Endometriosis classification: an update

G. David Adamson
Fertility Physicians of Northern California, San Jose
and Palo Alto, California, USA
Correspondence to G. David Adamson, 540 University
Avenue, Suite 200, Palo Alto, CA 94301, USA
Tel: +1 650 322 1900; e-mail: info@fpnc.com
Current Opinion in Obstetrics and Gynecology
2011, 23:213220
Purpose of review
Endometriosis remains an enigmatic disease for many reasons, not the least being a
continued inability to stage its clinical presentation so that prognosis and treatment for
both pain and infertility patients can be facilitated. This article reviews issues with
current staging systems.
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
treat, at least partially because of our historical inability
to develop validated staging systems for the associated
pain and infertility. There are important reasons to
stage endometriosis, or any other disease: to create a
common language, to enable specificity of diagnosis, to
standardize comparisons, and to facilitate research appli-
cations. The requirements of an ideal endometriosis
classification system are that it be empirically and
scientifically based, enjoy general consensus, have
unambiguous definition of terms, be comprehensive
for all cases, have a simple translation from anatomic
feature to verbal description, reflect disease, predict
fertility, predict pain relief, be useful to guide treatment,
indicate risk of recurrence, identify clinical situations in
which it does not apply, be simple to calculate, and be
easy to communicate to patients. This review will
address historical staging systems, the new validated
Endometriosis Fertility Index (EFI) for infertility
patients, and the ENZIAN and proposed AAGL systems
for pain.
1040-872X 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
In 1921, Sampson [1] first classified endometriosis when
he categorized hemorrhagic cysts, noted adhesions, and
proposed his theory of retrograde menstruation. Sub-
sequent classifications were based on histologic criteria;
anatomic presentation; histopathology and pain; clinical,
anatomical, and histopathological presentation; structure
involvement; or physical examination and surgical
findings.
In 1973, Acosta et al. [2] proposed a system based on the
site and distribution of lesions on the premise that
severity determined the success of surgery. There was
more emphasis on adnexal adhesions as a fertility factor
and recognition of the risk of the ovaries forming adhe-
sions. Others proposed systems based on malignancy,
lesions, site and distribution of lesions, laparoscopic find-
ings, and therapy; the two most commonly used being
those of Kistner et al. [3] and Buttram [4]. These systems
were all criticized for multiple reasons including their
inability to predict clinical outcomes, especially preg-
nancy rates, in infertile patients.
DOI:10.1097/GCO.0b013e328348a3ba

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 214 Reproductive endocrinology
American Fertility Society classification
In 1979, the American Fertility Society (AFS) first pro-
posed a classification system. This AFS system was
flexible enough to describe any case, had an associated
paper form to encourage complete documentation, was
quantitative and so allowed for analysis, and had assigned
cut-off points [5]. Several authors critiqued the AFS
system and made suggestions for its improvement. In
1982, Guzick et al. [6] used doseresponse methodology
to demonstrate that there was no correlation of pregnancy
rates with severity following surgery and recommended a
nonparametric monotonic estimate. In 1982, Adamson
et al. [7] utilized clustering techniques in an attempt to
identify anatomic factors that predict pregnancy rates,
but none were found. Further recommendations were
subsequently made to modify the AFS classification [8,9].
In 1985, the AFS revised the 1979 classification [10].
The new rAFS classification eliminated extensive disease
stage, removed tubal endometriosis as a separate
category, created a category for minimal disease, differ-
entiated superficial vs. deep lesions of peritoneum and
ovaries, required more detail for the adnexal adhesions,
quantified filmy vs. dense adhesions, considered posterior
cul-de-sac obliteration to be severe disease, doubled the
solitary adnexa score, and recorded additional pathology.
The system was republished in 1996 adding instructions
and illustrations for pelvic pain [11].
Limitations of the revised American Fertility
Society system
Despite these revisions, the current rAFS system has
serious limitations. First, it has an arbitrary scoring system
in which the point scores do not reflect empirically derived
relative weights, the stage demarcation by point score is
arbitrary, and score ranges within the categories are wide.
Second, there is potential for observer error because of
the many morphological presentations, some subtle and
microscopic. Accuracy of documentation and identifi-
cation of endometriomas can be problematic [12]. Staging
can be affected by timing of laparoscopy and whether the
staging is performed at laparoscopy or laparotomy [13].
Third, there is limited reproducibility of the staging. The
correlation of intraobserver restaging has been reported
to be only 0.38 and interobserver 0.52, with the greatest
variation occurring in documenting the ovary and
posterior cul de sac [14]. Only fair-to-good agreement
has been reported and multiple lesion types in the same
patient complicate staging [15].
Fourth, the rAFS system does not consider morphological
lesion type or age-related evolution nor associations with
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Key points

The American Fertility Society and revised
American Fertility Society endometriosis classifi-
cation system has been helpful for documenting
disease but is generally not clinically useful for
predicting prognosis or management options for
either pain or infertility.

The Endometriosis Fertility Index is a simple,
robust, and validated clinical tool that predicts
non-IVF pregnancy rates for patients following
surgical staging of endometriosis.

The current ENZIAN staging system is not com-
monly used and the AAGL classification system is
still being developed, but either or both may
become clinically useful, especially for description,
prognosis, and management of more severe endo-
metriosis and pain.

Multidisciplinary research in all aspects of endome-
triosis might yield information that can be used to
develop clinically useful classification systems in
the future.
hormones, pain, depth of lesions, and the possible appear-
ance and disappearance of lesions [16].
Fifth, there is poor correlation between the extent of
disease and pelvic pain [17]. Pelvic pain and dyspareunia
have been associated with deeply invasive nodules with
severe dysmenorrhea in stage III and IV disease [18].
Pelvic pain has been correlated with penetration depth
of lesions.
Sixth, the rAFS stages correlate poorly with infertility,
except for extensive disease [19]. Lesion site and type do
not predict pregnancy outcome and pregnancy rates have
been determined not to differ according to stage. There-
fore, the current staging system does not effectively
predict outcome of treatment.
Attempts subsequent to the revised American
Fertility Society (ASRM) staging system to
develop classification systems
Many potential modifications to the current rAFS (since
1996 renamed the American Society for Reproductive
Medicine or ASRM) classification system have been
suggested based on anatomic factors, histologic factors,
biomarkers, genetic markers, imaging findings, symp-
toms, and revisions of the current systems [2022].
In particular, efforts have been made to develop classifi-
cation systems for deeply infiltrating endometriosis.
Adamyan [23] published a classification of retrocervical
endometriosis in 1993, which was subsequently updated
[24]. Chapron et al. [25] proposed a classification for deeply
infiltrating endometriosis in 2003. These initiatives reflect

the wide variety of clinical presentations and problems
presented by endometriosis for which some type of classi-
fication system would be useful.
Recent endometriosis classification systems
After a quarter century when the only endometriosis
classification system in global use was the AFS and rAFS
systems, the past few years have seen a marked increase
in interest in new classification systems.
ENZIAN staging system
The ENZIAN staging system was published in 2005 to
take into account deep infiltrating endometriosis (DIE)
[26,27]. This system is meant to supplement the rAFS
score with regard to the description of DIE, retroperito-
neal structures, and involvement of other organs. The
ENZIAN score identifies organs (intestinal, uterine,
intrinsic ureteral, bladder, other). The ENZIAN score
also encompasses three axes or levels in compartments a,
b, and c, as well as classifies the severity of endometriosis
(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
describes the size of the lesion and the subsequent low-
ercase letter marks the location or the affected compart-
ment. Two letters signify bilateral disease. Compartment
a is a vertical plane extending from the pouch of Douglas
cavity. The ENZIAN score is descriptive in nature.
Factors such as principal symptoms or sterility are not
taken into account. As endometriosis commonly occurs
simultaneously in several organs and structures, the
ENZIAN score is a descriptive morphological classifi-
cation that permits multiple nominations when various
manifestations exist. The fact that the ENZIAN score
has been poorly accepted by gynecologists has been
attributed to the complexity of its documentation and
to the absence of significant factors such as pain or
infertility in the system, which both gynecologists and
patients consider essential to take into account [28

].
The ENZIAN system has been compared with the rAFS
system to determine what additional value it creates
[28

]. It is considered to supplement the rAFS system
because it is very precise in demonstrating DIE and
involvement with retroperitoneal structures and other
organs. A difficulty of the ENZIAN classification is that
the three compartments naturally intersect each other in
three-dimensional space and it is difficult to assign the
site of intersection itself to one of the planes. Addition-
ally, there is duplication of scoring between the rAFS and
ENZIAN systems, making it not just complementary to
the rAFS system. Modifications to ENZIAN nomencla-
ture that would simplify it, standardize the classification,
and enhance its descriptive value have been suggested
[28

]. There are also considerations to include clinical vs.
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Endometriosis classification Adamson 215
histological status, localization (organ spread), and extent
of endometriosis, pain, fertility, and residual status.
The Endometriosis Fertility Index
Adamson and Pasta [29

] have recently taken a different
approach to developing a system for fertility patients:
collect clinical data prospectively, utilize outcomes
assessment for infertility, do comprehensive statistical
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
modified to optimize the staging system. The clinical
tool that was developed is the EFI. It predicts pregnancy
rates in patients with surgically documented endometri-
osis who attempt non-IVF conception. Data were pros-
pectively collected on 579 patients at the time of surgery
on a standardized form. The data were then analyzed by
sophisticated statistical analysis to identify those factors
most predictive of pregnancy. Subsequent analyses com-
bined the most predictive variables and established a
simple scoring system, the EFI. After developing the
additional consecutive patients, the EFI calculated on
each patient, and pregnancy rates predicted prospectively.
In addition to historical factors that were identified as
predicting pregnancy (Fig. 1), not surprisingly, surgical
findings were also identified that helped predict the
outcome. These were the rAFS endometriosis lesion
score (i.e., not including adhesions) and total rAFS score,
as well as functional scores that were determined by the
surgeon for each of the tube, fimbria, and ovary bilater-
ally, where 0 absent or nonfunctional; 1, 2, and
3 severe, moderate, and mild dysfunction, respectively;
and 4 normal with respect to the capacity of the organ/
structure to effect their purpose in the reproductive pro-
cess. This means the ability of the tube to move over the
ovary, to be the passage for the sperm from the uterus, to
provide the early environment for the egg and embryo, and
to enable transport of the embryo to the uterus; the fimbria
to move over the ovary and to pick up an egg; and the ovary
to house eggs, develop follicles, ovulate eggs, and allow
them to be picked up by the fimbria. These three intrao-
perative scoring systems were considered supplements to
the historical factors that were found to predict pregnancy
rates: age, duration of infertility, and pregnancy history.
The Least Function Score was the sum of the lowest
score on each of the right and left sides (Fig. 1). It is to be
emphasized that the least function score is determined at
the completion of the surgical intervention, not before. It
therefore represents an estimate of functionality after the
surgical intervention.
From the three historical factors and the three surgical
factors, the EFI was developed statistically. The EFI
 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
prognosis and 10 the best prognosis. The estimated
cumulative percentage pregnant by value of the EFI
score is presented graphically (Fig. 1).
The EFI is useful only for infertility patients who
have had surgical staging of their disease. It is not
intended to predict any aspect of endometriosis-associ-
ated pain. It is required that the male and female
gametes are sufficiently functional to enable attempts
at non-IVF conception. One factor found to predict
pregnancy that is not included in the EFI is uterine
abnormality. Severe uterine abnormality that is clini-
cally significant is so uncommon in infertile endome-
triosis patients that it is not included in the EFI.
However, when this condition is found, it does need
to be taken into account in predicting pregnancy rates.
Deficiencies in the reproductive function of the
gametes or uterus will obviously affect the prognosis
and must be considered separately as fertility factors,

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just as they would with any patient with any other type
of disease.
A legitimate criticism can be made that the least function
score is subjective for any given surgeon, and even more
subjective among different surgeons. The least function
score in fact is an extremely robust measure of pelvic
reproductive potential with much less variability than one
might think. This was confirmed by rigorous sensitivity
analysis. The score is easy for most surgeons with any
degree of experience to determine for each structure.
The EFI can be used to decide what type of treatment
patients should undergo, for how long, and at what cost
before considering the assisted reproductive technologies
(ARTs) following endometriosis surgery. It can be used
to provide reassurance for many who have a good prog-
nosis and to avoid wasted time and treatment for those
with a poor prognosis. As very few patients overall actu-
ally engage ART procedures, the EFI can bring major
benefits to the vast majority of endometriosis patients
who wish to have children.
Potential new classification systems
The EFI and the ENZIAN systems currently exist and
are being implemented and assessed by clinicians. How-
ever, the possibility remains for additional classification
systems that could potentially bring value to other aspects
of endometriosis management.
AAGL endometriosis tabulation system
In 2007, the AAGL (formerly the American Association
of Gynecological Laparoscopists) initiated a project to
develop an endometriosis tabulation system. This is,
strictly speaking, not a classification system but a new
tabulation system that researchers and interested clini-
cians can use to document the morphology of endome-
triosis seen at surgery in their patients [30,31]. If the
disease can be described accurately, then a clinically
useful classification system may eventually be developed
from it. If not, at least this tabulation system can more
accurately gauge disease extent, which is important in
evaluating results of treatment. This system has been
developed with input from the worlds leading experts in
the research and surgical management of endometriosis.
It contains all of the basic information thought to be
important in quantifying the extent of disease in a
patient. It is based on Excel, a commonly used spread-
sheet with both Macintosh and PC versions, and can be
expanded or simplified by end-users with facility in
using Excel.
The interactive spreadsheet contained in AAGLEndo-
Tab allows entry of administrative and clinical data on
almost 1000 patients. As each patient is entered, the
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Endometriosis classification Adamson 217
program automatically computes totals for each patient
row as well as grand totals for all patient columns. Basic
statistical calculations are offered, including ranges,
sums, averages, and standard deviations. The data can
be exported to a more robust statistical package for more
in-depth analysis.
Since developing the tabulation format, AAGL has pro-
ceeded with a project to ask endometriosis experts to give
a weighted score to different anatomical factors that they
think are important with respect to pain and infertility.
After receiving responses from 30 individuals, data have
been analyzed and scores assigned. Currently, these same
surgeons are retrospectively entering scores for some of
their patients to determine whether the classification that
results will predict the outcomes for these patients.
Following analysis of the data, further refinement will
hopefully result in a classification system for pain and
possibly for infertility.
Current considerations for classifying endometriosis
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
patients in consistent time frames. Absence of use of
standardized and validated systems has made interpret-
ation of much of the data in the literature difficult with
respect to classification and outcomes [32
].
Newer imaging technologies might become useful in
classifying endometriosis. Transvaginal sonography
(TVS) has been found to be a good test for assessing
the severity of pelvic endometriosis. TVS was particularly
accurate in detecting severe disease and deep invasive
endometriosis and therefore potentially could add value
to a classification system [33
35
]. Thin-section oblique
axial T2-weighted magnetic resonance images to assess
uterosacral ligament endometriosis have been reported to
improve the success of conventional MRI and potentially
could contribute to new classification systems based on
imaging [36
]. Recent studies on histology of endome-
triosis could potentially provide the basis for histologic
classification of disease that could be associated with
pain. The histologic differentiation in superficial endo-
metriosis, deeply infiltrating endometriosis, and ovarian
endometriomas was evaluated according to a previously
proposed classification system and differences were
found [37]. In another study, endometrial biopsy, with
detection of nerve fibers, provided a reliability of diag-
nosis of endometriosis that was close to the accuracy of
laparoscopic assessment by experienced gynecological
laparoscopists [38]. Recent evidence also indicated that
ectopic endometriotic implants recruit their own unique
neural and vascular supplies through neuroangiogenesis.
It is believed that these nascent nerve fibers in endome-
triosis implants influence dorsal root neurons within the
 218 Reproductive endocrinology
central nervous system, increasing pain perception in
patients [39
]. Future understanding of these physiologic
mechanisms may one day provide a basis for classifying
endometriosis.
Other studies have evaluated serum and other concen-
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-
bilities for patients with endometriosis. Lower antimul-
lerian hormone serum levels and an association with the
severity were found in women with endometriosis. This
information might be useful in patients, especially those
with severe endometriosis, undergoing controlled ovarian
stimulation [40]. Leptin concentrations in the peritoneal
fluid of women with ovarian endometriosis have been
found to be different according to the presence of a deep
or superficial ovarian disease, suggesting that leptin
could play an active role in promoting the development
of superficial ovarian endometriomas and that super-
ficial and deep ovarian endometriomas could have a
different pathogenesis [41]. Seeber et al. [42

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

of special interest


of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 301).
1 Sampson JA. Perforating hemorrhagic (chocolate) cysts of ovary: their im-
portance and especially their relation to pelvic adenomas of endometriotic
type (adenomyoma of the uterus, rectovaginal septum, sigmoid, etc.). Arch
Surg 1921; 3:245261.
2 Acosta AA, Buttram VC Jr, Besch PK, et al. A proposed classification of pelvic
endometriosis. Obstet Gynecol 1973; 42:1925.
3 Kistner RW, Siegler AM, Behrman SJ. Suggested classification for endome-
triosis: relationship to infertility. Fertil Steril 1977; 28:10081010.
4 Buttram VC Jr. An expanded classification of endometriosis. Fertil Steril 1978;
30:240242.
5 American Fertility Society. Classification of endometriosis. Fertil Steril 1979;
32:633634.
6 Guzick DS, Bross DS, Rock JA. Assessing the efficacy of the American
Fertility Societys classification of endometriosis: application of a dose-
response methodology. Fertil Steril 1982; 38:171176.
7 Adamson GD, Frison L, Lamb EJ. Endometriosis: studies of a method for the
design of a surgical staging system. Fertil Steril 1982; 38:659666.
8 Buttram VC Jr. Evolution of the revised American Fertility Society classification
of endometriosis. Fertil Steril 1985; 43:347350.
9 Candiani GB. The classification of endometriosis: historical evolution, critical
review and present state of the art. Acta Eur Fertil 1986; 17:8592.
10 American Fertility Society. Revised American Fertility Society classification of
endometriosis: 1985. Fertil Steril 1985; 43:351352.
11 American Society for Reproductive Medicine. Revised American Society for
Reproductive Medicine classification of endometriosis: 1996. Fertil Steril
1997; 67:817821.
12 Vercellini P, Vendola N, Bocciolone L, et al. Reliability of the visual diagnosis of
ovarian endometriosis. Fertil Steril 1991; 56:11981200; comment in Fertil
Steril 1992; 58:221222; discussion 223224.
13 Canis M, Bouquet De Jolinieres J, et al. Classification of endometriosis.
Baillieres Clin Obstet Gynaecol 1993; 7:759774.
14 Hornstein MD, Gleason RE, Orav J, et al. The reproducibility of the revised
American Fertility Society classification of endometriosis. Fertil Steril 1993;
59:10151021.
15 Rock JA. The revised American Fertility Society classification of endometrio-
sis: reproducibility of scoring: ZOLADEX Endometriosis Study Group. Fertil
Steril 1995; 63:11081110.
16 Redwine DB. The distribution of endometriosis in the pelvis by age groups
and fertility. Fertil Steril 1987; 47:173175.
17 Vercellini P, Trespidi L, De Giorgi O, et al. Endometriosis and pelvic pain:
relation to disease stage and localization. Fertil Steril 1996; 65:299304.
18 Fedele L, Bianchi S, Bocciolone L, et al. Pain symptoms associated with
endometriosis. Obstet Gynecol 1992; 79:767769.
19 Adamson GD, Hurd SJ, Pasta DJ, Rodriguez BD. Laparoscopic endometriosis
treatment: is it better? Fertil Steril 1993; 59:3544.
20 Guzick DS, Silliman NP, Adamson GD, et al. Prediction of pregnancy in
infertile women based on the American Society of Reproductive Medicines
revised classification of endometriosis. Fertil Steril 1997; 67:822829.
21 Adamson GD. Disease classification and behavior. In: Giudice L, Evers H,
Healy D, editors. Endometriosis: science and practice. Oxford, England:
Wiley-Blackwell; 2011 (in press).
22 American Society for Reproductive Medicine. Management of endometriosis
in the presence of pelvic pain. Fertil Steril 1993; 60:950951.
23 Adamyan L. Additional international perspectives. In: Nichols DH, editor.
Gynecologic and obstetric surgery. St. Louis: Mosby Year Book; 1993.
pp. 11671182.
24 Martin DC, Batt RE. Retrocervical, rectovaginal pouch and rectovaginal
septum endometriosis. J Am Assoc Gynecol Laparosc 2001; 8:1217.
25 Chapron C, Fauconnier A, Vieira M, et al. Anatomical distribution of deeply
infiltrating endometriosis: surgical implications and proposition for a classi-
fication. Hum Reprod 2003; 18:157161.
26 Tuttlies F, Keckstein J, Ulruch U, et al. ENZIAN-score: a classification of deep
infiltrating endometriosis. Zentralbi Gynakol 2005; 127:275281.
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Endometriosis classification Adamson 219
27 Tuttlies F, Keckstein J, Ulrich U, et al. ENZIAN-Klassifikation zur Diskussion
gestellt: Eine neue differenzierte Klassifikation der tief infiltrierenden Endo-
metriose (ENZIANClassification presented for discussion: a new detailed
classification of deep infiltrating endometriosis). J Gynakol Endokrinol 2008;
18:713.
28 Haas D, Chvatal R, Habelsberger A, et al. Comparison of revised American


Fertility Society and ENZIAN staging: a critical evaluation of classifications of
endometriosis on the basis of our patient population. Fertil Steril 2011;
95:15741578.
This study compares the rAFS and ENZIAN staging systems and concludes that
there is duplication of scoring which makes the ENZIAN system not just com-
plementary to the rAFS system. Modifications to ENZIAN nomenclature that would
simplify it, standardize the classification, and enhance its descriptive value are
suggested.
29 Adamson GD, Pasta DJ. Endometriosis fertility index: the new, validated


endometriosis staging system. Fertil Steril 2010; 94:16091615.
This study took a different approach to developing a system for fertility patients:
collect clinical data prospectively, utilize outcomes assessment for infertility, do
comprehensive statistical 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 modified to optimize the staging system. The EFI
can be used to decide what type of treatment patients should undergo, for how
long and at what cost before considering the ARTs following endometriosis
surgery.
30 Endometriosis Classification Committee. Ad hoc committee of the AAGL.
AAGL Endometriosis Tabulation System. 2007. AAGL, Cypress, California,
USA 90630.
31 Martin DC, Adamson GD, Keckstein J, Chapron C. New classification of
endometriosis: do we need it? AAGL Annual Meeting; Orlando, Florida; 17
November 2009. AAGL, Cypress, California, USA 90630.
32 Droz J, Howard FM. Use of the short-form McGill pain questionnaire as a

diagnostic tool in women with chronic pelvic pain. J Minim Invasive Gynecol
2011; 18:211217.
This article discusses the uses of this questionnaire and its limitations in diagnos-
ing causes of chronic pelvic pain.
33 Coccia ME, Rizzello F. Ultrasonographic staging: a new staging system for

deep endometriosis. Ann N Y Acad Sci 2011; 1221:6169.
This article suggests a new staging system for deep, infiltrating endometriosis
based on ultrasonographic findings.
34 Ballester M, Santulli P, Bazot M, et al. Preoperative evaluation of posterior

deep-infiltrating endometriosis demonstrates a relationship with urinary dys-
function and parametrial involvement. J Minim Invasive Gynecol 2011; 18:36
42.
Patients with posterior deep infiltrating endometriosis have a high incidence of
urinary symptoms. Parametrial endometriosis is associated with altered urinary
function and should be systematically evaluated in these patients.
35 Holland TK, Yazbek J, Cutner A, et al. Value of transvaginal ultrasound in

assessing severity of pelvic endometriosis. Ultrasound Obstet Gynecol 2010;
36:241248.
Transvaginal ultrasound (TVS) is a good test for assessing the severity of
pelvic endometriosis. TVS is particularly accurate in detecting severe disease,
which could facilitate more effective triaging of women for appropriate surgical
care.
36 Bazot M, Gasner A, Ballester M, Darai E. Value of thin section oblique axial

T-2 weighted magnetic resonance images to assess uterosacral ligament
endometriosis. Hum Reprod 2011; 2:346353.
Thin-section oblique axial T2-weighted imaging can improve the success of
conventional MRI for assessment of uterosacral ligament endometriosis. Further
prospective studies are required before this new MR protocol is performed
routinely for suspected pelvic endometriosis.
37 Kamergorodsky G, Ribeiro PA, Galvao MA, et al. Histologic classification of
specimens from women affected by superficial endometriosis, deeply infil-
trating endometriosis, and ovarian endometriomas. Fertil Steril 2009;
92:20742077.
38 Al-Jefout M, Dezarnaulds G, Cooper M, et al. Diagnosis of endometriosis by
detection of nerve fibres in an endometrial biopsy: a double blind study. Hum
Reprod 2009; 24:30193024.
39 Asante A, Taylor RN. Endometriosis: the role of neuroangiogenesis. Annu Rev

Physiol 2011; 73:163182.
Recent evidence indicates that ectopic endometriotic implants recruit their own
unique neural and vascular supplies through neuroangiogenesis. It is believed that
these nascent nerve fibers in endometriosis implants influence dorsal root neurons
within the central nervous system, increasing pain perception in patients. Future
understanding of these physiologic mechanisms may one day provide a basis for
classifying endometriosis.
40 Shebl O, Ebner T, Sommergruber M, et al. Anti-Muellerian hormone serum
levels in women with endometriosis: a casecontrol study. Gynecol Endo-
crinol 2009; 25:713716.
 220 Reproductive endocrinology
41 Alviggi C, Clarizia R, Castaldo G, et al. Leptin concentrations in the peritoneal
fluid of women with ovarian endometriosis are different according to the
presence of a deep or superficial ovarian disease. Gynecol Endocrinol
2009; 25:610615.
42 Seeber B, Sammel MD, Fan X, et al. Proteomic analysis of serum yields six


candidate proteins that are differentially regulated in a subset of women with
endometriosis. Fertil Steril 2010; 93:21372144.
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-
step diagnostic algorithm, the authors were able to diagnose 55% of patients, with
99% accuracy as to the status of disease. Further combining this algorithm with
that derived by the authors previous study of serum putative markers (monocyte
chemoattractant protein 1, migration inhibitory factor, leptin, and cancer antigen-
125 or CA-125) improved their diagnostic capability to 73% of patients, with 94%
overall accuracy.
43 El-Kasti MM, Wright C, Fye HK, et al. Urinary peptide profiling identifies a

panel of putative biomarkers for diagnosing and staging endometriosis. Fertil
Steril 2011; 95:1261e61266e6.
Urinary proteomic analysis may provide a novel method of diagnosing and staging
endometriosis.
44 Lin W, Chen S, Li M, et al. Expression of macrophage migration inhibitory

factor in human endometriosis: relation to disease stage, menstrual cycle and
infertility. J Obstet Gynaecol Res 2010; 36:344351.
The expression of MIF was increased significantly in the eutopic and ectopic
endometrial tissue of women with endometriosis, and this factor may play a
possible role in endometriosis-associated infertility.
Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
45 Hsu AL, Khachikyan I, Stratton P. Invasive and noninvasive methods

for the diagnosis of endometriosis. Clin Obstet Gynecol 2010; 53:413
419.
Laparoscopic visualization, preferably with histologic confirmation, has been the
gold standard for endometriosis diagnosis. No good noninvasive tests exist,
although imaging might be helpful for more severe disease and there has been
a recent focus on the presence of nerve fibers in eutopic endometrium of
endometriosis patients.
46 Borghese B, Barbaux S, Mondon F, et al. Research resource: genome-

wide profiling of methylated promoters in endometriosis reveals a sub-
telomeric location of hypermethylation. Mol Endocrinol 2010; 24:1872
1885.
In line with the current theory of the endometrial origin of endometriosis, the overall
methylation profile was highly similar between the endometrium and the lesions. It
showed promoter regions consistently hypomethylated or hypermethylated (more
than 1.5 times, as compared with endometrium) and others specific to one given
subtype. Although there was no systematic correlation between promoter methy-
lation and expression of nearby genes, 35 genes had both methylation and
expressional alterations in the lesions. These genes, reported for the first time,
might be of interest in the development of endometriosis.
47 Rogers PA, DHooghe TM, Fazleabas A, et al. Priorities for endometriosis
research: recommendations from an international consensus workshop.
Reprod Sci 2009; 16:335346.
48 Adamson GD, Kennedy S, Hummelshoj L. Creating solutions in endome-
triosis: global collaboration through the World Endometriosis Research
Foundation. J Endometriosis 2010; 2:36.