1. EFFECTS OF TOBACCO ON FERTILITY
Mini-Lecture 1
Module: Tobacco and the
Reproductive System

2. Objectives of the Mini Lecture
Goals of Mini Lecture: Provide students with an understanding of the relationship between smoking, fertility, and reproduction.
Learning Objectives of Mini Lecture:
Students will be able to:
Describe how smoking affects the process of reproduction in women and men.
Describe how smoking affects the menstrual cycle.
Describe how chewing tobacco affects fertility.
Explain how tobacco cessation can be beneficial in infertility.

3. Contents Core Slides: Optional Slides: Smoking and Reproduction: Women
Smoking and Reproduction: Men
Smoking and Menstrual Cycle
Chewing Tobacco and Fertility
Tobacco cessation and Infertility
Optional Slides:
Smoking and Assisted Reproduction
Smoking Cessation and IVF
GOAL OF MODULE: Increase students’ knowledge of the potential problems related to fertility and tobacco use.
LEARNING OBJECTIVES: Students will be able to understand:
Core Slides:
Smoking and Reproduction: Women
Smoking and Reproduction: Men
Smoking and Menstrual Cycle
Chewing Tobacco and Fertility
Tobacco Cessation and Infertility
Optional Slides:
Smoking and Assisted Reproduction
Smoking Cessation and IVF

4. CORE SLIDES Effects of Tobacco on Fertility Mini Lecture 1
Module: Tobacco and Reproductive System

5. Smoking and Reproduction: Women1
Higher prevalence of infertility
Time taken to conceive is longer
Harmful to ovaries
Accelerates loss of ova
Impairs ability of ovarian cells to make estrogen
Oocytes more prone to genetic abnormalities
Notes:
Almost all scientific studies support the conclusion that smoking has an adverse impact on fertility. The prevalence of infertility is higher, and the time it takes to conceive is longer in smokers compared to nonsmokers. Active smoking by either partner has adverse effects, and the impact of passive cigarette smoke exposure is only slightly less than for active smoking. Research indicates that cigarette smoking is harmful to the ovaries, and the degree of harm is dependent upon the amount and the period of time a woman smokes. Smoking appears to accelerate the loss of ova and reproductive function and may advance menopause by several years. Components in cigarette smoke have been shown to interfere with the ability of cells in the ovary to make estrogen and to cause the oocytes to be more prone to genetic abnormalities.
Reference:
American Society for Reproductive Medicine. Patient’s fact sheet, 2003: Smoking and infertility. Available at:
1. American Society for Reproductive Medicine 2003

6. Smoking and Reproduction: Men
Lower sperm count and motility1
Increased abnormalities in sperm shape and function1
Increases risk of erectile dysfunction by 50%2
Parental peri-conceptional smoking: decreases frequency of conceiving male children3
Notes:
Men who smoke cigarettes have a lower sperm count and motility and increased abnormalities in sperm shape and function. There is substantial evidence that smoking adversely affects sperm quality.1 Smoking also tends to cause erectile dysfunction by several mechanisms, including adversely affecting intra-penile blood flow.2 Hence, smoking in men should be regarded as an infertility risk factor, due to its effect on men as well as the effect of passive smoking on fertility in women.
Fukuda et al. assessed whether the smoking habits of parents around the time of conception affect the likelihood of the offspring being male or female. They found that the offspring sex ratio (male to female) was lower when either one or both of the parents smoked more than 20 cigarettes per day compared with couples in which neither of the parents smoked. They found the lowest sex ratio among children whose mothers and fathers both smoked more than 20 cigarettes per day (p<0.0001). Thus, cigarette smoking seems to reduce the frequency of male babies, suggesting that parental smoking might be a contributing factor to the observed reduced sex ratio. 3
References:
American Society for Reproductive Medicine. Patient’s fact sheet, 2003: Smoking and infertility. Available at:
Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. A prospective study of risk factors for erectile dysfunction. J Urol. 2006; 176:217–21.
Fukuda M, Fukuda K, Shimizu T, Andersen CY, Byskov AG. Parental periconceptional smoking and male: female ratio of newborn infants. Lancet. 2002; 359:1407–8.
1. American Society for Reproductive Medicine 2003; 2. Bacon et al. 2006; 3. Fukuda et al. 2002

7. Smoking and the Menstrual Cycle
Causes menstrual irregularities1
Shortens luteal and follicular phase2
Increased risk of anovulatory cycles2
Earlier menopause2
Notes:
Cigarette smoke contains known reproductive toxicants, and smoking has been associated with adverse reproductive outcomes in women such as infertility, subfecundity, younger age at menopause, and menstrual disorders.1 Endothelial function was found to be significantly impaired in smoking women in the mid-luteal phase, when compared with non-smoking women. Both cigarette smoking and passive smoking are known to impair endothelial function in healthy adults. The increase in the estradiol level in the course of the menstrual cycle was lower in smoking women. This may be a partial explanation for the difference in endothelial function in the mid-luteal phase.2 Heavy smoking was associated with shorter and more variable cycle lengths, with the shortening occurring primarily during the follicular phase. There is also an increased risk of short luteal phase (< 11 days) and anovulation. The mechanism of these reported effects is not known but may reflect alterations in hormone function and anti-estrogenic effects by components of tobacco smoke. Some studies have reported that smokers have higher levels of FSH than do nonsmokers. Compared with nonsmokers, moderate to heavy smokers (≥ 10 cigarettes/day) had baseline levels (e.g., early follicular phase) of both steroid metabolites that were 25–35% higher, and heavy smokers (≥ 20 cigarettes/day) had lower luteal phase progesterone metabolite levels. The mean daily urinary FSH levels around the cycle transition were increased at least 30–35% with moderate smoking, even after adjustment.1 It has been shown that smoking leads to increased formation of 2-hydroxylated estrogen metabolites, which have lower estrogenic activity. 2 Chronic nicotine abuse may reduce estrogen production, and the anti-estrogenic properties of nicotine via interference with hepatic estrogen metabolism have been discussed as the underlying mechanism.2 These patterns suggest that chemicals in tobacco smoke alter endocrine function, perhaps at the level of the ovary, which in turn affects release of the pituitary hormones. This endocrine disruption likely contributes to the reported associations of smoking with adverse reproductive outcomes, including menstrual dysfunction, infertility, and earlier menopause. This pattern of higher FSH levels and shorter cycles in smokers is consistent with the observation that smokers tend to experience earlier menopause.1
References:
Windham GC, Mitchell P, Anderson M, Lasley BL. Cigarette smoking and effects on hormone function in premenopausal women. Environ Health Perspect. 2005; 113:1285–90.
Baumann G, Stangl K, Stangl V, Jochmann N, Müller S, Kuhn C, et al. Chronic smoking prevents amelioration of endothelial function in the course of the menstrual cycle. Circ J. 2009; 73:568–72.
1. Baumann et al. 2009; 2. Windham et al. 2005

8. Chewing Tobacco and Fertility
India
Chewing Tobacco and Fertility
Significantly decreased sperm concentration, motility, morphology, and viability in severe chewing tobacco users
Percentage of men with azoospermia increased with the level of addiction
Notes:
In one study on Indian men, sperm concentration, percentage motility, morphology, and percentage viability were significantly higher among mild chewing tobacco users vs. the moderate group and in the moderate group vs. the severe group. The percentage of men with azoospermia rose with the level of addiction (1%, 3%, and 14%) as did the percentage of men with oligoasthenoteratozoospermia (2%, 8%, and 29%), although the differences were not statistically significant.
Reference:
Said T, Ranga G, Agarwal A. Relationship between semen quality and tobacco chewing in men undergoing infertility evaluation. Fertil Steril. 2005; 84:649–53.
Said et al. 2005

9. Tobacco Cessation and Infertility
Both male and female infertility risk increased with tobacco use; therefore, advise cessation.
Cessation of smoking is associated with increase in sperm number and decrease in the frequency of sperm shape abnormalities.1
Notes:
Evidence so far suggests that both male and female infertility risk is increased due to tobacco use, both smoking and smokeless. In such a scenario, it is imperative that smoking cessation be actively promoted when couples present with infertility and before starting any treatment. Several small studies have demonstrated decreased sperm counts and an increased frequency of abnormal sperm morphology among male smokers. Cessation of smoking in several of these studies has been associated with an increase in sperm number and a decrease in the frequency of sperm shape abnormalities. The literature on smoking and fertility, however, is surprisingly small.
Reference:
Mattison DR. The effects of smoking on fertility from gametogenesis to implantation. Environ Res. 1982; 28:410–33.
Mattison 1982

10. OPTIONAL SLIDES Effects of Tobacco on Fertility Mini Lecture 1
Module: Tobacco and Reproductive System

11. Smoking and Assisted Reproduction1
Twice as many IVFs required
Fewer oocytes obtained
More missed cycles
Lower implantation rates
More failed fertilization cycles
Higher miscarriage rates
Notes:
Nearly twice as many in vitro fertilization (IVF) attempts are required to conceive in smokers as in nonsmokers. Studies of IVF have reported that female smokers require higher doses of gonadotropins to stimulate their ovaries, have lower peak estradiol levels, fewer oocytes obtained, more missed cycles, lower implantation rates, and undergo more cycles with failed fertilization than nonsmokers. Miscarriage rates are also increased. The adverse effect of cigarette smoking is more noticeable in older women. Overall, the reduction in natural fertility associated with smoking may not be overcome by assisted reproductive technologies.
Reference:
American Society for Reproductive Medicine. Patient’s fact sheet 2003: Smoking and infertility. Available at:
American Society for Reproductive Medicine 2003

12. Smoking Cessation and IVF1
Smoking cessation (at least two months before IVF) improves chances of conception significantly.
Long-term smoking: irreversible effect on ovarian function.
Notes:
Cessation of smoking for at least two months before attempting IVF was shown to significantly improved chances for conception. Although long-term cigarette smoking can have an irreversible effect on ovarian function, the harmful effect on treatment outcome may, in part, be reversed if smoking is discontinued prior to entering into fertility therapy.
Reference:
American Society for Reproductive Medicine. Patient’s fact sheet 2003: Smoking and infertility. Available at:
American Society for Reproductive Medicine 2003

13. Stop smoking for the health of your family!