REFERAT

Endometriosis In Pregnancy

Written by :

Dennely Yulisa 2016.061.098

Willy Wirawan Guslianto 2016.061.120

Kevin Wibawa 2016.061.161

Maria Yosephine 2016.061.117

Supervised by :

dr. Arie Adrianus Polim, D.MAS, Sp.OG-KFER

DEPARTMENT OF OBSTETRIC AND GYNECOLOGY

FACULTY OF MEDICINE ATMA JAYA CATHOLIC UNIVERSITY OF INDONESIA

APRIL 23rd 2018 – JULY 7th 2018

 FOREWORD

First of all, we thank God for only by His grace and His blessings we were able to
finish this paper entitled “Endometriosis in Pregnancy”, which is one of the assignments in
the Department of Obstetrics and Gynecology, Faculty of Medicine, Atma Jaya University.
We would also like to thank our supervisor, dr. Arie Adrianus Polim, D.MAS, Sp.OG (K),
who provided insight and expertise greatly that helped and supported us during the making of
this paper. The completion of this paper could have never been accomplished without support
and encouragements from our dear families, colleagues, and other parties that could not be
mentioned one by one.

We hope this paper could give useful information for the readers about endometriosis
in pregnancy. We realize this paper is far from perfect and has several limitations, therefore
we apologize for any mistakes encountered. We are hoping for future suggestions and critics
to help improve this paper in the future being.

Jakarta, May 2018

Authors

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 TABLE OF CONTENT

FOREWORD..................................................................................................................................i

TABLE OF CONTENT.................................................................................................................ii

LIST OF FIGURES......................................................................................................................iii

CHAPTER I : INTRODUCTION ..............................................................................................1

1.1. Background..............................................................................................................1
1.2. Aim of Study............................................................................................................2
1.3. Benefit of Study.......................................................................................................2

CHAPTER II : LITERATURE REVIEW...................................................................................3

2.1. Endrometriosis.........................................................................................................3
2.1.1. Definition of Endometriosis.........................................................................3
2.1.2. Etiology of Endometriosis............................................................................3
2.1.3. Epidemiology of Endometriosis in Pregnancy.............................................4
2.1.4. Risk Factor of Endometriosis in Pregnancy.................................................5
2.1.5. Pathophysiology of Endometriosis in Pregnancy.........................................6
2.1.6. Clinical manifestation of Endometriosis in Pregnancy..............................10
2.1.7. Diagnostic Evaluation................................................................................11
2.1.8. Treatment of Endometriosis in Pregnancy.................................................15
2.1.9. Prognosis of Endometriosis in Pregnancy..................................................16
2.1.10. Complication of Endometriosis in Pregnancy............................................18

CHAPTER III : CONCLUSION................................................................................................23

REFERENCES….........................................................................................................................24

ii
 LIST OF FIGURES

Figure
1. ...................................................................................................................................10
Figure 2.
...............................................................................................................................................
13

iii
 CHAPTER I

INTRODUCTION

1.1. BACKGROUND

Endometriosis is defined as the presence of endometrial-like tissue (stroma

and glands) outside the uterus, which induces a local inflammatory response. It is an
estrogen-dependent chronic condition that affects women of fertile age, and is
associated with pelvic pain and infertility. However, in recent years, evidence is
emerging in support of a relevant impact of endometriosis not only in reducing
fertility but also in affecting the pregnancy outcome.
Different mechanisms including endocrine/inflammatory balance, bleeding
from endometriotic implants, molecular and functional abnormalities of the eutopic
endometrium, defective deep placentation and decidualization of the endometriotic
tissue due to changes of the hormonal milieu that characterizes pregnancy are thought
to be involved. Noteworthy, this rising concept is in contrast with the historical
assumption that pregnancy may have a positive effect on endometriosis and its
symptoms due to anovulation and amenorrhea preventing bleeding of endometriotic
tissue but also to different metabolic, hormonal, immune and angiogenesis changes
related to pregnancy.
1.2. AIM OF STUDY

1.2.1 General Aim

To understand endometriosis in pregnancy.

1.2.2. Particular Aim

To understand patophysiology of endometriosis in pregnancy
To understand how to diagnose endometriosis in pregnancy
To understand treatment of endometriosis in pregnancy
To understand complication and prognosis of endometriosis in pregnancy

1.3. BENEFIT OF STUDY

1.3.1. Benefit for Educational Institutions

Authors hope that this study can be used as resources for college and medical
school students to deepen their knowledge.

1
1.3.2. Benefit for Public Services
Authors hope that this research can be a source of information for the public to
be more alarmed about endometriosis in pregnancy.
1.3.3. Benefit for Research Development
Researchers hope that this study can be used as a source of literature for other
research, particularly regarding endometriosis in pregnancy.

2
 CHAPTER II

LITERATURE REVIEW

2.1. ENDOMETRIOSIS

2.1.1. Definition of Endometriosis

Endometriosis is defined as the presence of endometrial-like tissue
(stroma and glands) outside the uterus, which induces a local inflammatory
response.1,2 It is a condition when the tissue that makes up the uterine lining is
present on other organs inside the body. It is an estrogen-dependent chronic
condition that affects women of fertile age, and is associated with pelvic pain
and infertility.3 Different mechanisms including endocrine/inflammatory
balance, bleeding from endometriotic implants, molecular and functional
abnormalities of the eutopic endometrium, defective deep placentation and
decidualization of the endometriotic tissue due to changes of the hormonal
milieu that characterizes pregnancy are thought to be involved.4

Majority of endometriosis found in the lower abdomen, or pelvis, but

can appear anywhere in the body including the anterior and posterior cul de
sacs.5 Endometriosis in the ovary appears as a cystic collection known as an
endometrioma. Other common sites include the most dependent parts of the
pelvis such as the posterior uterus and broad ligaments, the uterosacral
ligaments, fallopian tubes, colon, and appendix. Although not commonly
found, endometriosis has been identified as far away as the breast, lung, and
brain.6 Women with endometriosis often have lower abdominal pain, pain with
periods, or pain with sexual intercourse, and may having a hard time getting
pregnant. On the other hand, some women with endometriosis may not have
any symptoms at all.

2.1.2. Etiology of Endometriosis

There are three main theories about the etiology of endometriosis. The
Halban theory proposes that endometrial tissue is transported via the
lymphatic system to various sites in the pelvis, where it grows ectopically.
Meyer proposes that multipotential cells in peritoneal tissue undergo
3
 metaplastic transformation into functional endometrial tissue. Finally,
Sampson suggests that endometrial tissue is transported through the fallopian
tubes during retrograde menstruation, resulting in intra-abdominal pelvic
implants.
A prevailing theory is that women who develop endometriosis may
have an altered immune system that is less likely to recognize and attack
ectopic endometrial implants. These women may even have an increased
concentration of inflammatory cells in the peritoneum that contribute to the
growth and stimulation of the endometrial implants. Endometrial implants
cause symptoms by disrupting normal tissue, forming adhesions and fibrosis,
and causing severe inflammation. Interestingly, the severity of symptoms
does not necessarily correlate with the amount of endometriosis. Women
with widely disseminated endometriosis or a large endometrioma may
experience little pain, whereas women with minimal disease in the cul-de-sac
may suffer severe chronic pain.6
Another possible explanation is that the cells from the lining of the
uterus travel through the blood vessels or through the lymphatic system to
reach other organs or body areas. Also, endometriosis can spread at the time of
surgery. For example, a woman with endometriosis that undergoes a cesarean
section could inadvertently have some endometriosis cells attach to the
abdominal incision so that she has endometriosis in the scar from the surgery.

2.1.3. Epidemiology of Endometriosis in Pregnancy

The estimated prevalence of endometriosis is between 10% and 15%.
Because surgical confirmation is necessary for the diagnosis of
endometriosis, the true prevalence of the disease is unknown. It is found
almost exclusively in women of reproductive age, and is the single most
common reason for hospitalization of women in this age group.
Approximately 20% of women with chronic pelvic pain and 30% to 40% of
women with infertility have endometriosis.6

Ovarian endometrioma represents a common finding in women

affected by endometriosis, with an estimated prevalence of 30–40%. Besides
corpus luteal cysts, adnexal masses are detected in 0.5 –1.2% of pregnancies:
of these, 11% are endometriomas, while the reported rate of ovarian cancer is

4
 1%. Of the latter, a proportion of about 51% is epithelial (both invasive and
borderline) and 39% are germ cell tumors, mainly dysgerminomas and
malignant teratomas, in line with the young age of pregnant woman.7

2.1.4. Risk Factor Endmetriosis in Pregnancy

There are several risk factor associated with endometriosis :

Menstrual Factors

Earlier age at menarche and shorter menstrual cycles have both been
reported to influence the risk of endometriosis. 8 Early age at menarche (<12
years) may incrase frequency and duration of exposure to retrograde
menstruation and may also reflect an altered hormonal environment.

In Utero Environment

The in utero environment may reflect maternal exposures and

hormonal and inflammatory states that may have important implications for
disease risk later in life. Birth weight may reflect the maternal hormonal
milieu or adequecy of uteroplacental blood flow during the pregnancy. Women
born at lower birth weight (<5.5 pounds) were at a greater risk of
endometriosis compared to normal or high birth weight women (7.0-8.4
pounds). Decreased elasticity of the pelvic vessels and pathologic
development of connective tissue associated with low birth weight may
hamper menstrual flow throughout the cervix. This may increase in return the
volume of retrograde menstruation favoring the development of endometriotic
lesions.9

Family History

Many subsequent pedigree studies have supported the hypothesis that

the development of endomteriosis has a genetic basis. First degree relatives of
women with endometriosis have been reported to have endometriosis 4 to 8
times that of the general population. 10 There is a 11.6-fold increase in the risk
of endometriosis among sisters and 8-fold increase among mothers of those
diagnosed with endometriosis.

5
 Smoking and Environmental Toxin

Women that is not smoking at reproductive age can have a greater

reduction in the odds of endometriosis compared to the women that smokes in
the reproductive age. It is estimated that a person who smokes a pack of
cigarettes per day takes in about 4.3 pg of polychlorinated dibenzodioxins/kg
body weight/day. Based on early animal studies suggesting that
polychlorinated biphenyl (PCB) or dioxin exposure may influence
endometriosis risk. The other environmental toxin associated with
endometriosis are polychlorinated dibenzo-p-dioxin (PCCD), polychlorinated
dibenzo-furans (PCDF), dioxin like PCB, and coplanar PCB.11

Dietary Factors

Recently, the role of nutrition in maintenance as well as development

of endometriosis has been considered as a matter of interest. The risk of
developing endometriosis reduces with increasing fish, fish oil, low fat dairy
product, fruits, whole grain consumption. Consuption of these diets caused
reduced fat as well as reduced production of exogenous estrogen. 12 On the
other hand, consumption of foods such as eggs, bacon, and red meat is
associated with increased risk of endometriosis

2.1.5 Pathophysiology of Endometriosis in Pregnancy

Endometrial implants can occur throughout the body but generally

occur in the pelvic and abdominal cavities. Cyclic changes depend on the
blood supply of the implants and the presence of glandular and stromal cells.
Given that blood supply is sufficient, the ectopic endometrium proliferates,
break down, and bleeds with the normal menstrual cycle. The bleeding causes
inflammation, trigerring a cascade of cellular inflammatory mediators,
including cytokines, chemokines, growth factors, and protective factors such
as secretory leukocyte protease inhibitor and superoxide dismutase. 13 The
inflammation may lead to fibrosis, scarring, adhesions, and pain. There are
some mechanism how endometriosis can develop :

6
Endometrial Cell Survival

The endometrium from women with endometriosis shares certain

alterations with ectopic lesions that are not observed in the endometrium from
healthy women. Up-regulation of the antiapoptotic gene BCL-2 has been
shown in eutopic and ectopic endometrium from affected women.14 In addition
to decreased apoptosis, enhanced proliferation may confer a selevtive survival
advantage to the endometrium of women predisposed to endometriosis.

Altered Hormonal Milieu : Estrogen Dependence and P Resistance

Hormonal alterations may influence the ability of endometrial cell to

proliferate, attach to the mesothelium, and/or evade immune-mediated
clearence. The concept of endometriosis as an estrogen-dependent disorder is
well supported by molecular evidence. A striking finding in endometriosis
tissue is the increased expression of the aromatase enzyme and decreased
expression of 17β-hydroxysteroid dehydrogenase (17β-HSD) type 2.15 The
sum consequence of this differential expression profile is a marked increase in
the locally bioavaible E2 concentration. E2 stimulates the production of
prostaglandin E2, (PGE2) which further stimulates aromatase activity.

In addition to estrogen dependence, there is increasing evidence to

support a profile of P resistance in pathophysiology of endometriosis.
Endometriotic lesions exhibit an overall reduction in P receptor expression
relative to eutopic endometrium.

Evasion From Immune Clearence

Normally, refluxed endometrial tissue is cleared from the peritoneum

by the immune mechanism and the dysregulation of thix clearence mechanism
has been implicated in the predisposition to implantation and growth of
endometrial cells. The eutopic endometrium from women with endometriosis
was found to be more resistant to lysis by natural killer (NK) cells than the
eutopic endometrium from women without disease. Subsequent studies
identified the constitutive shedding of intercellular adhesion molecule-1
(ICAM-1) by endometrial stromal cells (ESCs) from women with
endometriosis as the potential mechanism by which these cells escape NK

7
cell-mediated clearence. Impaired NK cell and compromised machrophage
function may confer an immune-privileged status on the refluxed endometrial
cells, thereby predisposing to disease.16

Endometrial Cell Attachment and Invasion

A heritable or acquired condition of the peritoneum may predispose to

the attachment and transmesothelial invasion by refluxed endometrial cells. An
intact mesothelium is likely to act as protective barrier against the
implantation of regurgitated endometrial tissue. Indeed, in vitro studies have
shown that endometrial fragments adhered to the peritoneum only at locations
where the basement membrane or extracellular matrix was exposed owing to
mesothelial layer damage. Menstrual effluent has a harmful effect on the
mesothelium and may autologously induce the local injury that promotes the
implantation of endometrial cells.17 However, the exact factors involved in
mediating mesothelial damage are unknown.

Vasculogenesis and Growth

A rich vascular supply is necessary for the development and sustenance

of endometriotic lesions, particulary in the peritoneal microenvirontment,
which is relatively avascular compared with the eutopic endometrium.
Neuroangiogenesis and capillary recruitment are visiby associated with
endometriotic lesions. Inadditions, nerves frequently accompany angiogenesis
(neuroangiogenesis), likely contributing to the pain associated with this
disorder. Women with endometriosis demonstrated up regulation of tumor
necrosis factor-α (TNF-α), IL-8, and MMP-3. As IL-8 and TNF-α promote
proliferation and adhesion of endometrial cells and angiogenesis, an
overabudance of these cytokines may facilitate growth and local
neurovascularization.18

Endometriosis on Pregnancy

Endometriosis have alterations not only in ectopic but also in the

eutopic endometrium that associated with poor pregnancy outcomes.
Disturbances in women affected potentially related to defects during the peri-
implantation period that may prepetuate throughout pregnancy, including7 :

8
 1. The endometrial resistance to selective actions of progesterone.
Progesterone normally triggers a uterine endometrial response
characterized by transformation of stromal cells into specialized decidual
cells and induces an embryo receptive phenotype. As a consequence of
progesterone resistance, genes critical to embryo implantation, such as
prolactin FOXOA, IGF-II for decidual response or glycodelin for embryo
implantation, are dysregulated in the endometrium of affected women
2. The inflammatory process whose consequences can be manifested both at
endometrial and systemic level. Elevation in maternal systemic
inflammation has been long proposed as the cause of pre-eclampsia or
preterm birth
3. Inadequate uterine contractility. The contractions observed during
menstrual cycle have been termed "endometrial waces" and appear to
involve only the sub-endometrial layer of myometrium. Compared with
controls, patients with endometriosis have been shown to have uterine
contractions with higer frequency, amplitude, and basal pressure tone
4. An increased release of reactive oxygen species and an increased
expression of enzymes leading to the accumulation of free radicals in the
cells. Oxidative stress has been postulated as one of the central phenomena
involved in maternal endothelial dysfunction with consequent negative
obstetric outcomes
5. The alteration in the uterine junctional zone which is the highly specialized
inner third of the myometrium demonstrated to be greater in thickness in
women with endometriosis compared with non-affected patients. A normal
placentation process is characterized by a full conversion of the spiral
arteries into large uteroplacental vessels at the level of junction zone.
Defective placentation is characterized by an absent or incomplete
remodelling of these arteries and the primary site of the vascular
abnormalities responsible for defective placentation.

2.1.6 Clinical Manifestation

The clinical manifestations of endometriosis can be asymptomatic or

mimic other processes (PID, irritable bowel syndrome, ovarian cysts).
Symptoms are variable in frequency and severity and include primary
9
 infertility and pain, dysmenorrhea, dyschezia, dyspareunia, severe menstrual
pain and irregular flow and/or premenstrual spotting, and less commonly,
constipation and abnormal vaginal bleeding.19 If implants are located within
the pelvis they can cause an asymptomatic pelvic mass having irregular,
movable nodules, and a fixed, retroverted uterus. Most symptoms of
endometriosis can be explained by the proliferation, breakdown, and bleeding
of the ectopic endometrial tissue with subsequent formation of adhesions.
Adnexal mass and chronic pelvic pain can also presents in pregnant women
with endometriosis.

In most instances, however, the degree of endometriosis is not related

to the frequency or severity of symptoms. Dysmenorrhea, for example, does
not appear to be related to the degree of endometriosis. With involvement of
the rectovaginal septum or the uterosacral ligaments, dyspareunia develops.
Dyschezia occurs with bleeding of ectopic endometrium in the rectosigmoid
musculature and subsequent fibrosis.

Figure 1. McCance K, Huether S, Felver L, McCance K. Study guide for Pathophysiology, the biologic basis for
disease in adults and children, seventh edition. St. Louis: Mosby; 2015.

Twenty-five percent to 40% of women with infertility have endometriosis. The

link between endometriosis and infertility is strong, yet the degree of disease and
infertility is not as closely associated. That is, women with untreated minimal to mild
10
disease may have high pregnancy rates or may experience infertility. The exact
mechanism for infertility in women with endometriosis is unknown. Infertility may
result from mechanical interference with ovulation or ovum transport through the
fallopian tube because of adhesions and the effects of inflammation and cytokine.

2.1.7 Diagnostic Evaluation

During pregnancy, changes in the dimension and in the appearance of the
endometriotic cyst have been described. Ueda and colleagues observed that during
pregnancy size of the cysts decreased in 52% of the cases, went unchanged in 28%,
and increased in 20%.20 A more recent study reported that the number of
endometriotic cysts was unchanged in 33% of the cases, increased in 8%, reduced in
13%, and in the remaining 46% no cyst could be detected. 21 Different possible
explanations for this phenomenon have been hypothesized. The cessation of menstrual
cycles may be a factor potentially involved in the different endometrioma behavior
during pregnancy. In addition, the peculiar histological characteristics of each
endometrioma are likely related to this variability in modification during pregnancy,
since endometrioma shrinkage only occurs in selected cases.21
It has been suggested that only those covered by endometrium, which is more
prone to decidualization, may undergo shrinkage and even ‘vanishing’. Furthermore,
as mentioned above, pregnancy-related hormonal status may effectively lead to
changes in the histologic, sonographic and molecular appearance referred as
‘decidualization’, which may in some cases resemble malignant ovarian tumors,
potentially leading to an unnecessary surgical intervention. Formal assessment of the
frequency of this phenomenon is lacking, and on the basis of indirect evidence
supporting highly variable estimations, no definitive conclusion can be drawn. 20
Benaglia and coworkers conducted a study in order to assess modifications in number
and size of ovarian endometriomas before and after pregnancy in 24 women who
underwent IVF procedures. Forty endometriomas were identified and no sign of
decidualization of the ovarian cysts was detected. 22
Another study aimed at clarifying the frequency of pregnancies complicated
by ovarian endometriosis and to investigate the size change and outcome of ovarian
endometriosis during pregnancy. Twenty-four women carrying 25 endometriomas
were included in this study and signs of decidualization were seen in 3 cases (12%).
However, ovarian endometriosis in pregnancy is a rare condition with an estimated

11
frequency of about 0.05 –0.5% and literature on decidualized ovarian endometrioma
mainly consists of case reports of three or fewer patients. 23,24
Some larger studies have been recently published to define its peculiar
sonographic appearance.25,26 As borderline tumors and cystadenofibromas,
decidualized endometriomas are difficult to classify since they show sonographic
characteristics common to both malignant and benign adnexal masses. It is likely that
an under-diagnosis of such a transformation should be considered in explaining the
rarity of this event because the ovaries are not routinely evaluated during obstetric
ultrasound. Another possible explanation is the variability in levels and response to
steroid hormones among pregnant women.

Transvaginal sonography
Transvaginal sonography is the gold standard imaging method for the
diagnosis of ovarian endometriomas. A typical sonographic appearance has been
documented in up to 95% of cases, consisting of a round shaped cystic aspect, a
minimum diameter of 10 mm, thick walls, regular margins, homogeneous low
echogenic fluid content, scattered internal echoes and absence of papillae. However,
in 5% of cases, an atypical aspect is detected, which includes anechoic content, solid
appearance, and presence of punctuate echogenic foci within the cystic wall.
Noteworthy is the fact that the performance of ultrasonography in terms of sensitivity
and specificity is much lower during pregnancy. In addition, the potential
decidualization of ovarian endometriomas leads to serious diagnostic challenges. 27–29
Even considering all these studies, it is still difficult to define clear guidelines
for the diagnostic management of such cases. A retrospective study including 18
pregnant patients was the first specifically aimed at describing the ultrasound
characteristics of decidualized endometriomas according to the IOTA (International
Ovarian Tumour Analysis) terminology. The main strength of this study was the
standardized terminology used, although both the small sample size and the
retrospective design have limited its value. Typically, a decidualized endometrioma
appears as a uni- or multilocular cystic mass containing rounded vascularized
papillary projections with smooth contour and with a ground glass or low-level
echogenicity cystic content.

12
Figure 2 Ultrasonographic (a) and histologic (b, low-power magnification) patterns of a
decidualized endometrioma

Papillations have been detected in all cases reported in literature. Their

presence is relevant since papillary projections are a common sign of malignancy,
present both in borderline tumors and in the malignant degeneration of endometriotic
cysts.x The possibility of differentiating malignant papillations from those of
decidualized endometriomas would be crucial to avoid unnecessary surgery during
pregnancy. As mentioned, the different round-shaped sonography appearance
typically observed in benign papillations of decidualized endometriomas is the only
distinguishing sign while papillary projections usually have an irregular surface in
borderline malignancies. The majority of cases showed an increased blood flow at
color Doppler sonography, which therefore cannot be considered reliable in
distinguishing a benign decidualized endometrioma from a malignant adnexal mass.
Contrary to malignant tumors, the presence of septations was uncommon and their
absence could be considered a reassuring sign. The absence of growth in these
patients, followed up with serial sonographic evaluations, might be considered
another reassuring sign, even if the follow-up sonographic examination throughout
pregnancy was not available for all cases. In none of the cases was free pelvic fluid
detected during ultrasonography.30–33

CA125
CA125 levels are not diagnostic in these patients, since it is physiologically
elevated during pregnancy. However, some authors have suggested a potential
diagnostic role for serial CA125 measures or when levels are >1000 U/ml in the

13
second trimester or beyond. Human epididymis protein 4 (HE4) levels have been
found to be significantly lower in pregnant women compared with their
premenopausal counterparts and rarely increased in patients with ovarian
endometriotic cysts.Therefore, the role of a combined assessment of CA125 and HE4
for the differential diagnosis between benign and malignant adnexal tumors in
pregnancy should be further elucidated in future investigations. 22,34,35

MRI
Magnetic resonance imaging (MRI) without gadolinium is considered safe in
pregnancy and can be useful in evaluating sonographically undetermined adnexal
lesions. Although no well-controlled human studies have been conducted to evaluate
the teratogenic effect of gadolinium in pregnant women, no harmful effects have been
reported for human fetuses exposed to gadolinium in utero. Different studies have
demonstrated that the fetus can excrete, swallow, and reabsorb gadolinium into the
gastrointestinal tract, which persists in the amniotic fluid.36
Therefore, in clinical practice, it is wise to consider the use of gadolinium-
based contrast media in pregnant women only when the benefit to the mother
overwhelmingly outweighs the theoretic risks to the fetus. 37,38 MRI was performed in
35 cases, 23 of whom were included in two studies assessing the usefulness of this
technique in diagnosing decidualized endometriomas during pregnancy. These studies
provided evidence that the apparent diffusion coefficient (ADC) was significantly
higher for decidualized endometrial tissues as compared with malignant ovarian
tumors, probably due to the edematous vascularized nature of endometrial tissue with
abundant cytoplasm of stromal cells. 39,40
Takeuchi et al. (2008) have evaluated the MRI features of 5 decidualized
endometriomas. In 3 cases, diffusion weighted images were obtained, measuring ADC
of 10 decidualized mural nodules of 3 endometriomas and these were compared with
values from 7 ovarian cancers. The mean ADC of the decidualized mural nodules was
2.10+0.32 × 1023 versus 1.05+0.13 × 1023 mm2 /s for the malignant ovarian cyst
mural nodules (P < 0.001). 40
In a more recent study by Morisawa et al. (2014), the authors retrospectively
investigated the MRI findings of 18 decidualized endometriotic cysts and 24 ovarian
cancers, considering height, signal intensity of the solid component on T2-diffusion
weighted imaging, ADC of the solid component, size of the lesion, and signal
14
intensity of the intracystic fluid on T1-weighted imaging. The ADC values of the
intracystic decidualized solid component and of the cancer group were 1.77 × 1023
mm2 /s and 1.13 × 1023 mm2 /s, respectively (P < 0.0001). Another difference
between the two entities was found in the signal of the intracystic fluid on T1-
weighted imaging (higher in decidualized endometriotic cysts) as a possible result of
the repeated intracystic bleeding. A lower signal intensity of the intracystic fluid
during malignant transformation of the endometriotic cysts has already been
described. 40
Overall, in the presence of an endometrioma with prominent hyperintense
mural nodules on T2-weighted images, the suspicion of a decidualized endometrioma
should be high, but close follow-up should be provided to exclude the possibility of a
malignant transformation. ADC measurement was suggested as an additional tool to
help in the diagnosis.40

2.1.8 Treatment
Rarely do endometriomas cause problems in pregnancy. If they are identified
sonographically, they can be resected if cesarean delivery is performed. With vaginal
delivery, endometriotic tumors or cysts may be removed after the puerperium or
followed clinically depending on symptoms and cyst characteristics. Occasionally,
endometriosis can develop after delivery from endometrial implants within abdominal
incisions made at cesarean delivery or within episiotomy scars.41
The management of adnexal masses in pregnancy represents an actual
dilemma between expectant management and surgical intervention. This might lead to
an unnecessary removal of a benign mass on one hand, and to the conservative
observation of a malignant condition on the other. Decision on surgical intervention
should in any case undergo multidisciplinary discussion, balancing the level of
malignant suspicion, gestational age, and fetal and maternal risks.
Probably, the increasing number of decidualized endometriomas mimicking
ovarian malignancies published in these last years has contributed to moving
clinicians toward a more conservative approach. All other cases underwent either
cystectomy or salpingo-oophorectomy. Unfortunately, the detailed description of
surgical procedures and their timing were not available for all cases.
Of note, pregnancy outcome in those patients who underwent surgery has been
reported to be uneventful except for one, who suffered preterm rupture of membranes
15
 on the day of laparotomy at the 19th gestational week. However, surgery-related risks
are reported to increase after 23 weeks’ gestation, also considering that the enlarged
uterus might represent a technical problem for surgeons. If the decision on surgical
approach presents in the late third trimester, surgery should be postponed until after or
at the time of delivery. Surprisingly, all patients underwent laparotomy even though
laparoscopy has been reported to be a safe approach during pregnancy, provided it is
performed by an experienced surgeon.42,43

2.1.9 Prognosis

In general, pregnancy is possible but depends on the severity of the disease.

Endometriosis signs and symptoms generally regress with the onset of menopause and during
pregnancy.
 Miscarriage
Miscarriage is defined as the spontaneous end of pregnancy prior to 20 weeks
of gestation and is defined as ‘recurrent’ when at least three episodes occur. A
significant reduction of spontaneous abortion rate was found both after surgery
and after the expectant management, thus suggesting that endometriosis may
not be the causative factor of spontaneous abortion. In the retrospective
evaluation of 350 women. The frequency of spontaneous abortion was
significantly higher in the endometriosis group (38%) than in both the fertile
non-endometriosis group (10%) and the infertile non-endometriosis group
(19%).7
 Hypertensive disorders and pre-eclampsia
No correlation was detected, but this studywas conducted on a small
population and the definition of pre-eclampsia reported was not in line with
the definition by the American College of Obstetrician and Gynecologists
(ACOG).7
 Placenta previa
No cases of placenta praevia were observed in patients with ovarian
endometriomas only while an almost 6-fold increase in risk has been found in
women with rectovaginal endometriosis compared with allwomenwith ovarian
and peritoneal lesions.
 Obstetric hemorrhages (abruptio placentae, ante- and post-partum bleeding)

16
 Similarly, women with endometriosis do not seem to be at risk for developing
ante-partum hemorrhages 44,45
 Preterm birth
As previously mentioned, the pathophysiological link between endometriosis
and preterm birth has been suggested to be mainly represented by increased
local inflammation.46 Indeed, an inflammatory state associated with the
presence of ectopic tissue leading to a derangement of the endometrial
physiology may influence the decidua/trophoblast interaction which is
influenced by the same inflammatory factors and whose imbalance is thought
to be a possible pathogenic event in preterm birth.
 SGA
A SGA baby is defined as an infant weighing less than the tenth centile on
comparison of the birthweight with that expected for the same gestational age
(American College of Obstetricians and Gynecologists). The authors failed to
document an association between endometriosis in general and SGA babies.
However, a statistically significant increased risk for a SGA baby.7
 Gestational diabetes mellitus
Endometriosis was not found to be associated with GDM risk (. These results
were adjusted for several common risk factors, such as BMI, weight gain and
lifestyle changes. This was the first study evaluating GDM in which infertility
was categorized by various underlying reasons.7
 Caesarean delivery
This 2-fold increase of CD in women with endometriosis was explained by the
potential increased number of episodes of ante-partum hemorrhage in these
women47. In all study groups, the main indication for CD was fetal distress
(24%), followed by breech presentation (13%) and dystocia (13%). 48 In
common clinical practice, previous surgery mayhave influenced the choice of
an elective CD in women with endometriosis.

2.1.10 Complications7
Complications are rarely reported and consequently underestimated, and they
may represent life-threatening conditions for both the mother and the fetus. For this
reason, physicians managing pregnancy of women with endometriosis should be
aware of these insidious adverse events.
17
 Mechanisms underlying endometriosis complications during pregnancy.
Complications of endometriosis during pregnancy might be mostly attributed to the
following factors:
 Adhesions may create further traction on surrounding structures when the
uterus is enlarged during pregnancy. Adhesion formation in endometriosis may
be related to the disease itself or to the surgery for the disease. The normal
wound-healing process after injury to the peritoneum involves a complex
inflammatory cascade of fibrin deposition, coagulation and influx of
inflammatory cells. Adhesions form primarily as a result of an imbalance of
fibrin deposition and fibrin breakdown. Post-surgical adhesions that originate
from any abdominal/pelvic surgery, including Cesarean section, are well
known to lead to a number of complications including bladder and bowel
injuries. Indeed, complications (i.e. bowel obstruction or perforation)
occurring in pregnancy due to the presence of adhesions caused by previous
abdominal surgery have been described also in patients without endometriosis.
 Endometriosis-related chronic inflammation may make tissues and vessels
more friable. Indeed, while an appropriately driven and resolving
inflammatory process results in successful wound healing after tissue
damage, an inappropriately sustained inflammatory reaction is often related
to an overactive wound-healing response leading to tissue fibrosis, which can
present a threat to the maintenance of tissue structure and function.
Chronically inflamed tissues, such as those involved by endometriotic
lesions, are characterized by sustained, nonresolving inflammation and
fibrosis leading to tissue dysfunction. In this already compromise situation,
the hormone saturated environment of pregnancy might be critical in the
amplification of hormone-sensitive intrinsic inflammatory processes
attributed to ectopic endometriotic lesions.
 The intrusion of decidualized endometriotic tissue into the vessel wal and
structures can increase backpressure, predisposing to tissue rupture (O’Leary,
2006). Importantly in this regard, the decidualized endometrium transforms
into a well-vascularized tissue characterized by increased vascular
permeability, edema, vascular remodeling and angiogenesis and an increase
in luminal diameter. An alternative explanation to the vessel rupture due to

18
 the mechanical obstruction involves the involution of the decidualized
endometrium surrounding the distended vasculature. Decidualization is
dependent upon sustained progesterone signaling and progesterone
withdrawal triggers involution of the decidual vessels and bleeding. In
endometriosis, characterized by a progesterone resistance and suboptimal
expression of target genes, the necrosis of foci of decidualized ectopic
endometrium located in proximity to dilated utero-ovarian or parametrial
vessels could lead to a dysfunctional rupture of such vessels and bleeding of
unpredictable severity.
 Complication on Bowel 7
Intestinal perforation
The incidence of bowel endometriosis has been estimated at 5–12% in
women affected by endometriosis. The most frequent location is the sigmoid
colon, followed by the rectum, ileum, appendix and cecum. Intestinal
endometriosis may be found in every layer of the bowel wall but is most
commonly found within the subserosa as superficial implants. The locations
of the perforations were ileum, appendix, cecum, sigmoid colon and rectum.
Perforations occurred mostly in the third trimester (mean+SD gestational
age of 30+6.3 weeks). Nonspecific symptoms (acute abdominal pain, nausea
and vomiting) were experienced in 94% of the patients (15/16). Noteworthy,
in two cases, pyelonephritis was suspected delaying the diagnosis and in
three cases, bowel perforation was not diagnosed during the first exploratory
laparotomy, thus requiring a second laparotomy. Clinical and laboratory
signs of peritonitis were present in 13 patients (81%). Radiography or
computed tomography (CT) demonstrated free air in the peritoneal cavity in
31% of cases. In the only asymptomatic patient, the injury of rectal mucosa
localized 2 cmabove the intact external sphincter and a second degree
perineal tear were detected and repaired immediately after the vaginal
delivery.
Appendicitis
Although it is frequently asymptomatic, itmaypresent as acute appendicitis,
lower gastrointestinal bleeding, cecal intussusception and intestinal
perforation, in particular during pregnancy. The mean+SD gestational age at
diagnosis was 20+9.8 weeks and the most frequent presenting symptoms
19
 were nausea (29%), vomiting (43%) and abdominal pain (86%). The
diagnosis of an acute event involving the appendix (such as acute
appendicitis or bleeding of appendiceal endometriosis) is more challenging
in pregnancy than in non-pregnant women because (i) the symptoms of
nausea and vomiting are typical of early pregnancy, (ii) the localization of
pain may be variable due to upward displacement of the appendix by the
growing uterus and (iii) the white blood cell count ranging between 8000
and 20 000 cells/mm3 is normal during pregnancy.
 Complication on Vessels
Spontaneous hemoperitoneum (SH) during pregnancy from ruptured utero-
ovarian vessels is a rare but life-threatening complication. Sixteen
publications, reporting a total of 20 cases of endometriosis related SH in
pregnancy, were reviewed. Nulliparous women represented 70% of cases of
SH (14/20). Five women had twin pregnancies and six pregnancies were
achieved by IVF treatment. The mean+SD maternal age was 33+4.2 years.
The main presenting symptom was the sudden onset of abdominal pain with
different localizations (95%) and signs of hypovolemic shock (70%). One
patient complained of a lower quadrant pain associated with tachypnea
because of a combined hemothorax.
In most cases, the diagnosis of ruptured utero-ovarian vessel was established
at explorative laparotomy that was carried out in the 90% of cases for
maternal reasons (hypovolemic shock and progressive anemia; 67%), for
fetal reasons (fetal distress; 22%), or both (11%).
Laparoscopy was performed in only one hemodynamically stable patient
with extensive post-partum SH. There was only one case of a double uterine
artery embolization during pregnancy at 22th and at 24th gestational week
after the diagnosis of endometriosis from laparoscopic biopsy of a tumor
mass between the cervix and the bladder revealed by ultrasonography at 14th
gestational week. Two days after the last radiological procedure, a
spontaneous labor started and a Cesarean delivery of a live birth baby was
performed. The diagnosis was confirmed by explorative laparotomy 11 days
after the delivery. When acute abdominal pain with massive
hemoperitoneum occurs in pregnant nulliparous women or in the post-
partum period, particularly in presence of a history of endometriosis,
20
 spontaneous rupture of utero-ovarian vessels should be considered as a
possible cause of SH.
 Complication on Uterus
Uterine rupture
The reported endometriosis-related uterine acute complications in pregnancy
include three cases of uterine rupture and one case of uterine hemorrhage.
Uterine rupture represents a major obstetrical complication andmore
commonly involves a scarred uterus. Indeed, three patients had undergone
endometriosis surgery (excision of a rectovaginal nodule, bilateral ovarian
cystectomy and excision of cervical endometriosis) respectively, 6, 5 and 1
years before pregnancy. The uterine lesionwas revealed in one case during
manual exploration of the uterine cavity because of a retained placenta after
a vaginal delivery at term.
 Complication on Urinary tracts
Two cases of pregnancy complicated by uroperitoneum due to the presence
of endometriosis have been reported. Distortion of renal system anatomy
was observed in another two cases of endometriosis.
 Complication on Adnexa
Complications deriving from ovarian endometriotic cysts, such as infected,
enlarged and ruptured endometrioma, represent rare events but they should
be considered in the differential diagnosis of pelvic pain during pregnancy.
Conservative treatment with antibiotic therapy should represent the first-line
management for infected endometrioma, although in case of severe
abdominal pain and systemic involvement, drainage or surgery may be
required. Cyst rupture is highly symptomatic (acute abdomen,
hemoperitoneum, hypotension) and surgery (preferentially laparoscopy) is
required for the majority of the events.
 Complication on Extra-pelvic endometriosis
Endometriosis has also been described in virtually every location that can be
reached by hematogenous, lymphatic, or direct dissemination.
Manifestations of endometriosis in thoracic organs are very rare. Four cases
of spontaneous pneumothorax during pregnancy related to thoracic
endometriosis and a case of endometriosis involving thoracic aorta during
pregnancy have been reported. Shortness of breath was a complaint in all
21
four cases and two patients presented also with chest pain. The gestational
age at diagnosis was 8, 18, 24 and 28 weeks. Two of them had history of
catamenial pneumothorax before pregnancy. In one case treated with
hormonal therapy for catamenial pneumothorax before pregnancy, after
elective abortion, the patient underwent thoracoscopy to remove multiple
pleural cysts and a pleurodesis was performed.7

22
 CHAPTER III

CONCLUSION

Endometriosis during pregnancy are rarely causing complication and there is no

evidence that the disease has a major detrimental effect on pregnancy outcome. Therefore,
pregnant women with endometriosis can be reassured about the course of their pregnancies
although the physicians should be aware of the potential for increased risk of placenta previa.
Although it seems unlikely that hormonal or surgical treatment of endometriosis influences
the impact of the disease on pregnancy outcome, no study has investigated the incidence of
pregnancy complications in treated and untreated patients and this should be the objective of
further research.

23
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