partner recently smoked had a significantly lower live

birth rate with IVF or ICSI (7.8% vs 21.1% in nonsmoking

males) [24]. Furthermore, a significant association was identi-

fied between recent female smoking and the decreased ability

to retrieve ova during IVF [24]. A second study examined

221 couples undergoing IVF (aged

20 years) and found that

in couples in which either member had a positive smoking his-

tory, an increased relative risk (2.41) of not achieving a preg-

nancy was present (compared with nonsmoking couples) [25].

This relative risk was even higher (4.27) among couples that

had smoked for

5 years. This trend extended to women who

had smoked at some point in their lives (adjusted risk of

2.71 for not achieving a pregnancy).

Joesbury et al. [26] performed a study on 498 couples

undergoing IVF in which the male partner

’

s smoking resulted

in a significantly lower chance of achieving a 12-week preg-

nancy. These odds of pregnancy were decreased by 2.4% for

each additional year of male age, suggesting that smoking

and increasing male age acted in concert to affect fertility

potential. A study of 301 German couples demonstrated that

paternal smoking was associated with significantly reduced

success rates for IVF (18% vs 32% in nonsmokers) and ICSI

(22% vs 38% in nonsmokers) [27]. In fact, logistic regression

analyses found that paternal smoking was a significant risk

factor for IVF and ICSI failure, whereas maternal smoking

was a risk factor only for IVF failure. Thus, paternal smoking

may play at least as great a role in the success of assisted

reproduction techniques as maternal smoking.

Prenatal smoking exposure and future fertility

In addition to the effects of cigarette smoking on a man

’

semen parameters, exposure to cigarettes in utero may have

an impact on a man

’

s ultimate fertility in the future. Although

the studies in this area are limited, given the long-duration

follow-up that is required, several important pieces of data

are known.

A retrospective study of 1770 male European military

recruits demonstrated that men who had prenatal exposure to

smoking had a 20.1% lower sperm density as adults than

those recruits without such exposure [28]. Men with intrau-

terine smoking exposure also had modest but statistically sig-

nificant reductions in sperm motility and testis size. A more

focused study on 945 Danish men suggested a trend toward

decreasing sperm concentration in adult men with prenatal

exposure to maternal smoking, although the results did not

achieve statistical significance [29]. However, the cohort did

demonstrate a significantly increased risk for oligospermia

among men whose mothers smoked

10 cigarettes per day

during pregnancy. Unfortunately, the degree to which this

oligospermia translates to male fertility potential is not

known.

A further study by Storgaard et al. [30] observed that men

whose mothers were classified as high level smokers

(i.e.

10 cigarettes per day) during pregnancy had a 48%

lower sperm density than men who were not exposed to ciga-

rettes in utero. Of note, this association was not significant in

the subset of men whose mothers were in the lower smoking

category (i.e.

10 cigarettes per day during pregnancy),

suggesting dose dependence in the relationship between in

utero cigarette exposure and subsequent semen abnormalities.

Second-hand smoke and the effects on fertility

Smoking is not a risk factor but can still be considered in iso-

lation. Paternal first-hand smoking often results in maternal

second-hand smoke exposure, which can have further detri-

mental effects on female fertility. One retrospective study of

225 women undergoing IVF/ICSI found that women exposed

to second-hand smoke had implantation rates that were com-

parable to those of women who directly smoked (12.0% vs

12.6%) and were significantly lower than the implantation

rates of unexposed women (25.0%) [31]. Similarly, women

exposed to second-hand smoke experienced a significantly

lower pregnancy rate than women not exposed to cigarette

smoke (20.0% vs 48.3%) [31]. Although data examining the

direct effect of second-hand smoke on females attempting to

conceive naturally is limited, this exposure may decrease the

likelihood of achieving pregnancy by adversely affecting

both male and female factors.

Limitations and future directions

The previously published data on the effects of smoking on

infertility are not without limitations. First, much of the data

presented herein is retrospective in nature and, as such, there

is a dearth of longitudinal prospective literature examining

the relationship between smoking and infertility. Second, the

setting in which patients are selected for the studies are crit-

ical. For example, examination of the effects of smoking on

fertility among men with infertility and those undergoing vas-

ectomy reversal yields different results, as detailed above.

This dichotomy lends itself to diverse and sometimes con-

flicting study results. Nonetheless, evidence supporting an

adverse effect of smoking on several key semen parameters is

strong, irrespective of study design. Future studies should

attempt to further elucidate the possible mechanisms in this

relationship. Third, many of the studies reviewed utilize

semen analysis parameters as primary end points. Future

studies should also prospectively analyze the impact of smok-

ing on fertility while incorporating successful pregnancy rates

as main outcome measures.

Conclusion

Although a large volume of retrospective data exists examin-

ing smoking and the effects on semen analysis parameters

and IVF outcomes, large-scale, population-wide studies on

the effects of smoking on natural pregnancies are lacking.

Nevertheless, the majority of the evidence points to the fact

that men with infertility, or those having difficulty conceiv-

ing, should quit smoking to optimize their chances for suc-

cessful conception.

Declaration of interest

LI Lipshultz is a consultant and member of the speakers

’

bureaus of Auxilium, Lily, and Endo. JR Kovac is a National

340

J. R. Kovac et al.

Postgrad Med, 2015; 127(3):338

–

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