Open access peer-reviewed chapter

Smoking and Its Consequences on Male and Female Reproductive Health

Written By

Amor Houda, Jankowski Peter Michael, Micu Romeo and Hammadeh Mohamad Eid

Submitted: 28 March 2022 Reviewed: 14 April 2022 Published: 09 June 2022

DOI: 10.5772/intechopen.104941

From the Edited Volume

Studies in Family Planning

Edited by Zouhair Odeh Amarin

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Smoking contributes to the death of around one in 10 adults worldwide. Specifically, cigarettes are known to contain around 4000 toxins and chemicals that are hazardous in nature. The negative effects of smoking on human health and interest in smoking-related diseases have a long history. Among these concerns are the harmful effects of smoking on reproductive health. Thirteen percent of female infertility is due to smoking. Female smoking can lead to gamete mutagenesis, early loss of reproductive function, and thus advance the time to menopause. It has been also associated with ectopic pregnancy and spontaneous abortion. Even when it comes to assisted reproductive technologies cycles, smokers require more cycles, almost double the number of cycles needed to conceive as non-smokers. Male smoking is shown to be correlated with poorer semen parameters and sperm DNA fragmentation. Not only active smokers but also passive smokers, when excessively exposed to smoking, can have reproductive problems comparable to those seen in smokers. In this book chapter, we will approach the effect of tobacco, especially tobacco smoking, on male and female reproductive health. This aims to take a preventive approach to infertility by discouraging smoking and helping to eliminate exposure to tobacco smoke in both women and men.


  • tobacco
  • reproductive health
  • infertility
  • cessation therapies

1. Introduction

The higher predominance of smoking is seen among youthful men during their fertility period. It is estimated that almost half of smokers, in the world, are aged between 20 and 39 years old [1, 2].

Infertility is a complicated condition in which contribute environmental lifestyle, genetic, and epigenetic factors [3, 4].

Different studies showed that semen parameters may be affected by various lifestyles, advancement in technologies, environmental pollution [5], alcohol intake [6], smoking [7, 8, 9].

Smoking and chewing tobacco are the harmful addictions [10] that include a variety of toxic, mutagenic, and carcinogens substances, together with nicotine reported for adversely affecting semen quality and consequently male infertility [11, 12].

1.1 Hormone regulation disruption

The most toxic compound in tobacco products is nicotine. It is a psychoactive drug and an oxidizing substance, which is addictive. The nicotine in any tobacco product readily absorbs into the blood when a person uses it. Nicotine may change the hypothalamic–pituitary axis (HPG) by enhancing the release of cortisol, growth hormone, oxytocin, and vasopressin, which in turn inhibit the prolactin and the luteinizing hormone (LH) [13].

Heavy smokers are the most facing fertility problems than nonsmokers [14]. Studies showed that in smokers, the mean levels of prolactin (PRL), follicle-stimulating hormone (FSH), mean levels of LH were lower, and the mean estradiol (E2) levels were higher in comparison to nonsmokers [15]. The same is observed in another study where testosterone, E2, LH, and FSH levels are lower in smokers [16].

In contradiction, no differences in serum total testosterone, LH, and FSH levels were demonstrated among fertile male patients divided into heavy, moderate, and mild smokers [17].

Moreover, substances in tobacco smoke affect pituitary, thyroid, adrenal, and testicular functions and consequently alter semen quality of both infertile and fertile men [18], leading to a change in testosterone, E2, PRL, LH, and FSH levels, which may cause Leydig and Sertoli cell failure in smokers [19, 20, 21, 22].

1.2 Erectile dysfunction

Smoking have been demonstrated to be a hazard factor for erectile dysfunction, a condition in which man is incapable to induce or keep an erection firm sufficient for satisfactory sexual intercourse [23].

In Korea, after a survey among 600 men aged between 40 and 80, they found that ejaculatory and erectile functions malfunction was associated with previous and current smoking habit [24].

In Australia, a second study found that ED was associated with cigarette smoking, and even this association became stronger in heavier smokers [25].

Shiri and colleagues demonstrated that the risk for ED from smoking was generally little, and the smokers had decreased chances of recuperating from ED compared with nonsmokers [26].

A group of researchers showed an association between smoking more than 20 cigarettes daily and nearly 50% high risk of erectile dysfunction [27].

He et al. concluded a relationship between nearly 12 million cases of ED in Chinese men and smoking and reported a significant dose–response association between smoking and the risk of ED [28].

Cao et al. confirmed a significant association between smoking and the high risk of ED. Besides, quitting smoking significantly improved both physiological and sexual wellbeing in male smokers, notwithstanding the level of erectile dysfunction [29].

1.3 Smoking and oxidative stress

The compounds of a cigarette enhance superoxide generation by both endothelial and smooth muscle cells from NADPH oxidase (NOXs) and uncoupled endothelial nitric oxide synthase (eNOS) and upregulate proinflammatory cytokines and the Ras homolog gene family, member A (RhoA), and its downstream effector Rho-associated protein kinase (ROCK) (RhoA/ROCK) contractile pathway. This process leads to reduction of nitric oxide (NO) bioavailability, endothelial dysfunction, and increase of vasoconstriction [30].

Reactive oxygen species (ROS) also affect hypothalamic–pituitary-thyroid axis and reduce triiodothyronine (T3) and thyroxine (T4) secretion. Low levels of T3 reduce the levels of the protein in Leydig cells and the steroidogenic acute regulatory (StAR) mRNA, along with testosterone production [31]. ROS production interferes oxygen delivery to the testis, which is crucial for spermatogenesis [32, 33].

A possible cause of the harmful effects of nicotine and other compounds of tobacco, on the male genital tract, is the release of mediators of inflammation, such as interleukin-8 and interleukin-6, which may enroll and actuate leucocytes [34, 35].

Successively, activated leukocytes lead to excessive ROS production in semen. Studies reported high levels of oxidative stress markers such as ROS malondialdehyde (MDA) and smoking markers such as cotinine in seminal plasma of smokers [9, 36]. Even expression of antioxidant enzymes and seminal vitamin C was insufficient to provide full protection of spermatozoa [37].

Furthermore, the high levels of ROS and cotinine in seminal plasma were associated with the number of daily cigarettes. The higher consumption means a severe damage in the sperm membrane because of its polyunsaturated fatty acids composition [38].

1.4 Smoking and sperm parameters: Concentration, motility, and morphology

As mentioned before, tobacco and its compounds lead to an excessive production of ROS. The key mechanism responsible for sperm damage is the lipid peroxidation of spermatozoa membrane caused by ROS. As a result, sperm concentration, viability, mobility, and normal morphology decrease [39, 40].

It alters the fertilizing capacity of the sperm [41] and reduces antioxidant activity, which has possible adverse effect on sperm density, motility, and morphology [9, 42].

Calogero et al. demonstrated that Cigarettes Smoke Extract (CSE) in healthy nonsmokers men could suppress sperm motility and alters chromatin condensation. Besides, in a concentration- and time-dependent manner, CSE induces early apoptotic sign and a late apoptotic sign: fragmented sperm DNA [43].

In comparison to mainstream smoke, sidestream smoke contains several toxicants at higher levels including ROS such as superoxide and hydrogen peroxide [34, 40], as well as cadmium [34, 44]. They have also shown to affect semen quality and cause disturbance in sperm acrosome function [39].

Therefore, passive smokers are concerned with this problem. They are 2.5 times more exposed to cancerous substances in tobacco than active smokers [45, 46].

1.5 Smoking and sperm DNA fragmentation in sperm

The most frequent DNA anomaly is DNA fragmentation, which is associated with poor spermatozoa quality, low fertilization rates, and bad embryo quality [47].

Sperm DNA fragmentation is generally induced by oxidative stress and/or apoptosis [48, 49].

Oxidative stress (OS) caused by smoking induces oxidative DNA damage of the spermatozoa [50] and mutagenic adducts [51]. Thus, it leads to alteration of sperm quality and may cause male infertility [52].

Different techniques were used to measure the spermatozoa DNA damage. The latter showed an association with various assisted reproductive technology (ART) outcomes such as fertilization rate, embryo quality, implantation rate, pregnancy, and spontaneous abortion [53]. So, an elevated DNA damage is associated with low implantation and consequently, low pregnancy rate [54].

In men with idiopathic infertility, associated with cigarette smoking, an increase in sperm DNA stainability, sperm DNA fragmentation index, and spermatozoa with round head were noticed [55].

In addition, it has been suggested that DNA damage is the main cause of implantation failure in embryos derived from healthy eggs fertilized by sperm with chromatin defects [56, 57]. These negative effects of smoking on spermatozoa and the damage to the DNA may be due to excessive ROS production [58] and decrease the antioxidant levels in seminal plasma [42].

Dai et al. also reported that tobacco smoking negatively affects sperm parameters, such as volume, concentration, motility, morphology, and viability, leading to male infertility [59].

Moreover, an excessive production of ROS leads to oxidative stress; in turn it affects not only sperm nuclear DNA but also sperm mitochondrial respiratory activity [60] and the endocrine function resulting in several pathologies of the male reproductive system and may be leading to male infertility [61, 62].

1.6 Smoking and molecular alteration: epigenetics, miRNA/noncoding RNA of spermatozoa

Different lifestyles and environmental factors alter epigenetic profiles: chromatin modifications, DNA methylation, and noncoding RNAs, thereby altering chromatin structure and changing gene expression [63].

The protamines are fundamental in the sperm chromatin condensation and the protection of the paternal genomic DNA from alterations [56, 64, 65]. It has also been proposed that the deficiency in protamine may lead to the accumulation of lesions at the level of the spermatic DNA [66], morphological abnormalities, and the triggering of apoptotic pathways, the inactivation of mitochondria, and consequently, the decrease in the sperm motility [67].

The alterations of protamine ratio (P1/P2) at the level of the interval (0.8–1.2) in the semen have been clearly associated with the male infertility [68].

Hammadeh et al. also investigated the association between smoking and protamine deficiency of sperm chromatin and demonstrated that the high P1/P2 ratios in smoker are due to an underrepresentation of P2. This suggests that ROS production in smokers deteriorates chromatin condensation and change protamine 1 to protamine 2 ratio of spermatozoa [9].

Smoking is probably behind the underexpression of protamine ending with high levels of histone to protamines ratios [69]. Overall, the alteration from the normal P1/P2 ratio seems to be important in male fertility, although the precise manner by which this happens can differ from person to person.

Abnormalities during the arrangement of chromatin may also cause infertility [70, 71], affecting embryo development [72, 73].

Epigenetic modifications change the gene expression without altering the DNA sequence and can be transferred to next generation through both meiotic and mitotic cell divisions [74].

Different studies have investigated the relationship between the effects of smoking on epigenetic profiles such as chromatin modifications and DNA methylation and genes transcription [75, 76].

Cigarette smoking adversely affects DNA methylation patterns [77, 78, 79]. A previous study from our laboratory showed that smoking may lead to biochemical changes in many regions of the sperm DNA that are related to MAPK8IP and TKR gene. And that has negative effects on semen parameters [80].

Moreover, benzo[a]pyrene and nicotine induce alterations in sperm chromatin during histone-protamine transition, which may alter the methylation pattern of CpG in the promoter regions of DNA in the offspring of heavy smokers [81].

Furthermore, many studies took in considerations the interaction between the gene and the environment. They studied the association between tobacco smoking and genetic polymorphisms, involving DNA repair genes and genes involved in carcinogen metabolism [82, 83].

Over 100 miRNAs were found in spermatozoa. Twenty eight of them were differentially expressed between nonsmokers and smokers. In infertile men, the expression of has-miR-146b-5p, has-miR-509-5p, has-miR-146d, and has-miR-652 was altered [83]. These four miRNAs are involved in different pathways such as cell proliferation, differentiation, and apoptosis in spermatozoa as well as early embryogenesis [83].

Altered spermatozoal mRNA profiles and miRNA changes have been shown in smokers [84, 85].

An increased risk of idiopathic male infertility was reported in male smokers, while nonsmokers did not show an increased risk of infertility. These men carried 462Ile/Val genotype of the CYP1A1 gene [86].

Moreover, a significant relationship was observed between smoking and the GSTM1+/GSTT1 del genotypes and the GST gene GSTP1 105IV/GSTT1 polymorphisms in infertile men. The GSTP1, GSTM1, and GSTT1 genes are engaged in the development of idiopathic male infertility [87].

Amor et al. demonstrated that H2BFWT, TNP1, TNP2, PRM1, and PRM2 genes were differentially expressed (p < 0.01), and these genes were downregulated in the spermatozoa of heavy smokers [7].

1.7 Male smoking and assisted reproductive treatment (ART)

Almost 50 million couples worldwide are facing infertility issue [88, 89]. Infertility is described as a disease characterized by a failure to conceive after regular unprotected intercourse of 1 year and is used interchangeably with the term “subfertility” [90].

ART technique was the solution for such couples to solve their infertility issues and to achieve pregnancy. Different lifestyles and environmental factors showed to have an adverse effect on a male and female fertility and consequently conceiving. Tobacco smoking is one of the lifestyle factors that was associated with infertility.

A smoking habit in males also has an adverse effect on pregnancy outcomes among in vitro fertilization (IVF) intracytoplasmic sperm injection (ICSI) patients [8, 91]. An association between cigarette smoking and altered ICSI and IVF outcomes was reported [41]. In a study by Klonoff-Cohen et al., the number of retrieved oocytes decreased by almost 46% in smokers. The males were active smokers, and the females were passive smokers [92]. In addition, a decrease in live birth rates was noticed in 166 couples seeking pregnancy using ART [93].

Although spermatozoa with damaged DNA is still capable of fertilization, but its effect is prominent in the later stages such as apoptosis, poor fertilization rate, high frequency of miscarriage, and morbidity of off springs [94, 95].

Because of the faulty transition histones-protamines, sperm DNA breaks increased, and this may cause poor embryo morphology at early cleavage stages. An abnormal protamine ratio was associated with poor preimplantation [56].

However, other studies have reported that there is no significant relationship between smoking and fertility outcomes in humans [96].


2. Effect of tobacco on female infertility and reproductive health

2.1 Smoking and conception delay

Smoking women experience almost 50% conception delay for over 1 year than nonsmokers women. Besides, active and/or passive tobacco smoking by either partner had adverse effects on conception [97].

Smoking couples, with a conception of over 15 cigarettes daily, demonstrated low fecundity and an increased time to achieve pregnancy [98].

The majority of studies support the negative effects of smoking on fecundity, regardless of other factors [98, 99].

Several reviews have accumulated data on female fecundity and cigarette smoking. All of them concluded that smoking adversely affects female fertility [100].

2.2 Smoking and ovarian function

Compounds of tobacco smoke seem to accelerate the loss of reproductive function and follicular depletion [101].

Women who were exposed to tobacco during the fetal period showed an increase in ovarian dysgenesis [102]. A relation was found between smoking and short menstrual cycle length, that could lead to low fecundity [103]. Moreover, smoking women have their menopause 1–4 years in comparison to nonsmokers women [104].

Women consuming tobacco have high levels of nicotine, which can induce ovarian dysgenesis, resulting in increased infertility [102, 105]. On the other hand, other chemicals in cigarettes can affect the anatomy and function of the uterine tubes [106]. Another study reported that tobacco exposure during pregnancy can cause long-lasting effects in the reproductive system [52].

2.3 Smoking and early pregnancy loss

Tobacco smoke showed an association with bacterial vaginosis, which in turn is associated with second-trimester miscarriage and with preterm labor [107].

A case–control study demonstrated that smoking women (>20 cigarettes/day) had an increased risk of ectopic pregnancy in comparison to nonsmokers women [108]. An increase in spontaneous miscarriage is associated with tobacco smoke in both natural and ART cycles [109].

Moreover, 24% of women with experience of abortion and 19% of women without experience of abortion were passives smokers [110]. Passive smoker women had low fertility rate and a risk of abortion four times higher in comparison to nonsmokers [111].

A dose–response relationship has been found between miscarriage and smoking. One percent increase in relative risk of miscarriage per cigarette smoked daily. Besides, the risk of miscarriage increased by 11% among pregnant women exposed to secondhand smoke [112].

Pineles et al. demonstrated also that the amount of cigarette smoked by the pregnant woman increases the risks of stillbirth, neonatal death, and perinatal death [112].

In a large cohort study, parental smoking during pregnancy was found to increase the risk of stillbirth, and paternal smoking was an independent risk factor for stillbirth despite maternal passive smoking status [113].

2.4 Female smoking and assisted reproductive treatment (ART)

A smoking woman seems to have reduced fertility and difficulty in conceiving. Different studies showed that tobacco may affect hormone production, which makes it difficult for a woman to become pregnant [114].

Studies have also reported that smoking woman, during fertility treatment, had higher numbers of canceled cycles, lower peak estradiol levels, an elevated gonadotropin injection for ovarian stimulation, increased testosterone, fewer oocytes retrieved, thicker zona pellucida, and more cycles with failed fertilization and implantation compared with nonsmokers [92, 115, 116]. Besides, the success rates of IVF were lower in smoking woman compared with nonsmokers one [117].

Some have also shown that female smoking is associated with reduced numbers of oocytes [118], lower fertilization [115, 119] and pregnancy [119], and higher miscarriages rate [120]. In contrast, other studies have reported that smoking has no adverse effects on fertilization [3] and pregnancy outcomes [121].

Freour demonstrated that active smoking women presented poor ovarian response and lower clinical pregnancy rate [122]. Moreover, an association has been described between current smoking woman, undergoing IVF, and lower concentrations of anti-mullerian hormone (AMH) [122, 123]. In addition, AMH levels were 44% higher in nonsmokers compared with current smokers [124] and declined 21% faster yearly in smokers compared with nonsmokers [125].

Ozbakir and Tulay investigated the association between cigarette smoking and oocyte quality. They concluded that cigarette smoking did not affect the follicles count and the number of oocytes retrieved. However, a significant difference was detected in the morphological assessment of oocyte including cytoplasmic anomalies [126].


3. Effects of tobacco smoking on progeny

The birth defects among the offspring of smoking parents are high [127]. During their pregnancy, smoking woman showed an increased risk of trisomy 21 in the offspring, which results from maternal meiotic nondisjunction [128].

Maternal smoking increased the risk of spontaneous abortion, fetal growth restriction, preterm birth, stillbirth, and low birth weight [129]. A dose–response relationship was found between the risk of low-birth weight and the number of cigarettes smoked daily during pregnancy [129].

Maternal smoking was suggested to have even negative effects on the sperm count of men, whose mothers had smoked more than 10 cigarettes daily, in comparison to men having nonsmoker mothers.

Benzo[a] pyrene and nicotine in cigarette smoke have recently been shown to induce harmful alterations of sperm DNA that can be transmitted through the germ line to future generations [130, 131].

It has also been reported that preconception paternal tobacco smoking increases the chances and risk of multiple forms of morbidities in the fetus and offspring, which could be mediated through epigenetic modifications [132].

Kataoka et al. showed that the high number of daily cigarettes can be the reason behind the low weight at birth. Smoking mothers, who smoked 11–40 cigarettes/day, had infants with 435 g lower weight in comparison with infants born to nonsmoking women. The same was observed for infants whose mothers smoked 6–10 cigarettes/day. Their birth weight was 320 g lower than infants of nonsmoking mothers [133].

Liu et al. concluded also that low number of cigarettes smoked during either the first or second trimester of pregnancy, even as low as 1–2 cigarettes per day, showed an association with a high risk of preterm birth. This proves that during pregnancy, there is no safe level or safe trimester for maternal smoking [134].


4. Smoking cessation

4.1 Nicotine replacement therapies

Nicotine replacement therapies (NRTs) were the first smoking cessation medications the FDA approved for use in smoking cessation therapy. NRT is an effective and safe strategy for quit smoking. They diminished withdrawal sentiments by giving you a low, controlled amount of nicotine but none of the other dangerous compounds found in cigarettes. A low amount of nicotine makes a difference by fulfilling your need for nicotine and diminishes your smoking addiction [135, 136].

There are different varieties of NRTs, which are used in different ways. Each person can choose which variety that suits him. From person to person, the results of NRT are different. Current NRT products include transdermal patch, chewing gum, nasal sprays, lozenges, and inhalers. A combination of short- and long-acting forms of NRT is more effective for smoking cessation in comparison to the use of single forms of NRT [136, 137].

There are non-nicotine medications such as bupropion and varenicline, which are approved from FDA. Their targets are the nicotine receptors in the brain. That helps with withdrawal feelings and blocks the effects of nicotine [135, 136].

4.2 Smoking cessation, reproductive health outcomes, and ART treatment

Santos et al. evaluated sperm quality after a 3-month smoking cessation. They observed a remarkable improvement of different sperm parameters: sperm concentration, sperm vitality, motility, and percentage of spermatozoa recuperated after an enrichment technique [138].

Smoking is associated with oxidative stress. Therefore, antioxidants can be recommended in treatment of infertile smoking women [139]. In addition, patients should adopt lifestyle modifications and quitting smoking [3, 140], losing weight through different methods, such as diet, education, and exercise [141], and decreasing exposure to harmful toxins, such as phthalate [142].

Fecundity associated with smoking may be improved within 1 year of smoking cessation [143]. The physiological and sexual health in male smokers was improved after they quit smoking, regardless of their baseline level of erectile dysfunction [144].

If behavioral approaches did not work, the use of bupropion and/or varinecline have helped non-pregnant women to quit smoking [145]. Besides, the use of combined NRT was superior to any single NRT in treatment of individuals [146].


5. Conclusion

In the light of the present review, tobacco smoking has deleterious effects on reproductive health including gametes from both parents. Active or passive smoking negatively affects not only the parents but also the offspring. Therefore, the lifestyle factors are very important factors for pregnancy and delivering healthy children. Smoking women and men reproductive age should be strongly encouraged to quit smoking before trying to conceive. Besides, research is still needed to understand how and why smoking causes adverse outcomes in these patients.


Conflict of interest

The authors declare no conflict of interest.


  1. 1. Agarwal A, Said TM. Role of sperm chromatin abnormalities and DNA damage in male infertility. Human Reproduction Update. 2003;9(4):331-345. DOI: 10.1093/HUMUPD/DMG027
  2. 2. Öberg M, Jaakkola MS, Woodward A, Peruga A, Prüss-Ustün A. Worldwide burden of disease from exposure to second-hand smoke: A retrospective analysis of data from 192 countries. Lancet (London, England). 2011;377(9760):139-146. DOI: 10.1016/S0140-6736(10)61388-8
  3. 3. Wright C, Milne S, Leeson H. Sperm DNA damage caused by oxidative stress: Modifiable clinical, lifestyle and nutritional factors in male infertility. Reproductive Biomedicine Online. 2014;28(6):684-703. DOI: 10.1016/J.RBMO.2014.02.004
  4. 4. Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the globe. Reproductive Biology and Endocrinology. 2015;13(1):1-9. DOI: 10.1186/S12958-015-0032-1
  5. 5. Boeri L et al. Heavy cigarette smoking and alcohol consumption are associated with impaired sperm parameters in primary infertile men. Asian Journal of Andrology. 2019;21(5):478-485. DOI: 10.4103/aja.aja_110_18
  6. 6. Jensen TK et al. Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men. BMJ Open. 2014;4(9):1-11. DOI: 10.1136/bmjopen-2014-005462
  7. 7. Amor H, Zeyad A, Hammadeh ME. Tobacco smoking and its impact on the expression level of sperm nuclear protein genes: H2BFWT, TNP1, TNP2, PRM1 and PRM2. Andrologia. 2021;53(3):e13964. DOI: 10.1111/and.13964
  8. 8. Amor H, Nyaz S, Hammadeh ME. Paternal smoking in relation to sperm quality and intracytoplasmic sperm injection outcomes. International Journal of Women’s Health and Reproduction Sciences. 2019;7(4):451-460. DOI: 10.15296/ijwhr.2019.75
  9. 9. Hammadeh ME, Hamad MF, Montenarh M, Fischer-Hammadeh C. Protamine contents and P1/P2 ratio in human spermatozoa from smokers and non-smokers. Human Reproduction. 2010;25(11):2708-2720. DOI: 10.1093/humrep/deq226
  10. 10. Koskinen LOD, Collin O, Bergh A. Cigarette smoke and hypoxia induce acute changes in the testicular and cerebral microcirculation. Upsala Journal of Medical Sciences. 2000;105(3):215-226. DOI: 10.3109/2000-1967-177
  11. 11. Dupont C et al. Metabolic syndrome and smoking are independent risk factors of male idiopathic infertility. Basic and Clinical Andrology. 2019;29(1):1-7. DOI: 10.1186/S12610-019-0090-X/TABLES/2
  12. 12. Richthoff J, Elzanaty S, Rylander L, Hagmar L, Giwercman A. Association between tobacco exposure and reproductive parameters in adolescent males. International Journal of Andrology. 2008;31(1):31-39. DOI: 10.1111/J.1365-2605.2007.00752.X
  13. 13. Weisberg E. Smoking and reproductive health. Clinical Reproduction and Fertility. 1985;3(3):175-186. DOI: 10.1016/0020-7292(93)90282-2
  14. 14. Kim SJ, Han KT, Lee SY, Chun SY, Park EC. Is secondhand smoke associated with stress in smokers and non-smokers? BMC Public Health. 2015;15(1):1-10. DOI: 10.1186/S12889-015-2612-6/FIGURES/2
  15. 15. Ochedalski T, Lachowicz-Ochedalska A, Dec W, Czechowski B. Examining the effects of tobacco smoking on levels of certain hormones in serum of young men. Ginekologia Polska. 1994;65(2):87-93
  16. 16. Muthusami KR, Chinnaswamy P. Effect of chronic alcoholism on male fertility hormones and semen quality. Fertility and Sterility. 2005;84(4):919-924. DOI: 10.1016/J.FERTNSTERT.2005.04.025
  17. 17. Pasqualotto FF, Sobreiro BP, Hallak J, Pasqualotto EB, Lucon AM. Cigarette smoking is related to a decrease in semen volume in a population of fertile men. BJU International. 2006;97(2):324-326. DOI: 10.1111/J.1464-410X.2005.05906.X
  18. 18. Kapoor D, Jones TH. Smoking and hormones in health and endocrine disorders. European Journal of Endocrinology. 2005;152(4):491-499. DOI: 10.1530/EJE.1.01867
  19. 19. Trummer H, Habermann H, Haas J, Pummer K. The impact of cigarette smoking on human semen parameters and hormones. Human Reproduction. 2002;17(6):1554-1559. DOI: 10.1093/HUMREP/17.6.1554
  20. 20. Halmenschlager G, Rossetto S, Lara GM, Rhoden EL. Evaluation of the effects of cigarette smoking on testosterone levels in adult men. The Journal of Sexual Medicine. 2009;6(6):1763-1772. DOI: 10.1111/J.1743-6109.2009.01227.X
  21. 21. Shiels MS et al. Association of cigarette smoking, alcohol consumption, and physical activity with sex steroid hormone levels in US men. Cancer Causes & Control. 2009;20(6):877-886. DOI: 10.1007/S10552-009-9318-Y/TABLES/4
  22. 22. Ramlau-Hansen CH, Thulstrup AM, Aggerholm AS, Jensen MS, Toft G, Bonde JP. Is smoking a risk factor for decreased semen quality? A cross-sectional analysis. Human Reproduction. 2007;22(1):188-196. DOI: 10.1093/HUMREP/DEL364
  23. 23. Polsky JY, Aronson KJ, Heaton JPW, Adams MA. Smoking and other lifestyle factors in relation to erectile dysfunction. BJU International. 2005;96(9):1355-1359. DOI: 10.1111/J.1464-410X.2005.05820.X
  24. 24. Moreira ED, Kim SC, Glasser D, Gingell C. ORIGINAL RESEARCH—EPIDEMIOLOGY: Sexual activity, prevalence of sexual problems, and associated help-seeking patterns in men and women aged 40-80 years in Korea: Data from the global study of sexual attitudes and Behaviors (GSSAB). The Journal of Sexual Medicine. 2006;3(2):201-211. DOI: 10.1111/J.1743-6109.2006.00210.X
  25. 25. Weber MF et al. Risk factors for erectile dysfunction in a cohort of 108 477 Australian men. The Medical Journal of Australia. 2013;199(2):107-111. DOI: 10.5694/MJA12.11548
  26. 26. Shiri R, Hakama M, Häkkinen J, Tammela TLJ, Auvinen A, Koskimäki J. Relationship between smoking and erectile dysfunction. International Journal of Impotence Research. 2005;17(2):164-169. DOI: 10.1038/SJ.IJIR.3901280
  27. 27. Lam TH, Abdullah ASM, Ho LM, Yip AWC, Fan S. Smoking and sexual dysfunction in Chinese males: Findings from men’s health survey. International Journal of Impotence Research. 2005;18(4):364-369. DOI: 10.1038/sj.ijir.3901436
  28. 28. He J et al. Cigarette smoking and erectile dysfunction among Chinese men without clinical vascular disease. American Journal of Epidemiology. 2007;166(7):803-809. DOI: 10.1093/AJE/KWM154
  29. 29. S. Cao, X. Yin, Y. Wang, H. Zhou, F. Song, and Z. Lu, “Smoking and risk of erectile dysfunction: Systematic review of observational studies with Meta-analysis,” PLoS One, vol. 8, no. 4, p. e60443, Apr. 2013, doi: 10.1371/JOURNAL.PONE.0060443
  30. 30. Rose JE, Behm FM. Effects of low nicotine content cigarettes on smoke intake. Nicotine & Tobacco Research. 2004;6(2):309-319. DOI: 10.1080/14622200410001676378
  31. 31. Manna PR, Tena-Sempere M, Huhtaniemi IT. Molecular mechanisms of thyroid hormone-stimulated steroidogenesis in mouse Leydig tumor cells: INVOLVEMENT OF THE STEROIDOGENIC ACUTE REGULATORY (StAR) PROTEIN*. The Journal of Biological Chemistry. 1999;274(9):5909-5918. DOI: 10.1074/JBC.274.9.5909
  32. 32. Tostes RC et al. Cigarette smoking and erectile dysfunction: Focus on NO bioavailability and ROS generation. The Journal of Sexual Medicine. 2008;5(6):1284-1295. DOI: 10.1111/J.1743-6109.2008.00804.X
  33. 33. Sheynkin Y, Gioia K. Environmental and lifestyle considerations for the infertile male. AUA Update Series. 2013;32(4):30-38
  34. 34. Kumosani TA, Elshal MF, Al-Jonaid AA, Abduljabar HS. The influence of smoking on semen quality, seminal microelements and Ca2+-ATPase activity among infertile and fertile men. Clinical Biochemistry. 2008;41(14-15):1199-1203. DOI: 10.1016/J.CLINBIOCHEM.2008.07.013
  35. 35. Saleh RA, Agarwal A, Sharma RK, Nelson DR, Thomas AJ. Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: A prospective study. Fertility and Sterility. Sep 2002;78(3):491-499. doi: 10.1016/S0015-0282(02)03294-6
  36. 36. Soares SR, Melo MA. Cigarette smoking and reproductive function. Current Opinion in Obstetrics & Gynecology. 2008;20(3):281-291. Available from:
  37. 37. Linschooten JO et al. Incomplete protection of genetic integrity of mature spermatozoa against oxidative stress. Reproductive Toxicology. 2011;32(1):106-111. DOI: 10.1016/J.REPROTOX.2011.05.004
  38. 38. El-Melegy NT, Ali MEM. Apoptotic markers in semen of infertile men: Association with cigarette smoking. International Braz J Urol. 2011;37(4):495-506. DOI: 10.1590/S1677-55382011000400009
  39. 39. Arabi M, Moshtaghi H. Influence of cigarette smoking on spermatozoa via seminal plasma. Andrologia. 2005;37(4):119-124. DOI: 10.1111/J.1439-0272.2005.00664.X
  40. 40. Kao SH, Chao HT, Chen HW, Hwang TIS, Liao TL, Wei YH. Increase of oxidative stress in human sperm with lower motility. Fertility and Sterility. 2008;89(5):1183-1190. DOI: 10.1016/J.FERTNSTERT.2007.05.029
  41. 41. Zitzmann M et al. Male smokers have a decreased success rate for in vitro fertilization and intracytoplasmic sperm injection. Fertility and Sterility. 2003;79(SUPPL. 3):1550-1554. DOI: 10.1016/S0015-0282(03)00339-X
  42. 42. Pasqualotto FF, Umezu FM, Salvador M, Borges E, Sobreiro BP, Pasqualotto EB. Effect of cigarette smoking on antioxidant levels and presence of leukocytospermia in infertile men: A prospective study. Fertility and Sterility. 2008;90(2):278-283. DOI: 10.1016/j.fertnstert.2008.02.123
  43. 43. Calogero A et al. Cigarette smoke extract immobilizes human spermatozoa and induces sperm apoptosis. Reproductive Biomedicine Online. 2009;19(4):564-571. DOI: 10.1016/J.RBMO.2009.05.004
  44. 44. Xu LC, Wang SY, Yang XF, Wang XR. Effects of cadmium on rat sperm motility evaluated with computer assisted sperm analysis. Biomedical and Environmental Sciences. 2001;14(4):312-317
  45. 45. Anderson LN, Cotterchio M, Mirea L, Ozcelik H, Kreiger N. Passive cigarette smoke exposure during various periods of life, genetic variants, and breast Cancer risk among never smokers. American Journal of Epidemiology. 2012;175(4):289-301. DOI: 10.1093/AJE/KWR324
  46. 46. Louie KS et al. Smoking and passive smoking in cervical cancer risk: Pooled analysis of couples from the IARC multicentric case-control studies. Cancer Epidemiology, Biomarkers & Prevention. 2011;20(7):1379-1390. DOI: 10.1158/1055-9965.EPI-11-0284
  47. 47. García-Ferreyra J. Sperm DNA fragmentation and its relation with fertility. In: New Discoveries in Embryology. IntechOpen; 2015. pp. 1-3
  48. 48. Zribi N et al. Sperm DNA fragmentation and oxidation are independent of malondialdheyde. Reproductive Biology and Endocrinology. 2011;9(1):1-8. DOI: 10.1186/1477-7827-9-47/FIGURES/3
  49. 49. Kaufmann SH, Hengartner MO. Programmed cell death: Alive and well in the new millennium. Trends in Cell Biology. 2001;11(12):526-534. DOI: 10.1016/S0962-8924(01)02173-0
  50. 50. Fraga CG, Motchnik PA, Wyrobek AJ, Rempel DM, Ames BN. Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 1996;351(2):199-203. DOI: 10.1016/0027-5107(95)00251-0
  51. 51. Zenzes MT. Smoking and reproduction: Gene damage to human gametes and embryos. Human Reproduction Update. 2000;6(2):122-131. DOI: 10.1093/HUMUPD/6.2.122
  52. 52. Ernst A et al. Maternal smoking during pregnancy and reproductive health of daughters: A follow-up study spanning two decades. Human Reproduction. 2012;27(12):3593-3600. DOI: 10.1093/HUMREP/DES337
  53. 53. Saleh RA, Agarwal A, Sharma RK, Said TM, Sikka SC, Thomas AJ. Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele. Fertility and Sterility. 2003;80(6):1431-1436. DOI: 10.1016/S0015-0282(03)02211-8
  54. 54. Henkel R et al. Influence of deoxyribonucleic acid damage on fertilization and pregnancy. Fertility and Sterility. 2004;81(4):965-972. DOI: 10.1016/J.FERTNSTERT.2003.09.044
  55. 55. Elshal MF, El-Sayed IH, Elsaied MA, El-Masry SA, Kumosani TA. Sperm head defects and disturbances in spermatozoal chromatin and DNA integrities in idiopathic infertile subjects: Association with cigarette smoking. Clinical Biochemistry. 2009;42(7-8):589-594. DOI: 10.1016/j.clinbiochem.2008.11.012
  56. 56. Aoki VW, Liu L, Carrell DT. Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males. Human Reproduction. 2005;20(5):1298-1306. DOI: 10.1093/HUMREP/DEH798
  57. 57. Ramos L et al. Incomplete nuclear transformation of human spermatozoa in oligo-astheno-teratospermia: Characterization by indirect immunofluorescence of chromatin and thiol status. Human Reproduction. 2008;23(2):259-270. DOI: 10.1093/HUMREP/DEM365
  58. 58. Saleh RA, Agarwal A, Sharma RK, Nelson DR, Thomas AJ. Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: A prospective study. Fertility and Sterility. 2002;78(3):491-499. DOI: 10.1016/S0015-0282(02)03294-6
  59. 59. Dai JB, Wang ZX, Qiao ZD. The hazardous effects of tobacco smoking on male fertility. Asian Journal of Andrology. 2015;17(6):954. DOI: 10.4103/1008-682X.150847
  60. 60. Piomboni P, Focarelli R, Stendardi A, Ferramosca A, Zara V. The role of mitochondria in energy production for human sperm motility. International Journal of Andrology. 2012;35(2):109-124. DOI: 10.1111/J.1365-2605.2011.01218.X
  61. 61. Cho CL, Agarwal A, Majzoub A, Esteves SC. Clinical utility of sperm DNA fragmentation testing: Concise practice recommendations. Translational Andrology and Urology. 2017;6(Suppl 4):S366-S373. DOI: 10.21037/tau.2017.07.28
  62. 62. Darbandi M et al. Reactive oxygen species and male reproductive hormones. Reproductive Biology and Endocrinology. 2018;16(1):1-14. DOI: 10.1186/S12958-018-0406-2
  63. 63. Feil R, Fraga MF. Epigenetics and the environment: Emerging patterns and implications. Nature Reviews. Genetics. 2012;13(2):97-109. DOI: 10.1038/nrg3142
  64. 64. Laberge R-M, Boissonneault G. On the nature and origin of DNA Strand breaks in elongating spermatids 1. Biology of Reproduction. 2005;73:289-296. DOI: 10.1095/biolreprod.104.036939
  65. 65. Kempisty B, Jedrzejczak P, Jagodzinski PP. Structure and role of protamines 1 and 2 in spermatogenesis and male infertility. Ginekologia Polska. 2006;77(3):238-245
  66. 66. Seli E, Sakkas D. Spermatozoal nuclear determinants of reproductive outcome: Implications for ART. Human Reproduction Update. 2005;11(4):337-349. DOI: 10.1093/HUMUPD/DMI011
  67. 67. Miyagawa Y et al. Single-nucleotide polymorphisms and mutation analyses of the TNP1 and TNP2 genes of fertile and infertile human male populations. Journal of Andrology. 2005;26(6):779-786. DOI: 10.2164/JANDROL.05069
  68. 68. Aoki VW, Emery BR, Liu L, Carrell DT. Protamine levels vary between individual sperm cells of infertile human males and correlate with viability and DNA integrity. Journal of Andrology. 2006;27(6):890-898. DOI: 10.2164/JANDROL.106.000703
  69. 69. Hamad MF, Shelko N, Kartarius S, Montenarh M, Hammadeh ME. Impact of cigarette smoking on histone (H2B) to protamine ratio in human spermatozoa and its relation to sperm parameters. Andrology. 2014;2(5):666-677. DOI: 10.1111/J.2047-2927.2014.00245.X
  70. 70. Sakkas D et al. The use of two density gradient centrifugation techniques and the swim-up method to separate spermatozoa with chromatin and nuclear DNA anomalies. Human Reproduction. 2000;15(5):1112-1116. DOI: 10.1093/HUMREP/15.5.1112
  71. 71. Spano M, Seli E, Bizzaro D, Manicardi GC, Sakkas D. The significance of sperm nuclear DNA strand breaks on reproductive outcome. Current Opinion in Obstetrics and Gynecology. 2005;17(3):255-260. DOI: 10.1097/01.gco.0000169102.77504.66
  72. 72. Gannon AM, Stämpfli MR, Foster WG. Cigarette smoke exposure elicits increased autophagy and dysregulation of mitochondrial dynamics in murine granulosa cells. Biology of Reproduction. 2013;88(3):1-11. DOI: 10.1095/biolreprod.112.106617
  73. 73. Simon L, Zini A, Dyachenko A, Ciampi A, Carrell D. A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome. Asian Journal of Andrology. 2017;19(1):80-90. DOI: 10.4103/1008-682X.182822
  74. 74. Boissonnas CC, Jouannet P, Jammes H. Epigenetic disorders and male subfertility. Fertility and Sterility. 2013;99(3):624-631. DOI: 10.1016/J.FERTNSTERT.2013.01.124
  75. 75. Ostrow KL et al. Cigarette smoke induces methylation of the tumor suppressor gene NISCH. Epigenetics. 2013;8(4):383-388. DOI: 10.4161/EPI.24195
  76. 76. Zeilinger S et al. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS One. 2013;8(5):e63812. DOI: 10.1371/JOURNAL.PONE.0063812
  77. 77. Dogan MV et al. The effect of smoking on DNA methylation of peripheral blood mononuclear cells from African American women. BMC Genomics. 2014;15(1):1-13. DOI: 10.1186/1471-2164-15-151/TABLES/7
  78. 78. Sun YV et al. Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans. Human Genetics. 2013;132(9):1027-1037. DOI: 10.1007/S00439-013-1311-6/FIGURES/1
  79. 79. Zhu X et al. Genome-wide analysis of DNA methylation and cigarette smoking in a Chinese population. Environmental Health Perspectives. 2016;124(7):966-973. DOI: 10.1289/EHP.1509834
  80. 80. Laqqan M, Tierling S, Alkhaled Y, Lo Porto C, Solomayer EF, Hammadeh ME. Aberrant DNA methylation patterns of human spermatozoa in current smoker males. Reproductive Toxicology. 2017;71:126-133. DOI: 10.1016/J.REPROTOX.2017.05.010
  81. 81. Aston KI, Punj V, Liu L, Carrell DT. Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis. Fertility and Sterility. 2012;97(2):285-292.e4. DOI: 10.1016/J.FERTNSTERT.2011.11.008
  82. 82. Hecht SS. Smoking and lung cancer - a new role for an old toxicant? Proceedings of the National Academy of Sciences of the United States of America. 2006;103(43):15725-15726. DOI: 10.1073/PNAS.0607811103/ASSET/5181EAF3-2B37-43F3-A63A-F3E377A25E51/ASSETS/GRAPHIC/ZPQ0440640370001.JPEG
  83. 83. Marczylo EL, Amoako AA, Konje JC, Gant TW, Marczylo TH. Smoking induces differential miRNA expression in human spermatozoa: A potential transgenerational epigenetic concern? Epigenetics. 2012;7(5):432-439. DOI: 10.4161/EPI.19794
  84. 84. Linschooten JO et al. Use of spermatozoal mRNA profiles to study gene–environment interactions in human germ cells. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2009;667(1-2):70-76. DOI: 10.1016/J.MRFMMM.2008.12.014
  85. 85. Maccani MA, Avissar-Whiting M, Banister CE, McGonnigal B, Padbury JF, Marsit CJ. Maternal cigarette smoking during pregnancy is associated with downregulation of miR-16, miR-21, and miR-146a in the placenta. Epigenetics. 2010;5(7):583-589. DOI: 10.4161/EPI.5.7.12762
  86. 86. Yarosh SL, Kokhtenko EV, Starodubova NI, Churnosov MI, Polonikov AV. Smoking status modifies the relation between CYP1A1*2C gene polymorphism and idiopathic male infertility: The importance of gene-environment interaction analysis for genetic studies of the disease. Reproductive Sciences. 2013;2(11):1302-1307. DOI: 10.1177/1933719113483013
  87. 87. Yarosh SL, Kokhtenko EV, Churnosov MI, Solodilova MA, Polonikov AV. Joint effect of glutathione S-transferase genotypes and cigarette smoking on idiopathic male infertility. Andrologia. 2015;47(9):980-986. DOI: 10.1111/AND.12367
  88. 88. Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. National, regional, and global trends in infertility prevalence since 1990: A systematic analysis of 277 health surveys. PLoS Medicine. 2012;9(12):e1001356. DOI: 10.1371/JOURNAL.PMED.1001356
  89. 89. Inhorn MC, Patrizio P. Infertility around the globe: New thinking on gender, reproductive technologies and global movements in the 21st century. Human Reproduction Update. 2015;21(4):411-426. DOI: 10.1093/HUMUPD/DMV016
  90. 90. Zegers-Hochschild F et al. The international glossary on infertility and fertility care, 2017. Human Reproduction. 2017;32(9):1786. DOI: 10.1093/HUMREP/DEX234
  91. 91. Cinar O et al. Does cigarette smoking really have detrimental effects on outcomes of IVF? European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2014;174(1):106-110. DOI: 10.1016/J.EJOGRB.2013.12.026
  92. 92. Klonoff-Cohen H, Natarajan L, Marrs R, Yee B. Effects of female and male smoking on success rates of IVF and gamete intra-fallopian transfer. Human Reproduction. 2001;16(7):1382-1390. DOI: 10.1093/HUMREP/16.7.1382
  93. 93. Fuentes A, Muñoz A, Barnhart K, Argüello B, Díaz M, Pommer R. Recent cigarette smoking and assisted reproductive technologies outcome. Fertility and Sterility. 2010;93(1):89-95. DOI: 10.1016/j.fertnstert.2008.09.073
  94. 94. Aitken RJ, De Iuliis GN. On the possible origins of DNA damage in human spermatozoa. Molecular Human Reproduction. 2010;16(1):3-13. DOI: 10.1093/MOLEHR/GAP059
  95. 95. Chen X, Zhang W, Luo Y, Long X, Sun X. Predictive value of semen parameters in in vitro fertilisation pregnancy outcome. Andrologia. 2009;41(2):111-117. DOI: 10.1111/J.1439-0272.2008.00898.X
  96. 96. de Jong AME, Menkveld R, Lens JW, Nienhuis SE, Rhemrev JPT. Effect of alcohol intake and cigarette smoking on sperm parameters and pregnancy. Andrologia. 2014;46(2):112-117. DOI: 10.1111/AND.12054
  97. 97. Hull MGR, North K, Taylorb H, Farrow A, Christopher W, Ford L. Delayed conception and active and passive smoking. Fertility and Sterility. 2000;74(4):725-733. DOI: 10.1016/S0015-0282(00)01501-6
  98. 98. Hassan MAM, Killick SR. Negative lifestyle is associated with a significant reduction in fecundity. Fertility and Sterility. 2004;81(2):384-392. DOI: 10.1016/j.fertnstert.2003.06.027
  99. 99. Radin RG et al. Active and passive smoking and fecundability in Danish pregnancy planners. Fertility and Sterility. 2014;102(1):183-191.e2. DOI: 10.1016/J.FERTNSTERT.2014.03.018
  100. 100. Penzias A et al. Smoking and infertility: A committee opinion. Fertility and Sterility. 2018;110(4):611-618. DOI: 10.1016/J.FERTNSTERT.2018.06.016
  101. 101. Freeman EW, Sammel MD, Lin H, Gracia CR. Anti-Mullerian hormone as a predictor of time to menopause in late reproductive age women. The Journal of Clinical Endocrinology and Metabolism. 2012;97(5):1673-1680. DOI: 10.1210/JC.2011-3032
  102. 102. Uzumcu M, Zama AM, Oruc E. Epigenetic mechanisms in the actions of endocrine-disrupting chemicals: Gonadal effects and role in female reproduction. Reproduction in Domestic Animals. 2012;47(4): 338-347. DOI: 10.1111/J.1439-0531.2012.02096.X
  103. 103. Rowland AS et al. Influence of medical conditions and lifestyle factors on the menstrual cycle. Epidemiology. 2002;13(6):668-674. Available from:
  104. 104. Matikainen TM et al. Ligand activation of the aromatic hydrocarbon receptor transcription factor drives Bax-dependent apoptosis in developing Fetal ovarian germ cells. Endocrinology. 2002;143(2):615-620. DOI: 10.1210/ENDO.143.2.8624
  105. 105. Harlev A, Agarwal A, Gunes SO, Shetty A, du Plessis SS. Smoking and male infertility: An evidence-based review. The World Journal of Men's Health. 2015;33(3):143-160. DOI: 10.5534/wjmh.2015.33.3.143
  106. 106. Oyeyipo IP, Raji Y, Bolarinwa AF. Antioxidant profile changes in reproductive tissues of rats treated with nicotine. Journal of Human Reproductive Sciences. 2014;7(1):41. DOI: 10.4103/0974-1208.130823
  107. 107. Llahí-Camp JM, Rai R, Ison C, Regan L, Taylor-Robinson D. Association of bacterial vaginosis with a history of second trimester miscarriage. Human Reproduction. 1996;11(7):1575-1578. DOI: 10.1093/OXFORDJOURNALS.HUMREP.A019440
  108. 108. Saraiya M, Berg CJ, Kendrick JS, Strauss LT, Atrash HK, Ahn YW. Cigarette smoking as a risk factor for ectopic pregnancy. American Journal of Obstetrics and Gynecology. 1998;178(3):493-498. DOI: 10.1016/S0002-9378(98)70427-2
  109. 109. Winter E, Wang J, Davies MJ, Norman R. Early pregnancy loss following assisted reproductive technology treatment. Human Reproduction. 2002;17(12):3220-3223. DOI: 10.1093/HUMREP/17.12.3220
  110. 110. George L, Granath F, Johansson ALV, Annerén G, Cnattingius S. Environmental tobacco smoke and risk of spontaneous abortion. Epidemiology. 2006;17(5):500-505. DOI: 10.1097/01.EDE.0000229984.53726.33
  111. 111. Meeker JD, Missmer SA, Cramer DW, Hauser R. Maternal exposure to second-hand tobacco smoke and pregnancy outcome among couples undergoing assisted reproduction. Human Reproduction. 2007;22(2):337-345. DOI: 10.1093/HUMREP/DEL406
  112. 112. Pineles BL, Hsu S, Park E, Samet JM. Systematic review and Meta-analyses of perinatal death and maternal exposure to tobacco smoke during pregnancy. American Journal of Epidemiology. 2016;184(2):87-97. DOI: 10.1093/AJE/KWV301
  113. 113. Qu Y et al. Exposure to tobacco smoke and stillbirth: A national prospective cohort study in rural China. Journal of Epidemiology and Community Health. 2020;74(4):315-320. DOI: 10.1136/JECH-2019-213290
  114. 114. CDC. 2018 Assisted Reproductive Technology Manual. Atlanta, GA: US Department of Health and Human Services; 2020. [Online]. Available:
  115. 115. Gruber I, Just A, Birner M, Lösch A. Effect of a woman’s smoking status on oocyte, zygote, and day 3 pre-embryo quality in in vitro fertilization and embryo transfer program. Fertility and Sterility. 2008;90(4):1249-1252. DOI: 10.1016/J.FERTNSTERT.2007.06.108
  116. 116. Shiloh H et al. The impact of cigarette smoking on zona pellucida thickness of oocytes and embryos prior to transfer into the uterine cavity. Human Reproduction. 2004;19(1):157-159. DOI: 10.1093/HUMREP/DEH029
  117. 117. Depa-Martynów M, Pawelczyk L, Taszarek-Hauke G, Jósiak M, Derwich K, Jedrzejczak P. The effect of smoking on infertility treatment in women undergoing assisted reproduction cycles. Przeglaṃd Lekarski. 2005;62(10):973-975
  118. 118. Lambert-Messerlian GM, Harlow BL. The influence of depression, body mass index, and smoking on serum inhibin B levels in late reproductive-aged women. The Journal of Clinical Endocrinology and Metabolism. 2006;91(4):1496-1500. DOI: 10.1210/JC.2005-2515
  119. 119. Neal MS, Hughes EG, Holloway AC, Foster WG. Sidestream smoking is equally as damaging as mainstream smoking on IVF outcomes. Human Reproduction. 2005;20(9):2531-2535. DOI: 10.1093/HUMREP/DEI080
  120. 120. Kinney A, Kline J, Kelly A, Reuss ML, Levin B. Smoking, alcohol and caffeine in relation to ovarian age during the reproductive years. Human Reproduction. 2007;22(4):1175-1185. DOI: 10.1093/HUMREP/DEL496
  121. 121. Kharrazi M et al. Environmental tobacco smoke and pregnancy outcome. Epidemiology. 2004;15(6):660-670. DOI: 10.1097/01.EDE.0000142137.39619.60
  122. 122. Freour T et al. Active smoking compromises IVF outcome and affects ovarian reserve. 2008;16(1):96-102. DOI: 10.1016/S1472-6483(10)60561-5
  123. 123. Sowers MR, McConnell D, Yosef M, Jannausch ML, Harlow SD, Randolph JF. Relating smoking, obesity, insulin resistance, and ovarian biomarker changes to the final menstrual period. Annals of the New York Academy of Sciences. 2010;1204(1):95-103. DOI: 10.1111/J.1749-6632.2010.05523.X
  124. 124. Plante BJ, Cooper GS, Baird DD, Steiner AZ. The impact of smoking on antimüllerian hormone levels in women aged 38 to 50 years. Menopause. 2010;17(3):571-576. DOI: 10.1097/GME.0B013E3181C7DEBA
  125. 125. Butts SF, Sammel MD, Greer C, Rebbeck TR, Boorman DW, Freeman EW. Cigarettes, genetic background, and menopausal timing: The presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers. Menopause. 2014;21(7):694-701. DOI: 10.1097/GME.0000000000000140
  126. 126. Ozbakir B, Tulay P. Does cigarette smoking really have a clinical effect on folliculogenesis and oocyte maturation? Zygote. 2020;28(4):318-321. DOI: 10.1017/S0967199420000155
  127. 127. Zenzes MT, Bielecki R, Reed TE. Detection of benzo(a)pyrene diol epoxide–DNA adducts in sperm of men exposed to cigarette smoke. Fertility and Sterility. 1999;72(2):330-335. DOI: 10.1016/S0015-0282(99)00230-7
  128. 128. Yang Q et al. Risk factors for trisomy 21: Maternal cigarette smoking and oral contraceptive use in a population-based case-control study. 1999. DOI: 10.1097/00125817-199903000-00004
  129. 129. Kharkova OA, Grjibovski AM, Krettek A, Nieboer E, Odland J. Effect of smoking behavior before and during pregnancy on selected birth outcomes among singleton full-term pregnancy: A Murmansk County birth registry study. International Journal of Environmental Research and Public Health. 2017;14(8):867. DOI: 10.3390/IJERPH14080867
  130. 130. Holloway AC, Cuu DQ , Morrison KM, Gerstein HC, Tarnopolsky MA. Transgenerational effects of fetal and neonatal exposure to nicotine. Endocrine. 2007;31(3):254-259. DOI: 10.1007/S12020-007-0043-6/FIGURES/3
  131. 131. Mohamed ESA et al. The transgenerational impact of benzo(a)pyrene on murine male fertility. Human Reproduction. 2010;25(10):2427-2433. DOI: 10.1093/HUMREP/DEQ205
  132. 132. Jenkins TG, Aston KI, James ER, Carrell DT. Systems biology in reproductive medicine sperm epigenetics in the study of male fertility, offspring health, and potential clinical applications. Systems Biology in Reproductive Medicine. 2017;63(2):69-76. DOI: 10.1080/19396368.2016.1274791
  133. 133. Kataoka MC, Carvalheira APP, Ferrari AP, Malta MB, de Barros Leite Carvalhaes MA, de Lima Parada CMG. Smoking during pregnancy and harm reduction in birth weight: A cross-sectional study. BMC Pregnancy and Childbirth. 2018;18(1):1-10. DOI: 10.1186/S12884-018-1694-4/TABLES/5
  134. 134. Liu B et al. Maternal cigarette smoking before and during pregnancy and the risk of preterm birth: A dose–response analysis of 25 million mother–infant pairs. PLoS Medicine. 2020;17(8):e1003158. DOI: 10.1371/JOURNAL.PMED.1003158
  135. 135. Treating tobacco use and dependence: 2008 update U.S. Public Health Service clinical practice guideline executive summary. Respiratory Care. 2008;53(9):1217-1222
  136. 136. U.S. Department of Health and Human Services. Smoking Cessation. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; 2020
  137. 137. Smoking Cessation: A Report of the Surgeon General – Key Findings | Available from: [Accessed February 13, 2022]
  138. 138. Prentki Santos E et al. Impact of spontaneous smoking cessation on sperm quality: Case report. Andrologia. 2011;43(6):431-435. DOI: 10.1111/J.1439-0272.2010.01089.X
  139. 139. Paszkowski T, Clarke RN, Hornstein MD. Smoking induces oxidative stress inside the Graafian follicle. Human Reproduction. 2002;17(4):921-925. DOI: 10.1093/HUMREP/17.4.921
  140. 140. Sengupta P, Agarwal A, Pogrebetskaya M, Roychoudhury S, Durairajanayagam D, Henkel R. Role of Withania somnifera (Ashwagandha) in the management of male infertility. Reproductive Biomedicine Online. 2018;36(3):311-326. DOI: 10.1016/j.rbmo.2017.11.007
  141. 141. Reis LO, Dias FGF. Male fertility, obesity, and bariatric surgery. Reproductive Sciences. 2012;19(8):778-785. DOI: 10.1177/1933719112440053
  142. 142. Sedha S, Kumar S, Shukla S. Role of oxidative stress in male reproductive dysfunctions with reference to phthalate compounds. Urology Journal. 2015;12(5):2304-2316. DOI: 10.22037/uj.v12i5.3009
  143. 143. Bassiony MM. Smoking in Saudi Arabia. Saudi Medical Journal. 2009;30(7):876-881
  144. 144. Maiorino MI, Bellastella G, Esposito K. Lifestyle modifications and erectile dysfunction: What can be expected? Asian Journal of Andrology. 2015;17(1):5. DOI: 10.4103/1008-682X.137687
  145. 145. Windsor RA, Woodby LL, Miller TM, Hardin JM, Crawford MA, DiClemente CC. Effectiveness of Agency for Health Care Policy and Research clinical practice guideline and patient education methods for pregnant smokers in medicaid maternity care. American Journal of Obstetrics and Gynecology. 2000;182(1 Pt 1):68-75. DOI: 10.1016/S0002-9378(00)70492-3
  146. 146. Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: An overview and network meta-analysis. Cochrane Database of Systematic Reviews. 2013;5:2013. DOI: 10.1002/14651858.CD009329.PUB2/MEDIA/CDSR/CD009329/IMAGE_N/NCD009329-AFIG-FIG 04.PNG

Written By

Amor Houda, Jankowski Peter Michael, Micu Romeo and Hammadeh Mohamad Eid

Submitted: 28 March 2022 Reviewed: 14 April 2022 Published: 09 June 2022