Weight and Infertility by Dr. William Bucket - Spring 2008

Weight and Infertility
How both being overweight and underweight can affect female fertility and pregnancy
by Dr. William Buckett

Spring 2008

Introduction

Worldwide, much is made of obesity and the significant health problems associated with it. Weight excess and obesity are related to a multitude of health consequences, including diabetes, heart disease, stroke, osteoathritis, and reproductive dysfunction - most commonly manifested as irregular menstruation and infertility. However, being underweight also has significant consequences both to general and also reproductive health. Worldwide, low body weight and malnutrition are obviously a significant cause of death, but even in Canada, chronic underweight state and anorexia are also associated with osteoporosis and bone fracture as well as irregular or absent menstruation and infertility. Being either over- or under-weight is also associated with poorer obstetric and infant outcomes.

This article will discuss what is normal, how weight affects reproductive function, how maternal weight affects pregnancy and the newborn, and ways to avoid some of these risks.

So – what is normal?

An effective tool to measure abnormally high or low amounts of body fat is the calculation of the body mass index (BMI). This is the weight (in kilograms) divided by the height squared (in metres2) – although charts are available that also use imperial measurements (feet/inches and pounds/ounces). See Figure 1. A normal BMI is between 18.5 and 24.9 kg/m2. Being underweight is having a BMI below 18.5, being overweight is having a BMI of 25-29.9, and being obese is having a BMI over 301.

Figure 1. BMI chart for weight and height calculated in pounds and feet/inches.

The BMI has proved a clinically effective measurement over the past 30 years and much scientific literature has shown a poorer chance of pregnancy and pregnancy outcome with a BMI over 25 or under 18.5. The mechanisms for these findings will be discussed below.

BMI does have some limitations – particularly in very muscular adults, such as athletes, who may have a low percentage of body fat but a large amount of muscle tissue. This can result in a higher BMI erroneously suggesting higher amounts of body fat. Similarly, people who naturally have a very lean body build or young adults who have not attained their full growth, the BMI may underestimate the body fat content.

Another measure of body fat – more particularly central body obesity – is waist circumference. Excess fat around the waist and upper body (the 'apple' body shape) is associated with greater health risk than fat located more in the hip and thigh area (the 'pear' body shape).

A waist circumference over 88 cm (35 in.) – or 102 cm (40 in.) for men – is associated with an increased risk of developing general health and reproductive problems. The cut-off points are approximate, so a value just below these values should also be taken seriously. There is no lower value for waist circumference – and there is little scientific literature assessing the role of waist circumference in the underweight population.

Obesity and infertility

Historically, being overweight or obese – particularly in times of want – has been seen as sexually desirable. The women of the paintings of Rubens are amply proportioned and even arguably the oldest female image – the Venus of Willendorf (from about 23,000 BC) is similarly proportioned. See Figure 2.

Figure 2. Venus of Willendorf (22,000-24,000 BC). Vienna Naturhistorisches Museum.

Although many women who have had children are obese and, indeed, most obese women are able to conceive readily, it has been recognized since the 1970s in many studies both from Europe and North America that women who are overweight (BMI ≥ 25), as well as those who are obese (BMI ≥ 30), have a threefold (3x) higher chance of infertility than women of a normal weight-for-height.

The abdominal fat distribution in overweight and obese women significantly alters the function and production of the hormones (androgen and estrogen) which are responsible for ovulation. Therefore, overweight and obese women are more likely to not ovulate regularly and therefore have irregular menstruation and infertility.

Although the exact mechanisms of this are not clear – the higher circulating insulin levels and associated insulin resistance seem to play an important role. Insulin resistance is already associated with the later development of Type-II diabetes and increased circulating fats. This in turn is associated with cardiovascular disease and hypertension. In reproductive terms, high circulating insulin seems to play a role in the disruption of ovulation. This in turn leads to higher androgens from the ovary and higher estrogens from body fat. Both of these can further inhibit ovulation.

The original description of the polycystic ovary syndrome associated obesity with infertility and there remains a very strong association between weight and irregular periods. Although there is little in the way of published medical studies to separate predisposing or associated features such as polycystic ovary syndrome from 'simple' obesity - there are suggestions that women with polycystic ovaries suffer even more menstrual problems and infertility than overweight or obese women with normal ovaries, meaning that both obesity and polycystic ovary syndrome are synergistic on their effects on reproduction.

Even treatment of infertility is less successful in women who are overweight. Most published studies now show conclusive evidence that increasing BMI is associated with an increased requirement for drugs to treat infertility, such as clomiphene citrate or the injected gonadotropins. The procedure of insemination for unexplained infertility has been shown to be less successful in women with a BMI over 30kg/m2 and many studies have shown poorer success rates following IVF with increases in BMI. See Figure 3.

Figure 3. Decreasing efficacy of IVF with increasing BMI2.

Pregnancy problems associated with obesity

For those women who do become pregnant, excess body fat has also been shown to be associated with an increased risk of miscarriage within the first 3 months. Up to about three times more likely for women whose BMI is over 30kg/m2, although there is also an increased risk for those who are even mildly overweight3.

When pregnancies continue beyond the first 3 months, there is also an increased risk of fetal abnormality. Spina bifida is three times more common among women who are obese and the risk remains high even when folic acid supplementation is given. The risk of other abdominal and cardiac abnormalities is also increased two to three times in women who are overweight4.

The risk of developing gestational diabetes and hypertension during the pregnancy is also increased two to three times. This in turn can lead to premature delivery, induction of labour, caesarean section and even an increased risk of stillbirth. Furthermore, there are more post-partum complications - such as infection, bleeding, and thromboembolism – in women who are overweight when compared with normal weight women5,6.

More recently, population-based research shows a link between maternal obesity and cardiovascular disease in adult offspring. Also, higher adult rates of type II diabetes have been reported in offspring of mothers who were above average weight in pregnancy. Given that obesity and maternal insulin resistance is not only genetic but acquired, improvement of periconceptional maternal insulin sensitivity via activity or diet may not only improve a mother's health but also the future cardiovascular health of her children. This hypothesis is speculative, however, and further research is needed.

What can be done about being overweight

Women who are overweight or obese should receive appropriate counseling concerning their risks of infertility and poorer pregnancy outcome. Women should know that the efficacy of treatment is less when their BMI is increased. Folic acid supplements (up to 5mg) should be taken.

In the 1950s there were several reports that weight loss, in women who were overweight or obese, led to regular menstruation and the achievement of pregnancy. Since then many studies have gone on to confirm that weight loss restores the normal reproductive function.

Even overweight women with other causes of infertility not related to ovulation (such as male factor infertility or tubal disease) have shown a dramatic improvement in pregnancy rates with assisted reproductive treatments such as IVF following weight loss, when compared with overweight women who did not lose weight.

Weight loss, while easy to discuss, is always harder to achieve in practice. The most successful programs appear to have a positive attitude to help women who are overweight or obese to lose weight, rather than reaching for the prescription pad to prescribe fertility drugs. Exercise and good dietary advice seem to be more effective than merely concentrating on low-calorie diets.

Underweight and infertility
Unlike previous centuries where a ‘fuller figure’ was seen as more desirable, nowadays being underweight or even anorexic is seen as sexually desirable. See Figure 4. However, this is also associated with poorer fertility and pregnancy outcome.

Chronic malnutrition leads to decreased pulsatile secretion of gonadotropin-releasing hormones in the hypothalamic area of the brain. These hormones ultimately control pituitary and ovarian function. Absence of their normal secretion leads to absent normal ovarian function. Therefore, in young women who have not gone through puberty this will lead to a delay in pubertal development. This was often seen with gymnasts and ballerinas in the 1970s and 1980s. In women who have already gone through puberty and started to ovulate normally, this leads to a cessation of ovarian activity and ovulation and therefore infertility.

As noted above, BMI can sometimes overestimate body fat in women with muscular physiques. Furthermore, heavy exercise activity itself may have an effect on the hypothalamus inhibiting normal function, since menstrual cycles return in some female athletes when energy expenditure is reduced, such as after an injury, long before there is any change in body weight or an increase in body fat.

Eating disorders – primarily bulimia nervosa and anorexia nervosa – occur in 3-5% of young women. Although many recover, some do not and it is estimated that about 5-10% of infertility caused by a failure to ovulate is mediated by some form of eating disorder.

Chronic undernutrition (through eating disorders or excessive exercise) is also associated with chronic non-ovulation and therefore osteoporosis and bone fracture, either while still young and active or in early middle age. Being underweight does not seem to affect the efficacy of infertility treatments, either with injected gonadotropins or with IVF.

Pregnancy problems associated with being underweight

During pregnancy, women who are underweight have higher rates of morning sickness (hyperemesis gravidarum), anaemia, impaired weight gain during pregnancy and compromised intrauterine fetal growth. Premature delivery is four times more likely in underweight women7. See Figure 4. This leads to higher rates of neonatal admission to intensive care and later health consequences such as mental delay or cerebral palsy.

Figure 4. Pregnancy outcomes in women with low BMI compared with normal BMI8.

Rates of cesarean delivery, post-natal complications and post-partum depression are higher among mothers with anorexia nervosa. Undernutrition is also associated with low birthweight babies.

It is not known what the consequences of being born low birth weight are, but the ‘Barker Hypothesis’ suggests that many human fetuses need to adapt to a limited supply of nutrients when they are faced with chronic malnutrition in the mother. In doing so they may permanently change their structure and metabolism. These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease, diabetes and hypertension. These adult diseases are seen more frequently in adults who were themselves low-birth weight babies9.

What can be done about being underweight

As with women who are overweight, women who are underweight should be made aware of the risks of being underweight, both to themselves and any pregnancy they may carry. Treatment should be delayed until any eating disorder is treated and ideally until a more normal body fat content is achieved. Decreasing excessive exercise or increasing caloric intake should be done before starting infertility treatments.

Once pregnant, continued monitoring of weight gain and dietary intake should be done in order to decrease the risk of any adverse consequences to the pregnancy.

Does weight have any effect on male reproductive function?

Although deficiencies of certain trace elements affect sperm production, there is little evidence that being underweight affects male fertility. Being overweight, however, is associated with over 50% chance of erectile dysfunction This is probably mediated by abnormalities in insulin. Although much has been made about pharmaceutical treatments for erectile dysfunction, weight loss and increasing physical activity leads to a lasting improvement for this problem.

Conclusions

Weight is intimately related to sexuality, fertility, and pregnancy. Being either overweight or underweight leads to poor self-image, infertility, and adverse pregnancy outcomes. Possible long term risks to the next generation are also a serious concern.

Treatment, however, is relatively risk-free. Increasing or decreasing caloric intake and decreasing or increasing physical activity, as appropriate, leads to lasting benefits. This is best undertaken before treatment for infertility begins and continued into early pregnancy.

References
1. Canadian guidelines for body weight classification in adults. Health Canada. http://www.hc-sc.gc.ca/fn-an/nutrition/weights-poids/guide-ld-adult/qa-qr-pub_e.html#1
2. Wang JX, Davies M, Norman RJ. Body mass and probability of pregnancy during assisted reproduction treatment: retrospective study. BMJ (2000) 321:1320–1321.
3. Ramsay JE, Greer I, Sattar N. ABC of Obesity. Obesity and reproductive function. British Medical Journal 2006; 333: 1159-1162.
4. Watkins ML, Rasmussen SA, Honein MA, Botto LD, Moore CA. Maternal obesity and risk of birth defects. Pediatrics 2003; 111: 1152-1158.
5. Usha Kiran TS, Hemmadi S, Bethel J, Evans J. Outcome of pregnancy in women with increased body mass index. Br J Obstet Gynaecol 2005; 112: 768-772.
6. Bhattacharya S, Campbell DM, Liston WA, Bhattacharya S. Effects of body mass index on pregnancy outcomes in nulliparous women delivering singleton babies. BMC Public Health 2007; 7: 168.
7. The ESHRE Capri workshop group. Nutrition and female reproduction. Human Reproduction Update 2006; 12; 193-207.
8. Cnattingius S, Bergstrom R, Lipworth L, Kramer MS. Prepregnancy weight and the risk of adverse pregnancy outcomes. Lancet 1998; 338: 147-152.
9. Barker DJP. Fetal origins of coronary heart disease. Br Med J 1995; 311: 171–4.