Understanding the Role of
Oxidative Stress on Sperm
Function, and Why Men Should
Take Antioxidants While They
are Trying to Conceive
Oxidative stress to sperm
from free radicals can cause
both loss of motility and
damage to their DNA. This
oxidative damage can take
place within the male
reproductive tract (e.g. due
to infections) and can also
sometimes occur in the
laboratory during assisted
reproduction procedures
(e.g. excessive sperm
“washing”). It occurs more
readily in infertile men as
they often have only about
half of the levels of
naturally occurring
antioxidants in their semen,
as compared to fertile men.
The growing body of
literature in this area
might explain why some men,
in spite of having
apparently normal semen
samples, are still infertile
(“unexplained” infertility).
Several studies published
over the past 10 years or so
have suggested that taking
oral antioxidants can
protect sperm and improve
their function by increasing
the antioxidant levels in a
man’s semen (although, it
must be said, some others
did not show any benefit).
On the whole, however, it
would seem that men who are
trying to conceive – and
certainly those with poor
sperm quality or who are at
high risk of oxidative
damage to their sperm –
should consider taking a
vitamin preparation designed
for men who are trying to
conceive, e.g. FertilAid,
AstaCarox , or Fertile One.
References
Agarwal A, Saleh RA, Bedaiwy
MA. Role of reactive species
in the pathophysiology of
human reproduction. Fertil
Steril 2003; 79: 829-843.
Agarwal A, Prabakaran SA,
Said TM. Prevention of
oxidative stress injury to
sperm. J Androl 2005; 26:
654-660.
Aitken RJ, De Iuliis GN.
Origins and consequences of
DNA damage in male germ
cells. Reprod Biomed Online
2007; 14:727-733.
Balercia G, Regoli F, Armeni
T, et al. Placebo-controlled
double-blind randomized
trial on the use of L-carnitine,
L-acetylcarnitine, or
combined L-carnitine and L-acetylcarnitine
in men with idiopathic
asthenozoospermia. Fertil
Steril 2005; 84: 662-671.
Comhaire F, Mahmood A. The
role of food supplements in
the treatment of the
infertile man. reprod Biomed
Online 2003; 7: 385-391.
Eskenazi B, Kidd SA, Marks
AR, et al. Antioxidant
intake is associated with
semen quality in healthy
men. Hum Reprod 2005; 20:
1006-1012.
Greco E, Iacobelli M, Rienzi
L, et al. Reduction of the
incidence of sperm DNA
fragmentation b oral
antioxidant treatment. J
Androl 2005; 26: 349-353.
Kodama H, Yamaguchi R,
Fukuda J, et al. Increased
oxidative deoxyribonucleic
acid damage in the
spermatozoa of infertile
male patients. Fertil Steril
1997; 68: 519-524.
Loft S, Kold-Jensen T,
Hjollund NH et al. Oxidative
DNA damage in human sperm
influences time to
pregnancy. Hum Reprod 2003;
18:1265-1272.
Lopes S, Jurisicova A, Sun
J-G, et al. Reactive oxygen
species: potential cause for
DNA fragmentation in human
spermatozoa. Hum Reprod
1998; 13: 896-900.
Nakamura H, Kimura T,
Nakajima A, et al. Detection
of oxidative stress in
seminal plasma and
fractionated sperm from
subfertile male patients.
Eur J Obstet Gynecol Reprod
Biol 2002; 105: 155-160.
Pasqualotto FF, Sharma RK,
Kobayashi H, et al.
Oxidative stress in
normospermic men undergoing
infertility evaluation. J
Androl 2001; 22: 316-322.
Pasqualotto FF, Sharma RK,
Nelson DR, et al.
Relationship between
oxidative stress, semen
characteristics, and
clinical diagnosis in men
undergoing infertility
investigation. Fertil Steril
2000; 73: 459-464.
Potts RJ, Notarianni LJ,
Jefferies TM. Seminal plasma
reduces exogenous oxidative
damage to human sperm,
determined by the
measurement of DNA strand
breaks and lipid
peroxidation. Mutation
Research 2000; 447: 249-256.
Saleh RA, Agarwal A, Sharma
RK et al. Effect of
cigarette smoking on levels
of seminal oxidative stress
in infertile men. Fertil
Steril 2003; 79: 1469-1470.
Sigman M, Glass S,
Campagnone J, Pryor JL.
Carnitine for the treatment
of idiopathic asthenospermia:
a randomized, double-blind,
placebo-controlled trial.
Fertil Steril 2006; 85:
1409-1414.
Sikka SC. Relative impact of
oxidative stress on male
reproductive function. Curr
Med Chem 2001; 8: 851-862.
Twigg J, Fulton N, Gomez E,
et al. Analysis of the
impact of intracellular
reactive oxygen species
generation on the structural
and functional integrity of
human spermatozoa: lipid
peroxidation, DNA
fragmentation and
effectiveness of
antioxidants. Hum Reprod
1998; 13: 1429-1436.
Wang X, Sharma RK, Sikka SC,
et al. Oxidative stress is
associated with increased
apoptosis leading to
spermatozoa DNA damage in
patients with male factor
infertility. Fertil Steril
2003; 80: 531-535.
Whittington K, Harrison S.,
Williams, KM et al. Reactive
oxygen species (ROS)
production and the outcome
of diagnostic tests of sperm
function. Int J Androl 1999;
22: 236-242.
The
Beneficial Role of Dietary
Supplementation (Vitamins)
As mentioned already,
several studies published
over the past 10 years or so
have suggested that taking
oral antioxidants can
protect sperm and improve
their function by increasing
the antioxidant levels in a
man’s semen. There is now
sufficient evidence that
probably any man who is
trying to conceive, and
certainly those with poor
sperm quality or who are at
high risk of oxidative
damage, should take a
vitamin preparation designed
for men who are trying to
conceive, e.g. FertilAid;
AstaCarox , or Fertile One.
However, it also seems that
taking excessive amounts of
vitamin C can have adverse
effects upon sperm DNA and
actually decrease male
fertility.
Smoking can also decrease
the amount of ascorbic acid
(vitamin C) that is found
naturally in the semen,
adversely affecting male
fertility. Research has
shown that smoking (by
either the man or the woman)
can dramatically decrease
your chance of success with
assisted reproduction
treatment, and this is one
of the possible mechanisms
of action for how smoking
affects male fertility.
References
Akmal M, Qadri JQ, Al-Waili
NS, et al. Improvement in
human semen quality after
oral supplementation of
vitamin C. J Med Food 2006;
9: 440-442.
Comhaire F, Mahmood A. The
role of food supplements in
the treatment of the
infertile man. reprod Biomed
Online 2003; 7: 385-391.
Eskenazi B, Kidd SA, Marks
AR, et al. Antioxidant
intake is associated with
semen quality in healthy
men. Hum Reprod 2005; 20:
1006-1012.
Fraga CG, Motchnik PA,
Shigenaga MK, et al.
Ascorbic acid protects
against endogenous oxidative
DNA damage in human sperm.
Proc Natl Acad Sci USA 1991;
88: 11003-11006.
Greco E, Iacobelli M, Rienzi
L, et al. Reduction of the
incidence of sperm DNA
fragmentation b oral
antioxidant treatment. J
Androl 2005; 26: 349-353.
Keskes-Ammar L,
Feki-Chakroun N, Rebai T, et
al. Sperm oxidative stress
and the effect of an oral
vitamin E and selenium
supplement on semen quality
in infertile men. Arch
Androl 2003; 49: 83-94.
Lenzi A, Lombardo F, Sgro P,
et al. Use of carnitine
therapy in selected cases of
male factor infertility: a
double-blind crossover
trial. Fertil Steril 2003;
79: 292-300.
Matalliotakis I, Koumantaki
Y, Evangeliou A, et al. L-carnitine
levels in the seminal plasma
of fertile and infertile
men: correlation with sperm
quality. Int J Fertil Womens
Med 2000; 45: 236-240.
Ménézo YJ, Hazout A, Panteix
G, et al. Antioxidants to
reduce sperm DNA
fragmentation: an unexpected
adverse effect. Reprod
Biomed Online. 2007; 14:
418-421.
Mostafa T, Tawadrous G,
Roaia MM, et al. Effect of
smoking on seminal plasma
ascorbic acid in infertile
and fertile males.
Andrologia. 2006; 38:
221-224.
Song GJ, Norkus EP, Lewis V.
Relationship between seminal
ascorbic acid and sperm DNA
integrity in infertile men.
Int J Androl 2006; 29:
569-575.
Xu DX, Shen HM, Zhu QX, et
al. The associations among
semen quality, oxidative DNA
damage in human spermatozoa
and concentrations of
cadmium, lead and selenium
in seminal plasma. Mutat Res
2003; 534: 155-163.
Zhou X, Liu F, Zhai S.
Effect of L-carnitine and/or
L-acetyl-carnitine in
nutrition treatment for male
infertility: a systematic
review. Asia Pac J Clin Nutr
2007; 16 Suppl 1: 383-390.
Understanding the Role Sperm
DNA (Chromatin) Plays in
Fertility
There has been a great deal
of research in recent years
into how sperm DNA damage
affects fertility. This is
so important because sperm
can appear normal under the
microscope, but not be able
to make a healthy embryo –
and so miscarriages or other
complications can occur.
Many women have gone through
all kinds of expensive
procedures, only to find
after a great deal of time
and money, that their
husband’s sperm chromatin
quality was insufficient to
support a term pregnancy.
There are many sperm DNA
tests out there, but none
have been as thoroughly
validated as the “Sperm
Chromatin Structure Assay”
or SCSA®
(see some of the review
articles listed below about
this). Dr. Don Evenson, who
developed this test, has a
laboratory dedicated solely
to this assay and can work
with you and your doctor to
both get the assay done and
to interpret the results.
Have a look at their website
(www.SCSAdiagnostics.com)
for more information about
sperm chromatin and sperm
DNA damage and diagnostic
testing (including lots more
references), about how to
have a sperm sample
evaluated for chromatin
damage using the SCSA®.
If your infertility
specialist doesn’t know
about this test, or won’t
order it for you, you can
actually send the sample to
the SCSA®
Diagnostics lab yourself and
Dr. Evenson will provide the
interpretation!
Consider having the SCSA®
done:
● if you
have been trying to
conceive for more than
one year, or
● if you have had two or
more miscarriages in a
row, or
●
if your husband smokes,
is on antidepressants or
has had a vasectomy
reversal, or
● before you go for
assisted reproduction.
References
Agarwal A, Said TM. Role of
sperm chromatin
abnormalities and DNA damage
in male infertility. Hum
Reprod Update 2003; 9:
331-345.
Aitken RJ, De Luliis GN.
Origins and consequences of
DNA damage in male germ
cells. Reprod Biomed Online
2007; 14: 727-733.
Alvarez JG, Sharma RK,
Ollero M, et al. Increased
DNA damage in sperm from
leukoctyospermic semen
sample. Fertil Steril 2002;
78: 319-329.
Boe-Hansen GB, Fedder J,
Ersbøll AK, Christensen P.
The sperm chromatin
structure assay as a
diagnostic tool in the human
fertility clinic. Hum Reprod
2006; 21: 1576-1582.
Bungum M, Humaidan P, Axmon
A, et al. Sperm DNA
integrity assessment in
prediction of assisted
reproduction technology
outcome. Hum Reprod 2007;
22: 174-179.
Bungum M, Humaidan P, Spano
M, et al. The predictive
value of sperm chromatin
structure assay (SCSA)
parameters for the outcome
of intrauterine
insemination, IVF and ICSI.
Hum Reprod 2004; 19:
1401-1408.
De Jonge. The clinical value
of sperm nuclear DNA
assessment. Hum Fertil 2002;
5: 51-53.
Erenpreiss J, Bungum M,
Spano M, Elzanaty S,
Orbidans J, Giwercman A.
Intra-individual variation
in sperm chromatin structure
assay parameters in men from
infertile couples: clinical
implications. Hum Reprod
2006; 21: 2061-2064.
Evenson DP, Jost LK,
Marshall D, et al. Utility
of sperm chromatin structure
assay as a diagnostic and
prognostic tool in the human
fertility clinic. Hum Reprod
1999; 14: 1039-1049.
Evenson DP, Jost LK, Corzett
M, et al. Characteristics of
human sperm chromatin
structure following an
episode of influenza and
high fever. J Androl 2000;
21: 739-776.
Evenson D, Wixon R.
Meta-analysis of sperm DNA
fragmentation using the
sperm chromatin structure
assay. Reprod Biomed Online
2006; 12: 466-472.
Evenson DP, Wixon R.
Comparison of the Halosperm
test kit with the sperm
chromatin structure assay (SCSA)
infertility test in relation
to patient diagnosis and
prognosis. Fertil Steril.
2005; 84: 846-849.
Giwercman A, Richthoff J,
Hjolland H, et al.
Correlation between sperm
motility and sperm chromatin
structure assay parameters.
Fertil Steril 2003; 80:
1404-1412.
Irvine DS, Twigg J, Gordon
E, et al. DNA integrity in
human spermatozoa:
relationship with semen
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Janny L, Menezo YJR.
Evidence for a strong
paternal effect on human
preimplantation embryo
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Larson-Cook KL, Brannian JD,
Hansen KA, et al.
Relationship between the
outcomes of assisted
reproductive techniques and
sperm DNA fragmentation.
Fertil Steril 2003; 80:
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Razavi S, Nasr-Esfahani MH,
Mardani M, et al. Effect of
human sperm chromatin
anomalies on fertilization
outcome post-ICSI.
Andrologia 2003; 35:
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Saleh RA, Agarwal A, Sharma
RK, et al. Evaluation of
nuclear DNA damage in
spermatozoa from infertile
men with varicocele. Fertil
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Spano M, Bonde JP, Hjollund
HI, et al. Sperm chromatin
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Tarozzi N, Bizzaro D,
Flamigni C, Borini A.
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Virro MR, Larson-Cook KL,
Evenson DP. Sperm chromatin
structure assay (SCSA)
parameters are related to
fertilization, blastocyst
development, and ongoing
pregnancy in in vitro
fertilization and
intracytoplasmic sperm
injection cycles. Fertil
Steril 2004; 81: 1289-1295.
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