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

smoked

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

“

light

”

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-

ogy.

Interestingly,

smokers

with

normal

seminal

zinc

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

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