Clinical utility of sperm DNA fragmentation tests Aboubakr Elnashar Benha University Hospital, Egypt
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Transcript of 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
Aboubakr Elnashar
CONTENTS 1. Origin of SDF
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
6 Aboubakr Elnashar
1. ORIGIN OF SDF (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 tract Aboubakr Elnashar
2. ETIOLOGY OF SDF (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
3. ASSESSMENT OF SDF
Test Principle Method
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)
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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
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4. CORRELATION BETWEEN SEMEN
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
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5. CORRELATION BETWEEN
CLINICAL PARAMETERS & 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)
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6. CLINICAL UTILITY OF 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}
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2. Does SDF test 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.
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3. Is SDF predictive 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.
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4. Is SDF predictive 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.
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Meta-analysis [Zini et al, 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.
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5. Is SDF predictive 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
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II. British Fertility Society, 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.
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III. Evgni et al, 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
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Semen analysis
Abnormal
SDF T
DFI≤30
ICSI
DFI≥30
Lifestyle, antioxidant
SDF T after 3 months
Normal+ Female factor
ICSI Failed
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)
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Osman et al, 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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Conclusion
There is insufficient 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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