severe stress, infection, tubal damage and other structural problems, and chromosomal abnormalities (Table 2.3).5,6 Conditions that modify fertility appear to affect hormones that regulate ovulation, the presence or length of the luteal phase, sperm production, or the tubular passageways that ova and sperm must travel for conception to occur. Sexu-ally transmitted infections, for example, can result in pelvic inflammatory disease (PID), which may lead to scarring and blockage of the fallopian tubes.9 Endometriosis is also a common cause of reduced fertility. It develops when por-tions of the endometrial wall that build up during men-strual cycles become embedded within other body tissues.
Endocrine abnormalities that modify hormonal regulation of fertility are the leading diagnoses related to infertility.
“Unknown cause” is the second leading diagnosis, how-ever, and is applied to about one-half of all cases of male and female infertility.10,11
between chronic undernutrition and fertility are compli-cated by differences in the use of contraception, age of pu-berty and marriage, breastfeeding duration (longer periods of breastfeeding increase the time to the next pregnancy), access to induced abortions, and social and economic incen-tives or constraints on family size.17 In less developed coun-tries with poor access to contraception, births per woman average 6 to 8, whereas in developed countries (where con-traception is generally available) they average at or below the replacement level of 2.1 births per woman.18 Without careful study, it might appear that fertility is lower19 in better-nourished women in developed countries than in poorly nourished women in less developed countries.
Of the environmental factors that influence fertility, education and child survival appear to be the most im-portant. Fertility rates in poor countries decline substan-tially as women become educated and as child survival increases.19,20
Acute Undernutrition Undernutrition among previously well-nourished women is associated with a dramatic decline in fertility that recovers when food intake does.15 Periods of feast and famine in the nomadic Kung tribe of Botswana and among the Turkana people of Kenya, for example, are associated with major shifts in fertility.21,22 These groups of hunter-gatherers (although relatively few survive now) processes.14 Nutrient intake and body fat before
concep-tion also influence the mother’s health during pregnancy and the growth and development of the fetus. Nutritional factors generally exert only temporary influence on fertil-ity; normal fertility returns once the problem is corrected.
Undernutrition and Fertility
Does undernutrition decrease fertility in populations? The answer depends on whether the undernutrition is long-term (chronic) or short-long-term (acute). Chronic undernutri-tion appears to reduce fertility by only a small amount.1 Acute undernutrition due to famine or deliberate weight loss in normal-weight women clearly decreases fertility.
Chronic Undernutrition The primary effect of chronic undernutrition on reproduction in women is the birth of small and frail infants who have a high likelihood of death in the first year of life.15 Infant death rates in developing countries where malnutrition is common often exceed 50 per 1000 live births. By contrast, infant death rates are less than 3 per 1000 live births in places such as Hong Kong, Japan, and Singapore.16
The effect of chronic undernutrition on fertility is diffi-cult to study accurately, and conclusions about relationships will change as more is learned. Investigations of relationships
Table 2.3 Factors related to altered fertility in women and men
Females and Males Females Males
Weight loss
• .10 to 15% of
normal weight
Inadequate antioxidant status
•
(selenium, vitamins C and E) Inadequate body fat
•
Excessive body fat, especially
•
central fat
Extreme levels of exercise
•
High alcohol intake
•
Endocrine disorders (e.g.,
hypothy-•
roidism, Cushing’s disease) Structural abnormalities of the
•
reproductive tract
Chromosomal abnormalities in
•
sperm and eggs Celiac disease
•
Oxidative stress
•
Severe psychological stress
•
Infection (sexually transmitted
•
diseases)
Diabetes, cancer, other disorders
•
Some medications
•
Recent oral contraceptive use
•
(within 2 months)
Anorexia nervosa, bulimia nervosa
•
Vegan diets
• Age
• .35 years Metabolic syndrome
•
Pelvic inflammatory disease (PID)
•
Endometriosis
•
Polycystic ovary syndrome
•
Poor iron stores
•
Inadequate zinc status
•
Heavy metal exposure (lead,
•
mercury, cadmium, manganese) Halogen (in some pesticides) and
•
glycol (in antifreeze, de-icers) exposure
Estrogen exposure (in DDT,
• PCBs)
Sperm defects (quality, motility)
•
Excessive heat to testes
•
Steroid abuse
•
High intake of soy foods
•
33411_02_Ch02_p051-069.indd 57
33411_02_Ch02_p051-069.indd 57 4/30/10 7:31:15 PM4/30/10 7:31:15 PM
Copyright 2011 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.
infertile, but they are more likely to experience delays in the time it takes to become pregnant.1,26 Obese women tend to have higher levels of estrogen, androgens, and leptin than non–obese women.1,27 These hormonal changes favor the development of menstrual-cycle irregularity (it occurs in 30 to 47% of overweight and obese women), ovulatory failure and anovulatory cycles, and amenorrhea.26 Obesity in men is associated with lower levels of testosterone and increased estrogen and leptin levels.28
These changes are related to reduced sperm produc-tion in 16% of obese men and higher-than-average rates of erectile dysfunction.26,29 The existence of excessive body fat is generally indicated by body mass index values over 30 kg/m2.3,30 Infertility treatments, such as the use of drugs to induce ovulation, are less effective in obese than in normal-weight women.31 Loss of body fat is related to improvements in hormone levels, reduced oxidative stress, and improved conception rates in both men and women.1
Approximately one in three men and women in the United States is obese (or has a body mass index of 30 kg/m2 or greater), making infertility related to excess body fat a common problem and an important health and quality-of-life concern.1 The topic of obesity and fertility is revis-ited in more detail in the next chapter.
Inadequate Body Fat and Fertility It appears that a critical level of body fat (usually indicated by a body mass index over 20 kg/m2) is needed to trigger and sus-tain normal reproductive functions in women.32,33 Low levels of body fat during adolescence is related to delays in the age of onset of menstruation and to reduced fertil-ity later in life.32 Impaired fertility in underweight women often takes the form of delayed time to conception and amenorrhea.15,33 Lowered libido and reduced sperm pro-duction have been identified in underweight men with low levels of body fat.34
Weight Loss and Fertility in Normal-Weight Women and Men In normal-weight women, weight loss that exceeds approximately 10–15% of usual weight decreases estrogen, LH, and FSH concentrations.35 Conse-quences of these hormonal changes include amenorrhea, anovulatory cycles, and short or absent luteal phases. It is estimated that about 30% of cases of impaired fertility are related to simple weight loss. In the past, this form of amenorrhea was called “weight-related amenorrhea.” It is now called “hypothalamic amenorrhea.” Hormone lev-els tend to return to normal when weight is restored to within 95% of previous weight.15 Case Study 2.1 provides an example of the effect of weight loss on fertility.
Weight gain is the recommended first-line treatment for amenorrhea related to low body weight. In many cases, however, the advice is more easily given than ap-plied. About 10% of underweight women will not con-sider weight gain and may change health care providers in search of a different solution to infertility.12
experience sharp seasonal fluctuations in body weight depending on the success of their hunting and foraging for plant foods. Birthrates decline substantially during periods of famine and increase with food availability. When these hunter-gatherers become farmers and food supply is more dependable, body weight increases, activity levels decrease, and pregnancy rates go up.
Other evidence also suggests a connection between undernutrition and infertility. Food shortages in Europe in the seventeenth and eighteenth centuries were accompa-nied by dramatic declines in birthrates. Famine in Holland during World War II led to calorie intakes of about 1000 per day among women. One out of two women in famine-affected areas stopped menstruating, and the birth-rate dropped by 53%. Fertility status improved within 4 months after the end of the famine, but for many women it took as long as a year for their menstrual cycles to return to normal.23 Similarly, the 1974–1975 famine in Bangladesh resulted in a 40% decline in births.24
Famines are associated with more than disruptions in the food supply. They are usually accompanied by low avail-ability of fuel for heating and cooking, poor living condi-tions, anxiety, fear, and despair. These factors also probably contribute to the declines in fertility observed with famine.
Acute reduction in food intake appears to reduce re-productive capacity by modifying hormonal signals that regulate ovulation and menstrual cycles in females.24 It also appears to impair sperm maturation in males.
Body Fat and Fertility
Excessive and inadequate levels of body fat are related to declines in fertility in women and men. Body fat–related declines in fertility are prima-rily related to changes in hor-mone concentrations.1,25 In obese individuals, increased levels of oxidative stress and exposure of eggs and sperm to oxidative damage are also related to infertility.1
Fat cells produce estro-gen, androgens, and leptin, and the availability of these hormones changes with body fat content. Changes in the availability of these hormones interfere with re-productive processes such as follicular development, ovu-lation, and sperm matura-tion and producmatura-tion.1 Excessive Body Fat and Infertility Most obese women and men are not Oxidative Stress A condition that occurs
when cells are exposed to more reactive oxygen molecules (such as free radicals) than to antioxidant molecules. Certain environmental pollutants, ozone, smoke, radiation, excess body fat, high-fat diets, and inflammation are sources of reactive oxygen molecules.
Leptin A protein secreted by fat cells that, by binding to specific receptor sites in the hypothalamus, decreases appetite, increases energy expenditure, and stimulates gonadotropin secretion. Leptin levels are elevated by high, and reduced by low, levels of body fat.
Anovulatory Cycles Menstrual cycles in which ovulation does not occur.
Amenorrhea Absence of menstrual cycle.
Body Mass Index (BMI) Weight in kg/
height in m2. BMIs ,18.5 are considered underweight, 18.5–24.9 normal weight, 25–29.9 overweight, and BMIs of 30 and higher obesity.
33411_02_Ch02_p051-069.indd 58
33411_02_Ch02_p051-069.indd 58 4/30/10 7:31:15 PM4/30/10 7:31:15 PM
Copyright 2011 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part.
Exercise and Infertility
The adverse effects of intense levels of physical activity on fertility were observed over 40 years ago in female competitive athletes. Since then, a number of studies have shown that young female athletes may experience delayed age at puberty and lack menstrual cycles. Average age of menarche for competitive female athletes and ballet danc-ers is often delayed by 2 to 4 years. The delay in menarche increases if females begin training for events that require thinness (such as gymnastics) before menarche normally would begin. Very high levels of exercise can also inter-rupt previously established, normal menstrual cycles.
The presence of abnormal cycles reportedly ranges from about 23% in joggers to 86% in female bodybuilders (Table 2.4).34,35
Delays and interruptions in normal menstrual cycles appear to result from hormonal and metabolic changes pri-marily related to caloric deficits rather than intense exer-cise.36 Metabolic and hormonal status generally reverts to normal after high levels of training and caloric deficits end.
Some of the hormones involved in fertility impair-ments perform other important functions in the body, Treatment of underweight women with Clomid
(clo-miphene citrate, a drug that induces ovulation) generally does not improve fertility until weight is regained. Fertil-ity may be improved through the use of GnRH, FSH, and other hormones. However, twice as many infants born to underweight women receiving such therapy are small for gestational age compared to infants born to underweight women who gain weight and experience unassisted conception.15
The eating disorder anorexia nervosa is associated with similar, but more severe, changes in endocrine and hypothalamic functions than those seen with weight loss in normal-weight women. (This topic, as well as hypotha-lamic amenorrhea, is covered in Chapter 3.)
Weight loss decreases fertility in men just as it does in women. In the classic starvation experiments by Keys dur-ing World War II,34 men experiencing a 50% reduction in caloric intake reported substantially reduced sexual drive early in the study. Sperm viability and motility decreased as weight reached 10 to 15% below normal, and sperm production ceased entirely when weight loss exceeded 25% of normal weight. Sperm production and libido returned to normal after weight was regained.
Photodisc