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Infertility: it’s chemistry

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Infertility is a devastating health problem that affects 15-20 per cent of
couples in the developed world- and these rates are on the rise. While many
experts blame the trend towards later mother-hood for this pattern, others
suspect that something far more difficult to control is responsible: our
exposure to an increasing array of toxic chemicals.
Scientists have known for some time that certain chemicals can cause
reproductive problems in wildlife and laboratory animals, but only now are
they beginning to discover the impact of such agents on humans. As the
latest research shows, even at relatively low levels, common chemicals-found
in the food we eat, the water we drink and the air we breathe-can have
dramatic consequences for our reproductive health.

Female infertility
Infertility-which refers to the inability to either conceive or carry a baby
to term-can be due to both male and female factors. However, recent studies
have focused on women, showing that everyday chemical exposures could be
destroying their reproductive health.
Earlier this year, US scientists looked at the perfluorinated chemicals
(PFCs) perfluorooctanoate (PFOA) and perfluorooctane sulphonate (PFOS),
ubiquitous man-made compounds used in a variety of consumer goods-from
non-stick cookware (Teflon) and carpets to pesticides and personal-care
products. PFCs, already known to contaminate food and water supplies, are
persistent in the environment and have been detected at worrying levels in
wildlife and humans around the world (Environ Sci Technol, 2004; 38:
On analyzing data from more than 1200 women in the Danish National Birth
Cohort study (1996-2002), the researchers found that those who had high
blood levels of PFOA and PFOS took significantly longer to become pregnant
than those with lower levels.
Alarmingly, compared with women who had the lowest levels of exposure, the
likelihood of infertility-defined as taking more than 12 months to become
pregnant or having to use infertility treatments to establish the current
pregnancy-increased by 70-134 per cent and 60-154 per cent for women in the
higher three quartiles of PFOS and PFOA exposures, respectively.
The study concluded that exposure to these chemicals at levels commonly seen
in the general population could affect a woman’s ability to reproduce (Hum
Reprod, 2009; 24: 1200-5).
Although such results are not proof of cause and effect, they add to the
convincing evidence showing that PFCs can cause abnormal hormone levels
and spontaneous miscarriages in animals, effects that might explain the
mechanism by which such chemicals reduce fertility. According to the
researchers, “PFCs may interfere with hypothalamic-pituitary-ovarian
regulation, possibly causing irregular menstrual cycles, delayed ovulation
or early abortions not recognized by the mother.”
Although more studies are needed before PFCs can be added to the current
list of risk factors for infertility, for couples trying to become pregnant,
detoxing from these chemicals may be a case of better safe than sorry.
Another chemical that appears to be wreaking havoc on the female
reproductive system is bisphenol A (BPA), used in the production of plastic
consumer products, and in the epoxy resins used to line the inside of food
and drink cans. Like PFCs, BPA is pervasive in the environment and in
people, too-mostly because it leaches from containers into the food we eat
(for more information on BPA, see WDDTY vol 18 no 8). Indeed, US studies
have found detectable levels of BPA in more than 90 per cent of the general
population (JAMA, 2008; 300: 1303-10).
Concerns that BPA could be damaging to reproductive health were first raised
in 2003, when scientists from Case Western Reserve University in Cleveland,
OH, observed a sudden, dramatic rise in chromosomal abnor-malities in the
oocytes (eggs) of mice they were studying. Such abnormalities lead to a
condition called ‘aneuploidy’ that, in humans, can cause early miscarriages
and birth defects such
as Down’s syndrome. The surprising pattern was eventually traced to the
use of a harsh detergent to wash the animals’ polycarbonate plastic cages
and water bottles. Follow-up experi-ments revealed that the detergent
damaged the plastic, causing BPA to leach from the bottles and cages, and it
was this exposure to the hormone-disrupting chemical that had caused the
sudden increase in aneuploidy (Curr Biol, 2003; 13: 546-53).
Although such animal findings may not apply to humans, recent studies in
women have also suggested that BPA is a potent reproductive toxicant.
Indeed, Japanese scientists found that women who’d suffered recurrent
miscarriages had significantly higher levels of BPA in their blood than
women with no history of infertility (Hum Reprod, 2005; 20: 2325-9).
Blood levels of BPA in women have also been linked to endometrial
hyperplasia, where the lining of the womb becomes thickened, and to
poly-cystic ovarian syndrome, one of the most common causes of female
infertility (Endocr J, 2004; 51: 595-600; Endocr J, 2004; 51: 165-9).
The most worrying aspect is that, while traditional toxicology asserts that
the higher the dose, the greater the harm, BPA tests show that low doses may
be the most toxic of all. This suggests that it might well be BPA-even at
extremely low concentrations-that is contributing to the increase in
infertility rates worldwide (Endocrinology, 2006; 147 [6 Suppl]: S56-69).
Yet another chemical-or, rather, group of chemicals-linked to female
infertility is chlorinated hydrocarbons (CHCs), a class of persistent agents
that includes dioxins, polychlorinated biphenyls (PCBs) and organochlorine
pesticides. Widely used in industry and agriculture for decades, they are
known to make their way into our food and so, eventually, our bodies (J
Lipid Res, 1982; 23: 474-9).
In women with occupational and accidental exposures to CHCs, a wide range of
reproductive effects has been observed, including miscarriages, a prolonged
time to achieve pregnancy and endometriosis, frequently linked to
infertility (Environ Health Perspect, 2008; 116: 599-604; Ann Epidemiol,
2007; 17: 503-10; Environ Health Perspect, 1998; 106: 675-81).
Even more worrying, however, is the evidence that CHCs may be harmful at
levels commonly seen in the general population. When the blood levels of
various CHCs in 89 women with repeated miscarriages were compared with those
of a reference population, more than 20 per cent had at least one CHC level
that exceeded the reference range. Significant correlations were also found
between increasing CHC levels, and immunological and hor-monal changes,
which may explain how CHCs have the potential to affect the course of
pregnancy (Environ Health Perspect, 1998; 106: 675-81).
In another study by the same team of researchers, a considerably larger
group of women was analyzed to see how CHCs affected various aspects of
fertility. What they found was that women with uterine fibroids,
endo-metriosis, miscarriages, hormonal disturbances and persistent
infertility had higher concentrations of CHCs in their blood. The study
concluded that CHCs may be an underlying factor in certain gynaecological
conditions, and may play a significant role in female infertility (Environ
Res, 1999; 80: 299-310).

Male infertility

However, it’s not only women who are vulnerable to the effects of toxic
chemicals in the environment. Many of the chemicals known to damage women’s
reproductive health have also been found to affect male fertility, primarily
by reducing sperm quality. Indeed, in industrialized countries, the evidence
suggests that sperm quality has been steadily decreasing over the past 50
years, and a number of experts claim tha
t environmental contam-inants could
be to blame (J Androl, 2009; 30: 566-79).
The most consistent evidence implicates CHCs and, in particular, PCBs.
Several studies show that men with elevated levels of PCBs in their blood
have reduced sperm motility, which hinders its ability to propel itself
towards an egg (Semin Reprod Med, 2006; 24: 156-67). In one study of 212 men
attending the Massachusetts General Hospital for fertility treatment, a
significant dose-response relationship was found between sperm motility and
blood levels of an agent known as PCB-138-in other words, the higher a man’s
PCB-138 levels, the lower his motile sperm count (Environ Health Perspect,
2003; 111: 1505-11).
In addition, PCBs can affect other sperm parameters such as ejaculate
volume, total sperm count, normal morphology (shape) and fertilizing
capacity. These compounds, found at particularly high concentrations in
fish-eaters, “may be instrumental in the deterioration of semen quality in
infertile men without an obvious aetiology”, the researchers concluded
(Fertil Steril, 2002; 78: 1187-94).
As if that’s not bad enough, PCBs have also been found to interact with
other chemicals to produce even more damage. Scientists at the Harvard
School of Public Health looked at male fertility in relation to PCBs and
another family of ubiquitous pollutants: the phthalates (Environ Health
Perspect, 2005; 113: 425-30). Used to make plastics more flexible and also
as solvents, phthalates are found in a huge array of consumer items-from
toys and food packaging to cosmetics and detergents. They’re also inside us.
A recent US study found detectable levels in more than 75 per cent of the
people tested (Environ Health Perspect, 2004; 112: 331-8).
On their own, phthalates have been linked to poor sperm quality in infertile
men at levels similar to those seen in the general population (Hum Reprod,
2007; 22: 688-95; Epidemiology, 2003; 14: 269-77). But the Harvard team then
also found that they are particularly potent when combined with PCBs. Using
data from over 300 men from couples seeking infertility treatment, they
found evidence of interactions between certain PCBs and phthalates in the
men’s blood that were associated with
a “greater than additive” risk of poor sperm motility (Environ Health
Perspect, 2005; 113: 425-30). In other words, some PCBs alone correlate with
decreased sperm motility and some phthalates correlate with decreased sperm
motility but, when they’re mixed together, the impact of the interaction is
greater than the sum of the two.
The implications are alarming, as most men are likely to be exposed to both
pollutants. Other chemicals in the body are also probably adding to the
toxic mix. A wide variety of common contaminants are linked to poor sperm
quality, including pesticides, heavy metals, solvents and cigarette smoke
(see ‘Challenged conceptions: Environ-mental chemicals and fertility’, Table
1, at

A chemical legacy

While infertility is clearly an adult problem, its causes may have their
roots in fetal development. Indeed, mounting evidence in animals shows that
chemical exposures in the womb (in utero) or during the early stages of
development can cause abnormalities at birth or later that have impacts on
adult reproductive functioning.
Some of the latest evidence concerns BPA, which has been detected in urine,
breast milk, maternal and fetal plasma, amniotic fluid and placental tissues
in various populations worldwide. Scientists at the US National Institute of
Environmental Health Sciences (NIEHS) investigated whether prenatal BPA
exposure at “environmentally relevant” doses-levels seen in the general
population-could cause long-term adverse effects in the reproductive tissues
of female mice. After dosing pregnant mice with either BPA or corn oil (the
control group) for eight days and evaluating their offspring after 18 months
(young adulthood), they found that, compared with the controls, the pups of
the mothers given BPA were significantly more likely to have both benign and
malignant lesions, such as ovarian cysts, in their reproductive tissues
(Environ Health Perspect, 2009; 117: 879-85). These effects could ultimately
have a negative impact on fertility.
The results add to previous animal evidence showing that very low doses of
BPA can cause abnormalities in the uterus, vagina and ovary when those
exposures take place during early development (Environ Health Perspect,
2009; 117: A256).
And it appears that even male reproductive health can be affected, too, as
recently revealed by scientists from the National Institute for Research in
Reproductive Health in Mumbai, India. When they injected newborn male rats
with relatively low doses of BPA, they found dramatic effects on fertility
in adulthood. Females mated with these male rats had significant increases
in pregnancy loss and decreases in litter size, while the males themselves
had altered sperm counts and hormonal imbalances. What’s more, the
BPA-exposed rats showed changes in the expression of Sertoli cell junctional
proteins in the testes. These proteins are crucial for sperm production, and
their altered expression by BPA could be the mechanism by which the chemical
contributes to infertility (Toxicology, 2009 Sep 24; Epub ahead of print).
Besides BPA, a variety of other chemicals, such as pesticides, CHCs,
perfluorinated compounds and heavy metals, appears to have an impact on
adult reproductive health when animals are exposed to them early on in life.
Effects range from hormonal changes and altered puberty onset to reduced
fertility and malformations of the reproductive tract (see ‘Challenged
conceptions: Environmental chemicals and fertility’, Table 2).
Although these findings may not apply to people, a handful of human studies
suggest similar effects. In one, US researchers examined cord blood stored
at birth, and found a link between raised levels of
dichloro-diphenyltrichloroethane (DDT)-a ban-ned pesticide that is still
pervasive in the environment-and an increased time to pregnancy three
decades later (Lancet, 2003; 361: 2205-6).
In another study, prenatal exposure to phthalates was linked to shortened
perineal distances (from the genitals to the anus) in boys, an effect that
was most striking in those whose mothers had the highest urinary
concentrations of phthalates (Environ Health Perspect, 2005; 113: 1056-61).
Usually, this distance in boys is about twice as long as in girls, so it
serves as an indicator of normal male development. In rodents, a shortened
distance is associated with reduced testosterone in the womb.
Although such results may seem inconsequential on their own, previous
research shows that, when testosterone levels are lowered enough to cause
reduced perineal distances in animals, other effects tend to appear later in
life, such as ‘undermasculinization’ and reduced fertility. More worrying,
the Rochester team observed such effects at phthalate levels equivalent to
those seen in about one in four American women (see ‘Challenged conceptions:
Environmental chemicals and fertility’, at pubs).

Our toxic future

Although the evidence linking chem-icals to infertility is still in its
early stages, there’s already a compelling case to be made against many of
the contaminants we encounter on a daily basis. This suggests that, along
with factors such as age, nutrition and body weight, other influences are
clearly involved in whether or not a couple successfully makes a baby,
including the increasingly polluted world in which they live.
While more research is needed, the current facts suggest that if we don’t
start cleaning up our act, we’re not only risking our health, but our entire
human existence.
Joanna Evans

A world of chemistry

Every year, around 100,000 different types of chemicals are produced and
used around the world, many of which eventually find their way into our
environment. Even chemicals that were banned from manufacture years ago can
still be lingering in the atmosphere, soil and water. As a result, we’re now
being exposed to tens of thousands of chemicals that were never part of the
environment in which our ancestors lived.
The impact of all this pollution on our health is not yet known, but a
number of experts claim that it may well be behind the growing fertility
problems worldwide. Data from the US National Center for Health Statistics
2002 National Survey of Family Growth revealed that almost 7.3 million women
reported impaired fecundity (the biological capacity to have children)
compared with 6.1 million in 1995 and 4.9 million in 1998. Although this
could perhaps be explained by the trend of more couples waiting until they
are older before trying to have children, surprisingly, the survey found
that the most striking increase in self-reported problems was
in women aged under 25-who showed a 42-per-cent increase between 1982 and
1995. Results from more recent surveys suggest this pattern is continuing
(see ‘Challenged conceptions: Environmental chemicals and fertility’, at pubs).
In addition, according to the 2006 report of the environmental group
Greenpeace (see ‘Fragile: Our Reproductive Health and Chemical Exposure’, at, the rise in infertility rates-as well the
increase in medical conditions that contribute to infertility (such as poor
semen quality in men and endometriosis in women)-has paralleled the rise in
the manufacture and use of chemicals, suggesting that it is more than just
“What is clear,” the report states, “is that many chemicals commonly found
in the environment and in human bodies have shown themselves in laboratory
tests to be capable of causing the type of effects which may underlie the
trends in reproductive human health that we are witnessing across the
This laboratory evidence-together with observations made in wildlife,
numerous occupational studies, and more and more research in the general
population-suggests that chemical exposures should now be recognized as one
possible factor underlying human infertility.

Minimizing the risk

Although we can’t avoid chemicals completely, it is possible to reduce our
exposure to the more common contaminants, so couples should especially watch
out for the following.
– Bisphenol A (BPA) is found in polycarbonate plastics and food-can
linings, so exposure is mainly through food and drink.
– Consume fresh, unprocessed foods and avoid canned goods as much as
– Avoid polycarbonate plastic food containers marked with the number
‘7’ in the recycling logo (generally, these are rigid, transparent plastic
containers); plastics that are numbered 1, 2 and 4 are safer.
– Choose glass instead of plastic for water bottles, or use water from
the tap (filtered); also, avoid metal water bottles as they may be lined
with BPA-containing plastic.
– Avoid using plastic containers in the microwave, and opt instead for
ceramic, glass and other microwaveable dishware.
– Avoid storing food and drink in plastic containers; glass and
stainless steel are the safer choices.
– Phthalates are found in PVC products such as vinyl flooring, food
packaging and children’s toys, as well as in numerous personal-care
products. Exposure can occur via ingestion, skin absorption or inhalation of
polluted air.
– Choose PVC-free building products. Avoid vinyl windows and doors,
and choose wood instead. For flooring, use linoleum, cork, bamboo or wood.
Adhesives, caulk, grout and sealants may also contain phthalates, so check
ingredients before purchasing.
– Avoid vinyl shower curtains and use natural fibres, polyester or
nylon instead.
– Choose PVC-free packaging, and always examine the recycling symbol
on products you buy in plastic packaging; plastics marked with the number
‘3’ contain PVC.
– Use PVC-free food storage. Buy plastic wrap and storage bags made
from polyethylene rather than PVC. For storing food, use glass, or plastic
containers marked with recycling symbols containing numbers other than ‘3’
and ‘7’ (to avoid BPA, too).
– Buy PVC-free toys. Although the use of certain phthalates has been
restricted in children’s toys in some countries, it’s still a good idea to
select products from manufacturers that have pledged to stop using
phthalates altogether such as Lego, Brio and Chicco.
– Use phthalate-free cosmetics. Check out ingredient lists and avoid
products that include ‘fragrance’ or phthalates. Choose products from
companies such as Dr Hauschka, Lavera and Green People, which make it a
point to use natural ingredients.
– Perfluorochemicals (PFCs) are found in carpets, clothes, cookware
and fast-food wrappers; we’re usually exposed through contaminated water or
– Avoid non-stick pans and kitchen utensils, and choose stainless
steel and cast iron instead.
– Avoid greasy packaged and fast foods, as these usually come in
treated wrappers.
– Opt for clothing that doesn’t carry Teflon or Scotchgard tags. This
includes fabric treated to be stain- or water-repellent.
– Resist the optional anti-stain treatment on new carpets and
furniture and, instead, choose products that haven’t been pretreated; if you
have a sofa that’s been treated, get a slipcover for it.
– Choose personal-care products with no ‘PTFE’ or ‘perfluoro’ listed
in the ingredients.
– Chlorinated hydrocarbons (CHCs) are persistent chemicals that are
mainly present in food, but also intap water.
– Limit consumption of animal fats, particularly fatty fish and
high-fat meats.
– Choose organic produce whenever possible.
– Install a good-quality water filter.
– Other chemicals (such as heavy metals) and additional factors such
as nutrition, allergies and infections can also affect fertility. For a
comprehensive preconception programme, contact the registered UK charity
Foresight, the association for the promotion of preconceptual care (tel:
01243 868 001;

The damage of DES

The most convincing evidence of a connection between developmental chemical
exposures and future fertility comes from studies of diethylstil-boestrol
(DES), a synthetic oestrogen widely prescribed from the 1940s through to the
1970s for pregnancies at risk of miscarriage. This compound serves as a
model for environmental agents that are hormonally active-in other words,
endocrine disruptors. BPA, phthalates, PCBs, DDT and a number of other
pollutants linked to reproductive problems can all be considered
endocrine-disrupting agents.
The DES research clearly shows that prenatal exposure to a synthetic
oestrogen can adversely affect reproductive physiology and impair fertility
later in life. While doses of DES ingested by pregnant women were much
greater than those from environmental exposures, many underlying mechanisms
of action nevertheless appear to be similar (Semin Reprod Med, 2006; 24:

Vol. 20 08 November 2009

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Article Topics: fertility, infertility, pregnancy
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