found in a study by Saaranen et al. [8], who noted smokers
had lower semen volumes per ejaculate than nonsmokers
with a more specific inhibition occurring in men who
16 cigarettes per day.
Several smaller studies have corroborated the aforemen-
tioned findings. Zhang et al. [9] studied 362 Chinese men
attending an infertility clinic and found that smokers demon-
strated decreased semen volumes, sperm concentrations, and
rates of forward progression compared with nonsmokers. The
authors also examined the physiological basis for these
changes by testing seminal plasma levels of superoxide dis-
mutase, which is an enzyme that participates in the oxidative
stress pathway and has been previously shown to be lower in
the seminal plasma of infertile men [10,11]. Zhang et al.
found that superoxide dismutase levels were inversely corre-
lated with the amount and duration of cigarette smoking, sug-
gesting a relationship among smoking, oxidative stress, and
infertility. Another study of 200 infertile men found higher
rates of reduced sperm motility and abnormal sperm mor-
phology among smokers [12]. Chia et al. [13] reported simi-
lar results in 618 Chinese men. Within the cohort studied by
Chia et al., the lower sperm concentrations and higher rates
of abnormal sperm morphology identified in smokers were
also found to be dose dependent.
Merino et al. [14], who studied 358 Mexican men stratified
into 3 categories based on the number of cigarettes smoked
per day, also confirmed this type of dose dependency. The
authors confirmed the effects of smoking on reduced sperm
density and abnormal morphology, but also extended these
findings to note that men who smoked
10 cigarettes per day
experienced significant changes in their semen analysis param-
eters. Therefore, even
smokers appeared to be at risk
for adverse effects on fertility.
Interestingly, some studies have failed to establish the rela-
tionship between cigarette smoking and adverse effects on
semen parameters. The largest of these was a case-control
study of
2000 British men being treated for infertility [15].
Results from this study suggested that smoking was not an
independent risk factor for decreased concentrations of motile
sperm. However, additional sperm parameters, including
sperm morphology, were not assessed. Dikshit et al. [16]
found that neither cigarette smoking nor chewing tobacco
were significant risk factors for impaired semen quality
among 626 men presenting to infertility clinics. Hassa and
colleagues [17] noted similar results in a cohort of 223 Turk-
ish men. Furthermore, when 889 men presenting for vasec-
tomy were examined, no significant differences in sperm
density or motility were observed between smoking and non-
smoking men [18]. Of note, this particular study population
was not drawn from patients presenting for an evaluation of
male infertility, in contrast to many of the aforementioned
studies. Indeed, men presenting for vasectomy can be pre-
sumed to be fertile, suggesting variable effects of smoking in
men with infertility and those without. While highlighting the
importance of patient selection in examining the effects of
smoking on fertility, these studies do suggest that men with
difficulty conceiving should be counseled to stop smoking in
order to optimize their fertility outcomes.
In addition to the observational studies mentioned above,
a small number of meta-analyses have also been performed
to explore the relationships between cigarette smoking and
semen parameters [19,20]. One meta-analysis by Li et al.
[20] included 57 observational studies and
29000 men.
Findings were applied to infertile as well as fertile men, and
cigarette smoking had adverse effects on all sperm parame-
ters, including semen volume, sperm density, total sperm
counts, and percentage of sperm with progressive motility.
An earlier, second meta-analysis by Vine et al. [19] found
that smokers had a 13% to 17% lower sperm density than
nonsmokers. To summarize, cigarette smoking affects semen
analysis outcomes in infertile men. Thus, those men with fer-
tility difficulties should be counseled to stop smoking as soon
as possible to optimize their reproductive potential.
Mechanisms by which smoking affects male
reproductive outcomes
Some authors have attempted to provide mechanistic explana-
tions for the observed link between cigarette exposure and
abnormal semen parameters. In a study of 147 Chinese men,
Liu et al. [21] examined the relationship between seminal zinc
levels and semen parameters. The authors found that smokers
had lower seminal zinc levels than nonsmokers, with associ-
ated decreases in sperm concentration, motility, and morphol-
concentrations did not experience the same degree of abnor-
mal semen parameters as those smokers with decreased semi-
nal zinc, suggesting that zinc concentrations could play a role.
There is also evidence to suggest that the adverse effects
of smoking may not be due exclusively to the toxins found in
cigarette smoke. Indeed, a study examining the effects of oral
nicotine on male rats found that rats exposed to oral nicotine
experienced significant decreases in sperm motility and sperm
count [22]. Thus, nicotine may also play an important role in
the adverse effects of smoking on fertility, independent of the
toxins found in the smoke. Interestingly, parameters affected
by oral nicotine were improved following 30 days of cessa-
tion, suggesting a component of reversibility to these effects.
Furthermore, a study of 210 men suggested that men with
higher cotinine concentrations in the seminal plasma also had
a greater percentage of abnormal sperm morphology [23].
Because cotinine is a metabolite of nicotine, these findings
further the theory that nicotine itself may be a possible driver
of the adverse effects of smoking on fertility. Further studies
are needed to determine the exact role of nicotine in the
pathogenesis of semen analysis and morphology changes.
Smoking and assisted reproduction
Not only can smoking have unfavorable effects on male semen
parameters, it may also reduce the success of assisted repro-
duction techniques, such as
in vitro
fertilization (IVF) and
intracytoplasmic sperm injection (ICSI). Paternal smoking has
been suggested to contribute to decreased IVF success rates.
Indeed, a study of 166 couples undergoing assisted reproduc-
tion techniques demonstrated that couples in which the male
DOI: 10.1080/00325481.2015.1015928
Smoking and male fertility
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