The Effect of Lifestyle and Diet on Fertility: Fertility-Enhancing Lifestyle Modifications

part 1 of a series on fertility

By Susan T. Marcolina, MD, FACP. Dr. Marcolina is a board-certified internist and geriatrician in Issaquah, WA; she reports no financial relationship to this field of study.

More than 7% of married couples (2.1 million) in the united States are infertile.1 Defined as the failure to conceive after one year of regular unprotected sexual intercourse, infertility is a chronic health problem for young adults. According to the American Society for Reproductive Medicine, clinical evaluation is recommended after the one-year benchmark because by this time 85% of couples have successfully achieved a pregnancy. Since both male and female infertility require evaluation to identify the probable cause(s), most couples require an initial work-up, which includes semen analysis; an assessment of ovulatory function, such as mid-luteal phase serum progesterone levels and urinary luteinizing hormone (LH) determinations; uterine morphology assessment with a sonohysterogram or hysterosalpingogram (HSG); and fallopian tube patency with either a HSG or laparoscopy.2

Follow-up treatments often require accurate determinations of optimal ovulatory intervals during each menstrual cycle with ovulatory test kits for timed intercourse. Judicious use of these ovulation predictor kits makes it easier for patients to identify optimal fertility days within their cycle and time intercourse accordingly.3 Such intense evaluation and treatment, however, can be ongoing for months or years and involves a significant investment of time, energy, thought, and monetary expense, which can result in disappointment with recurrent failed attempts, and marital stress.

Among infertile couples, problems with ovulation are identified in 18-30% of cases.4,5 Although treatment options are available for ovulatory dysfunction including in vitro fertilization (IVF), the cost ($9,500 per cycle in the United States) and complexity of treatment make it available to less than 10% of couples. In addition, it is associated with potentially adverse effects such as multiple pregnancies; ovarian hyperstimulation syndrome; premature deliveries, which can occur with singleton and multiple births; spontaneous abortions; and premature menopause. It is important to identify potentially modifiable risk factors that can augment fertility and be readily available to all patients.6

Primary care physicians can recommend initial lifestyle and dietary measures to couples planning a pregnancy that might increase their chances for successful conception within the initial year of attempt. Chavarro et al have identified several "fertility-friendly" dietary and lifestyle interventions.7 Such factors aim to reduce infertility due to ovulation disorders, but can also improve sperm quality issues.7 The first part of this series reviews lifestyle measures that have been shown to augment fertility. Since these modifications also result in improved overall health, it is important such changes be incorporated at young ages.

Age Discrimination in Fertility

Though not strictly a modifiable characteristic, it has been shown in multiple studies that increasing age for both men (> 45 years) and women (> 35 years) adversely affects fertility8,9 and success with assisted reproductive technologies (ART). Older women were less inducible with ART10 and, once pregnant, had a lower live birth rate due primarily to spontaneous abortion. In a study of 201 pregnancies from women undergoing ovulation induction, Smith et al found a 2.1% risk of spontaneous abortion for women younger than 35 years compared to a 16.1% risk for women older than 36 years.11

Smoking

Smoking has a wide range of adverse effects on fertility for both general and infertile populations. Cigarette smoking distorts sperm morphology, causes DNA damage, and decreases sperm production and motility in men,12 and alters the ovarian follicular fluid microenvironment and luteal phase hormone levels in women.13 Components of cigarette smoke (nicotine; cotinine, a stable metabolite of nicotine; and cadmium) have been detected in follicular fluid of female smokers as well as females exposed only to passive environmental smoking. Since cotinine easily crosses the blood-follicle barrier and has a relatively long plasma half-life of 19 hours, levels of cotinine in follicular fluid provide a reliable test of tobacco smoke exposure.14 Paszkowski et al have shown that cigarette smoking in women undergoing IVF treatment for infertility was associated with an increased intensity of oxidative stress within the ovarian follicle, which resulted in free radical-mediated cytotoxicity for oocytes and granulosa cells. Such cytotoxicity is associated with a statistically significant increase in follicular fluid cotinine concentration and a significantly lower yield of oocytes per cycle in smokers compared to nonsmokers. It is important to also note that the onset of menopause occurs 1-4 years earlier in smokers.15

Alcohol

Alcohol consumption has been associated with reduced fertility at levels as low as one drink per week.15 Alcohol directly impairs ovum maturation, blastocyst development, and implantation, as well as sperm development and maturation.16,17 Most importantly, however, alcohol is a teratogen.18 Since the most vulnerable time for adverse effects on the fetus is during the first few weeks after conception, women who plan a pregnancy should avoid consuming alcohol.19

Caffeine

As one of the most commonly consumed drugs, caffeine is present in common beverages such as coffee, tea, soft drinks, products containing cocoa or chocolate, and in various medications such as Excedrin®. Although the literature is mixed, certain studies are noteworthy. Nawrot et al, in a review of several human studies, concluded that reproductive age women are an "at-risk" population that requires specific medical advice about caffeine intake. They suggest consumption of less than 300 mg/d for this subgroup.20 On the other hand, Tolstrup noted that caffeine intake of only 75 mg/d prior to pregnancy significantly increased the risk of spontaneous abortion.21 Combination studies with alcohol suggest that caffeine enhances the negative effects of alcohol on fertility.16

Insulin Resistance

Certain factors known to increase insulin resistance, such as increased body weight and decreased physical activity, have been associated with an increased risk of infertility secondary to ovulatory dysfunction.22 For instance, insulin resistance is strongly implicated in the etiology of polycystic ovarian syndrome (PCOS), the most common form of ovulatory disorder. Approximately one of 16 women is affected and the clinical triad of menstrual dysfunction, hyperandrogenism (hirsutism, acne, and elevated androgens—testosterone, dehydroepiandrosterone, and androstenedione), and infertility are cardinal features. Elevated insulin levels augment basal pituitary LH release, resulting in overstimulation of the theca internal cells of the ovary, which produce the elevated androgen levels. Many PCOS patients develop impaired glucose tolerance or type 2 diabetes mellitus and the metabolic syndrome with its attendant risks of cardiovascular disease.23

In vitro and in vivo animal and human studies have identified specific nuclear receptors for fatty acids present throughout the body that regulate glucose and lipid metabolism and impact immune function, and thus play important roles in regulation of insulin sensitivity. Currently, three isoforms of these nuclear receptors have been identified in humans: the peroxisome proliferator-activated receptor gamma (PPAR-G), PPAR alpha, and PPAR delta. All three are expressed in a wide variety of tissues including the ovary, adipose tissue, skeletal muscle, heart, kidney, and liver. As a result, ligands that activate these receptors and potentiate their actions have important ramifications upon folliculogenesis and fertility. Ovarian expression of both PPAR alpha and PPAR delta is relatively stable throughout the ovulatory cycle, whereas the expression of PPAR-G in the ovary is more dynamic with an increase in early folliculogenesis. At the time of the LH surge, PPAR-G expression is downregulated. The highest concentrations of PPAR-G are present in granulosa cells, which are responsible for estradiol production and the regulation of follicular fluid content responsible for the growth and development of oocytes.24-26

The thiazolidinediones (TZDs), insulin sensitizers whose actions are mediated via activation of PPAR-G, improve reproductive metabolic profiles and ovulatory function in women with PCOS. However, despite these favorable effects, PPAR-G agonists also downregulate leptin, an adipocyte-selective protein that inhibits feeding behavior and increases lipid catabolism. This effect may explain the weight gain seen in diabetic patients who take synthetic PPAR-G ligands such as TZDs.27

Association of Weight with Infertility

Several studies of male infertility have shown statistically significant negative correlations between body mass index (BMI), waist circumference, and waist:hip ratios with testosterone levels, semen volume, and total sperm count, thus strongly suggesting a link between obesity, hypogonadism, and infertility.28,29

After correction for multiple variables including illness, caffeine, alcohol, and cigarette exposure, and abstinence prior to sample collection, Jensen et al found sperm concentration and total sperm count to be decreased 26% and 24%, respectively among a group of 1,558 Danish men with a BMI greater than 25 kg/m2 compared to a reference group with BMIs between 20-25 kg/m2.30

Rich-Edwards et al observed a U-shaped association between BMI and relative risk of infertility secondary to ovulatory dysfunction in 20,417 American nurses from the Nurses' Health Study II, a cohort of married female nurses ages 24-42 followed prospectively for eight years.22 In comparison to women with a BMI of 21-24 kg/m2, women with BMIs below 20 kg/m2 or above 24 kg/m2 exhibited increasing age-adjusted relative risks of ovulatory infertility.

Exercise

Regular exercise improves general medical health and well-being and provides protection from chronic diseases such as hypertension, cardiovascular disease, diabetes, osteoporosis, and depression. Rich-Edwards et al also found that exercise, specifically vigorous exercise, was associated with a reduced risk of ovulatory infertility. Although this improvement in ovulatory fertility can partly be attributed to diminished weight, it was also noted that even after adjustment for BMI, each hour of vigorous exercise per week produced a relative risk reduction of 5%, suggesting that such regular physical activity protects ovarian function through a mechanism independent of BMI, such as increased insulin sensitivity. Interestingly, nulliparous women benefitted most in terms of improved fertility from this activity, with each hour of vigorous exercise per week resulting in an 8% relative infertility risk reduction, even after multivariable adjustments for smoking, caffeine, alcohol intake, and prior oral contraceptive use. When specific vigorous activities were separately examined, the largest reductions in estimated relative risk were for running (one mile in less than 10 minutes; 34% risk reduction), jogging (one mile in more than 10 minutes; 22% risk reduction), and smaller estimated risk reductions observed for racquet sports (12%), lap swimming (5%), aerobics/calisthenics (5%), and biking (5%).21 Furthermore, vigorous activity had the strongest protective effect among women in the normal weight range (BMI 20-25 kg/m2).22

For men, it is clear that risk factors for cardiovascular disease such as smoking, hypertension, and type 2 diabetes mellitus have strong links epidemiologically to erectile dysfunction.31 Esposito et al showed that a treatment group of 55 obese men without chronic disease (ages 35-55) who received ongoing, detailed advice about a 10% body weight reduction through caloric restriction and increased physical activity to 195 minutes per week experienced a statistically significant higher rate of weight loss, improvement in erectile dysfunction, and decrease in C-reactive protein levels compared to a control group.32

Conclusion

Implementation of fertility-friendly and overall healthy lifestyle changes, including those listed below, results in improved fertility outcomes for male and female partners. Since these lifestyle interventions also improve general health, it is important to implement them prior to initiation of more complex, expensive and invasive assisted reproductive technologies.

1. Avoidance of active or passive exposure to cigarette smoking;

2. Avoidance of alcohol for women attempting to conceive;

3. Loss of 10-15% of excess weight in overweight/ obese infertile couples;

4. Regular vigorous daily aerobic exercise, including running, swimming, cycling; and

5. Avoidance of caffeine ingestion from common foods and beverages.

Recommendations: Primary Care

Primary care physicians can support fertility-friendly lifestyles by:

1. Identifying at-risk patients with measurements of height, weight, waist circumference, and BMI calculation;33

2. Screening for the presence of medical illnesses such as sleep apnea,34 depression,35 endocrine disorders such as hypothyroidism, PCOS, diabetes, etc., followed by treatment and referral as clinically needed;

3. Avoiding the use of medications that might cause weight gain and substitute alternatives that are weight-neutral;36

4. Providing guidance or dietitian referral regarding appropriate dietary caloric restrictions to promote realistic weight-loss goals tailored to patient needs;37

5. Emphasizing the importance of smoking cessation;38

6. Recommending patients incorporate physical exercise into their daily life with documentation of caloric intake and exercise in daily food and activity diaries;39 and

7. Monitoring and reviewing progress with sequential measurements and diet, medication, and activity log reviews during office visits.

References

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2. The Practice Committee of the American Society for Reproductive Medicine. Definition of "Infertility." Fertil Steril 2004;82(suppl):S206.

3. When the test really counts. Part 2: The fertility window. Consum Rep 2003;68:48-50.

4. Hull MG, et al. Population study of causes, treatment, and outcome of infertility. Br Med J (Clin Res Ed) 1985;291:1693-1697.

5. Smith S, et al. Diagnosis and management of female infertility JAMA 2003;290:1767-1770.

6. American Society for Reproductive Medicine; Society for Assisted Reproductive Technology Registry. Assisted reproductive technology in the United States: 1999 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 2002;78:918-931.

7. Chavarro JE, et al. Diet and lifestyle in the prevention of ovulatory disorder infertility. Obstet Gynecol 2007;110:1050-1058.

8. Hassan MA, Killick SR. Effect of male age on fertility: Evidence of the decline in male fertility with increasing age. Fertil Steril 2003;79(Suppl 3):1520-1527.

9. Dunson DB, et al. Changes with age in the level and duration of fertility in the menstrual cycle. Hum Reprod 2002;17:1399-1403.

10. Chuang CC, et al. Age is a better predictor of pregnancy potential than basal follicle-stimulating hormone levels in women undergoing in vitro fertilization. Fertil Steril 2003;79:63-68.

11. Smith KE, Buyalos RP. The profound impact of patient age on pregnancy outcome after early detection of fetal cardiac activity. Fertil Steril 1996;65:35-40.

12. Kunzle R, et al. Semen quality of male smokers and nonsmokers in infertile couples. Fertil Steril 2003; 79:287-291.

13. Baron JA, et al. The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol 1990;162: 502-514.

14. Zenzes MT, et al. Cotinine, a major metabolite of nicotine, is detectable in follicular fluids of passive smokers in in vitro fertilization therapy. Fertil Steril 1996;66:614-619.

15. Paszkowski T, et al. Smoking induces oxidative stress inside the Graafian follicle. Hum Reprod 2002;17: 921-925.

16. Hakim RB, et al. Alcohol and caffeine consumption and decreased fertility. Fertil Steril 1998;70:632-637.

17. Eggert J, et al. Effects of alcohol consumption on female fertility during an 18-year period. Fertil Steril 2004;81;379-383.

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21. Tolstrup JS, et al. Does caffeine and alcohol intake before pregnancy predict the occurrence of spontaneous abortion? Hum Reprod 2003;18;2704-2710.

22. Rich-Edwards JW, et al. Physical activity, body mass index, and ovulatory disorder infertility. Epidemiology 2002;13:184-190.

23. Dunaif A. Insulin resistance and the polycystic ovary syndrome: Mechanism and implications for pathogenesis. Endocr Rev 1997;18:774-800.

24. Lambe KG, Tugwood JD. A human peroxisome proliferator-activated receptor gamma is activated by inducers of adipogenesis, including thiazalidinedione drugs. Eur J Biochem 1996;239:1-7.

25. Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med 2002;53:409-435.

26. Minge CE, et al. PPAR Gamma: Coordinating Metabolic and Immune Contributions to Female Fertility. PPAR Research; 2008. Available at: www.pubmedcentral.nih.gov/picrender.fcgi?artid=2246065&blobtype=pdf. Accessed Sept. 5, 2008.

27. Kallen CB, Lazar MA. Antidiabetic thiazolidinediones inhibit leptin (ob) gene expression in 3T3-L1 adipocytes. Proc Natl Acad Sci U S A 1996;93:5793-5796.

28. Fejes I, et al. Is semen quality affected by male body fat distribution? Andrologia 2005;37:155-159.

29. Kort HI, et al. Impact of body mass index values on sperm quality and quantity. J Androl 2006;27:450-452.

30. Jensen TK, et al. Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril 2004;82:863-870.

31. Feldman HA, et al. Erectile dysfunction and coronary risk factors: Prospective results from the Massachusetts Male Aging Study. Prev Med 2000;30:328-338.

32. Esposito K, et al. Effect of lifestyle changes on erectile dysfunction in obese men: A randomized controlled trial. JAMA 2004;291:2978-2984.

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34. National Institutes of Health, National Heart, Lung and Blood Institute, and the National Center on Sleep Disorders Research. Guide to Selected Publicly Available Sleep-Related Data Resources, 2006. Available at: www.nhlbi.nih.gov/about/ncsdr/research/sleep-database-appendix-complete.pdf. Accessed Sept. 9, 2008.

35. Kroenke K, et al. The Patient Health Questionnaire-2: Validity of a two-item depression screener. Med Care 2003;41:1284-1292.

36. Cheskin LJ, et al. Prescription medications: A modifiable contributor to obesity. South Med J 1999;92: 898-904.

37. American Dietetic Association. Available at: www.eatright.org. Accessed Sept. 2, 2008.

38. National Heart, Lung and Blood Institute, National Institutes of Health. Quitting Smoking. Available at: www.nhlbi.nih.gov/hbp/prevent/q_smoke/q_smoke.htm. Accessed Sept. 2, 2008.

39. Public Resources from the American College of Sports Medicine. Available at: www.acsm.org/AM/Template.cfm?Section=General_Public. Accessed Sept. 2, 2008.