Tobacco smoke is the most studied exposure to be examined in the proposed study, yet decades of research have failed to provide the evidence needed to make a definitive statement about its effects on sperm quality. Considered collectively, it is challenging to describe the pattern of results produced by previous studies due to large variability across study populations and numerous methodological limitations, however, there is some indication that smoking may alter testicular and post-testicular events, though exactly how and for which parameters is undetermined. There is also some suggestion that the effects may be small (251), possibly limited to subgroups (e.g. fertility status) and are likely to act in concert with other modifiable behaviors, particularly alcohol consumption and/or caffeine intake (138, 139). The epidemiologic data on alcohol consumption, though much more limited, is clearer to the extent that heavy, long-term drinking has been demonstrated to severely impair spermatogenic function and hormonal regulation in a cascade of pathologic events. However, the impacts of moderate alcohol consumption, a more prevalent and socially-accepted behavior, on sperm count and quality have not been established. Moreover, early evidence suggesting that even small amounts may induce aneuploidy,
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underscores the importance of continued research in this area. Data on the effects of caffeine intake and BMI in relation to sperm quality are limited, but suggestive, although there is not enough information to draw conclusions. Additional research, such as that which is described in this dissertation research, is necessary to foster a clearer
understanding of the effects these prevalent lifestyle factors are having on the reproductive health of men.
Inconsistency in the effects of lifestyle factors reported by previous sperm quality studies is likely a function of two primary factors. The first factor is the heterogeneity in both the country of study and source population. Thirty-three countries are represented in the literature. Variation in the source population of study subjects is another consideration, as men were recruited from the community, sperm donors clinics, urology offices, hospitals and birthing centers, although the majority of subjects (~ 60%) were recruited form infertility clinics. Geographic variation in sperm quality has been reported in the literature (231) and could account for some of the inconsistency observed in sperm count and concentration. From an exposure standpoint, cultural differences as determinates of socially acceptable behaviors may lead to differential reporting by country of study origin. There may also be differences across countries with respect to constituents and production of tobacco and alcohol products, which may also explain some of the variability in results.
Limitations in methodology are also likely to have contributed to the lack of consistency in sperm quality study results. Threats to internal validity are the most
concerning. Having the greatest impact on internal validity have been the limitations related to biases introduced with respect to subject selection, exposure classification and
uncontrolled confounders. Other limitations include lack of consideration for etiologically relevant time frame, small sample sizes, crude exposure assessment and probable low participation rates.
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Recruitment of study subjects from infertility clinics introduces the potential for selection bias because those that presented themselves for evaluation and treatment related to the inability to conceive may also be different with respect to factors associated with the exposures of interest. For example, this population, which by definition had been attempting conception for at least one year, may have also abstained from other activities such as tobacco smoking and alcohol use; it is also possible that the couple’s infertility is due to exposures to other potential toxicants (137). Nearly two-thirds of the tobacco literature comes from cross-sectional studies of men attending infertility clinics.
Another potential source of selection bias was likely to arise from low participation rates. As this information was rarely, if ever, reported it is not possible to directly make such an assessment. However, sperm quality studies are known to have very low participation rates and there is no reason to expect the studies examining the role of lifestyle factors to be markedly different.
Subject selection for case-control studies was problematic as well. Unfortunately, each of the seven studies incorrectly selected subjects for the control group by recruiting only subjects with proven fertility, using either men with a pregnant partner or those with a normal spermiogram (23, 36, 76, 158, 174, 264, 265). The inclusion of only healthy men in the control group introduces bias in the odds ratio because the control group does not represent the base population that gave rise to the cases (181). Selecting “healthy” controls usually leads to an upward bias of the study results (Rothman and Greenland, 1995).
Differential misclassification of exposure is another possible source of bias introduced by sperm quality studies. In several studies, exposure status (smoker v. non- smoker) was assigned based on either fertility status or one of the outcome parameters measured in the study. The most typical scenario was selecting the unexposed such that they had proven fertility and normal semen analyses according to the standards of the World
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Health Organization (123, 148, 282). This leads to a mixing of the effects of fertility and the exposure of interest when analyzing the sperm parameter outcomes measured in a study. Validity is, to some extent, compromised and conclusions about the etiologic role of lifestyle factors on sperm quality parameters are unclear.
Few studies adjusted for potential confounders, which by definition are factors
related to both the exposure and outcome. Sperm count and quality are influenced by many factors, which may also be related to lifestyle factors. Age, duration of abstinence, presence of medical conditions, occupational exposures and other lifestyle habits are some of the potential confounders that must be considered in etiologic research of sperm quality studies so that the influences of the exposure(s) of interest can be isolated. Without adjusting for confounders there is a mixing of effects and it is not clear if the putative agent is responsible for the observed effect or another factor that was not evaluated. While most studies
controlled medical conditions through restriction of study subjects, statistical adjustment for other potential confounders was often neglected.
Use of simple exposure assessment is another area in which there is room for improvement. Exposure assessment was also lacking in the use of time frames that are relevant to spermatogenesis, which is approximately three months. In addition, many studies suffer from very small sample sizes, affecting the power of the study to detect smaller effect sizes (21, 272).
Not all of the semen quality literature is flawed, as there are several robust studies (196, 249, 252, 279). These methodologically stronger studies provide a basis from which to better gauge the range of exposure/outcome effect estimates. In a systematic literature review of 24 studies conducted from 1966 to 1996 on cigarette smoking and sperm quality, Vine et al. (249) reported a mean reduction of 13% in sperm concentration, a mean
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In another-well designed study of twenty-five eighteen year old men from the Czech
Republic, results indicated a range of alterations in sperm count and quality associated with smoking status, with a 41% decrease in sperm count, a 54% decrease in sperm
concentration, and a 69% decrease in total number of motile sperm cells (279). In another small, but well-conducted study of 29 infertility clinic patients, decrements in seminal parameters were also associated with smoking status. Specifically, current smokers had a reduction of 20% in total sperm count, 21% in motility and 27% in normal morphology compared to smokers (196). Other strong studies on the effects of smoking and sperm quality did not observe differences in standard sperm quality parameters between smokers and non-smokers (201). Data on the sperm quality impacts for the other exposures (alcohol consumption, caffeine intake, increased adiposity) are much more limited.
Additional research is needed to supplement the information provided by these high- quality studies. The present study incorporates the necessary improvements needed to refine and extend our understanding of the etiologic relationship between lifestyle exposures and measures of sperm quality.