Background

Infertility is a common health problem in today’s world and is defined as the failure to become pregnant after at least 12 months of regular and unprotected intercourse [1]. The existing reports indicate an infertility prevalence of 9–18% in the general population, so approximately 48.5 million couples experience this problem worldwide [2, 3]. According to Kazemijaliseh et al., the prevalence of infertility in Iran was higher than that at the global level [4].

The impact of environmental and occupational factors on reproductive health cannot be ignored due to the modernization of life and societies. Some studies reported the effect of occupational hazards, including the methods of pest control by agricultural pesticides [5], heat stress [6], prolonged sitting, and long working hours [7] on the rate of preterm birth and low birth weight [8], spontaneous abortion [9], and menstrual disorders [7].

Limitless waste, use of fossil fuels, deforestation, air pollution [10], the release of hazardous gases from car exhausts and factories [11], and consumption of fast foods along with excessive consumption of canned foods [12] can be a danger alarm for couples by lowering the semen quality [13], hormonal changes, endocrine disruptions, and depletion of ovarian reserves [14]. Infertility has increased due to new lifestyles because today’s people are at a higher risk compared to the people in the past [12].

Giaccio et al. found that environmental exposure to heavy metals was correlated with the poor quality of human semen [15]. Chemicals such as bisphenol A and phthalates can endanger reproductive health although their impact on the prevalence of infertility requires further discussion [16, 17]. Further, researchers reported that exposure to phthalates is associated with decreased sperm concentration, number, and motility [18].

Occupational factors also increase infertility, especially male infertility. Government jobs are an example. The high prevalence of abnormal semen in government employees can be due to their long hours of sitting or standing [19, 20]. In a study by Chia et al., the prevalence of abnormal sperm disorders such as asthenospermia and teratosthenospermia in government employees was higher compared to that in other occupations. Self-employed, driving, simple, and industrial workers had the most abnormal semen parameters after employee jobs. Lower-quality semen was found in simple and industrial workers, which may be due to prolonged standing, more contact with pollutants and environmental toxins, and the use of various paints and industrial coatings [21]. In a study conducted on urban people, the level of asthenospermia and asthenotratospermia was higher than that of other sperm disorders. This is probably due to the fact that the effects of environmental pollutants and polluted air as well as the density of factories are higher in the city, justifying the further reduction of the sperm quality in these areas [22]. Owing to the increasing prevalence of infertility in the world, it is essential to identify its causes in order to help infertile couples. Various studies reported that several factors cause infertility, including environmental and occupational factors. Accordingly, the present systematic review study sought to evaluate the impacts of environmental and occupational factors on the increased risk of infertility.

Main text

Search strategy

In the present study, PubMed, SID, Scopus, and Web of Science databases were searched to access related papers using the keywords of ‘Environmental exposure’ OR ‘Environmental pollutants’ OR ‘Occupational exposure’ OR ‘Environmental pollution’ AND ‘Couple infertility’ OR ‘Sterility’ OR ‘Subfertility’ as well as their Persian equivalents. Totally, 6825 studies were extracted using the advanced search features in the initial review. The titles and abstracts were then examined to determine the extent to which they met the inclusion criteria.

Inclusion criteria

The inclusion criteria were observational (i.e., cohort, cross-sectional, and case-control) systematic review, meta-analysis, and clinical trial studies examining the impact of environmental and occupational factors on reproductive parameters and the increased risk of infertility, access to full texts of studies, and papers published in Persian and English between 2007 and January 2019.

Extract data related to exposure

All the studies related to environmental and occupational factors affecting infertility were collected, and a list of abstracts of the articles was prepared after completing the search. At this point, all articles using the selected keywords in their titles were added to the initial list while removing other articles that examined other issues related to infertility. Then, a checklist of the necessary information for the study was provided, including the name of the researcher, the title of the article, the year and place of the study, the sample selection method, the number of samples, and the type of study in the subgroups, followed by reviewing the final checklist. The articles were separately evaluated by two reviewers (SZM and SA). Further, in cases of disagreement, the opinion of a third party (FK) was taken into account. Finally, articles related to the title of the study were reviewed to find the required data, and a total of 5842 papers that were not related to the topic of the study were excluded from this review, and 983 studies that were related to the topic of the present study remained. Among these, 283 studies were duplicates (studies published by one author on several databases), and 634 animal studies were excluded from the study. In line with research objectives, 66 papers met the inclusion criteria, and their full texts were obtained from the databases (Fig. 1).

Fig. 1
figure 1

Flowchart of the paper selection process

Full size image

Quality evaluation

The quality of observational studies was investigated based on the Newcastle and Ottawa [23] checklist, which examines the selection, comparison, and consequence items for evaluating the quality of studies (i.e., cohort, case-control, and cross-sectional types). This checklist includes items for investigating six sections: title and abstract, introduction, method, results, discussion, and other information. Accordingly, the studies were divided into good, medium, and poor-quality groups. Good quality studies included three or four stars in the selection section, one or two star(s) in the comparison, and two or three stars in the consequence. Medium-quality studies had two stars in the selection, one or two star(s) in the comparison, and two or three stars in the consequence. Finally, poor-quality studies were those receiving zero or one star in the selection, zero star in the comparison, and zero or one star in the consequence. Additionally, the quality of systematic review and meta-analysis studies [24] was evaluated based on the AMSTAR checklist. It contains 16 items related to the content of one systematic review and meta-analysis, consisting of the title, abstract, introduction, methods, results, discussion, and funding. Furthermore, the quality of the clinical trial study was evaluated according to Juni’s study [25].

Results

In the present study, 66 papers met the inclusion criteria, the findings of which are presented in Tables 1, 2, and 3.

Table 1 Papers assessing the impact of various conditions on reproductive and infertility indices
Full size table
Table 2 Papers assessing the impact of heavy metals on reproductive and infertility indices
Full size table
Table 3 Papers assessing the impact of occupational factors on reproductive and infertility indices
Full size table

Some studies compared living conditions and the prevalence of risk factors in two groups of fertile and infertile individuals. Other studies focused on the role of environmental and occupational factors in reproductive ability through in vitro examinations. The present study investigated the impacts of heavy metals, cigarette smoking, exposure to chemicals through consumer goods, urban living, and proximity to main roads on reproductive parameters. It also explored the effects of occupational factors such as heavy physical activity, prolonged sitting, presence in a hot environment, and exposure to formaldehyde, pesticides, insecticides, mechanical vibration, and ionizing radiation on reproductive indices.

Table 1 provides data regarding articles evaluating the impact of chemicals and environmental pollutants (n=33), air pollution (n=5), smoking (n=4), ambient temperature (n=1), and ionizing radiation (n=4) on reproductive and infertility indices.

It was found that exposure to chemicals and environmental pollutants is associated with decreased sperm concentration, motility, and count [27], increased androgen-estrogen ratios [29], decreased semen volumes [28], decreased antral follicle growth [34], endocrine disruption [38], and increased oxidative stress [26, 48]. The effect of smoking on spermatogenesis, ovarian reserve, hormonal balance, semen quality, and oxidative stress was also discussed in the reviewed investigations [26, 59]. In addition, two studies comparing infertile people and those with children reported a higher rate of smoking in the infertile group [60, 62].

One cohort study revealed that proximity to major roads was associated with an increased incidence of primary and secondary infertility due to a high rate of air pollution [63]. Environmental contamination with sperm DNA damage can also affect fertility in an individual [64]. Contact with ionizing radiation is also associated with mutations in sperm genetic material [68, 69]. Moreover, one study pointed to the impact of iodine therapy in childhood on infertility in adulthood [70]. In addition, high-temperature environments may affect fertility in men by affecting semen quality and spermatogenesis [72] as illustrated in Table 1.

Table 2 summarizes the literature (eight articles) evaluating the impact of heavy metals on reproductive indices and the increased risk of infertility. Exposure to heavy metals through the environment and food was associated with decreased sperm concentration, motility, and morphology [73, 74, 78, 80]. The serum levels of heavy metals were found to be higher in infertile women compared to those in fertile women [77].

Table 3 provides data related to studies on the effect of occupational factors on reproductive parameters and the risk of infertility (11 articles). Based on the findings, performing heavy and long-term physical activity was correlated with a decrease in the number of antral follicles [82]. Workers with heavy physical activity are also more prone to infertility due to damage to the testicles and a decrease in semen quality [88]. Moreover, coal furnace workers experienced greater reductions in sperm motility and normal morphology in comparison with the control group [90]. Further, people exposed to contaminated areas and industrial chemicals had higher percentages of lead and cadmium in their semen plasma [85] (Tables 4, 5 and 6).

Table 4 Quality assessment of studies (cohort, case-control, and cross-sectional) (Newcastle and Ottawa checklist)
Full size table
Table 5 Quality assessment of systematic review and meta-analysis studies (AMSTAR checklist)
Full size table
Table 6 Quality assessment of clinical trial study (according to Juni’s study)
Full size table

Discussion

The present study reviewed the effects of environmental and occupational factors on reproductive parameters after collecting 66 papers according to the inclusion criteria. However, the risk of infertility was somewhat unclear in the studied populations.

In a prospective study by Minguez-Alarcon et al. women working longer and moving heavier objects had a lower number of antral follicles and mature oocytes [82]. In a cohort study by Gaskins et al. on 1739 women, those working more than 40 h per week became pregnant later than those who worked 21–40 h per week [83]. Similarly, Mahboubi et al. found that workers who worked hard were more likely to have lower fertility because of damage to testicles, which reduced semen quality [88]. However, Celina Lepecka-Klusek et al. studied 224 men and reported that difficult activity was not significantly correlated with a semen quality decline [81]. Dangerous physical conditions (e.g., carrying heavy loads, bending over, and straightening while working) may have a negative effect on pregnancy and fertility efficiency in women, especially when they are threatened by other hazards such as a history of miscarriage or other hazardous conditions at work. The mechanism of the action of these factors is unknown, and their negative effect may be due to reduced oxygen and nutrient supply or hormonal system disruption [93]. Prolonged physical activity with an increase in body temperature and the testis may adversely affect the process of spermatogenesis. Previous research demonstrated that the mean scrotal temperature in infertile men with varicocele was higher than normal, and high testicular temperature changes the integrity of sperm DNA [94].

In the field of exposure to pesticides and insecticides, Aneck-Hahn et al. conducted a study in South Africa and found that men using pesticides to control malaria have a lower ejaculatory volume [52]. In their cross-sectional study, Daoud et al. observed that occupational exposure to pesticides was associated with asthenozoospermia, necrozoospermia, and oligozoospermia [87]. Occupational toxins such as organochlorine, organophosphate, carbamate, pyrethroids, and other pesticides directly impair sperm structure by damaging testicular cells or indirectly by disrupting the hormonal regulation of spermatogenesis. These disorders occur as decreased sperm production, incomplete sperm production, and androgen production disorders [95].

Hai-xu Wang examined the impact of occupational exposure to formaldehyde in two groups of men with and without exposure to formaldehyde. Based on their results, there were no statistically significant differences in the semen volume, concentration, and total count in both groups although the total number of the motile sperm was lower in the formaldehyde-exposed group compared to control men [84]. De Fleurian concluded that various physical and chemical occupational factors such as mechanical vibration, heat, prolonged sitting, exposure to chemicals, and heavy metals could affect semen quality. More precisely, mechanical vibration was associated with oligospermia and teratospermia, while exposure to high temperatures and prolonged sitting was related to lower mobility. However, no association was found between exposure to ionizing radiation and electromagnetic fields with lower semen quality [86], and oxidative stress caused by heavy metals was reported in abnormal sperm function and male infertility [96].

Toxic metals have been studied for centuries. These pollutants affect human health through the food chain, water pollution, and inhalation of air pollutants. To rehabilitate land damaged by heavy metals, some low-cost efficiencies and approaches need to be widely promoted. Research has demonstrated that there is a direct link between high concentrations of heavy metals in the blood and urine and abnormal spermograms. Part of the toxic effects of heavy metals on the sperm is due to impaired motility and cessation of sperm motility [74]. In another study, Moran-Martinez et al. determined the effects of heavy metals on the performance of reproductive indices and indicated that exposure to lead in the environment was associated with decreased sperm concentrations and motility and increased sperm abnormalities [73]. Furthermore, Meeker analyzed the serum levels of 219 males, reporting that high-serum levels of molybdenum were associated with lower sperm concentrations and normal morphology [80]. Likewise, Wu conducted a prospective study and found that a high concentration of lead in the semen was correlated with lower sperm counts; however, it had no effects on sperm volume, motility, and morphology [97].

Some studies reported the effects of chemicals and environmental pollutants on reproductive parameters. Ji et al. conducted a cross-sectional study on 433 men and detected that environmental pollutants (e.g., aromatic hydrocarbons) were associated with lower sperm concentrations, motility, and counts through damaging sperm DNA [27]. Moreover, Xia et al. studied 513 men with idiopathic infertility and 273 men with fertility as the control group, finding that the urinary concentrations of aromatic hydrocarbon metabolites were higher in men with idiopathic infertility compared to those in the control group. Exposure to polycyclic aromatic hydrocarbons in the environment may increase the risk of infertility in men [31]. Petersen et al. investigated 226 men who were exposed to polychlorinated biphenyls and found that environmental chemicals (e.g., polychlorinated biphenyls) might adversely affect fertility by increasing the androgen-estrogen ratio although the serum levels of substances were not correlated with semen quality [29]. Similarly, Gennings et al. reported that exposure to polychlorinated biphenyls is related to prolonged pregnancy [32]. In their study, Smith et al. determined the urinary concentrations of paraben metabolites in 192 women who visited the infertility center, observing that the urinary concentrations of butylparaben or methylparaben were not related to antral follicle counts and follicle-stimulating hormone levels. However, exposure to propylparaben might affect fertility by disrobing the endocrine system and reducing ovarian reserves [42]. Furthermore, Meeker et al. indicated no association between paraben concentrations in the urine and lower semen quality, but a direct relationship was found between the urinary concentrations of butylparaben and damage to sperm DNA [43].

Du et al. examined urinary concentrations of phthalate metabolites in 415 women and reported that there is an insufficient correlation between the urinary concentration of phthalate and anti-Mullerin hormone levels, but exposure to phthalates was associated with decreased antral follicle growth [34].

Cigarette smoke contains harmful chemicals, many of which are mutagenic and affect sperm production and function. However, in addition to the effect of smoking on fertility decline, there are factors that can lead to inconsistent findings between studies, including medical diseases, use of other drugs along with smoking, as well as social and economic status. However, despite these issues, every man and woman who intends to become pregnant should be warned to quit smoking. It can also be difficult to examine people who are indirectly exposed to smoking [61]. According to Schuh-Huerta et al., smoking negatively affected ovarian reserves and reproductive hormone levels, and subsequently, fertilization [59]. On the contrary, Shin et al. concluded that cigarette smoke did not affect menstruation and reproductive hormones and reported that the overall smoking rates are higher in infertile people when compared with other people [60]. These agents include natural or synthetic chemicals. The prevalence of testicular cancer and some congenital anomalies (e.g., cryptorchidism or hypospadias), along with the apparent decrease in sperm production and its quality in the male population, is closely related to the widespread use of chemicals with hormonal properties. Nonetheless, there is no definite consensus on this issue, and these changes probably occur during the embryonic period [98]. Most studies indicated that environmental and occupational pathogens can negatively affect fertility, while many studies did not find this relationship since many factors affect a couple’s fertility, including socioeconomic factors, medical problems, and psychological issues. In addition, methodological review of studies can also affect the results such as sample selection method, sample size, statistical analysis, and the type of used questionnaires and checklists. In sum, all the abovementioned factors have caused the results of some studies to be inconsistent with other studies.

Strengths of the study

In this study, an attempt was made to discuss all the environmental factors that lead to a decrease in fertility and subsequent infertility. Further, by taking the systematic review, observational studies, and clinical trials into account as the criteria for entering the study, a large number of studies have been examined so that the obtained results are close to certainty.

Strengths and limitations of the study

One of the strengths of this study is the investigation of databases by the search strategy. All databases were carefully examined. One of the limitations of this study is that because the role of environmental and occupational factors in causing infertility is more or less accepted, the investigation of these factors may not be among the priorities of researchers in the world. At the same time, parallel to the advancement of technology, the role of the above factors in causing infertility will be more effective. Furthermore, meta-analysis was not possible due to severe heterogeneity in the independent variables, different measurement methods, variation in the studied outcomes, and the small number of similar studies to perform subgroup analysis.

Conclusions

In general, this systematic review study examined the environmental and occupational factors affecting infertility. According to the results, chemicals and environmental pollutants, cigarette smoking, air pollution, ionizing radiation, ambient temperature, and heavy metals are effective on male and female infertility. Environmental and occupational factors cause disorders in the quality and quantity of semen and natural forms, movements, and the number of sperms, along with ovulation disorders and hormonal imbalances in women. Therefore, identifying and eliminating the affecting factors are effective in reducing the prevalence of infertility worldwide. Accordingly, it is suggested to conduct prospective studies with a larger sample size so that the obtained results are close to certainty.