EURURO Vol. 71 No. 5

791 844

1. Introduction
Endometriosis is traditionally classified as one of three main
forms: ovarian endometriosis, superficial peritoneal endo-
metriosis, and deep infiltrating endometriosis (DIE). DIE is
the most severe type, with an estimated prevalence of 1%
among women of reproductive age and is defined as
endometriosis infiltrating the peritoneum by >5 mm. More
frequently, these lesions are located in the most declivous
part of the pelvis (including the pouch of Douglas, the
anterior aspect of the sigma, the uterosacral ligaments, the
broad ligaments, the ureter, and the bladder), while other
locations (such as other sites in the abdomen, the external
genitalia, and distant sites) are less common. Urinary tract
endometriosis (UTE) involves the bladder and/or the
ureters. UTE is present in approximately 1% of women
with endometriosis , but its prevalence increases to
19–53% among patients with DIE . Bladder involve-
ment is the most frequent type of UTE, occurring in 70–85%
of cases, while ureteral involvement accounts for 9–23% of
UTE cases Bladder endometriosis (BE) is defined as the
presence of endometrial glands and stroma in the detrusor
muscle; the base and the dome are the most frequently
affected sites. According to its origin, BE may be classified as
primary BE when it occurs spontaneously, or as secondary
BE when it is related to an iatrogenic lesion occurring after
pelvic surgery, such as cesarean delivery or hysterectomy.
Endometriotic nodules of the bladder are frequently
associated with other forms of pelvic endometriosis,
supporting the notion that BE should be not considered
an independent form of the disease. The presence of at least
one other site involved (superficial peritoneal implants,
ovarian endometriomas, adhesions, and extravesical deep
peritoneal endometriosis) has been documented in approx-
imately 90% of cases . In most cases, BE is associated with
lower urinary tract symptoms such as frequency, dysuria,
haematuria, and, less frequently, bladder pain and urgency
. These symptoms may worsen during menstruation, or
may have a noncyclical presentation. Depending on the
clinical manifestation, both urologists and gynecologists
may deal with BE, and their collaboration may be required
for clinical management.
To provide more information on this rare and challeng-
ing condition, we conducted a systematic review to
summarize available knowledge on BE and to identify
research needs. The main objective of the review was to
systematically evaluate evidence regarding the pathogene-
sis, diagnosis, medical and surgical treatment, impact on
women’s fertility, and risk of malignant transformation
of BE.
2. Evidence acquisition
This review was performed according to the Preferred
Reporting Items for Systematic Review and Meta-analysis
statement and was registered in the PROSPERO register
; CRD42016039281). No in-
stitutional review board approval was needed because only
published, de-identified data were analyzed. All authors
participated in the design of the search strategy and of the
inclusion and exclusion criteria.
2.1. Search strategy
PubMed/Medline was systematically searched from incep-
tion until October 2016 (last research October 21, 2016; the
search was run every month fromMarch 2016 until October
2016) using the following keywords and MeSH terms:
‘‘bladder endometriosis’’ alone or in combination with
‘‘aromatase inhibitors’’, ‘‘ART’’, ‘‘assisted reproductive tech-
niques’’, ‘‘cancer’’, ‘‘clinical examination’’, ‘‘combined oral
contraceptives’’, ‘‘cystoscopy’’, ‘‘diagnosis’’, ‘‘dienogest’’,
‘‘fertility’’, ‘‘hormonal treatment’’, ‘‘ICSI’’, ‘‘infertility’’, ‘‘in
vitro fertilization’’, ‘‘intrauterine insemination’’, ‘‘IVF’’, ‘‘IUI’’,
‘‘magnetic resonance imaging’’, ‘‘norethindrone acetate’’,
‘‘painful bladder syndrome’’, ‘‘pathogenesis’’, ‘‘pregnancy’’,
‘‘progestogen’’, ‘‘questionnaire’’, ‘‘segmental resection’’,
‘‘surgery’’, ‘‘symptoms’’, ‘‘transurethral surgery’’, ‘‘treat-
ment’’, ‘‘ultrasonography’’, ‘‘ultrasound’’, ‘‘urodynamics’’.
All pertinent articles were carefully assessed and their
reference lists were evaluated to identify any other study
that could be included in this review. All the authors
reviewed the articles, and discrepancies were resolved by
consensus. The reviewers were not blinded to the names of
the investigators or the sources of publication. The
eligibility of the studies was first based on titles and
abstracts. Full manuscripts were obtained for all selected
papers, and the decision for final inclusion was made after
detailed evaluation of the articles.
2.2. Inclusion and exclusion criteria
In this systematic review, only peer-reviewed, English-
language journal articles concerning BE were included. In
particular, the following topics were covered: pathogenesis,
diagnosis, medical and surgical treatment, BE in women
wishing to conceive, and the risk of malignant transforma-
tion. As described later, medical management of BE should
be intended as an alternative to surgery, and thus only long-
term therapies are included in this review.
2.3. Study eligibility and quality assessment
This review included randomized controlled trials (RCTs),
prospective controlled studies, prospective cohort studies
or retrospective studies, reviews, case series, and case
reports. Case reports and small case series (<10 cases) were
considered only if they provided highly valuable informa-
tion. Letters to the editor and abstracts accepted at
conferences were excluded from the review. The Quality
Assessment of Diagnostic Accuracy Studies (QUADAS)-2
tool was used to assess the methodological quality
of studies investigating diagnostic techniques for BE
included in the review (Supplementary Tables 1 and 2)
. In addition, the Newcastle-Ottawa Scale was used
to assess the methodological quality of studies investigating
medical and surgical treatment of BE (Supplementary
Tables 3 and 4)
E U R O P E A N U R O L O G Y 7 1 ( 2 0 1 7 ) 7 9 0 – 8 0 7 791