertile couple {level C} ????????? For diagnostic test 1. Results must be reproducible 2. Applicable to a given patient 3. Change management of patient
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