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Table 1 Papers assessing the impact of various conditions on reproductive and infertility indices

From: Environmental and occupational factors and higher risk of couple infertility: a systematic review study

Effective factor

First author (year)

Type of study

Research instrument

Sample size and research place

Result

Chemicals and environmental pollutants

Kumar et al. (2014) [26]

Cross-sectional

Questionnaire-Measurement

240 men (India)

Exposure to environmental toxins (cigarette smoke, pesticides) increases infertility in men by affecting the spermatogenesis, hormonal balance, semen quality, and oxidative stress. The occurrence of asthenozoospermia and azoospermia was significantly (P<0.05) higher among the exposed subjects as compared to the non-exposed subjects. Total progressive motility (P<0.05) and percentage of normal morphology (P<0.001) were significantly lower among chewers in comparison to non-chewers among the oligozoospermic subjects.

Ji et al. (2013) [27]

Cross-sectional

Questionnaire-Measurement

433 men (China)

Environmental pollutants including aromatic hydrocarbons are associated with decreased sperm concentration, motility and count by creating covalent bonding with sperm DNA and damage to it. Compared with men who had the lowest sperm PAH-DNA adducts category, men with the highest sperm PAH-DNA adducts level had a suggestive decline in sperm concentration, sperm count, sperm motility, and VCL. Trend P values of sperm concentration, sperm count, sperm motility, and curvilinear velocity were <0.001, <0.001, 0.004, and <0.001, respectively

Jurewicz et al. (2013) [28]

Cross-sectional

Interview- Measurement-

277 men (Poland)

Contact with aromatic hydrocarbon metabolites was associated with reduced semen volume and a low percentage of motile sperm. (P = 0.014, P = 0.0001, respectively)

Petersen et al. (2015) [29]

Cross-sectional

Questionnaire-Measurement Physical examination

266 fertile men (Denmark)

Environmental chemicals like polychlorinatedbiphenyls may adversely affect fertility by increasing the ratio of androgen to estrogen (P=0.04) but their serum levels are not correlated with semen quality.

Vestergaard et al. (2012) [30]

Prospective cohort

Questionnaire-Measurement

222 women (Denmark)

The entry of perfluorinated compounds into the body through foods and drinking water can have a negative impact on the reproduction and length of time to become pregnant. Odds ratio for a longer time to pregnancy>6 cycles for those with PFC concentrations above the median were 0.96 [95% confidence interval (CI): 0.54–1.64] for perfluorooctane sulfonic acid (PFOS).

Xia et al. (2009) [31]

Case-control

Questionnaire-Measurement- Physical examination

513 idiopathic infertile male subjects and 273 fertile males as controls (China)

Urinary concentrations of aromatic hydrocarbon metabolites in men with idiopathic infertility were higher than the control group. 1-hydroxypyrene and 2-hydroxyfluorene and Sum PAH metabolites (polycyclic aromatic hydrocarbons): (P value for trend = 0.034, 0.022, and 0.022, respectively). Exposure to polycyclic aromatic hydrocarbons in the environment may increase the risk of infertility in men.

Gennings et al. (2013) [32]

Cohort

Questionnaire-Measurement

289 daughters (Oakland, California area)

Exposure to environmental Polychlorinated biphenyl pollutants is associated with increased time needed to become pregnant. (average weight, 89%)

Nishihama et al. (2017) [33]

Cross-sectional

Questionnaire-Measurement

(n = 42) (Tokyo)

Exposure to paraben chemicals does not affect semen quality.

Du et al. (2018) [34]

Retrospective cohort

Questionnaire-Measurement

415 women (China)

There was an insufficient correlation between the urinary concentration of phthalate and the level of anti-Mullerian hormone. However, exposure to phthalate was associated with reduced antral follicle growth. Further studies should be conducted to investigate its effect on ovarian function and fertility.

Meeker et al. (2008) [35]

Cross-sectional

Questionnaire-Measurement

207 men (Massachusetts)

Contact with pyrethroid insecticides is associated with lower quality of semen (concentration, motility, and morphology) and damage to sperm DNA and may threaten reproductive health.

Velez et al. (2015) [36]

Cohort

Questionnaire-Measurement

1743 (Canada)

The cumulative probabilities of pregnancy at 1, 6, and 12 months were 0.42 (95% confidence interval (CI) 0.40–0.45), 0.81 (95% CI 0.79–0.83), and 0.90 (95% CI 0.89–0.92), respectively.

Increased serum levels of Perfluorinated compounds is associated with a decline in women’s ability to become pregnant.

Yang et al. (2008) [37]

Cohort study

Questionnaire- Interview- Measurement

412 women (Taiwan)

Contact with polychlorinated biphenyls and dibenzofurans is associated with the prolongation of time needed to become pregnant. the infertility odds ratio was 2.34 (95% CI, 1.23–4.59) for Yucheng women compared with the reference group.

Chen et al. (2018) [38]

Cross-sectional

Questionnaire-Measurement

68 pregnant women (Taiwan)

Exposure to organochlorine pesticides in the environment and through eating habits can cause infertility by disturbing the endocrine glands.

Ji et al. (2010) [39]

Cross-sectional

Questionnaire-Measurement

n= 465 (China)

Improper dietary habits and increased industrial production can have an adverse effect on the fertility and damage sperm DNA by exposing people to polycyclic aromatic hydrocarbons.

Harville et al. (2017) [40]

Cross-sectional

Questionnaire-Measurement

1524 women (southeastern Louisiana)

There was no conclusive evidence of the impact of environmental exposure to oil spills and reproductive failure.

Bastos et al. (2013) [41]

Cross-sectional

Questionnaire-Measurement

Fertile (n = 21), infertile (n = 15) (Brazil)

pp’DDE was detected in 100% of infertile women, at higher mean levels than in pregnant women (3.02 mcg/L vs. 0.88 mcg/L; P= 0.001; the power of 69%)

Canned foods and exposure to organochlorine chemicals may affect fertility in women.

Smith et al. (2013) [42]

Prospective cohort

Measurement of patients’ medical record

192 women (USA)

There were no correlations between the urinary concentration of butylparaben or methylparaben and antral follicle count and follicle-stimulating hormone levels. However, exposure to propylparaben chemicals may affect fertility by disrobing the endocrine system and reducing ovarian reserves.

Meeker et al. (2011) [43]

Cross-sectional

Measurement

Serum hormone levels (n = 167), semen quality parameters (n = 190), and sperm DNA damage measures (n = 132) (USA)

There was no correlation between paraben concentration in urine and low semen quality, but there was a direct correlation between Urinary concentration of butylparaben, bisphenol A and damage to sperm DNA. (p for trend = 0.03)

Meeker et al. (2010) [44]

Cross-sectional

Measurement

167 men )Massachusetts(

Exposure to bisphenol A chemicals is associated with impaired hormone levels (estradiol, testosterone, and thyroid-stimulating hormone) in men.

There was a positive trend between urinary BPA quartiles and FSH to inhibin B ratio (p for trend = 0.01) and a suggestive inverse trend between urinary BPA quartiles and E2:T ratio (p for trend = 0.06). There was a positive dose-response trend between urinary BPA concentration quartiles and serum FSH levels (p for trend = 0.002) and an inverse trend between urinary BPA quartiles and inhibin B (p for trend = 0.04)

Cohn et al. (2011) [45]

Prospective

Questionnaire-Measurement

289 daughters (Oakland, California area(

Probability of pregnancy fell by 38% (95% CI 17–53%) and infertility was higher (30% not pregnant after 13 cycles vs.11% not pregnant after 13 cycles).

Mothers, who had serum levels of polychlorinatedbiphenyl, their daughters were facing an extended time to be pregnant. Therefore, mothers’ exposure to Polychlorinatedbiphenyl chemicals reduces pregnancy power in their daughters.

Crawford et al. (2017) [46]

Cohort

Measurement

99 women (North Carolina)

Measuring the antimalarial hormone, the present study indicated that exposure to perfluorinated chemicals through consumer goods, pesticides, etc. affected thyroid hormone levels (Thyroid hormones were weakly correlated with PFCs. Specifically, PFOA and PFNA were positively correlated with T3 (r=0.23, p=0.03) PFNA was positively correlated with free T4 (r=0.24, p=0.02) but there was no correlation with TSH.) but did not affect the ovarian reserve and fertility.

Thurston et al. (2016) [47]

Cross-sectional

Measurement

420 men (USA)

Exposure to environmental pollutants, phthalate, did not affect semen parameters, but monobenzyl phthalate was associated with decreased sperm motility. (β = −1.47, 95% CI −2.61, −0.33)

Guo et al. (2014) [48]

Prospective cohort

Measurement

469 couples from Michigan and Texas

Exposure to phthalates because of increased oxidative stress can have a harmful effect on fertility.

Jurewicz et al. (2018) [49]

Cross-sectional

Questionnaire-Measurement

315 men (Poland)

High urinary concentration of triclosan 50th–75th percentile and ≥ 50 percentile was associated with increasing the abnormal morphology of sperm. (p = 0.016 and p = 0.002, respectively). The exposure to triclosan can endanger fertility in men by reducing semen quality.

Conti et al. (2017) [50]

Cross-sectional

Questionnaire-Measurement

86 males (Catania, Italy)

Exposure to dangerous pollutants, Benzo(a)pyrene, through cigarette smoke, frozen foods, incomplete combustion of fossil fuels, etc. adversely affects male fertility by bonding with sperm DNA.

Messerlian et al. (2018) [51]

Prospective cohort

Questionnaire-Measurement

)N = 799 women, N = 487 men( (Massachusetts ,USA)

The high urinary concentration of phthalate metabolites in women was associated with a decrease in oocytes and a decrease in live births in men. The chemicals had a negative effect on fertility.

Aneck-Hahn et al. (2007) [52]

Cross-sectional

Questionnaire-Measurement

311 males (South Africa)

Exposure to DDT pesticide was associated with decreased ejaculation volume (b= −0.0003; P = .024) as well as serum concentration of DDT in people with asthenozoospermia, oligozoospermia, and teratozoospermia. There was a significant positive association between participants with asthenozoospermia (32%) and p,p9-DDT (OR 1.003, P = .006) and p,p9-DDE (OR 1.001, P = .02).

Wang et al. (2016) [53]

Systematic review and meta-analysis

Electronic databases

9 studies (7 cross-sectional, 1 case-control, and 1 pilot study) were analyzed for classic EDCs (5 studies for phthalate esters and 4 studies for organochlorines).

Organochlorine and phthalate ester were associated with poor sperm quality.

Risk of abnormal sperm quality was found in the phthalate ester group (OR=1.52; 95% CI: 1.09–1.95) and organochlorine group (OR=1.98; 95% CI: 1.34–2.62).

Hipwell et al. (2019) [54]

Systematic review

Electronic databases

The search returned 3456 articles. There were 15 papers from 12 studies which met inclusion criteria, of which eight included biomarkers of chemical exposure.

Although there is a link between exposure to chemicals (phthalates, BPA, TCS, TCC, benzophenones, parabens, and glycol ethers) and reduced fertility in men and women, more studies are being done

Bonde et al. (2017) [55]

Systematic review and meta-analysis

Electronic databases

Papers included in qualitative synthesis (n = 33)

Exposure to environmental pollutants can adversely affect the male reproductive system.

The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35).

exposure to one of the four compounds, p,p′-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04–1.74).

Caserta et al. (2011) [56]

Systematic review

Electronic databases

---

Studies have shown that environmental pollutants that disrupt the endocrine glands affect the reproductive system.

Martenies and Perry (2013) [57]

Systematic review

Electronic databases

17 studies

Contact with pesticides was associated with decreased sperm concentration and motility. In two studies, the relationship between pesticides and sperm morphology was reported.

Machtinger et al. (2013) [58]

Randomized trial

Measurement

352 GV-stage oocytes from 121 patients (Brigham)

The higher the dose of bisphenol-A, oocytes the lower the progression in metaphase 2 (P = 0.002) also the higher the percentage of degeneration (P = 0.01).

Cigarette smoking

Schuh-Huerta et al. (2011) [59]

Cohort

Questionnaire measurement

232 Caucasian and 200 African American (California) women (USA)

Smoking adversely affects the ovarian reserve and levels of reproductive hormones and subsequently the fertility.

Shin et al. (2017) [60]

Cross-sectional

Questionnaire

785 women (Korea)

Prevalence of current, secondhand, past, and never smokers were 12.7%, 45.7%, 0.9%, and 40.6%, respectively. Primary infertility was more frequent in secondhand smokers.

Cigarette smoke did not affect menstruation and reproductive hormones, but the rate of smoking was higher in infertile people.

Axelsson et al. (2013) [61]

Cross-sectional

Register-based data, Questionnaire-Measurement, physical examination

295 adolescents (Sweden)

Paternal smoking was associated with 46% lower total sperm count (95%CI 21%, 64%) during the adulthood and affects fertility. Both paternal and maternal smoking were associated with a lower sperm concentration (mean differences: 35%; 95%CI 8.1%, 55% and 36%; 95%CI 3.9%, 57%, respectively

Keshavarzi et al. (2016) [62]

Analytical - cross-sectional

Questionnaire measurement

514 individuals who were divided into two groups of infertile men, and those with children and no history of infertility (Iran - Kermanshah)

142 infertile men smoked, while 112 once smoked in a group of men with children. It can be concluded that smoking can be an effective factor in causing the infertility. P<0/05

Air pollution

Mahalingaiah et al. (2015) [63]

Prospective cohort

Questionnaire

36,294 women (USA)

Proximity to main roads due to air pollution is associated with an increased incidence of primary and secondary infertility.

For women living closer to compared to farther from a major road, for primary infertility hazard ratios = 1.05 (CI 0.94–1.17) while for secondary infertility hazard ratios = 1.21 (CI 1.07–1.36)

Vecoli (2017) [64]

A Pilot Study

Measurement

Normospermic men (n= 57, high group) (n= 55, low group) (Grouping is based on the environmental pressure) (Italy)

High levels of environmental pollution can adversely affect reproductive health by increasing sperm telomere length.

Joffe et al. (2008) [65]

Retrospective

Questionnaire

(‘unexposed’ group, n=400)، (‘exposed’ group, n=200) (UK)

Environmental pollution sources in two study groups (pregnant local residents living within 3 km of a landfill site or elsewhere in the Rhondda valleys) had no effect on the time needed for female pregnancy.

Najafi et al. (2015) [66]

Meta-analysis

Electronic databases

11 articles

The CI for pooled means were as follows: 2.68 ± 0.32 for ejaculation volume (mL) 62.1 ± 15.88 for sperm concentration (million per milliliter) 39.4 ± 5.52 for sperm motility (%) 23.91 ± 13.43 for sperm morphology (%) and 49.53 ± 11.08 for sperm count.

Air pollution was associated with decreased sperm motility but did not affect other sperm parameters.

Carré et al. (2017) [67]

Systematic review

Electronic databases

61 articles

Air pollution affects the reproductive capacity of men and women by affecting gametogenesis.

Ionizing radiation

Sharma et al. (2017) [68]

Experimental study

Measurement

Group I: normal, control males of proven fertility (n=40)

Group II: males with oligoasthenozoospermia (OAT) (n=36)

Group III: Males with unexplained infertility (MUI) (n=42) (India)

Groups 2 and 3 exposed to ultraviolet radiation showed a higher percentage of immature sperm than group 1; hence, exposure to UV adversely affected the fertility by damaging the sperm DNA.

Moghbeli-Nejad et al. (2012) [69]

Experimental study

Questionnaire-measurement

Oligospermia with mean sperm count (15×106±2.4) n=10, azoospermia with no sperm in semen n=10, and normal males with mean sperm count (50×106±3.1) n=10 (Tehran, Iran)

Exposure to ionizing radiation reduces male reproductive capacity by causing anomalies and mutations in sperm DNA (genomic instability).

Although the high background frequency of micronucleus in oligospermia and azoospermia samples is statistically different compared to normal control (P<0.05). the difference between oligospermia and azoospermia groups is not significant (P>0.05).

Stone et al. (2013) [70]

Prospective cohort

Interview questionnaire—physical examination

1466 (USA)

Childhood thyroid radiation dose was possibly associated with infertility [adjusted odds ratio (AOR) = 1.17; 95% CI 0.82, 1.67 and AOR = 1.35; 95% CI 0.96, 1.90 for the middle and upper tertiles vs. the first tertile of exposure, respectively].

Exposure to radioactive substances (iodine therapy) in childhood to treat thyroid diseases can be associated with infertility in the adulthood.

Adams et al. (2014) [71]

Systematic review and meta-analysis

Electronic databases

10 studies

Exposure to mobile phones was associated with reduced sperm motility (mean difference −8.1% (95% CI −13.1, −3.2)) and viability (mean difference −9.1% (95% CI −18.4, 0.2)), but the effects on concentration were more equivocal.

Ambient temperature

ShaiShefi et al (2007) [72]

Cohort

Questionnaire-measurement

11 infertile men (USA)

Decrease in ambient temperature was associated with increased sperm count and motility. ( This increase was largely the result of a statistically significant increase in sperm motility from a mean of 12% at baseline to 34% post-intervention (p = 0.02)). As a result, high-temperature environments such as Jacuzzi, and hot baths endanger male fertility by affecting semen quality and spermatogenesis.