Chapter 21 Infertility
Introduction
Infertility, defined as the inability to conceive after 1 year of trying, differs from sterility, as many couples are able to conceive after a 1-year period. Sterility is the total inability to produce offspring; that is, the inability to conceive (female sterility) or to induce conception (male sterility),1 summarised in Table 21.1. Sterility is estimated to occur in 1% of cases. In about 80% of couples, the cause of infertility can be found.2 Infertility affects 10–15% of couples, 35% of which is attributed to female infertility and 30% to male infertility.3 This figure is now as high as 1 in 6 couples suffering infertility in New South Wales (Australia).4 It is essential infertile couples are investigated thoroughly to exclude reversible organic causes such as infections requiring antibiotics, or polyps requiring surgery.
| Origin of sterility | Cause |
|---|---|
| No eggs | Due to: |
(Source: adapted from Jansen R, 1998 Getting Pregnant. Allen and Unwin, Sydney)
Causes of infertility
Females
The following factors contribute to female infertility
General CM use
Complementary medicine use amongst infertile couples is common. In an Australian study of 100 women at a fertility clinic, 66% were using complementary medicines alongside prescribed medication, namely multivitamins, mineral and herbal supplements.5
Age as a risk factor
The risk of infertility in women and men increases with age and this is becoming a bigger problem as more women choose to delay childbearing. Infertility increased from 8% amongst women aged 19–26 and up to 18% in those aged 35–39 according to a European survey.6 Male age was significant after 30 years of age with estimated incidence of infertility of 18–28% between the ages of 35–40 years. The authors concluded that whilst older couples may have increased infertility, they may conceive if they keep trying for an additional year.
In a more recent study in the UK, data from a total of 7172 women at a fertility clinic, found there was an association between female age and the cause of female infertility and more women over 35 had unexplained infertility.7
Ovarian and uterine disorders
Other disorders include endometriosis plus ovarian causes of infertility including polycystic ovary syndrome (PCOS), which is commonly linked with autoimmune thyroid disorders.9
Nutrient deficiencies as risk factors
Deficiencies in essential vitamins and minerals can contribute to infertility by affecting sperm count and motility in men, and hormonal processes in women.
Males
Antioxidants
It has been reported that in approximately 25% of couples, infertility can be attributed to decreased semen quality. In a recent convenience sample of healthy non-smoking men from a non-clinical setting, it was concluded that higher antioxidant intake was associated with higher sperm numbers and motility.10
Also, antioxidant deficits in males can lead to a decline in sperm motility. Spermatozoa cell membranes contain high concentrations of fatty acids, which are highly susceptible to oxidative damage. Adequate levels of antioxidants are required in order to maintain healthy cell membranes.11
Selenium
Selenium is an important nutrient for male fertility. Two of the proteins found to be structurally important in sperm require adequate levels of selenium.12 Deficiency is associated with decreased sperm motility and increased abnormal sperm.13
Females
Folate
An early study has suggested that blood folate level recovery in women following a normal pregnancy delivery and 1 year of breastfeeding may require supplementation with a multivitamin in order to re-establish blood folate levels before further conceiving.15 Folic acid deficiency can play a role in ovulatory infertility.16 Women trying to conceive within this 2-year period of folate replenishment may continue to experience difficulty with conception. Deficiency may also be caused by digestive disorders such as celiac disease.
Vitamin B2
Insufficient levels of vitamin B2 can lead to altered levels of oestrogen and progesterone, often causing irregular menstruation. Treatment of menstrual problems, such as irregular periods, PMT and general menstrual difficulties, often results in a correction of infertility issues also.17
Zinc
The effect of zinc deficiency on female fertility has not been extensively studied, however animal trials have linked low zinc levels with impaired ovulation and an increased amount of deteriorated ovocytes.19 Zinc supplementation can be beneficial for women experiencing fertility problems however an excessive presence of zinc also appears to be detrimental.20
General signs
Hormonal signals and Billings Ovulation Method (BOM)
A trial conducted by the World Health Organization in 5 different countries demonstrated up to 97% of women had an excellent or good interpretation of the BOM. However, couples should be encouraged not to use this method alone to assist conception. Similarly, the BOM can be used to help prevent conception as a natural method of contraception and if used correctly, can achieve a failure rate as low as 0.5–1.0% with accurate teaching and vigilant implementation.21, 22 However, higher reported failure rates, up to 3%, have been documented worldwide and occurred due to factors such as inadequate teaching, poor compliance and poor understanding of the BOM.23, 24, 25
Urinary ovulation predictors can be useful in identifying urinary LH surges at the time of ovulation, but requires the woman to estimate the timing of the ovulation and a LH surge is not necessarily followed up with an ovulation, as commonly occurs in PCOS and in luteinised unruptured follicle where some LH is released by the follicle but not enough to cause an ovulation. This method can be expensive for couples wanting to identify time of ovulation.
Scent of a woman
Interestingly studies indicate that the scent of a woman may provide a clue as to when she is ovulating and alert men to her current state of fertility. A study demonstrated that men could detect differences in body odour in women correlating to different stages of their menstrual cycle.26 Women menstruating were rated as the most intense and least attractive odour; whilst during the most fertile period they were rated by men as least intense smelling and the most attractive.
Lifestyle and diet
Lifestyle factors play an important part in successful fertility outcomes.27
A recent study has reported that couples who succeed in becoming fertile, especially those diagnosed with unexplained infertility, do so by adhering to lifestyle changes.28 Only those couples who sought information to help them conceive found the experience empowering.
Females
A cohort of 17 544 women monitored over an 8-year period found that women who adhered to a healthy lifestyle and fertility diet pattern were associated with a lower risk of ovulatory infertility disorder.29 This risk was reduced to 69% for women in the highest quintile group compared to those in the lowest quintile for adherence to the fertility diet pattern in healthy women. Furthermore, women’s age (older than 35 years of age), parity and body weight (Body Mass Index ≥ 25) were inversely associated with infertility.
The following lifestyle factors were protective towards infertility for women:
Mind–body medicine
Psychological factors
The therapeutic dilemma is how to use psychotherapy.30 Recently it was reported that medical and psychosexual therapies are not 2 distinct therapeutic entities to be used in different clinical settings. They are, however, 2 important tools to be simultaneously considered (as well as often simultaneously employed) to fully rescue the sexual satisfaction of the couple that is trying to conceive.
In vitro fertilisation (IVF) can be quite a stressful experience for many couples. Women who undergo IVF are more likely to have parenting difficulties and be admitted into a special unit for postnatal mood disturbance or infant sleeping disorder compared with women conceiving naturally.31 Couples undergoing IVF require additional support.
Support groups
A randomised controlled trial (RCT) was conducted to assess the benefits of a web-based education and support program for women with infertility and assessed for psychological outcomes such as infertility distress, infertility self-efficacy, decisional conflict, marital cohesion and coping style.32 At 4-weeks follow-up women exposed to the online program were observed to significantly improve in the area of social concerns related to infertility distress, and felt better informed about a challenging medical decision and experienced less global stress, sexual concerns, distress related to child-free living, increased infertility self-efficacy and decision-making clarity. Those women who spent more time online (>60 minutes) gained more psychological benefits.32
Stress reduction and/or meditation
Relaxation therapy
In a study measuring the effects of stress reduction on fertility, 54 women were enrolled in a behavioural treatment program and taught a relaxation response technique over 10 weeks. The women were instructed to utilise this practice twice daily for 20 minutes at home. At the end of the trial the women were reported as experiencing significantly less stress, depression and fatigue. Within months of completion of the study, 34% of the women became pregnant — a figure much higher than what is expected in women undergoing typical infertility treatment.33
Sexual activity
Infrequent or lack of sexual activity and difficulties with sex, such as erectile dysfunction in males, can interfere with fertility. Lifestyle factors such as overwork, exhaustion and night-shift can all impact on the frequency of sex and the chances of conception. Erectile dysfunction is a common problem in men over 60 years of age. Researchers in Finland found in over 1000 middle-aged men, that those who had infrequent intercourse (less than once weekly) were more likely to experience sexual dysfunction compared with men who had sex weekly.35 Stress and fatigue is a large contributor to lack of sexual activity.
Sleep
Shiftwork is associated with menstrual irregularities, reproductive disturbances, risk of adverse pregnancy outcome and sleep disturbances in women. A study of 68 nurses, aged less than 40 years, evaluated sleep, menstrual function, and pregnancy outcome and found 53% of the women noted menstrual changes when working shiftwork; menstrual irregularities which may impact on fertility.36
Sunshine
A number of animal studies have demonstrated vitamin D deficiency can cause infertility.37 Vitamin D is an important factor in the biosynthesis of both female and male gonads. No reliable human data are available yet to recommend vitamin D for infertility. Nevertheless, in view of the multiple health benefits of vitamin D from safe sun exposure, if blood levels are reduced then vitamin D supplementation should be advised in order to improve overall wellbeing.
Environment
Smoking
Smoking is well documented as contributing to problems with fertility in both men and women.38 Smoking reduces fertility in women by having a direct detrimental effect on the uterus, on the oocytes and embryos by increasing the zona pellucida thickness.39 Of interest, in a study of women who received donated eggs through an IVF program, those that smoked or had a history of smoking did not affect pregnancy outcome.40 Nevertheless, it is still advisable to instruct women to avoid smoking due to harmful effects on the fetus.
Infertile men who smoke have higher levels of seminal oxidative stress and sperm DNA damage41 and lower levels of antioxidant levels in the seminal fluid.42 Smoking was associated with a 48% increase in seminal leukocyte concentrations and a 107% increase in seminal oxidative stress compared with infertile non-smokers, suggesting men who smoke should quit.
Smoking increases the risk of impotence and erectile dysfunction in men who smoke or have a past history of smoking compared with those who have never smoked.43
External heat
Men should avoid high scrotal temperatures such as the use of hot tubs, long hours of sitting, and tight clothing as heat can inversely impact on sperm quality and count.44 Men who drove for more than 2 hours a day recorded significant scrotal temperature rises by 1.7–2.2°C than that recorded while walking. This rise in scrotal temperature indicates a potential cause for male infertility in some professions; for example, taxi drivers and office workers.
Chemicals and toxins
Exposure to environmental toxins such as radiation, heavy metals and chemicals can cause oxidative stress and sperm DNA damage.45–48 Oxidative damage to DNA may also impact on female fertility.49
Increased industrialisation and use of agricultural chemicals in the 20th century has contributed to exposure of thousands of chemicals which has contributed to impaired fertility in both men and women.50
Males
Semen quality, concentration and counts have declined significantly in a number of countries implicating exogenous oestrogens, heavy metals and pesticides as causes.51, 52
A US study of males found that sperm concentration was inversely related to the number of maternal beef meals per week.53 Son’s of mothers who consumed more than 7 beef meals per week had lower sperm concentration by up to 24% than in men whose mothers ate less beef. No other meat intake, such as lamb, was associated with low sperm. Also sperm concentration was lowest in men who ate more beef.53
Heavy metals
Exposure to heavy metals, such as lead and mercury, can interfere with fertility processes in men. For example, mercury can decrease the ability of the sperm to penetrate the ova for fertilisation, and causes breakages in sperm DNA strands. In women, lead can contribute to infertility, as well as other reproductive disorders such as premature membrane rupture, pregnancy-related disorders and premature delivery.54, 55
Cadmium exposure has also been associated with altered concentrations of serum estradiol, FSH and testosterone, the latter can lead to a decrease in testicular size.19
A study assessing heavy metals in premenopausal women found an association between cadmium and endometriosis.56 The study concluded that further investigations in properly designed studies were needed.
Seasonal and regional variations in sperm quality
Researchers noted regional variation in sperm quality across European nations and higher levels of sperm concentration noted over the winter period compared to summer (summer about 70% of winter).57 For instance, Finnish men have higher sperm counts than in Danish men. Environmental exposures and lifestyle factors may be contributors to these regional differences.
Physical activity
Exercise
Exercise plays an important role in fertility. Obese women with PCOS who suffered anovulatory infertility demonstrated a significant improvement in menstrual cycles and fertility equally in a structured exercise training (SET) program and to dietary interventions.58 Both the frequency of menses and the ovulation rate were significantly higher in the SET group than in the dietary group but the increased cumulative pregnancy rate was not significant.
However, a study of women undergoing IVF found that regular exercise before IVF may negatively affect outcome, especially in women who exercised 4 or more hours per week.59
Nutritional influences
As stated earlier under lifestyle, the high fertility diet has been shown to promote fertility.29 It includes a lower intake of trans fat, greater intake of monounsaturated fat, lower intake of animal protein, greater vegetable protein intake, higher intake of high-fibre, low glycaemic carbohydrates, preference for high-fat dairy products, and higher non-haeme iron intake (found in fruits, vegetables, grains, eggs milk, meat).
Alcohol
Excessive alcohol consumption can cause hyperprolactinemia which is associated with female infertility.61 In males, a high intake of alcohol has been shown to have a negative effect on Leydig cells, and therefore possibly on testosterone production.62 This is specifically caused by the ethanol in alcohol, and the degree of damage depends on the length of exposure and quantity ingested.63
Of interest, some alcohol consumption (1–20 standard drinks per week) is associated with reduced incidence of erectile dysfunction by 25–30% compared with non-drinkers.64
Caffeine
Caffeine promotes dopamine production, and this in turn inhibits the production of prolactin, a deficiency or excess of which increases the risk of infertility in women. Consuming as little as 1 caffeinated drink per day is associated with a temporary reduction in conception.65, 66
