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Endometriosis classification: an update

G. David Adamson
Fertility Physicians of Northern California, San Jose Purpose of review
and Palo Alto, California, USA
Endometriosis remains an enigmatic disease for many reasons, not the least being a
Correspondence to G. David Adamson, 540 University continued inability to stage its clinical presentation so that prognosis and treatment for
Avenue, Suite 200, Palo Alto, CA 94301, USA
Tel: +1 650 322 1900; e-mail: info@fpnc.com both pain and infertility patients can be facilitated. This article reviews issues with
current staging systems.
Current Opinion in Obstetrics and Gynecology
2011, 23:213220
Recent findings
The revised American Fertility Society (rAFS) classification system has historically been
the only classification system. Recently, the ENZIAN classification system, developed
as an adjunct to the rAFS to describe more severe disease, has been introduced but is
rarely used. More recently, the Endometriosis Fertility Index (EFI) that has been validated
to predict pregnancy rates in infertility patients following surgical diagnosis and
treatment of endometriosis was published. Currently, the AAGL is developing a
categorization system that will be more focused on pain. Novel research in imaging,
biomarkers, histology, and the human genome may provide useful information to
develop future classification systems.
Summary
The only validated endometriosis classification system that predicts a clinical outcome is
the EFI. It is to be hoped that renewed interest in the importance and utility of
classification systems will result in novel classification systems that are clinically useful.

Keywords
classification, endometriosis, fertility, pain, staging

Curr Opin Obstet Gynecol 23:213220


2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
1040-872X

Introduction Classification systems of historical interest


Endometriosis is a complex disease to diagnose and In 1921, Sampson [1] first classified endometriosis when
treat, at least partially because of our historical inability he categorized hemorrhagic cysts, noted adhesions, and
to develop validated staging systems for the associated proposed his theory of retrograde menstruation. Sub-
pain and infertility. There are important reasons to sequent classifications were based on histologic criteria;
stage endometriosis, or any other disease: to create a anatomic presentation; histopathology and pain; clinical,
common language, to enable specificity of diagnosis, to anatomical, and histopathological presentation; structure
standardize comparisons, and to facilitate research appli- involvement; or physical examination and surgical
cations. The requirements of an ideal endometriosis findings.
classification system are that it be empirically and
scientifically based, enjoy general consensus, have In 1973, Acosta et al. [2] proposed a system based on the
unambiguous definition of terms, be comprehensive site and distribution of lesions on the premise that
for all cases, have a simple translation from anatomic severity determined the success of surgery. There was
feature to verbal description, reflect disease, predict more emphasis on adnexal adhesions as a fertility factor
fertility, predict pain relief, be useful to guide treatment, and recognition of the risk of the ovaries forming adhe-
indicate risk of recurrence, identify clinical situations in sions. Others proposed systems based on malignancy,
which it does not apply, be simple to calculate, and be lesions, site and distribution of lesions, laparoscopic find-
easy to communicate to patients. This review will ings, and therapy; the two most commonly used being
address historical staging systems, the new validated those of Kistner et al. [3] and Buttram [4]. These systems
Endometriosis Fertility Index (EFI) for infertility were all criticized for multiple reasons including their
patients, and the ENZIAN and proposed AAGL systems inability to predict clinical outcomes, especially preg-
for pain. nancy rates, in infertile patients.
1040-872X 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI:10.1097/GCO.0b013e328348a3ba

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
214 Reproductive endocrinology

Key points
American Fertility Society classification
In 1979, the American Fertility Society (AFS) first pro-  The American Fertility Society and revised
posed a classification system. This AFS system was American Fertility Society endometriosis classifi-
flexible enough to describe any case, had an associated cation system has been helpful for documenting
disease but is generally not clinically useful for
paper form to encourage complete documentation, was
predicting prognosis or management options for
quantitative and so allowed for analysis, and had assigned
either pain or infertility.
cut-off points [5]. Several authors critiqued the AFS
 The Endometriosis Fertility Index is a simple,
system and made suggestions for its improvement. In
robust, and validated clinical tool that predicts
1982, Guzick et al. [6] used doseresponse methodology non-IVF pregnancy rates for patients following
to demonstrate that there was no correlation of pregnancy surgical staging of endometriosis.
rates with severity following surgery and recommended a  The current ENZIAN staging system is not com-
nonparametric monotonic estimate. In 1982, Adamson monly used and the AAGL classification system is
et al. [7] utilized clustering techniques in an attempt to still being developed, but either or both may
identify anatomic factors that predict pregnancy rates, become clinically useful, especially for description,
but none were found. Further recommendations were prognosis, and management of more severe endo-
subsequently made to modify the AFS classification [8,9]. metriosis and pain.
 Multidisciplinary research in all aspects of endome-
In 1985, the AFS revised the 1979 classification [10]. triosis might yield information that can be used to
The new rAFS classification eliminated extensive disease develop clinically useful classification systems in
stage, removed tubal endometriosis as a separate the future.
category, created a category for minimal disease, differ-
entiated superficial vs. deep lesions of peritoneum and hormones, pain, depth of lesions, and the possible appear-
ovaries, required more detail for the adnexal adhesions, ance and disappearance of lesions [16].
quantified filmy vs. dense adhesions, considered posterior
cul-de-sac obliteration to be severe disease, doubled the Fifth, there is poor correlation between the extent of
solitary adnexa score, and recorded additional pathology. disease and pelvic pain [17]. Pelvic pain and dyspareunia
The system was republished in 1996 adding instructions have been associated with deeply invasive nodules with
and illustrations for pelvic pain [11]. severe dysmenorrhea in stage III and IV disease [18].
Pelvic pain has been correlated with penetration depth
of lesions.
Limitations of the revised American Fertility
Society system Sixth, the rAFS stages correlate poorly with infertility,
Despite these revisions, the current rAFS system has except for extensive disease [19]. Lesion site and type do
serious limitations. First, it has an arbitrary scoring system not predict pregnancy outcome and pregnancy rates have
in which the point scores do not reflect empirically derived been determined not to differ according to stage. There-
relative weights, the stage demarcation by point score is fore, the current staging system does not effectively
arbitrary, and score ranges within the categories are wide. predict outcome of treatment.

Second, there is potential for observer error because of


the many morphological presentations, some subtle and Attempts subsequent to the revised American
microscopic. Accuracy of documentation and identifi- Fertility Society (ASRM) staging system to
cation of endometriomas can be problematic [12]. Staging develop classification systems
can be affected by timing of laparoscopy and whether the Many potential modifications to the current rAFS (since
staging is performed at laparoscopy or laparotomy [13]. 1996 renamed the American Society for Reproductive
Medicine or ASRM) classification system have been
Third, there is limited reproducibility of the staging. The suggested based on anatomic factors, histologic factors,
correlation of intraobserver restaging has been reported biomarkers, genetic markers, imaging findings, symp-
to be only 0.38 and interobserver 0.52, with the greatest toms, and revisions of the current systems [2022].
variation occurring in documenting the ovary and
posterior cul de sac [14]. Only fair-to-good agreement In particular, efforts have been made to develop classifi-
has been reported and multiple lesion types in the same cation systems for deeply infiltrating endometriosis.
patient complicate staging [15]. Adamyan [23] published a classification of retrocervical
endometriosis in 1993, which was subsequently updated
Fourth, the rAFS system does not consider morphological [24]. Chapron et al. [25] proposed a classification for deeply
lesion type or age-related evolution nor associations with infiltrating endometriosis in 2003. These initiatives reflect

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Endometriosis classification Adamson 215

the wide variety of clinical presentations and problems histological status, localization (organ spread), and extent
presented by endometriosis for which some type of classi- of endometriosis, pain, fertility, and residual status.
fication system would be useful.

The Endometriosis Fertility Index


Recent endometriosis classification systems Adamson and Pasta [29] have recently taken a different
After a quarter century when the only endometriosis approach to developing a system for fertility patients:
classification system in global use was the AFS and rAFS collect clinical data prospectively, utilize outcomes
systems, the past few years have seen a marked increase assessment for infertility, do comprehensive statistical
in interest in new classification systems. analysis of the data, and derive a new staging system from
the data rather than from a priori assumptions. This new
staging system has been validated prospectively and
ENZIAN staging system modified to optimize the staging system. The clinical
The ENZIAN staging system was published in 2005 to tool that was developed is the EFI. It predicts pregnancy
take into account deep infiltrating endometriosis (DIE) rates in patients with surgically documented endometri-
[26,27]. This system is meant to supplement the rAFS osis who attempt non-IVF conception. Data were pros-
score with regard to the description of DIE, retroperito- pectively collected on 579 patients at the time of surgery
neal structures, and involvement of other organs. The on a standardized form. The data were then analyzed by
ENZIAN score identifies organs (intestinal, uterine, sophisticated statistical analysis to identify those factors
intrinsic ureteral, bladder, other). The ENZIAN score most predictive of pregnancy. Subsequent analyses com-
also encompasses three axes or levels in compartments a, bined the most predictive variables and established a
b, and c, as well as classifies the severity of endometriosis simple scoring system, the EFI. After developing the
(except for other). The prefix E indicates the presence EFI, the same data were prospectively collected on 222
of a tumor of endometriosis. The number that follows additional consecutive patients, the EFI calculated on
describes the size of the lesion and the subsequent low- each patient, and pregnancy rates predicted prospectively.
ercase letter marks the location or the affected compart-
ment. Two letters signify bilateral disease. Compartment In addition to historical factors that were identified as
a is a vertical plane extending from the pouch of Douglas predicting pregnancy (Fig. 1), not surprisingly, surgical
cavity. The ENZIAN score is descriptive in nature. findings were also identified that helped predict the
Factors such as principal symptoms or sterility are not outcome. These were the rAFS endometriosis lesion
taken into account. As endometriosis commonly occurs score (i.e., not including adhesions) and total rAFS score,
simultaneously in several organs and structures, the as well as functional scores that were determined by the
ENZIAN score is a descriptive morphological classifi- surgeon for each of the tube, fimbria, and ovary bilater-
cation that permits multiple nominations when various ally, where 0 absent or nonfunctional; 1, 2, and
manifestations exist. The fact that the ENZIAN score 3 severe, moderate, and mild dysfunction, respectively;
has been poorly accepted by gynecologists has been and 4 normal with respect to the capacity of the organ/
attributed to the complexity of its documentation and structure to effect their purpose in the reproductive pro-
to the absence of significant factors such as pain or cess. This means the ability of the tube to move over the
infertility in the system, which both gynecologists and ovary, to be the passage for the sperm from the uterus, to
patients consider essential to take into account [28]. provide the early environment for the egg and embryo, and
to enable transport of the embryo to the uterus; the fimbria
The ENZIAN system has been compared with the rAFS to move over the ovary and to pick up an egg; and the ovary
system to determine what additional value it creates to house eggs, develop follicles, ovulate eggs, and allow
[28]. It is considered to supplement the rAFS system them to be picked up by the fimbria. These three intrao-
because it is very precise in demonstrating DIE and perative scoring systems were considered supplements to
involvement with retroperitoneal structures and other the historical factors that were found to predict pregnancy
organs. A difficulty of the ENZIAN classification is that rates: age, duration of infertility, and pregnancy history.
the three compartments naturally intersect each other in The Least Function Score was the sum of the lowest
three-dimensional space and it is difficult to assign the score on each of the right and left sides (Fig. 1). It is to be
site of intersection itself to one of the planes. Addition- emphasized that the least function score is determined at
ally, there is duplication of scoring between the rAFS and the completion of the surgical intervention, not before. It
ENZIAN systems, making it not just complementary to therefore represents an estimate of functionality after the
the rAFS system. Modifications to ENZIAN nomencla- surgical intervention.
ture that would simplify it, standardize the classification,
and enhance its descriptive value have been suggested From the three historical factors and the three surgical
[28]. There are also considerations to include clinical vs. factors, the EFI was developed statistically. The EFI

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216 Reproductive endocrinology

Figure 1 The Endometriosis Fertility Index surgery form

Least function (LF) score at conclusion of surgery

Score Description Left Right

4 = Normal Fallopian tube +


3 = Mild dysfunction
2 = Moderate dysfunction Fimbria +
1 = Severe dysfunction
0 = Absent or Nonfunctional Ovary +

To calculate the LF score, add together the lowest score for


the left side and the lowest score for the right side. If an overy Lowest score + =
is absent on one side, the LF score is obtained by doubling the
lowest score on the side with the ovary. Left Right LF score

Endometriosis fertility index (EFI)


Historical factors Surgical factors
Factor Description Points Factor Description Points

Age LF score
If age is < 35 years 2 If LF score = 7 to 8 (high score) 3
If age is 36 to 39 years 1 If LF score = 4 to 6 (moderate score) 2
If age is > 40 years 0 If LF score = 1 to 3 (low score) 0

Years infertile AFS endometriosis score


If years infertile is < 3 2 If AFS endometriosis lesion score is < 16 1
If years infertile is > 3 0 If AFS endometriosis lesion score is > 16 0

Prior pregnancy AFS total score


If there is a history of a prior pregnancy 1 If AFS total score is < 71 1
If there is no history of prior pregnancy 0 If AFS total score is > 71 0
Total historical factors Total surgical factors

EFI = Total historical factors + Total surgical factors: + =


Historical Surgical EFI score

Estimated percent pregnant by EFI score


100%

EFI score
80%
910
78
60%
6

40% 5

4
20%
03
0%
0 6 12 18 24 30 36 months

Reproduced from [29].

score ranges from 0 to 10, with 0 representing the poorest at non-IVF conception. One factor found to predict
prognosis and 10 the best prognosis. The estimated pregnancy that is not included in the EFI is uterine
cumulative percentage pregnant by value of the EFI abnormality. Severe uterine abnormality that is clini-
score is presented graphically (Fig. 1). cally significant is so uncommon in infertile endome-
triosis patients that it is not included in the EFI.
The EFI is useful only for infertility patients who However, when this condition is found, it does need
have had surgical staging of their disease. It is not to be taken into account in predicting pregnancy rates.
intended to predict any aspect of endometriosis-associ- Deficiencies in the reproductive function of the
ated pain. It is required that the male and female gametes or uterus will obviously affect the prognosis
gametes are sufficiently functional to enable attempts and must be considered separately as fertility factors,

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Endometriosis classification Adamson 217

just as they would with any patient with any other type program automatically computes totals for each patient
of disease. row as well as grand totals for all patient columns. Basic
statistical calculations are offered, including ranges,
A legitimate criticism can be made that the least function sums, averages, and standard deviations. The data can
score is subjective for any given surgeon, and even more be exported to a more robust statistical package for more
subjective among different surgeons. The least function in-depth analysis.
score in fact is an extremely robust measure of pelvic
reproductive potential with much less variability than one Since developing the tabulation format, AAGL has pro-
might think. This was confirmed by rigorous sensitivity ceeded with a project to ask endometriosis experts to give
analysis. The score is easy for most surgeons with any a weighted score to different anatomical factors that they
degree of experience to determine for each structure. think are important with respect to pain and infertility.
After receiving responses from 30 individuals, data have
The EFI can be used to decide what type of treatment been analyzed and scores assigned. Currently, these same
patients should undergo, for how long, and at what cost surgeons are retrospectively entering scores for some of
before considering the assisted reproductive technologies their patients to determine whether the classification that
(ARTs) following endometriosis surgery. It can be used results will predict the outcomes for these patients.
to provide reassurance for many who have a good prog- Following analysis of the data, further refinement will
nosis and to avoid wasted time and treatment for those hopefully result in a classification system for pain and
with a poor prognosis. As very few patients overall actu- possibly for infertility.
ally engage ART procedures, the EFI can bring major
benefits to the vast majority of endometriosis patients Current considerations for classifying endometriosis
who wish to have children. A major difficulty in classifying endometriosis with
respect to pain is the need to utilize standardized and
validated pain assessment tools that are used by the
Potential new classification systems patients in consistent time frames. Absence of use of
The EFI and the ENZIAN systems currently exist and standardized and validated systems has made interpret-
are being implemented and assessed by clinicians. How- ation of much of the data in the literature difficult with
ever, the possibility remains for additional classification respect to classification and outcomes [32].
systems that could potentially bring value to other aspects
of endometriosis management. Newer imaging technologies might become useful in
classifying endometriosis. Transvaginal sonography
AAGL endometriosis tabulation system (TVS) has been found to be a good test for assessing
In 2007, the AAGL (formerly the American Association the severity of pelvic endometriosis. TVS was particularly
of Gynecological Laparoscopists) initiated a project to accurate in detecting severe disease and deep invasive
develop an endometriosis tabulation system. This is, endometriosis and therefore potentially could add value
strictly speaking, not a classification system but a new to a classification system [33 35]. Thin-section oblique
tabulation system that researchers and interested clini- axial T2-weighted magnetic resonance images to assess
cians can use to document the morphology of endome- uterosacral ligament endometriosis have been reported to
triosis seen at surgery in their patients [30,31]. If the improve the success of conventional MRI and potentially
disease can be described accurately, then a clinically could contribute to new classification systems based on
useful classification system may eventually be developed imaging [36]. Recent studies on histology of endome-
from it. If not, at least this tabulation system can more triosis could potentially provide the basis for histologic
accurately gauge disease extent, which is important in classification of disease that could be associated with
evaluating results of treatment. This system has been pain. The histologic differentiation in superficial endo-
developed with input from the worlds leading experts in metriosis, deeply infiltrating endometriosis, and ovarian
the research and surgical management of endometriosis. endometriomas was evaluated according to a previously
It contains all of the basic information thought to be proposed classification system and differences were
important in quantifying the extent of disease in a found [37]. In another study, endometrial biopsy, with
patient. It is based on Excel, a commonly used spread- detection of nerve fibers, provided a reliability of diag-
sheet with both Macintosh and PC versions, and can be nosis of endometriosis that was close to the accuracy of
expanded or simplified by end-users with facility in laparoscopic assessment by experienced gynecological
using Excel. laparoscopists [38]. Recent evidence also indicated that
ectopic endometriotic implants recruit their own unique
The interactive spreadsheet contained in AAGLEndo- neural and vascular supplies through neuroangiogenesis.
Tab allows entry of administrative and clinical data on It is believed that these nascent nerve fibers in endome-
almost 1000 patients. As each patient is entered, the triosis implants influence dorsal root neurons within the

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218 Reproductive endocrinology

central nervous system, increasing pain perception in lation between promoter methylation and expression of
patients [39]. Future understanding of these physiologic nearby genes, 35 genes had both methylation and expres-
mechanisms may one day provide a basis for classifying sional alterations in the lesions. These genes, reported for
endometriosis. the first time, might be of interest in the development of
endometriosis and could potentially be used to categorize
Other studies have evaluated serum and other concen- disease types.
trations of hormones and other substances in the body.
Levels of these substances may eventually be categorized
such that they provide prognostic and/or treatment capa- Conclusion
bilities for patients with endometriosis. Lower antimul- Multiple systems have been proposed for classifying
lerian hormone serum levels and an association with the endometriosis. Unfortunately, none have met with much
severity were found in women with endometriosis. This success because of their inability to meet recognized
information might be useful in patients, especially those clinical needs. However, the EFI is a simple, robust,
with severe endometriosis, undergoing controlled ovarian and validated clinical tool that predicts pregnancy rates
stimulation [40]. Leptin concentrations in the peritoneal for patients following surgical staging of endometriosis. It
fluid of women with ovarian endometriosis have been is the first endometriosis classification tool that has been
found to be different according to the presence of a deep validated to predict an important clinical outcome. The
or superficial ovarian disease, suggesting that leptin EFI should be very useful in developing treatment plans
could play an active role in promoting the development in infertile endometriosis patients. It is hoped that further
of superficial ovarian endometriomas and that super- prospective validation by other clinical investigators
ficial and deep ovarian endometriomas could have a will encourage widespread application of the EFI to
different pathogenesis [41]. Seeber et al. [42] found six the benefit of patients.
proteins that were differentially expressed between those
with and without endometriosis and that had good diag- Further efforts by AAGL and other investigators to
nostic properties. Taken together in a two-step diagnostic develop tabulation and staging systems that will help
algorithm, the authors were able to diagnose 55% of predict outcomes for endometriosis patients with pelvic
patients, with 99% accuracy as to the status of disease. pain for both surgical and nonsurgical treatment will
Further combining this algorithm with that derived by hopefully bring additional value to the management of
the authors previous study of serum putative markers our patients. It is very possible that different classification
(monocyte chemoattractant protein 1, migration inhibi- systems might be necessary to predict different clinically
tory factor, leptin, and CA-125) improved their diagnostic meaningful outcomes, for example, infertility treatment
capability to 73% of patients, with 94% overall accuracy. without IVF; infertility treatment with IVF; response to
Others have found that urinary proteomic analysis may ovarian stimulation; pain (acute vs. chronic, dysmenor-
provide a novel method of diagnosing and staging endo- rhea vs. dyschezia vs. dysuria vs. dyspareunia, etc.); bowel
metriosis [43]. Another study demonstrated that the or bladder function; response to medical vs. surgical
expression of macrophage migratory inhibitory factor treatment; recurrence; transmission to offspring; among
(MIF) was increased significantly in the eutopic and others.
ectopic endometrial tissue of women with endometriosis,
and this factor may play a possible role in endometriosis- There is still much to learn and much to do with respect
associated infertility and its potential classification [44]. to classification of this complex and challenging disease.
However, Hsu et al. [45] discussed different diagnostic Much research is now being performed globally on many
modalities, demonstrating that there are many candidates aspects of endometriosis. It is likely that creating new
but no good noninvasive tests to replace laparoscopic classification systems will require a multidisciplinary
visualization for diagnosis and staging, preferably with approach. A consensus international research priorities
histologic confirmation. statement recommended that researchers be encouraged
to develop new interdisciplinary research proposals
Much new research is occurring in genetics. Genome- that will attract increased funding support for work on
wide profiling of methylated promoters in endometriosis endometriosis, including classification and prognosis
revealed a subtelomeric location of hypermethylation [47]. Furthermore, the World Endometriosis Research
[46]. In line with the current theory of the endometrial Foundation, an international professional nonprofit
origin of endometriosis, the overall methylation profile organization committed to providing the global platform
was highly similar between the endometrium and the for collaboration among those who wish to contribute to
lesions. It showed promoter regions consistently hypo- finding solutions for endometriosis, has stated that
methylated or hypermethylated (more than 1.5 times, as chances for success will be dramatically increased if all
compared with endometrium) and others specific to one stakeholders pool their resources and intelligence and
given subtype. Although there was no systematic corre- work together [48].

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Endometriosis classification Adamson 219

27 Tuttlies F, Keckstein J, Ulrich U, et al. ENZIAN-Klassifikation zur Diskussion


References and recommended reading gestellt: Eine neue differenzierte Klassifikation der tief infiltrierenden Endo-
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been highlighted as: classification of deep infiltrating endometriosis). J Gynakol Endokrinol 2008;
 of special interest 18:713.
 of outstanding interest 28 Haas D, Chvatal R, Habelsberger A, et al. Comparison of revised American
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220 Reproductive endocrinology

41 Alviggi C, Clarizia R, Castaldo G, et al. Leptin concentrations in the peritoneal 45 Hsu AL, Khachikyan I, Stratton P. Invasive and noninvasive methods
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gold standard for endometriosis diagnosis. No good noninvasive tests exist,
42 Seeber B, Sammel MD, Fan X, et al. Proteomic analysis of serum yields six
although imaging might be helpful for more severe disease and there has been
 candidate proteins that are differentially regulated in a subset of women with
a recent focus on the presence of nerve fibers in eutopic endometrium of
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endometriosis patients.
Six proteins were found that were differentially expressed between those with and
without disease and that had good diagnostic properties. Taken together in a two- 46 Borghese B, Barbaux S, Mondon F, et al. Research resource: genome-
step diagnostic algorithm, the authors were able to diagnose 55% of patients, with  wide profiling of methylated promoters in endometriosis reveals a sub-
99% accuracy as to the status of disease. Further combining this algorithm with telomeric location of hypermethylation. Mol Endocrinol 2010; 24:1872
that derived by the authors previous study of serum putative markers (monocyte 1885.
chemoattractant protein 1, migration inhibitory factor, leptin, and cancer antigen- In line with the current theory of the endometrial origin of endometriosis, the overall
125 or CA-125) improved their diagnostic capability to 73% of patients, with 94% methylation profile was highly similar between the endometrium and the lesions. It
overall accuracy. showed promoter regions consistently hypomethylated or hypermethylated (more
than 1.5 times, as compared with endometrium) and others specific to one given
43 El-Kasti MM, Wright C, Fye HK, et al. Urinary peptide profiling identifies a
subtype. Although there was no systematic correlation between promoter methy-
 panel of putative biomarkers for diagnosing and staging endometriosis. Fertil
lation and expression of nearby genes, 35 genes had both methylation and
Steril 2011; 95:1261e61266e6.
expressional alterations in the lesions. These genes, reported for the first time,
Urinary proteomic analysis may provide a novel method of diagnosing and staging
might be of interest in the development of endometriosis.
endometriosis.
47 Rogers PA, DHooghe TM, Fazleabas A, et al. Priorities for endometriosis
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The expression of MIF was increased significantly in the eutopic and ectopic 48 Adamson GD, Kennedy S, Hummelshoj L. Creating solutions in endome-
endometrial tissue of women with endometriosis, and this factor may play a triosis: global collaboration through the World Endometriosis Research
possible role in endometriosis-associated infertility. Foundation. J Endometriosis 2010; 2:36.

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