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Best Practice & Research Clinical Obstetrics and Gynaecology 88 (2023) 102347

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Best Practice & Research Clinical


Obstetrics and Gynaecology
journal homepage: www.elsevier.com/locate/bpobgyn

Effects of endocrine disrupting compounds on


female fertility
Periklis Panagopoulos a, Despina Mavrogianni b, *,
Chryssi Christodoulaki c, Eirini Drakaki b, Georgios Chrelias a,
Dimitrios Panagiotopoulos a, Anastasios Potiris a,
Peter Drakakis a, b, Sofoklis Stavros a
a
Third Department of Obstetrics and Gynecology, University Hospital “ATTIKON”, Medical School of the
National and Kapodistrian University of Athens, Greece
b
First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School of the National and
Kapodistrian University of Athens, Greece
c
Department of Obstetrics and Gynecology, Chania General Hospital “St. George”, Greece

a b s t r a c t
Keywords:
Endocrine disrupting compounds (EDCs) Endocrine Disrupting Compounds or Chemicals (EDCs) constitute
Female fertility an extensive and varied group of mostly non-natural chemicals
Phthalates that have the ability to imitate any aspect of hormone action,
Pesticides perturbing many physiological functions in humans and animals.
Bisphenol A (BPA) As for female fertility, several EDCs are associated with adverse
Bisphenol S (BPS)
effects in the regulation of steroidogenesis, higher miscarriage
rates as well as lower fertilization and embryo implantation rates
and some of them are considered to decrease the number of high-
quality embryos in assisted reproductive technology (ART) preg-
nancy. The most common EDCs are pesticides, hexachlorobenzene
(HCB), hexachlorocyclohexane (HCH) and especially phthalates
and bisphenols which are used in thousands of products as plas-
ticizers. Among all, Bisphenol A (BPA) is one of the most perme-
ating and well-studied EDCs. BPA's action resembles that of
estradiol affecting negatively the female reproductive system in
various ways. This review summarizes the most recent literature
on the impact of EDCs in female fertility.
© 2023 Elsevier Ltd. All rights reserved.

* Corresponding author.
E-mail address: depy.mavrogianni@yahoo.com (D. Mavrogianni).

https://doi.org/10.1016/j.bpobgyn.2023.102347
1521-6934/© 2023 Elsevier Ltd. All rights reserved.
P. Panagopoulos, D. Mavrogianni, C. Christodoulaki et al. Best Practice & Research Clinical Obstetrics and Gynaecology 88 (2023) 102347

Introduction

Over the past 50 years, the global production of well-known and emerging chemical pollutants has
continued to increase despite efforts to avoid their use [1]. Exposure to harmful chemicals lasts a
lifetime and affects humans, animals and the environment [1]. This exposure occurs both indoors and
outdoors, as these harmful chemicals diffuse through water, air and soil and are still used in everyday
products and may cause immediate or delayed disruption of physiological functions [1].
Even though there are plenty of substances that interact with the endocrine system, and they do not
cause adverse effects, there is also a wide variety of natural and synthetic substances that can cause
hormonal disruption and may have detrimental effects in both humans and wildlife [2]. These sub-
stances are defined as Endocrine Disruptors Compounds or Chemicals (EDCs) and they are investigated
by different research teams, as they are involved in several public health problems [3]. They have also
been associated with various effects on the reproductive system of diverse wildlife species, from fish
and reptiles to birds and mammals, leading even to population declines in some cases [4].
Hormones are chemical agents released by endocrine glands, allowing intercellular and inter tissue
communication between different organs [5]. Through this signaling process, hormones affect most of
the physiology, including growth, the onset of puberty, maintenance of fertility, regulation of meta-
bolism and play an important role in cellular function throughout the body and in the central nervous
system [5]. Even the slightest interference with hormone release, secretion, transport or binding to
their receptors can disrupt body homeostasis [6].
Some substances produced by plants (phytoestrogens) have various endocrine effects. Because of
their structural similarities to endogenous human hormones, they act like estrogens [7]. They are
polyphenolic molecules (isoflavones, prenylflavonoids, coumestans, lignans), found mainly in legumes
(soybeans) and in smaller amounts in grains, fruits and vegetables [7]. Phytoestrogens are considered
natural EDCs, but some studies have linked them to be beneficial to the human body [8]. Conflicting
results can be attributed to differences in phytoestrogen's type, concentration and bioavailability, as
well as consumer's health status, hormone levels and ethnicity [8].
Synthetic EDCs are chemicals found in thousands of commonly used products such as plastics,
cleaners, food preservatives, insecticides, cosmetics, etc., even in water sources [9,10]. EDCs interfere
with hormonal action and they are associated with the initiation or exacerbation of endocrine disor-
ders, while many of these substances interact with each other, thereby increasing the effect on the
endocrine system [11]. In humans, EDCs can theoretically affect all hormonal functions in the body and
over the last few decades have been suggested to cause metabolic syndromes (e.g. diabetes, obesity)
and several abnormalities of ovarian and testicular function, for example, declining sperm counts and
changes in fertility and the onset of puberty [10e12]. Links between EDCs and increased risk of thyroid
cancer, breast cancer, and other endocrine tumors have also been suggested [10].
This review focuses on the effects of synthetic EDCs on female fertility by attempting to summarize
the information provided by the literature.

Literature search strategy and results

In order to determine all potentially relevant articles related to female fertility and EDCs, an
extensive literature search in the PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) database was
accomplished, using the following search terms (keywords): (“Endocrine disrupting chemicals” OR
“Endocrine disrupting compounds” OR “Endocrine disruptors” OR “EDCs” AND “Female fertility”),
(“Phthalates” AND “Female fertility”), (“Parabens” AND “Female fertility”), (“Triclosan” AND “Female
fertility”), (“PCBs” AND “Female fertility”), (“Pesticides” AND “Female fertility”), (“PFCs” AND
“Female fertility”), (“Bisphenol A” AND “Female fertility”), (“Bisphenol S00 AND “Female fertility”).
As of December 31, 2022, a total of 194 articles were located in PubMed database, of which the full
texts were 188. Firstly, the titles and abstracts of the articles were scanned by two independent sci-
entific researchers to find all eligible articles and avoid duplication. The included articles are in English
and concern reviews, systematic reviews, meta-analyses, and studies, while all search results that
could be related to editorials, conference abstracts and commentaries were excluded from the

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beginning. After removing the duplicates, examining the full texts and selecting the most relevant
articles, the final number of included ones, for this review, is 27.

EDCs and female fertility

As previously mentioned, EDCs can be found in plenty of items and products with which both
adults, infants and children come into contact on a daily basis, such as plastic bottles and containers,
food preservatives and coloring additives, toys, pesticides, cosmetics and many more. Most of them
degrade at a very slow rate, accumulating in water and soil over long periods of time and entering the
food chain [13]. EDCs are divided into two groups, depending on whether they accumulate in tissues
over a long period of time (persistent EDCs) or are metabolized and excreted from the body (non-
persistent EDCs) [14].
Additionally, some can be transferred from plastic packaging into food and liquids, while others are
released into the atmosphere as gaseous waste [15,16]. It is also worth noting that EDCs may transfer
across the placenta to the fetus or enter the neonatal system through breastfeeding [17,18]. In sum-
mary, all organisms could come into contact with EDCs through drinking, eating, or simply breathing.
As a result, they are detected in various organs and tissues as well as blood and urine, while it is pointed
out that almost the majority of the population has been exposed to these toxic compounds over the last
decades [14e19].
Although it is not feasible to eliminate all sources of exposure to EDCs due to modern lifestyle, there
is an urgent need to reduce the duration and extent of this exposure wherever possible and to
continually increase the awareness of the scientific community, industry and general public regarding
this significant health issue. Already 30 years ago, several attempts were made to identify potential
substances as EDCs. A comprehensive definition of EDCs was given by the World Health Organization
(WHO) and the International Programme on Chemical Safety (IPCS) in 2002, and ten years later, these
compounds were characterized as an Emerging Policy Issue under the UN Strategic Approach to In-
ternational Chemicals Management (SAICM), at the third session of the International Conference on
Chemicals Management (ICCM 3) [20].
In the following years, some of the most important international and European organizations
published a series of identified and potential substances to act as EDCs. These lists are updated
continuously, so that national and international committees around the world compose regulations
and laws that ensure consumer and worker safety in addition to environmental protection. As this
review focuses on the effects of EDCs on female fertility, Table 1 presents the most widely studied
compounds that appear to be negatively associated with female reproductive system physiology in the
literature, over the past decade.
The recently observed drop-offs in male and female fertility are associated with exposure to various
chemical contaminants [21]. Since EDCs interfere with the endocrine system, they inevitably disrupt
the homeostasis of the reproductive system as well. More specifically, the health issues of female

Table 1
Most widely studied EDCs associated with adverse effects in female fertility.

Category or Name of EDC Persistent or not- Persistent compound

Bisphenol A (BPA) and Bisphenol S (BPS) Non-persistent


Phthalates Non-persistent
Parabens Non-persistent
Triclosan (TCS) Non-persistent
Polychlorinated biphenyls (PCBs) Persistent
Dichlorodiphenyltrichloroethane and its metabolite (DDT an DDE) Persistent
Chlordane Persistent
Lindane (BHC or g-HCH) Persistent
Pentachlorobenzene (PeCB) Persistent
Hexachlorobenzene (HCB) Persistent
Perfluorinated compounds (PFCs) Persistent
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) Persistent

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fertility against which EDCs have been blamed for many years include reduced number of viable oo-
cytes, early onset of puberty, shortened reproductive life span, complications in embryo implantation,
endometriosis and fibroids [22]. Although the ways in which EDCs affect the physiology of the human
reproductive system have not been fully clarified to date, their most typical mechanism of action has
been attributed to both agonistic and antagonistic binding to androgen and estrogen receptors, which
means that they either mimic androgen and estrogen activity or block the interaction between these
hormones and their receptors [23].

Phthalates

Phthalates are derived from acids and specifically from phthalic acids, as they belong to the organic
compounds of esters. They are considered as non-persistent EDCs. Low molecular weight phthalates
were used in the past as plasticizers, contributing to the flexibility and durability of plastics such as
polyvinyl chloride (PVC) [24,25]. The USA, the European Union, and many other countries have been
replacing low molecular weight phthalates, due to their negative association with male fertility and
child development problems, with higher molecular weight phthalates [26]. Effects on female fertility
are still unclear. Phthalates mimic the effects of estrogen and, in addition to other mechanisms of
action, also inhibit the production of the male hormone testosterone and as a result, they were banned
from use in toys [26,27].
The effects of phthalates and their metabolites on the human menstrual cycle remain to be eluci-
dated. However, high concentrations of monocarboxyoctyl phthalate in women's urine are associated
with a shorter luteal phase [28]. Conversely, studies in other animal species show that exposure to
DEHP [Di(2-ethylhexyl) phthalate] and its metabolite MEHP [Mono(2-ethylhexyl) phthalate] reduces
serum estradiol levels and extends the length of the menstrual cycle [25].
Phthalates are strongly associated with the risk of endometriosis, both in studies examining urinary
levels in women and in vitro, although some studies have not been able to prove this association [28].
Uterine fibroids have also been associated with increased levels of DEHP and its metabolites MEHP,
MEHHP [Mono(2-ethyl-5-hydroxyhexyl) phthalate] and MEOHP [Mono(2-ethyl-5-oxohexyl) phtha-
late] as well as other phthalates in the urine of women [28]. Regarding the correlation of phthalate
effects on human female fertility, studies are conflicting and it is believed that further research on this
topic is needed [28]. Furthermore, the effects of phthalates, especially DEHP, on the outcome of in vitro
fertilization (IVF), high levels of their metabolites in urine are associated with a lower number of
oocytes retrieved, an increased risk of implantation failure as well as a lower probability of clinical
pregnancy and live birth following assisted reproductive technology (ART) [25].

Parabens

Parabens are esters of para-hydroxybenzoic acid and are also considered as non-persistent EDCs
[25e29]. Due to their antibacterial and antifungal properties, they are widely used in a variety of
everyday products (cosmetics and pharmaceuticals), but they are also used as food preservatives [29].
In vitro and in vivo studies have reported estrogenic effects of parabens, as they bind to the estrogen
receptors a and b (ER-a and ER-b) [30]. The greater the length and branching of the alkyl chains of
parabens, the higher the estrogenic activity [25].
Parabens and their metabolites have been associated with elevated estradiol levels in healthy
premenopausal women [28]. Exposure to high levels of methyl and ethyl parabens was also associated
with a shorter time to pregnancy (TTP) [28]. One study also associated a decrease in the number of
antral follicles with an increase in urinary phenyl paraben levels [28]. Lastly, while previous studies
have linked paraben exposure with decreased odds of live birth and poorer day 3 embryo quality, the
EARTH study showed no such association [25].

Triclosan

Triclosan (TCS) is an antibacterial chemical used in a variety of products (cosmetics, soaps, tooth-
paste, etc.) [31]. It has a low affinity for both androgen and estrogen receptors and is considered an

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agonist and antagonist, non-persistent EDC [25e32]. It is worrisome that TCS is found in the liver,
blood, urine and even human breast milk [32].
Studies on rats have shown that exposure to TCS modulates various estrogen-dependent responses
[31]. Studies on the effects of TCS and hormones have also been realized in humans. As to endome-
triosis, endometrial stromal cells exposed to TCS were found to exhibit increased decidualization ef-
fects, but no other studies support this correlation [28]. The effect of TCS on polycystic ovary syndrome
(PCOS) is still uncertain [28]. Most of the studies do not show the direct effects of TCS on female
fertility, except for one that demonstrated an association of TCS with decreased oocyte yield during IVF
[25].

PCBs

Polychlorinated biphenyls (PCBs) are potent carcinogenic compounds (e.g. endometrial cancer) and
have also been characterized as persistent EDCs [33]. They were widely used in industrial and con-
sumer products until the 1960s when their manufacture was banned by United States Federal Law of
1979 and the United Nations Environment Programme in May 2001 [34]. However, they are still
present in many biological and environmental samples today. PCBs can inhibit female fertility through
effects on ovarian physiology [25]. They are also linked to uterine fibroids, reduced parity and
fecundability and several worse outcomes in IVF treatments (such as a longer TTP) in women [35].

DDT/DDE

Dichlorodiphenyltrichloroethane, known as DDT, belongs to the group of organochlorines [25].


Since 2004 there has been a global ban on agricultural use, although it still has limited use due to its
effectiveness in killing mosquitoes and reducing malaria infections [36,37]. DDT is a persistent organic
pollutant that readily adsorbs soils and sediments, where it is stored for very long periods of time,
eventually affecting all species [36].
DDT and its metabolite, dichlorodiphenyldichloroethylene (DDE), are considered persistent EDCs
[35]. It accumulates in tissues and organs with high levels of lipids and interferes with fertility [22].
Indirect maternal exposure by workers who have direct contact with DDT/DDE is associated with
increased spontaneous abortions [22]. Both PCBs and organochlorine pesticides (DDT) have also been
associated with adverse effects on IVF outcomes, including decreased implantation and fertility rates,
as well as lower levels of anti-Müllerian hormone [25].

Other pesticides, insecticides and fungicides

Chlordane is an organochlorine compound and a persistent EDC. In the past chlordane was used as a
pesticide and especially as a termite treatment in food crops and its use has been banned since the
1970s [35e38]. It has been associated with an altered cycle length in women [35]. Lindane or benzene
hexachloride (BHC) or gamma-hexachlorocyclohexane (g-HCH) was used as an insecticide as well as a
pharmaceutical treatment for lice and scabies [35e39]. Lindane is a persistent EDC and it was linked to
endometriosis and increased spontaneous abortion in women [35]. Pentachlorobenzene (PeCB) and
hexachlorobenzene (HCB) were used as agricultural fungicides, but today they are categorized as
persistent EDCs and are banned [35]. They are associated with increased spontaneous abortion and
failed implantation in women [35].

PFCs and PFASs

Perfluorinated compounds (PFCs) are organofluorine chemicals, which bioaccumulate due to their
chemical stability and so they are characterized as persistent EDCs [25e40]. They are widely used in the
manufacture of various industrial products, and although the production of some PFCs has declined

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over the years, they continue to be detected in small amounts in the blood, umbilical cord, and breast
milk [25]. Some of these (perfluoroalkyl and polyfluoroalkyl substances, PFASs) are also found in food
and drinking water [35]. PFCs have been shown to interact with estrogen and androgen receptors
in vitro and cause irregular menstrual cycles [25e41]. Studies on the outcome of IFV when a woman is
exposed to PFCs, are few and unclear [25]. PFASs are also associated with endometriosis and worse
outcomes in IVF treatments (such as a longer TTP) in women [35].

Bisphenol A

Bisphenol A (BPA) is a chemical compound belonging to the phenol group (alkylphenols), which
was first synthesized in 1891 but is now all-pervading in the environment and it is used in the pro-
duction of various industrial and consumer products, especially plastics [42]. BPA's production is ex-
pected to reach tens of millions of tons in the next few years, although its use has been limited mainly
to children's products, due to its association with harmful effects on public health [43,44]. However, it
is still used via high-carbon and epoxy resins in plastic bottles, containers and bags, sports equipment,
receipt paper, soaps, shampoos, detergents, to coat the inside of water pipes and the inside of food and
drink cans, as a dye developer in thermal paper and many more [25e45]. BPA can enter the body
through inhalation, ingestion and skin absorption [46]. Although BPA has a short half-life, it accu-
mulates in tissues such as the placenta, and is also detected in urine, saliva, amniotic fluid, breast milk,
etc. [47].
BPA is a fairly well-studied case of non-persistent EDC, especially associated with adverse effects on
the female reproductive system and thus female fertility [25]. It acts by activating or inhibiting es-
trogenic function through binding to the ER, while it has been found that it can also bind to the AR and
progesterone receptors [48]. The results are various hormonal, morphological and functional disorders
of the female reproductive system. It must be also mentioned that prenatal and neonatal exposures to
BPA are particularly crucial and have been shown to have intergenerational effects, as well [49].
Both in vivo animal and in vitro human studies associate exposure to BPA during the fetal period
with disturbances in oogenesis due to abnormal meiosis, while other animal studies suggest a link
between BPA exposure and harmful effects on the oviduct [50]. Furthermore, in animal studies, BPA has
been found to affect normal function and development of the hypothalamus, through its involvement
in the hypothalamic-pituitary-gonadal axis (HPG axis) and decreased expression of kisspeptin [50]. It
has also been found that BPA can directly affect the function of the pituitary gland, either by reducing
the synthesis of gonadotropins or by causing pituitary proliferation and increasing the number of
gonadotrophs [50]. In addition, BPA has been associated with follicle atresia and decreased oocyte
survival, as well as PCOS in women [50].
However, those negative effects on the female reproductive system seem to be dependent on the
BPA dose and the duration and timing of exposure, ultimately leading to female infertility [28e50].
Distinctive examples are the association of BPA with endometriosis and uterine receptivity. In the first
case, animal studies indicated that BPA exposure could lead to endometriosis, although human
epidemiological studies have not led to similar results [28e50]. Likewise, the effects of BPA exposure
on the menstrual cycle in rodents are dose-dependent, although human studies have not shown
similar results [28].
As to uterine fibroid, human epidemiological studies are conflicting, but in vitro studies associate
BPA with a potentially increased uterine fibroid profile [28]. Moreover, a few studies have shown an
adverse relation between serum and urinary BPA levels and IVF outcomes, such as reduced implan-
tation and rate of successfully fertilized oocytes, decreased oocyte maturity, yield and count and
diminished embryo cell number and embryo fragmentation score [25].

Bisphenol S

Bisphenol S (BPS) is one of the industrial analogs of BPA [51]. BPS has replaced BPA in a variety of
products such as plastic bottles and toys, receipt paper, canned food and personal care products, as it

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was thought to be safer due to its greater stability at high temperatures and its significantly lower
estrogenic activity [52e54]. However, nowadays it has been suggested to have adverse effects on
human and animal health [55e57].
Regarding its adverse effects on the female reproductive system, in a study by Shi et al. BPS has been
shown to accelerate the onset of puberty, disrupt estrous cyclicity, impair adult reproductive function
with age and inhibit germ cell nest breakdown in developing ovaries in mice [58]. Additionally, in the
study by Eldefrawy et al. in chickens, exposure to BPS resulted in morphological alterations in both
ovarian size and follicular development, similar to those induced by BPA, along with changes in the
ovarian and immune responses in adult laying chickens [59]. Of interest is the study by Nevoral et al. in
which it showed that a low BPS dose in female pups, via breast milk exposure, impairs oocyte
developmental competence and cytoskeletal damage, as well as in vitro matured oocytes of BPS-
exposed donors are prone to spindle defects [60]. Concerning steroidogenesis, the study by Te teau
al. has shown a decrease in the secretion of both progesterone and oestradiol in ovine granulosa cells
[61].
Although at the time of writing this review, no studies on human female fertility and the effects of
BPS have been reported, in vitro and animal studies suggest that the increasing use of BPS should not
ultimately be considered a safer alternative to BPA and further research in human is crucial.

Summary

Through the last decade scientific community is trying to characterize chemical compounds as
potential EDCs and fully understand their mechanisms of action in the human body. Although most
in vitro and animal studies have linked various EDCs to the pathophysiology of the female reproductive
system and consequent effects on female fertility, human epidemiological studies are still conflicting.
The reason for this probably lies in the methodology used to collect and interpret the research data but
also due to the dosage and the duration of exposure to EDCs. As people around the world are exposed to
simultaneous environmental and different EDCs, and their adverse effects on the human body may be
exacerbated, it would also be beneficial to conduct studies examining the synergistic effects of different
combinations of EDCs.
Summarizing the findings discussed earlier in this review, it appears that phthalates, found in
women's urine, can affect the menstrual cycle and is linked to endometriosis and uterine fibroids. In
addition, high levels of certain phthalates result in a shorter luteal phase, while others extend the cycle
and reduce estradiol levels. Besides, high levels of phthalate metabolites in urine can lower success
rates in ART.
The effect of TCS on female fertility is still ambiguous, having been mainly linked to decreased
oocyte yield in IVF treatment. On the other hand, the effect of parabens and their metabolites on female
fertility, is associated with lower antral follicle numbers, shorten TTP and a possible effect on live birth
chances and embryo quality. They are also associated with raised estradiol levels in healthy premen-
opausal women.
Pesticides, insecticides and fungicides have been linked to adverse effects on IVF outcomes, while
lindane is further associated with endometriosis. PFCs are shown to cause irregular menstrual cycles.
As for the PFASs, they are associated with endometriosis and poor outcomes in IVF treatments.
BPA is strongly linked to negative effects on female reproductive function and it has even been
shown that prenatal and neonatal exposures to this endocrine disruptor have intergenerational effects,
like disturbing oogenesis and oviduct function, affecting HPG axis development and kisspeptin
expression. It can also lead to decreased oocyte survival and follicle atresia. BPA is also associated with
an increased risk of PCOS, endometriosis, uterine receptivity and poor outcomes in IVF treatments.
Animal studies on BPS have shown that it can cause morphological alterations in ovarian size and
follicular development and affect steroidogenesis. It may also accelerate the onset of puberty, disrupt
estrous cyclicity, impair adult reproductive function, as well as, oocyte developmental competence and
cytoskeletal damage, and inhibit germ cell nest breakdown in developing ovaries.

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Further research and understanding of the EDCs disruptive functional mechanisms in human
physiology will assist medical professionals in guiding couples toward lifestyles that will help them
achieve pregnancy. In this direction, it should be an increased focus on human studies which would
also examine the combined effects of multiple EDCs on female fertility, even explore the effects of low-
dose exposure during different stages of life, as it occurs in real life. This kind of future research could
contribute as well to updating and expanding the lists of EDCs that are harmful to humans, animals and
the environment, and to limit, if not ban, their production and use.

Practice Points

 Endocrine Disrupting Compounds have been suggested to cause metabolic syndromes and
several abnormalities of ovarian and testicular function.
 Chemical compounds interfere with the outcome of IVF, such as a lower number of oocytes
retrieved, an increased risk of implantation failure as well as a lower probability of clinical
pregnancy and a live birth following ART.
 They have been also associated with elevated estradiol levels in healthy premenopausal
women.
 They have been found to affect normal function and development of the hypothalamus, and
they can directly affect the function of the pituitary gland either by reducing the synthesis of
gonadotropins or by causing pituitary proliferation and increasing the number of
gonadotrophs.

Research Agenda

 Pathophysiological mechanisms associated with Endocrine Chemical Compounds should be


further studied and clarified
 A genetic profile associated with infertility after exposure to chemical compounds is
proposed
 Molecular and cellular mechanisms associated with BPS should be fully investigated

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or
not-for-profit sectors.

Declaration of Competing Interest

None.

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MCQs
1. Female fertility against which EDCs have been blamed include.

A. number of oocytes
B. quality of oocytes
C. number of embryos

The health issues of female fertility against which EDCs have been blamed for many years
include reduced number of viable oocytes, early onset of puberty, shortened reproductive life
span, complications in embryo implantation, endometriosis and fibroids.
2. The effects of phthalates, on the outcome of IVF, include.

A. lower number of oocytes retrieved.


B. more days of treatment
C. ovarian hyperstimulation

Regarding the effects of phthalates, especially DEHP, on the outcome of IVF, high levels of their
metabolites in urine are associated with a lower number of oocytes retrieved, an increased risk
of implantation failure as well as a lower probability of clinical pregnancy and a live birth
following ART.
3. Studies associate exposure to BPA during the fetal period with disturbances in.

A. Oogenesis
B. Spermatogenesis
C. None of the above

In vivo animal and in vitro human studies associate exposure to BPA during the fetal period
with disturbances in oogenesis due to abnormal meiosis.
4. BPS has been shown to.

A. accelerate the onset of puberty


B. disrupt estrous cyclicity
C. A þ B

BPS has been shown to accelerate the onset of puberty and to disrupt estrous cyclicity.

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