The effects of environmental chemicals on fertility and fecundity

THE FERTILITY SOCIETY OF AUSTRALIA - The effects of environmental chemicals on fertility and fecundity

There is increasing evidence demonstrating the negative effects of environmental chemicals,
especially endocrine disrupting chemicals (EDCs), on reproduction and development
[1, 2], including several studies that have found elevated levels for several chemicals
among those seeking assisted reproductive technologies. This is a summary of the available
human data for the effects of environmental chemicals on adult male and female fertility
and fecundity. There are also potential associations of environmental chemicals with
recognised reproductive disorders (e.g. cryptorchidism or endometriosis), however
these are outside the scope of this summary.

EVIDENCE REVIEW

Chemical and where it is found: Phytoestrogens

Includes isoflavonoids, flavonoids, coumestans,
stilbenes, and lignans.
Phytoestrogens are naturally occurring
plant-derived compounds found in a variety
of foods with oestrogenic and anti-oestrogenic
properties [3].

Effects on male fertility/fecundity:

Few studies with conflicting findings.
In fertile men, one study found no effect
while another found an association between
higher urinary levels of isoflavones and
reduced normal sperm morphology.
Urinary phytoestrogen concentrations have
not been associated with increased time to
pregnancy (TTP) in fertile couples or with
clinical outcomes in couples undergoing ART

Effects on female fertility/fecundity:

Few studies with conflicting findings.
In premenopausal women, higher
phytoestrogen intake was associated with
reduced LH and FSH concentrations and
longer menstrual cycles [4].
Among women undergoing ART, isoflavone
intake was positively associated with having
a live birth.

Chemical and where it is found: Bisphenols (BPA/BPS/BPF)

Widely used in plastic products, lining of tin
cans and thermal sales receipts. Leaches from
many products.
Present in the urine of 95% of people tested.

Effects on male fertility/fecundity:

Few studies of BPA with conflicting findings [5].
No studies on the analogues BPS or BPF which
are used as replacement in ‘BPA free’ products.
Urinary BPA is associated with altered oestrogens,
androgens, gonadotrophins and sex hormone
binding globulin (SHBG) concentrations. In
occupationally exposed men, higher BPA levels
were associated with worse sperm parameters.
In general populations, one study found detectable
urinary BPA increased risk of low sperm
parameters. Another study found no association.
Among people trying to conceive, no associations
has been found between BPA concentration
and TTP, fertilisation and live birth rates [5].
May exert secondary negative effects on
fertility, due to their association with obesity
and type 2 diabetes.

Effects on female fertility/fecundity:

Higher serum BPA concentrations have been
reported in infertile women, compared with
those of fertile women.
Among healthy women, BPA exposure has
not been associated with increased TTP or
reduced fecundity [6].
Among women undergoing ART, several
studies and meta-analyses have identified that
BPA exposure and urinary concentrations are
associated with lower circulating oestrogen
levels; oocyte yield and quality; blastocyst
formation; as well as higher implantation
failure and miscarriage rates.
May exert secondary negative effects on
fertility, due to their association with obesity
and type 2 diabetes.

Chemical and where it is found: Phthalates

Includes di-esters and mono-esters.
Added to plastics to increase flexibility and
durability and found in toys, footwear, food
packaging, medical devices, and personal
care products.
Detected in >95% of people tested.

Effects on male fertility/fecundity:

Epidemiological studies provide evidence
for negative associations between mono-ester
phthalate exposure and reproductive
hormones; sperm concentration, count, and
morphology; and TTP [7]. Stronger evidence
exists for detrimental effects on sperm
motility and quality.

Effects on female fertility/fecundity:

No firm conclusions can be made regarding
possible effects of phthalates on female
fertility and fecundity, despite the growing
body of evidence of negative effects from
animal studies [8].
Conflicting evidence exists for their effects
on TTP and early pregnancy loss.

Chemical and where it is found: Parabens

Structurally similar to BPA. Sub-classes
include methyl, propyl and butyl parabens.
Used as preservative and anti-microbial agents,
and found in food, cosmetics and personal
care products.
Detected in >90% of people tested and levels
are > five-fold higher in women than in men.

Effects on male fertility/fecundity:

Urinary paraben concentrations have not
been associated with changes in plasma
steroid hormone concentrations or semen
parameters in idiopathic infertility but butyl
parabens have been linked to sperm DNA
damage [9].
In couples undergoing ART, paternal urinary
paraben concentrations were not associated
with fertilisation rates, embryo quality or
implantation rates [10].

Effects on female fertility/fecundity:

Insufficient evidence exists to determine
effects of parabens on female fertility and
fecundity.

Chemical and where it is found: Persistent organic pollutants (POPs)

Compounds in the environment that often
accumulate in adipose tissues.
Includes ‘superfamilies’ that have different
characteristics and biological effects:
a) Polychlorinated biphenyls (PCBs),
polybrominated biphenyls (PBBs) and
diphenyl ethers (PBDEs). Used in electrical
devices, industrial lubricants, paints until 1979
(PCBs). Found in flame retardants of furniture
(PBB and PBDEs).
b) Polychlorinated dibenzo-p-dioxins
(PCDDs or dioxins). By-products of industrial
processes – metal and paper production, wood
incineration, or heating plastics.

Effects on male fertility/fecundity:

a) Evidence for a negative effect of PCBs
on sperm motility is robust. There is weak
evidence for effects of PBBs, PCBs and
PBDEs on hormone concentrations
(including testosterone), stronger evidence
for negative effects on sperm parameters
(particularly for PCBs on motility and DNA
integrity) and fecundity [11].
b) Occupational exposure was associated
with increased gonadotrophins and decreased
testosterone in the serum among chemical
production workers.
As data are limited, no statement can be
made about the possible effects of dioxin
concentrations in non-occupational
environments.

Effects on female fertility/fecundity:

a) High PCB exposure was associated with
longer menstrual cycles [12] and early onset
menopause.
In ART, PCBs and PBDEs were associated
with decreased fertilisation rates, lower rates
of high-quality embryos and increased
implantation failure [13].
Exposure to certain PCBs is linked to
longer TTP.
b) No clear evidence exists to allow
conclusions of effects of dioxin on female
fertility and fecundity.

Chemical and where it is found: Pesticides, herbicides and insecticides

The many chemicals classified under these
categories (e.g. organochlorines and
organophosphates) can act via several
hormonal pathways. Because people often
are simultaneously exposed to multiple
chemicals and concentrations, it is difficult
to assess their effects on fertility and
fecundity

Effects on male fertility/fecundity:

Two of the most well-studied are DDT
and DDE. Studies of numerous chemicals
have identified adverse effects on sperm
characteristics (quality and function),
including decreased motility, increased DNA
damage, and mitochondrial dysfunction [1].
Occupational exposure is associated with
lower in vitro fertilisation rates, increased
TTP [14], and higher miscarriage rates.

Effects on female fertility/fecundity:

In several studies, occupational exposure
to combinations of pesticides or individual
pesticides appears to alter menstrual cycle
lengths, reduce fertility and can result in an
increased TTP and risk of miscarriage [14].

Chemical and where it is found: Heavy metals

Includes aluminium, arsenic, cadmium,
chromium, lead, mercury, molybdenum
and nickel.
Exposure occurs through smoking, air
pollution, dental fillings, consumption of
contaminated food and drink, and contact
with petrol, industrial and household
products.
Bioaccumulation of heavy metals in tissues
is common over a lifetime.

Effects on male fertility/fecundity:

The strongest evidence exists for the negative
effects of lead, and to a lesser extent cadmium
and mercury, on sperm parameters and
hormone concentrations [15]. Lead seminal
plasma concentrations are negatively
associated with sperm parameters [15] and
IVF success rates, and positively associated
with a premature acrosome reaction.
Occupational exposure to high [8] lead
levels is associated with a longer TTP.
Increased urinary cadmium is positively
associated with serum LH and testosterone
in occupationally exposed workers [16]. In
the general population cadmium is found to
negatively affect sperm parameters, especially
sperm counts that are reduced in some but
not in other studies [15]. In ART, couples
semen concentrations are not linked to a
longer TTP.
Only limited evidence exists about the
possible association between concentrations
of mercury, aluminium, arsenic, chromium,
molybdenum and nickel and steroid hormone
concentrations or semen characteristics;
existing evidence is conflicting [15,16].

Effects on female fertility/fecundity:

Relatively few studies in women compared
with those in men have investigated
associations between heavy metals and fertility.
Among women receiving fertility treatment,
blood lead concentrations are negatively
associated with fertilisation rates.
Higher blood cadmium levels in women,
independent of their partners, are associated
with longer TTP [17], although other studies
report equivocal effects of cadmium on fertility.
Menstrual cycle abnormalities are identified
in women occupationally exposed to
mercury. Dental assistants with high
mercury vapour exposure have a longer
TTP than unexposed women.
In the general population, however, no
associations have been found between blood
mercury concentrations and fertility [17].
Equally, in women receiving fertility
treatment, no association between mercury
and IVF outcomes have been identified.

Chemical and where it is found: Fossil fuels and air pollutants

Air pollution encompasses numerous
compounds (particulate matter between 2.5
to 10 μm in diameter), nitrogen dioxide,
sulphur dioxide, and ozone released by the
combustion of fossil fuels [25].

Effects on male fertility/fecundity:

A systematic review of the effects of
occupational and residential exposure to oil
and gas extraction activities identified strong
evidence for effects on steroid hormone
receptors and some evidence for detrimental
effect on sperm motility, with inconsistent
findings with respect to other sperm
parameters [18].
No robust studies have been undertaken
on air pollution and male fecundity

Effects on female fertility/fecundity:

Exposure to oil and gas extraction activities
identified increased miscarriage rates in
women with occupational exposure, with
conflicting findings for women with
residential exposure [18].
Studies of the effects of air pollutants, report
equivocal results [19], however fertility rates
are decreased in the general population with
higher traffic-related pollution.

Chemical and where it is found: Ionising and electromagnetic radiation

Ionising radiation exposure can be
medical-related or caused by atomic disaster.
Electromagnetic field (EMF) radiation
exposure occurs daily through emission
from mobile phones, microwave ovens,
high voltage power lines and other electrical
appliances.

Effects on male fertility/fecundity:

Occupational and low-level ionising
radiation exposures are associated with
reduced sperm counts, perturbed sperm
motility and increased morphological
abnormalities, DNA fragmentation and
global hypermethylation [20, 21]. However,
it is not associated with change in TTP
among occupationally-exposed men [22],
residents near nuclear power plants [23],
or after gonadal X-ray examinations [24].
Both occupational and general population
exposure studies report equivocal effects of
EMF, although sperm motility and DNA
fragmentation and blood hormone levels
are commonly affected negatively [15, 25].
Mobile phone usage is negatively associated
with several sperm parameters. The effects
of EMF are mainly believed to occur from
disruption of testicular heat regulation.
EMF effects related to fecundity are
currently unclear.

Effects on female fertility/fecundity:

Little robust evidence exists on adverse effects
of low-dose radiation exposure on fertility.
Peri-conceptional exposure to low-dose
radiation is not associated with a change in
TTP in female nuclear plant workers [22]
or those couples living near nuclear waste
processing plants [23]. However, diagnostic
radiography in adolescent girls is associated
with an increased TTP and miscarriage rate
in adulthood [26].
EMF effects on female fertility have rarely
been studied in the general population, with
no clear evidence to substantiate possible
effects. Occupational shortwave EMF
exposure has been associated with an
increased TTP, but not in all studies [27].
Evidence exists for exposure-dependent
increases in miscarriage risk [28].

Abbreviations:
ART Assisted reproductive technology
DDE Dichlorodiphenyldichloroethylene
DDT Dichlorodiphenyltrichloroethane
FSH Follicle stimulating hormone
IVF In-vitro fertilisation
LH Luteinizing hormone
TTP Time to pregnancy

SUMMARY

For most environmental chemicals, including EDCs, no
or few large reproductive human studies exist. Evidence
from these suggest that several have a direct negative effect
on male and female fertility and fecundity [1, 2]. In men
there is strong evidence to support negative effects on
sperm motility and DNA integrity of phthalates
(monoesters MEHP and MBP), PCBs, PBDEs, pesticides
including DDE, lead, ionising and EMF radiation, and
on sperm count and morphology of lead and ionising
radiation. For male fecundity (TTP), moderate evidence
supports a negative association with monoester phthalates,
PCBs and pesticides including DDE.
Fewer studies have been undertaken in women, with only
moderate evidence of negative effects on oocyte quality,
implantation and miscarriage rates of BPA or PCBs.
Stronger evidence exists of a negative association with
fecundity (TTP) for PCBs and pesticides including DDE.
To date, fewer fertility effects are identified in women than
men, though this likely reflects the difficulty in accessing
oocytes relative to sperm for study, rather than the lack
of actual effects. It should also be noted that commonly a
statement cannot be made regarding many environmental
chemicals, most likely due to a lack of study, not because
an association does not exist. Determining the effect of an
individual EDC is also confounded by the presence and
action of multiple EDCs in the environment. This may
explain why low levels of a single EDC are often not
associated with fertility issues, as these may result instead
from added effects of many EDCs working at low
concentrations. Far more research is thus required to
categorically establish the effects of individual EDCs on
fertility and fecundity of both males and females.
Clinical recommendations
Men and women should limit their exposure to
environmental chemicals, especially EDCs, where
possible. Clinical advice as to the management strategies
that may help lower exposures to improve fertility and
fecundity includes:
• drink water/soft drinks from glass or hard plastic
bottles, rather than soft plastic bottles. BPA,
phthalates and other plasticisers are used to make
plastics in bottles flexible.
• avoid heating food in soft plastic takeaway containers
or those covered in cling wrap or foil. Instead, place
food in china or glass bowls and cover with paper
towel or a china plate before heating
• consume fewer processed/pre-canned/pre-packaged
foods as this will reduce the intake of BPA, phthalates
and plasticisers that coat the inside of cans and plastic
wrappings
• wash fresh produce prior to consumption to reduce
the intake of pesticides, fungicides, herbicides and
chemicals that may have been sprayed on them
• limit the amount of oily fish and fatty meats to reduce
the intake of POPs, pesticides, heavy metals and fat
-soluble chemicals that can accumulate in animals
• reduce the use of personal care products with high
concentrations of chemicals (make-up, shampoos,
hair colourings etc.) and choose paraben free products
• avoid handling sales receipts and exposure to strong
solvent based chemicals (paints, cleaning products,
glues etc), industrial processing chemicals, heavy
metals, smoke, ionising radiation
• limit mobile phone usage and contact to reduce
exposure to electromagnetic radiation
• be aware that replacement analogues, such as for BPA
(e.g. BPS and BPF), are not necessarily ‘safer’ options.
For individuals or couples receiving fertility treatment,
in particular those diagnosed with idiopathic infertility,
it is recommended to obtain detailed information on their
lifestyle, and possible occupational and general exposure
to environmental chemicals. It may also prove informative
to analyse urine, reproductive fluids and tissues, as well as
non-reproductive tissues (hair and adipose) for current and
cumulative environmental chemical concentrations.

For more information about pre-conception health visit www.yourfertility.org.au

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