Clinical utility of sperm DNA fragmentation tests

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

2. 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 reproduAbcoutbiavkr eEln atsrhaar ct

3. 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

4. Assessment of SDF
Method Principle Test
Direct Incorporation of probes
at the site of damage
TUNEL
ISNT
Indirect Susceptibility of DBs to
denature in acid
solution
SCSA
SCD
Comet
Chromatin
incorporation
Incorporation of probes
to nuclear proteins
Aniline blue
Toluidine blue
(Feijo and Esteves, 2014)
Aboubakr Elnashar

5. 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
Aboubakr Elnashar

6. 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)
Aboubakr Elnashar

7. Clinical utility of SDF tests
I.ASRM, 2013
1. Does SDF test predict male fertility with natural
conception?
Fair evidence (Level B) that increased SDF is
associated with reduced fertility
Insufficient evidence (Level C) to use the test as a
predictor of fertility since cut-points have not been
clearly established and validated.
Aboubakr Elnashar

8. 2. Does SDF test predict pregnancy with IUI?
Insufficient evidence (Level C) to recommend the
use of SDF tests to predict pregnancy with IUI.
3. Is SDF predictive of pregnancy with in IVF?
Insufficient evidence (Level C) to recommend
routine use of SDF testing for patients undergoing
IVF.
4. Is SDF predictive of pregnancy with IVF and
ICSI?
Insufficient evidence (Level C) to recommend
routine DNA integrity testing for patients undergoing
IVF/ICSI.
Aboubakr Elnashar

9. 5. Is SDF predictive of pregnancy loss?
 Insufficient evidence (Level C) to recommend
routine DNA integrity testing to predict
pregnancy loss.
 Recommendation
There is insufficient evidence to recommend the
routine use of SDF testing in evaluation and
treatment of infertile couple {level C}
Aboubakr Elnashar

10. 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.
Aboubakr Elnashar

11. 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
Aboubakr Elnashar

12. Sources
1.Evgini E, Charalabopoulos K, Asimakopoulos B.
Sperm DNA fragmentation and its correlation with
conventional semen parameters. J Reprod Infertil.
2014;15:2-14.
2.ASRM. The clinical utility of DNA fragmentation
testing, Guidelines. Fertil Steril 2013;99:673-77
3.Lo´pez J, Lafuente R, Checa M, Carreras R and
Brassesco M. Diagnostic value of sperm DNA
fragmentation. Asian J Androl 2013;15:790–4
4.Feijo C, and Esteves S. Diagnostic accuracy of sperm
chromatin dispersion test. Fertil Steril 2014,101:58-63
5.Marín C, Gosálvez J, Roy R. Types, causes, detection
and repair of DNA fragmentation in animal and human
sperm cells. Int J Mol Sci. 2012,13:14026-52 Aboubakr Elnashar

13. Aboubakr Elnashar
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