English communication Module 1
English Paper
Rasmussen University
Priyal Patel
December 6, 2020
A professional development Action Plan
A professional development action plan refers to a list of outlines showing a person intends to achieve career goals. A professional development action plan helps a professional to set timelines for achieving career goals. The sample below represents a professional development action plan.
Goals
Attend annual AICPA
Enroll for refresher CPA course
Win the accountant of the year award
Increase my salary by at least 20%
Action step
Attending AICPA (American Association of CPAs) summit for accountants and financial professionals will help me to learn more concerning the dynamics of accounting. Besides, will also attend the Cayman Islands Institute of CPAs) summit to get more exposure to strengths of the most successful accounting organization across the US. This will help to increase my professional accountancy rating in the States.
Enrolling in refresher continuing professional education (CPE) for CPAs at AICPA will help to improve skills and promote increased value in the line of customer service and record keeping. In addition, will offer another opportunity to learn about the current accounting digital skills.
Performance due to added skills in accounting will help me secure a salary increase by the end of the next year.
Resources
AICPA College
The Starbucks management to fund by part-time refresher course and the meet the cost of attending the conferences.
Jordan’s online webinar’s
Deadline
In the first three months of the year enroll and graduate from the refresher course at AICPA
April attend the annual conference at AICPA
In august attend the Cayman Islands Institute of CPA summit
By the end of the year win the accountant of the year award
Status
Work in progress. Planning on how I will achieve the goals
Resume letter
Job Application Letter
Subject: Job Application
Dear
Chief Accountancy
126 E, 14th Street, Texas, TX 2045
Texas.
With Regards,
I hereby send my application letter and curriculum value in response to your advertisement in American Times on Friday, 4th 2020.
I have experience in accounting having worked for six years as chief accounting officer at Amazon online retail shop, Pay pal, and Boston Red serving the same position. I have had a remarkable performance in all the organization has worked, and I have a strong belief that given the same position will deliver to your expectations and beyond.
Thereby, am hoping there will be an interview where I can explain the potential in me and the tremendous assets form my services that are preserved for your organization.
Sincerely,
Priyal Patel. REVIEW Open Access
Radiations and female fertility
Roberto Marci1,2,3* , Maddalena Mallozzi4, Luisa Di Benedetto4, Mauro Schimberni4, Stefano Mossa5, Ilaria Soave4,
Stefano Palomba6 and Donatella Caserta4
Abstract
Hundreds of thousands of young women are diagnosed with cancer each year, and due to recent advances in
screening programs, diagnostic methods and treatment options, survival rates have significantly improved.
Radiation therapy plays an important role in cancer treatment and in some cases it constitutes the first therapy
proposed to the patient. However, ionizing radiations have a gonadotoxic action with long-term effects that
include ovarian insufficiency, pubertal arrest and subsequent infertility. Cranial irradiation may lead to disruption of
the hypothalamic-pituitary-gonadal axis, with consequent dysregulation of the normal hormonal secretion. The
uterus might be damaged by radiotherapy, as well. In fact, exposure to radiation during childhood leads to altered
uterine vascularization, decreased uterine volume and elasticity, myometrial fibrosis and necrosis, endometrial atrophy
and insufficiency. As radiations have a relevant impact on reproductive potential, fertility preservation procedures
should be carried out before and/or during anticancer treatments. Fertility preservation strategies have been employed
for some years now and have recently been diversified thanks to advances in reproductive biology. Aim of this paper is
to give an overview of the various effects of radiotherapy on female reproductive function and to describe the current
fertility preservation options.
Keywords: Radiotherapy, Radiation, Infertility, Fertility preservation
Introduction
In modern society people are frequently exposed to differ-
ent types of radiations and this exposure comes form
different sources. It could be either related to everyday life
(e.g. televisions, mobile phones, computer devices, occupa-
tional equipment) or to the necessity of medical care (e.g.
diagnostic imaging, interventional radiology procedures,
anticancer therapy). Usually radiations are divided into two
big subgroups, ionizing and non-ionizing, depending on
the energy of the radiated particles.
Non-ionizing radiations
These type of radiations are basically electromagnetic fields
(EMFs) that do not have enough energy to release elec-
trons (nonionizing), but are able to excite the movement
of an electron to a higher energy state. Several classification
of EMFs have been proposed, but generally 4 big
subgroups are recognized [1, 2]:
(i) extremely low frequency EMFs that have
frequencies below 300 Hz (military equipment,
railroads)
(ii) intermediate frequency EMFs characterized by
frequencies ranging from 300 Hz to 10 MHz
(televisions, computer monitors, industrial cables)
(iii)hyper frequency EMFs characterized by frequencies
ranging from 10 MHz to 3000 GHz (mobile
phones, radio)
(iv) static EMFs that have zero frequency (MRI,
geomagnetism)
The biological reaction of the human body to EMFs is
still open to discussion, given the fact that many factors
can influence the degree to which people may be affected
(gender, body mass index, bone density, period of life,
frequency and duration of the exposure) [3, 4]. EMFs have
a high penetration power that could have disastrous con-
sequences on tissues characterized by high concentrations
of ions and electrons. Essentially the effects of non-ioniz-
ing radiations can be divided into thermal effects, caused
by the heat generated by EMFs on a specific area, and
non thermal effects, related to the absorption of the
* Correspondence: [emailprotected]
1Department of Morphology, Surgery and Experimental Medicine, University
of Ferrara, via L. Borsari, 46, 44121 Ferrara, Italy
2Faculty of Medicine, University of Geneva, Geneva, Switzerland
Full list of author information is available at the end of the article
The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Marci et al. Reproductive Biology and Endocrinology (2018) 16:112
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mailto:[emailprotected]
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energy of the radiation [5]. Several studies have been pub-
lished about the cytotoxicity of non-ionizing radiations,
but most of them are based on animal models (rats) or on
cell line cultures (fibroblasts, melanocytes, lymphocytes,
monocytes, muscular cells) [6]. Concerning their effect on
the female genital system, different studies on mice have
shown that EMFs are able to prevent the formation of an-
tral follicle [7], to inhibit ovulation and to reduce the total
number of corpora lutea [8] and given their capacity to ex-
tend the lifetime of free radicals they favor cell apoptosis
by increasing the oxidative stress resulting in DNA dam-
age [9]. Some authors also observed that mice exposed to
non-ionizing radiation have an increased number of mac-
rophages in granulosa cells and lipid drops in theca cells
[10]. Combined with the fact that an elevated number of
macrophages has also been found in rats growing follicles
and corpora lutea, some authors postulate that EMFs ex-
posure could accelerate apoptosis in ovarian cortical tissue
(responsible for oocytes degeneration) [11]. Some studies
conducted on pregnant women have focused on the effect
of occupational exposure to video display terminals and
pregnancy outcome: an elevated abortion rate and an
increased number of birth defects have been found [12, 13].
However, these results need to be carefully considered,
because controversial conclusions have been obtained on
animal models [14].
Ionizing radiations
These are high energy radiations that are capable to
knock electrons off an electron shell leaving the atoms
with a net positive charge (ionization). The biological
consequence on human cells of this electron strip is dir-
ect or indirect damage of cells DNA. In case of a direct
damage, the displaced electron breaks the DNA strand,
where in case of an indirect damage the electron reacts
with a water molecule resulting in the creation of free
radicals that in the end damage the cells DNA. A
double-strand DNA break allows the potential for incor-
rect DNA repair leading to cell death or for symmetrical
translocation, which could lead to the expression of an
oncogene during cell replication or to abnormal division
in gonads with potential hereditary disorders. The effects
of ionizing radiations can be divided into two types:
(i) deterministic effects, which are dose-dependent.
They take place only once the threshold has been
exceeded and cause a functional impairment of a
tissue/organ (e.g. impaired fertility related to altered
ovarian function);
(ii) stochastic effects, which are the result of
symmetrical translocation during cell replication. In
this case there is no threshold level, but the odds of
a stochastic effect to occur increases linearly with
the dose (linear no-threshold hypothesis).
Charged particles, X-rays and gamma-rays represent
ionizing radiations commonly used in medical care
(diagnostic imaging and procedures, radiotherapy).
Given the extent of the topic, this review is focused on
the most relevant clinical effects of radiotherapy on
female fertility and on possible options for fertility pres-
ervation in young cancer survivors.
Radiation therapy
In Europe, 130,500 new cancer diagnoses (non-melanoma
skin cancers being excluded) are made per year in pre-
pubertal children and adolescents. The most common
types of cancer occurring in this group of patients include
lymphomas (21%), melanomas (15%), cancers of the male
genital system (11%), cancers involving the endocrine sys-
tem (11%) and cancers of the female genital tract (9%)
[15]. Nowadays, radiotherapy represents a cornerstone in
cancer treatment and, in some cases, constitutes the first
therapy proposed both to adolescents and young women
(< 45 years old) with different tumors (e.g. sarcomas, me-
dulloblastomas, advanced cervical cancer, rectal cancer,
anal cancer and Hodgkins lymphomas) [16, 17]. Several
types of cancer may require radiation therapy before or
after surgery. In women, pelvic irradiation can be recom-
mended in case of cervical cancer, endometrial cancer,
bladder cancer and rectal cancer, where cranio-spinal ir-
radiation can be useful in case of central nervous system
cancers or haematological malignancies (e.g. Hodgkins
disease). Total body irradiation is often required before
bone marrow transplantation in Hodgkins disease [18].
The impact of irradiation on reproductive potential
depends on several factors, such as age of the patient, ir-
radiation field, type, dose and duration of the treatment
[19]. Pelvic irradiation affects both the ovary and the
uterus and cranial irradiation could affect the
hypothalamic-pituitary-gonadal axis. Even if reproduct-
ive organs dysfunctions following radiation may be tem-
porary, the recovery is often unpredictable and in some
cases the damage could be permanent [20].
Ovarian effects
At birth, female ovaries contain approximately 1000,000
non-renewable primordial follicles, the number of which
declines over time, primarily through apoptosis and atresia
[9]. With age the number of human oocytes peaks at 67
million during fetal life (around midgestation) and de-
creases progressively in quantity and quality and does not
regenerate. Approximately 12 million oocytes are present
at birth, 30,000050,0000 at puberty, and 1000 at 51,
which is the average age of menopause [21, 22]. Quantity
and quality of a womans oocytes can be influenced by sev-
eral factors including genetics, lifestyle, environment,
medical procedures and diseases (e.g. endometriosis, ovar-
ian surgery, chemo- and radiotherapy).
Marci et al. Reproductive Biology and Endocrinology (2018) 16:112 Page 2 of 12
During radiotherapy, besides the tumor itself, the radi-
ation field may also include healthy tissues close to the
tumor that are unavoidably exposed to radiations. Although
in some tissues the damage is reversible, in the ovary it is
progressive and permanent. Radiation therapy is commonly
applied because of its ability to control cell growth. Gener-
ally, cells with high mitotic activity and active DNA replica-
tion are more vulnerable to radiation-induced damage,
whereas those with low mitotic division rates appear to be
more resistant to it. However, oocytes seem to be an excep-
tion to this general rule: although arrested at the diplotene
stage of the first meiotic division, they are extremely sensi-
tive to radiations. In the past it was thought that the oocyte
was not able to repair the genomic damage induced by
ionizing radiations because of a lack in DNA repair mecha-
nisms. However, recent studies conducted on animal
models, have shown that mammalian oocytes have the en-
zymatic repair capacity to face and correct DNA modifica-
tions and that their radiosensitivity is closely linked to their
degree of development [23, 24]. Human oocytes also
express different DNA repair genes [25], but their function
in the repair of radiation-induced genomic damage is still
unclear. Indeed, radiotherapy has a profound impact on
ovarian function, characterized by follicular atrophy and
reduced follicle stores. This can hasten the natural decline
of follicles number that therefore leads to impaired ovarian
hormones production, uterine dysfunction due to inad-
equate estrogen exposure, early menopause and infertility
[22, 26, 27]. The extent of the damage that occurs in the
ovary depends on several factors such as age of the patient
(the younger is the patient at the time of radiation, the
greater is the damage), exposure dose, exposure time and
eventually associated chemotherapy [28]. In prepubertal
age the gonads are extremely vulnerable to radiations [22,
29]; it is estimated that 2 Gy of radiation would destroy
half of immature oocytes [30], while 2550 Gy would pro-
duce infertility in a third of young women and in almost all
women over 40 years of age [3134] (Table 1).
Nevertheless, if only one side of the ovary is irradiated,
ovarian dysfunction would occur in only half of all
patients [35]. Furthermore, the risk of ovarian damage
induced by gonadal tissue radiation exposure can be
augmented when combined with alkylating chemother-
apy drugs such as cyclophosphamide [36].
Ovarian reserve assessment
Ovarian reserve testing represents a cornerstone in coun-
seling and selection of treatment in all patients who under-
went gonadotoxic regimens. The ideal ovarian reserve test
should be non-invasive, affordable, reproducible, rapidly in-
terpretable with high specificity and little inter/intracycle
variability. At the present time, there is no perfect test and
common methods to assess the ovarian reserve include:
i) dosage of follicle-stimulating hormone (FSH) and
estradiol (E2) levels at day 3 of the menstrual cycle
ii) dosage of anti-mullerian hormone (AMH),
iii) transvaginal ultrasound (antral follicle count).
Day 3 FSH In case of impaired fertility, FSH is normally
elevated. FSH an indirect measure of the ovarian reserve
and is based on the negative feedback of FSH pituitary
secretion. It has a higher inter/intracycle variability and
many studies agree that a normal FSH determination
does not exclude ovarian dysfunction [37]. AMH meas-
urement and antral follicle count (AFC) evaluation have
been shown to have a higher predictive value when com-
pared to day 3 FSH. To enhance its sensitivity it could
be combined with E2 levels measurement [38].
AMH AMH is produced by the granulosa cells of early
developing follicles and inhibits the transition from the
primordial to the primary follicular stage. Its level is
relatively independent of circulating gonadotropins con-
centration, allowing untimed testing. AMH production
declines with age and results undetectable after meno-
pause [39, 40]. Among all ovarian tests it is considered
the most stable throughout the menstrual cycle [4043].
However, this issue remain still debated because some
intracycle fluctuations have been reported in several
Table 1 Radiation doses and risk of gonadal failure (High risk: > 80% sterilized; Mild risk: 2080% sterilized; Low risk: < 20% sterilized) Radiation Doses Risk of Ovarian Failure Prepubertal girls 1540 years > 40 years
Pelvic/abdominal irradiation
< 6Gy Mild risk No adverse effects No adverse effects 15 Gy High risk Low risk Mild risk 2550 Gy High risk Mild risk High risk 5080 Gy High risk Mild risk High risk > 80 Gy High risk High risk High risk
Cranio-spinal irradiation > 25 Gy Mild risk Mild risk Mild risk
Total body irradiation High risk High risk High risk
Marci et al. Reproductive Biology and Endocrinology (2018) 16:112 Page 3 of 12
studies [4446]. The main disadvantage of AMH testing is
mainly related to the lack of a standardized international
assay method that leads to high intra/inter-assay variabil-
ity (laboratory differences, sample stability and storage is-
sues) [47]. Recently, in order to overcome this limitation
and to improve precision and sensitivity of the test, new
automated AMH assay platforms have been developed
and are currently used in Europe and Asia [48].
Antral follicle count (AFC) Numerous studies have
demonstrated the usefulness of transvaginal ultrasound,
particularly at day 3 of the menstrual cycle. It provides
two essential parameters that significantly correlate with
ovarian reserve and fertility [49]: the measurement of
the ovarian volume and the AFC, which defines the
number of follicles between 2 and 10 mm in diameter.
AFC is easy to carry out and provides immediate results
with a good intercycle reliability. However, the precision
of the measurement could be compromised by several
factors such as differences in the criteria used for the
evaluation of antral follicles, differences in ultrasound
technology (resolution, 2D vs 3D) and ultrasound scans
carried out by multiple sonographers with different de-
gree of training [50, 51].
Nowadays, AMH testing represents the preferred bio-
marker to asses the ovarian reserve. In patients who
underwent radiation therapy, AMH dosage before and
after treatment is considered a useful tool in the selec-
tion of future fertility treatment. However, it should be
taken into account that up to now there is no evidence
that AMH pre-treatment levels can predict subsequent
fertility and that the effect of different types of malignan-
cies and treatment regimens on AMH level may vary
considerably. Future research in this field is needed.
Uterine effects, pregnancy outcomes and neonatal
comorbidities
Besides ovarian failure, also the uterus could be affected by
radiotherapy and the consequent radiation-induced dam-
age could be irreversible. In fact, exposure to radiation dur-
ing childhood leads to altered uterine vascularization,
decreased uterine volume and elasticity, myometrial fibro-
sis and necrosis, endometrial atrophy and insufficiency.
Moreover, ulceration and necrosis last several months, and
the damaged tissue may be replaced by dense collagen
deposition. The cervix gets quite atrophic and loses its
elasticity, especially in older patients [52, 53]. In a study
published by Larsen et al., the authors report that cytotoxic
treatment during childhood does not affect adult uterine
size, but, in contrast, uterine irradiation at young age re-
duces adult uterine volume. The reported results indicate
that cancer survivors with spontaneous menstrual cycles
have a diminished ovarian reserve. Therefore, reproductive
dysfunctions may occur much earlier than anticipated [54].
In adults, an exposure to Total Body Irradiation (TBI) of
12 Gy is associated with significant uterine damage. During
childhood, radiation doses of > 25 Gy focused directly to
the uterus appear to induce irreversible damage and so far,
there is no consensus on the dose of radiation to the
uterus, above which a pregnancy would not be sustainable
[55]. In 2014 Teh et al. have suggested that patients receiv-
ing > 45 Gy during adulthood and > 25 Gy in childhood
should be counseled to avoid pregnancies [52]. In fact,
radiation could affect embryo implantation and, at the
present time, uterine transplantation represent the only
possible option for patients with childbearing desire, who
underwent uterine radiation. Actually uterine transplant-
ation is not routinely performed for medical and ethical
reasons and until now it has been described only one live
birth after this procedure [56]. Irradiation may lead to pla-
cental disorders (e.g. placenta accreta or placenta percreta),
fetal malposition, preterm labor and premature delivery
[56, 57]. Although rare, these alterations in uterine archi-
tecture can also increase the risk of uterine rupture [58].
Norwitz et al. showed reduced uterine volume and im-
paired uterine blood flow in a young woman who had a
uterine rupture at 17 weeks of gestation. The patient had a
remote history of total body irradiation for bone marrow
transplantation for childhood leukemia. Although some
radiation effects were observed, the severity of injuries was
inferior as expected due to low doses of irradiation [59].
Mueller et al. compared the obstetric outcomes among fe-
male survivors of childhood and adolescent cancer to those
of women without a history of cancer. The children of can-
cer survivors were more likely to be preterm and to weigh
less than 2500 g, while the risk of malformations or death
were not increased [60]. Several studies demonstrated an
increased risk of adverse pregnancy and neonatal outcomes
associated with prior history of abdominal irradiation [22].
In a study published by Chiarelli et al. cancer patients re-
ceiving abdominopelvic radiation with or without surgery
were more likely to have low birth weight infants and pre-
mature low birth weight infants, with higher perinatal mor-
tality rates when compared to patients treated with surgery
alone. Additionally, the likelihood of perinatal infant mor-
tality and low birth weight were significantly related to the
radiation dose [61]. The results reported by Signorello and
colleagues in 2006 are in line with these findings. Authors
report that the offspring of patients treated with high-dose
radiotherapy have an increased risk of preterm delivery,
low birth weight and small-for-gestational-age births when
compared to offspring of patients who did not undergo
radiotherapy [62]. In addition, in 2009 the British Cancer
Survivor study concluded that female survivors of child-
hood cancer treated with abdominal radiotherapy have a
3-fold increased risk of preterm delivery, a 2-fold increased
risk of low birth weight and a small increased risk of mis-
carriage [63]. Green et al. reviewed the pregnancy outcome
Marci et al. Reproductive Biology and Endocrinology (2018) 16:112 Page 4 of 12
among childhood cancer survivors treated with radio- or
chemotherapy [64]. One thousand nine hundred fifteen fe-
males with 4029 reported pregnancies were considered. Pa-
tients, whose ovaries where in the radiation field or close
to it or shielded, showed a higher risk of miscarriage, al-
though not statistically significant. Furthermore, the off-
spring of patients who received pelvic irradiation were
more likely to weight < 2500 g at birth. In addition, several
studies conducted on female survivors of Wilms tumor
(WT) who underwent radiotherapy during childhood, ana-
lyzed the effect of low-dose flank irradiation on pregnancy
and neonatal outcomes and demonstrated that they are at
increased risk of preterm labor, fetal malposition, and pre-
mature delivery of low birth weight infants [6570]. A re-
cent study published in 2010 evaluated the impact of prior
radiotherapy for unilateral WT on pregnancy outcomes
[71]. Green and colleagues report that women who re-
ceived flank radiation therapy during childhood are at in-
creased risk of hypertension complicating pregnancy, fetal
malposition, premature labor and that the offspring of
these women are at risk for low birth weight at delivery(<
2500 g) and premature birth (< 37 weeks of gestation) [64].
Hypothalamic-pituitary-gonadal axis effects
Brain tumors constitute approximately 17% of all malig-
nant tumors in patients younger than 20 years of age
[72] and radiotherapy plays an important role in the
curative and palliative treatment of patients with primary
and/or metastatic brain tumors [73]. As survival rates of
patients with childhood brain tumors have increased to
75%, the side effects of cancer treatment are of particular
importance [74]. Radiations induced anterior pituitary
hormone deficiency represents the most common irre-
versible and progressive long-term complication of anti-
cancer treatment and up to 50% of childhood cancer
survivors will deal with an endocrinopathy requiring
strict follow up to minimize the subsequent effects on
growth, bone density, pubertal development and quality
of life [75]. The hypothalamic-pituitary-gonadal axis
(H-P-G axis) is a hormone system extremely vulnerable
to radiotherapy; indeed, both brain surgery and cranial
radiation could determine gonadotropin deficiency [76].
The exact mechanism by which radiations influence the
H-P-G axis is still poorly understood. A direct injury to
H-P cells, rather than reduced hypothalamic blood flow
seems to be the major cause of H-P-G axis dysfunction
[77]. This hypothesis is supported by the fact that anter-
ior pituitary hormone deficiencies follow a predictable
pattern [78] where the growth hormone (GH) axis is the
more radiosensitive (GH levels are reduced more than
90% after irradiation), followed by gonadotropin, adreno-
corticotropic hormone (ACTH) and thyroid-stimulating
hormone (TSH) axis. This is consistent with a direct
radiation-induced selective hypothalamic neuronal and
pituitary cell damage rather than a universal insult to the
H-P axis [79, 80]. Furthermore, the evolution of these hor-
mone deficiencies in time suggests possible delayed effects
of radiotherapy on the development of secondary pituitary
atrophy after hypothalamic damage [8183].
The degree of neurotoxicity of radiation depends on
total radiation dose, fraction size and duration of the radi-
ation schedule. These variables determine the so called
biological effective dose and as it increases, so does the
risk of H-P axis dysfunction [81, 8385]. To minimize the
risk, current irradiation regimens call for several fractions
(with no more than 2Gy per fraction) spread out several
days/weeks (with no more than 5 fractions per week) [86].
It is well known that the secretion of gonadotropin-re-
leasing hormone (GnRH), FSH, luteinizing hormone (LH),
estradiol, progesterone, and prolactin follows a pulsatile
rhythm which is responsible for the reproductive hormo-
nal environment [87]. Radiation-induced gonadotropin de-
ficiency depends on irradiation dose and tumor location
and has a wide spectrum of clinical manifestations, ran-
ging from subclinical (detected only with GnRH testing)
to severe forms. Clinically, significant gonadotropin defi-
ciency is usually a late complication with a cumulative in-
cidence of 2050% on long-term follow-up, regardless of
whether radiation was administered in childhood or dur-
ing adulthood [86]. However, disturbances of the pulsatile
rhythm of FSH/LH production can affect fertility and li-
bido and can disrupt the menstrual cycle.
Precocious puberty can occur after radiation doses of
< 30 Gy and it may be caused by a disinhibition of cor-
tical influence on the hypothalamus. Studies on rats have
shown that low irradiation doses (56 Gy) are associated
with lower levels of inhibitory transmitter
-aminobutyric-acid (GABA) and higher expression of
GnRH in the pre-optic area [88, 89]. Therefore,
radiation-induced early puberty may be the result of a
direct damage to the inhibitory GABA system with sub-
sequent premature activation of GnRH neurons. In
humans low irradiation doses (1824 Gy) are associate
with precocious puberty only in girls, where higher
doses (2550 Gy) affect both sexes equally [90, 91].
Hyperprolactinemia is another possible consequence
of radiation therapy and is manly related to decreased
levels of the inhibitory neurotransmitter dopamine. Mild
to modest increase in PRL levels are mostly reported in
adult females (20 to 50%) after low radiation doses, but
also children can be affected (5% of the cases) [92]. Most
of the time elevated levels of PRL do not have clinical
manifestation, but occasionally may be responsible for
amenorrhea and galactorrhea in women and for delayed
puberty in children.
Despite optimal medical and surgical management of
pituitary tumors, ovulation-induction therapy with go-
nadotropins is often required in these women [93]. In a
Marci et al. Reproductive Biology and Endocrinology (2018) 16:112 Page 5 of 12
recent questionnaire-based study published by Koustenis
et al., the authors evaluated fertility characteristics in brain
tumor survivors treated with brain irradiation. They found
that patients receiving 30 Gy, when compare to those
who received 1829 Gy or 017 Gy, reported less preg-
nancies and showed higher rates of permanent amenor-
rhea and infertility [94]. In a study published in 2002,
Green et al. showed that the relative risk of miscarriage is
increased in women who received cranial or craniospinal
irradiation and in those patients where the ovaries were
within or near the radiation field or within 5 cm of the
field edge. On the other hand, the risk of miscarriage ap-
pears not to be higher when the ovaries are shielded [64].
Furthermore, these data also suggest that spinal irradi-
ation could harm the pregnancy outcome, but further
studies are needed to confirm these results.
Fertility preservation options
In patients diagnosed with cancer the main concern is, ob-
viously, the treatment of the disease. However, given the
increased number of young patients that undergo antican-
cer therapy, long-term side effects, including infertility,
should be taken into account [19]. Before anticancer treat-
ment, oncologists should discuss with their patients the
consequences of surgery, radio- or chemotherapy, the in-
fertility risk and the fertility preservation options, in order
to established an effective, patient-tailored fertility preser-
vation program [55]. Both chemo- and radiotherapy have
a relevant impact on reproductive potential, thus fertility
preservation procedures should be carried out before and/
or during these treatments. Fertility preservation requires
a team effort. It should be managed by an oncology centre
that has built a close collaboration between oncologists,
fertility specialists, psychologists, and primary care physi-
cians to allow early discussion and to offer a full range of
options to these patients. Which method of fertility pres-
ervation a woman should choose depends on several fac-
tors, including the type of disease, the treatment required,
the age of the patient, whether she has a long-term part-
ner, and whether treatment can be delayed [95]. Around
7075% of young cancer survivors are interested in
parenthood, but the percentage of patients who undergo
fertility preservation techniques before or during cancer
treatment is s
