Aub 1

Accepted Manuscript
Practical Aspects of the Two FIGO Systems for Management of AUB in the
Reproductive Years
Malcolm G. Munro, MD, FACOG, FRCS(c)
PII: S1521-6934(16)30088-8
DOI: 10.1016/j.bpobgyn.2016.09.011
Reference: YBEOG 1647
To appear in: Best Practice & Research Clinical Obstetrics & Gynaecology
Received Date: 15 September 2016
Accepted Date: 23 September 2016
Please cite this article as: Munro MG, Practical Aspects of the Two FIGO Systems for Management of
AUB in the Reproductive Years, Best Practice & Research Clinical Obstetrics & Gynaecology (2016),
doi: 10.1016/j.bpobgyn.2016.09.011.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
PT
Practical Aspects of the Two FIGO Systems for Management of AUB in the Reproductive
Years
RI
SC
Malcolm G. Munro MD, FACOG, FRCS(c)
Departments of Obstetrics and Gynecology, David Geffen School of Medicine, University of
U
California, Los Angeles and Kaiser Permanente, Los Angeles Medical Center
AN
Word Count Without References: 7,101
M
D
Corresponding author:
TE
Malcolm G Munro,
Departments of Obstetrics and Gynecology,
David Geffen School of Medicine at UCLA
Kaiser Permanente, Los Angeles Medical Center
EP
Station 3-B, 4900 Sunset Boulevard

Los Angeles, CA 90027
mmunro@ucla.edu
(M) 01-818.599.0323
C
AC
The author has no disclosures related to the content of this manuscript.

ACCEPTED MANUSCRIPT
Munro PALM-COEIN Practical Applications 2
ABSTRACT
The FIGO systems defining nomenclature and symptoms of abnormal uterine bleeding
(AUB) in the reproductive years (System 1), and the PALM-COEIN classification of causes of
AUB (System 2), are designed to facilitate research, education, and the provision of optimum
clinical care for affected women. Development of these systems has been the result of a
collaborative effort of experts in bench, translational and clinical research from six continents
aided by a spectrum of representatives from relevant medical societies, journals and regulatory
PT
bodies. Integral to this development has been a decision to cease the use of poorly defined and
inconsistently used terms such as menorrhagia, metrorrhagia, and dysfunctional uterine bleeding,
to name a few, and replace them with a set of terms and definitions that are relatively easily
RI
understood and translated into the spectrum of languages used by medical providers and patients
throughout the world. The utilization of these systems requires a disciplined approach to
obtaining a menstrual history, relatively simple laboratory investigations, and the appropriate use
SC
of imaging techniques accessible to most clinicians worldwide. This section describes the two
systems, their crucial role in guiding investigation, and an approach to implementation, all
designed to facilitate the creation of therapeutic options considering the identified factors
contributing to the problem of nongestational AUB.
U
AN
Key Words: Abnormal uterine bleeding; heavy uterine bleeding; heavy menstrual
bleeding; menorrhagia; metrorrhagia; irregular uterine bleeding; irregular menstrual bleeding;
intermenstrual bleeding; FIGO; PALM-COEIN; adenomyosis, leiomyoma, endometrial polyp,
endometrial hyperplasia, anovulatory bleeding, coagulopathy, isthmocele, arteriovenous
M
malformation.
D
TE
C EP
AC
ACCEPTED MANUSCRIPT
I. INTRODUCTION
Nongestational abnormal uterine bleeding (AUB) in the reproductive years is defined as
bleeding from the uterine corpus, that is abnormal in duration, volume, frequency and/or
regularity and has been present for the majority of the previous six months(1).The AUB may be
acute or chronic and can be caused by disorders of ovulatory function, abnormalities in local or
systemic hemostasis or any of a number of structural abnormalities including polyps,
adenomyosis, leiomyomas (also known as fibroids or myomas) and premalignant endometrial
PT
disease or uterine carcinoma or sarcoma. In addition, AUB may be a consequence of the use of
intrauterine contraceptive devices or one of a spectrum of pharmacologic agents ranging from
gonadal steroids to medications that impact dopamine metabolism, and, subsequently, ovulatory
function. Symptoms experienced by patients comprise one or a combination of heavy menstrual
RI
bleeding (HMB), intermenstrual bleeding (IMB), and irregular menstrual bleeding as well as
associated symptoms that may include dysmenorrhea and fatigue related to iron deficiency and
iron deficiency anemia (IDA).
SC
The worldwide impact of AUB varies from modest to severe disruption of work
productivity and quality of life (2, 3) to contribution to maternal morbidity and mortality for
pregnant women with pre-existing AUB-related anemia (4, 5). The importance of effective
U
clinical care cannot be overestimated – approaches that can range from common sense
interventions such as iron therapy, to a range of simple and complex pharmaceutical and
procedural therapies.
AN
Determination of the extent and severity of symptoms can be difficult as most women lack
a metric with which to quantify their menstrual flow and indeed may have been told that their
M
heavy bleeding is normal, a circumstance that frequently makes them “prisoners” of their own
experience, unaware of the magnitude of their blood loss and the resulting impact on their quality
of life.
D
Key elements of successful therapy include identification of the potential contributors to

the symptoms as well as determination of the patient’s desires including her plans for immediate
or future fertility. While hysterectomy remains an intervention that reliably treats AUB from any
TE
cause, it is an unreasonable option for those who wish to preserve or enhance fertility, and, even
for those who do not, incurs morbidity, time, and both direct and indirect costs. Successful uterine
preserving therapy for women with acute and chronic AUB requires a thoughtful and usually
EP
complete evaluation for the potential causes or contributors to the symptoms.
The process of investigation can be optimized by initiating the process with a structured
history based upon use of the two FIGO systems; the first defining normal and abnormal uterine
C
bleeding(6, 7); the second the PALM-COEIN classification system of AUB in the reproductive
years(1). Together, these systems can be used to structure and organize the investigation that is
AC
based upon a structured history, appropriate laboratory tests and appropriate imaging procedures.
II. The SYSTEM for DEFINITION of NORMAL MENSTRUAL BLEEDING and

NOMENCLATURE of SYMPTOMS
The first FIGO system is designed to standardize both nomenclature and the
parameters of normal and abnormal uterine bleeding defined by the 5th to 95% percentiles
based on the available large-scale epidemiological studies (Figure 1)(6, 7). First published
simultaneously in 2007, in Fertility and Sterility and Human Reproduction, what is now
FIGO’s system of nomenclature and definitions has undergone very modest modifications
that will continue to be clarified, modified, and revised as appropriate (6, 7). Important to
this system is replacement of ill-defined terms such as “menorrhagia”, “menometrorrhagia”,
and “dysfunctional uterine bleeding”, replacing them with unambiguous terms describing
ACCEPTED MANUSCRIPT
frequency, regularity, duration and volume. Included is the term HMB, a symptom (not a
diagnosis), that has been described by the National Institute for Health and Clinical
Excellence as “excessive menstrual blood loss, which interferes with a woman's physical,
social, emotional and/or material quality of life (8). Details regarding this system can be
found elsewhere in this symposium (Harlow S and Fraser, IS “Internal” Reference “The
spectrum of menstrual symptomatology and patterns of bleeding).
PT
III. The PALM-COEIN SYSTEM for CLASSIFICATION of CAUSES
The second of the two FIGO systems is the classification of potential causes of AUB in
RI
the reproductive years (Figure 2). The classification system, known by the acronym “PALM-
COEIN”, was developed and first published in a textbook (9), then ultimately accepted by
FIGO in 2010 and finally published together with the nomenclature system and definitions
SC
in 2011 (1). The nine basic categories are as follows: Polyp; Adenomyosis; Leiomyoma;
Malignancy and hyperplasia; Coagulopathy; Ovulatory Disorders; Endometrium; Iatrogenic; and
Not Otherwise Classified. The components of the “PALM” group are discrete structural entities
that are measurable using imaging techniques, and/or with histopathology while the “COEI”
U
group comprises entities that are not defined by imaging or histopathology – they are “non-
structural”. Each of the categories was created to facilitate sub-classification systems designed to
AN
further facilitate clinical management or basic or clinical research. The system was constructed
recognizing that any patient could have one or a spectrum of entities that could cause or
contribute to the AUB and that definable entities such as adenomyosis, leiomyomas and
endocervical or endometrial polyps may frequently be asymptomatic and, therefore, not a
M
contributor to the presenting symptoms.
D
1. Polyps (AUB-P)
Polyps are categorized as either being present or absent based on one or a combination of
TE
ultrasound, ideally, contrast hysterosonography, and hysteroscopic imaging with or without

histopathology. While there is no distinction regarding the size or number of polyps it is probably
important to exclude polypoid appearing endometrium from this category, for such an appearance
may well be a variant of normal. While not currently included in the classification system, the
EP
clinician should describe polyp dimensions, location, number, morphology and, following
removal, the histopathology of the lesion.
C
2. Adenomyosis (AUB-A)
AC
Whereas the role of adenomyosis in the genesis of AUB is unclear (10, 11), most would consider
that in at least some instances there is a cause and effect relationship. While criteria for
diagnosing adenomyosis have traditionally been based on the histopathological determination of
the depth of “endometrial” tissue beneath the endometrial-myometrial junction as determined at
hysterectomy, these criteria vary substantially (12) and, regardless, have little value when
evaluating women with AUB. There exist both highly sensitive sonographic and MRI based
diagnostic criteria (13-15). Given this evidence, and recognizing the limited access of women to
MRI in the world community, the FIGO system relies on sonographic criteria for the diagnosis of
adenomyosis (16).
As with polyps and leiomyomas, adenomyosis is a disorder that should have its own sub-
classification system (17), and it is clear that there should be an initiative to standardize methods
ACCEPTED MANUSCRIPT
of both imaging and histopathological diagnosis.
3. Leiomyomas (AUB-L)
Leiomyomas are extremely common benign fibromuscular tumors of the myometrium. They
manifest with a spectrum of size, number and location, (submucous, intramural, subserous and
combinations of same) and, because of their prevalence, and variable relationship to symptoms,
PT
have a unique PALM-COEIN sub-classification system.
The primary classification system reflects only the presence or absence of one or more
leiomyomas, regardless of the location, number and size. The criterion for determining the
RI
presence of leiomyomas requires only sonographic examination confirming that one or more
myomas are present.
SC
In the secondary system, the clinician is required to distinguish myomas that contact the
endometrium (submucous or “sm”) from others (o), this because it is generally considered that
such (sm) lesions are those that most likely contribute to the genesis of AUB.
U
The tertiary system is based on the predicate Wamsteker system for submucous leiomyomas
(Type 0, 1 and 2)(18) and expanded to include tumors that just contact the endometrium without
AN
distortion of the endometrial cavity (Type 3) intramural tumors that have myometrium between
their central and peripheral boundaries and the endometrium and serosa (Type 4) and subserous
tumors that are categorized according to the relative proportions of the tumors within and
extruding from the myometrium (Types 5, 6, & 7) (Figure 2). When a myoma abuts or distorts
M
both the endometrium and serosa, it is categorized first by the sm classification, then by the
subserosal location, with these two numbers separated by a hyphen. This tertiary classification is
not only useful for basic and clinical investigators but also for surgeons who perform
D
myomectomy to facilitate the identification of situations where resectoscopic myomectomy is not

appropriate.
TE
Although not part of the system, clinicians and investigators are encouraged to include such data
as the size of the uterus in weeks gestation and/or the single longest measurement and/or volume
in cubic centimeters, the location of the myoma or myomas (eg fundus, lower segment, cervix
EP
etc), and the estimated number of tumors.
4. Malignancy and Premalignant Conditions (AUB-M)

Although relatively uncommon, atypical hyperplasia (now frequently called endometrial
C
intraepithelial neoplasia or EIN (19)) and malignancy are important potential causes of, or
findings associated with AUB, and must be considered in virtually any woman in the reproductive
AC
years. The PALM-COEIN classification system is not designed to replace those of the WHO and
FIGO for categorizing endometrial hyperplasia and neoplasia (20, 21). Consequently, when
investigation of women in the reproductive years with AUB identifies a premalignant hyperplastic
or malignant process, they are classified as AUB-M and then “sub-classified” by the appropriate
WHO or FIGO system.
5. Coagulopathy (Systemic Disorders of Haemostasis)(AUB-C)

Abnormal uterine bleeding, and particularly the symptom of HMB, that is associated with any of
the spectrum of systemic disorders of haemostasis that are called coagulopathies, is designated as
AUB-C. There is a relatively high prevalence of these disorders in several developing (22, 23) and
developed countries (24-26). Indeed, there exists high quality evidence that about 13 per cent of
women with the symptom of HMB have a diagnosis of von Willebrand Disease if adequate
ACCEPTED MANUSCRIPT
laboratory investigation is performed (27). It is important to understand that most of these are
mild variants and may often have a minor role in the symptoms of AUB in a given individual.
Nevertheless, it also seems important to consider these disorders in part because they likely do
contribute to some cases of AUB and the information may be valuable for future surgical
procedures and the counseling of children and other blood relatives. Women with AUB while on
therapeutic anticoagulation, formerly designated AUB-C are now categorized as AUB-I (below).
6. Ovulatory Disorders (AUB-O)
PT
When ovulatory dysfunction manifests with AUB there is generally some combination of
unpredictable timing of bleeding and a variable amount of flow, which in some cases results in the
symptom of HMB (28). Indeed, while anovulation may result in amenorrhoea, many women may
RI
actually ovulate infrequently or randomly, a circumstance that results in a variety of symptoms
ranging from extremely light and infrequent bleeding, to episodes of unpredictable and extreme
HMB that require medical or surgical intervention. When HMB is associated with delayed or
absent ovulation, the loss of luteal progesterone results in persistent proliferative endometrium,
SC
which appears to be associated with reduced local levels of F2α, one of the necessary ingredients
for efficient endometrial haemostasis (29).
In the late reproductive years there is emerging evidence that another disorder exists in ovulatory
U
women - the “luteal out-of-phase” (LOOP) event (28, 30). These women ovulate, but recruit
follicles early in the luteal phase, a circumstance that results in high circulating levels of
oestradiol and related HMB. AN
While in most instances there is no definable cause for ovulatory disorders, many can be traced to
endocrinopathies such as polycystic ovarian syndrome, hypothyroidism, and hyperprolactinemia
M
as well as other factors including mental stress (31), obesity, anorexia, weight loss, and extreme
aerobic exercise(32, 33). In some instances, the disorder may be iatrogenic, caused by gonadal
steroids or drugs that impact dopamine metabolism such as phenothiazines and tricyclic
D
antidepressants – in such instances, they may be included in AUB-I. It is also apparent that
otherwise unexplained ovulatory disorders frequently occur at the extremes of reproductive
TE
age(34, 35).
7. Endometrial Causes (AUB-E)

When AUB occurs in the context of predictable and cyclical menstrual cycles, suggesting
EP
ovulation, and particularly but not only when no other definable causes are identified, the
mechanism is likely a primary disorder residing in the endometrium (36). If the symptom is HMB
(previously called “menorrhagia”), there may exist a primary disorder of local endometrial
haemostasis. There exists high quality evidence demonstrating deficiencies in the local production
C
of vasoconstrictors such as endothelin-1 (37) and prostaglandin F2α (38, 39), and it is evident that
affected women typically have accelerated breakdown of endometrial clot secondary to excessive
AC
production of plasminogen activator (40), and increased local production of substances that
promote vasodilation such as prostaglandin E2 and prostacyclin (PGI2)(38, 41). Unfortunately,
and despite this longstanding evidence, laboratory testing for such abnormalities are not currently
available to clinicians.
It is likely that there exist other primary endometrial disorders that do not manifest in the
symptom of HMB, instead causing intermenstrual or prolonged menstrual bleeding. Prolonged
bleeding may be a manifestation of deficiencies in the molecular mechanisms of endometrial
repair (42). These disorders may be secondary to any or a combination of mechanisms including
endometrial inflammation or infection, abnormalities in local inflammatory response, and
abnormal endometrial vasculogenesis (39). However, the role of infection and other local
inflammatory disorders in the genesis of AUB is not well defined, and is sometimes confounded
ACCEPTED MANUSCRIPT
by the normal presence of inflammatory cells in the endometrium (39).
Currently, despite this evidence and spectrum of potential mechanisms, and for the foreseeable
future, the FIGO system will categorize all suspected primary endometrial disorders as AUB-E
and will encourage clinicians to consider the diagnosis in women with apparently normal
ovulatory function with either no other definable cause, or when it is suspected that a structural
abnormality is asymptomatic (example Type-6 leiomyoma).
PT
8. Iatrogenic (AUB-I)
There exists a spectrum of medical devices and pharmacological interventions that can cause or
contribute to AUB, that are collectively termed iatrogenic. These include both inert and drug-
RI
eluting intrauterine systems (e.g. levonorgestrel-releasing IUS) and pharmacologic agents that
directly impact the endometrium (e.g. all oral or systemic progestins), interfere with blood
coagulation mechanisms (e.g. warfarin, low molecular weight heparin preparations) or influence
the systemic control of ovulation. When abnormal bleeding is deemed to be related to iatrogenic
SC
causes it is categorized as AUB-I.
If combination oestrogen and progestogen (E+P) formulations are administered cyclically,

scheduled uterine bleeding generally occurs in conjunction with the periodic withdrawal of the
U
steroidal agents. Unscheduled endometrial bleeding is termed “breakthrough bleeding” or BTB.
Frequently, gonadal steroid preparations, including combined E+P formulations, progestogens,
AN
and rarely androgens, are administered continuously with the goal of establishing amenorrhoea;
any bleeding unrelated to other causes is considered to be AUB-I. There exist other
pharmacological interventions including selective progesterone receptor modulators (SPRMs) and
gonadotrophin releasing hormone agonists and antagonists that are administered with a goal of
M
attaining amenorrhoea, but which frequently are associated with BTB.
For orally administered agents at least, many episodes of BTB are related to reduced circulating
D
gonadal steroid levels secondary to compliance issues, resulting in reduced suppression of FSH
production, and subsequent follicular development and increased endogenous oestradiol (43).
TE
Other potential causes of reduced circulating levels of circulating oestrogens and progestins
include the use of anticonvulsants such as valproic acid (44) and antibiotics such as rifampin and
griseofulvin (45) and cigarette smoking and related enhanced hepatic metabolism of gonadal
steroids (46). Valproic acid may also impact gonadal steroid metabolism by increasing serum
EP
androgen levels and otherwise being associated with features of PCOS(44).
As many as 55 per cent of women using a 52 mg levonorgestrel-releasing intrauterine system

(LNG-IUS) can be expected to experience BTB in the first six months after placement, after
C
which it reduces to about 15-20%. Approximately 20% become amenorrhoeic by the end of the
second year, rising to 50% by year five (47).
AC
Another contributor to AUB-I can be pharmaceuticals used to treat depression (48) or those that
interfere with dopamine metabolism, disordered prolactin release, and resulting disorders of
ovulation (49).
An important cause of AUB-I, in particular the symptom of HMB, is the use of anticoagulant
drugs such as warfarin, heparin, low molecular weight heparin and some of the new orally active
anticoagulants. Initially included in AUB-C, the FIGO MDC has determined that the rightful
place for AUB related to these agents is in the AUB-I category.
9. Not Otherwise Classified (AUB-N)

ACCEPTED MANUSCRIPT
There are a number of conditions and abnormalities, possible causes AUB, that are either rare or
their role in pathogenesis is not well defined. Examples include arteriovenous malformations (50)
and Caesarean scar defects (“Isthmocele”) (51). In addition, there may exist other disorders, not
yet identified, that would be defined only by biochemical or molecular biological assays.
Collectively, these entities (or future entities) have been placed in a category termed “Not
Otherwise Classified” or AUB-N. As further evidence becomes available, such abnormalities may
be allocated a separate category, or they could be assigned to one of the existing categories in the
classification system.
PT
IV. SYSTEMATIC APPROACH TO INVESTIGATION
1. Overview
RI
The information obtained by a structured approach to investigation may identify one or
more possible causes of the AUB. When multiple potential causes or contributors are identified or
suspected, it is incumbent on the clinician to thoughtfully integrate the information and identify
SC
the most likely mechanism in a given patient. For girls and women with chronic AUB these
strategies include:
a. Identification of the symptom-type of chronic AUB - HMB, irregular uterine bleeding,
U
IMB, or unscheduled or breakthrough bleeding in the context of the use of gonadal
steroids or other agents for contraception or therapy.
AN
b. Determination of the clinical impact of the symptom(s) on the individual patient such
as interference with lifestyle or the presence of iron deficiency with or without related
anemia.
c. Evaluation for the underlying cause(s) of the AUB using a systematic and
M
appropriately comprehensive approach based upon the PALM-COEIN system for
classification of causes. The progress and results of this investigation may be recorded
in an investigational matrix like those shown in Figures 3 and 5a-d (52).
D
Optimal management of patients with chronic AUB requires a menstrual history obtained
TE
with detail at a level rarely taught in medical school or residency training programs. Not only is
this necessary to distinguish among those with ovulatory cycles, ovulatory disorders, and bleeding
between normal periods, but also to understand the impact of the AUB on the patient’s quality of
life. This information is typically followed by available investigative techniques that preferably
EP
start with transvaginal ultrasonic imaging of the uterus, if possible, during the initial evaluation.
Absent immediately available transvaginal ultrasound, or where it is not appropriate because of
factors such as virginal status or patient reticence, the clinician arranges for appropriate imaging
and laboratory testing based upon the history and physical examination.
C
The results of the investigation will allow the clinician to identify one or a combination of
causes or contributors to the abnormal bleeding. This information, together with insight into the
AC
patient’s previous history and desires regarding immediate and future pregnancy will allow for the
design of a menu of appropriate therapeutic options.
When a patient presents with nongestational acute abnormal uterine bleeding defined as
that which, in the opinion of the clinician, is of sufficient severity to warrant urgent intervention
(1), the initial strategy and goals are different. For such bleeding, the primary aims are threefold,
and investigation is critically integrated with management:
a. Assessment for haemodynamic status and stabilization as appropriate.
b. Identification of the most likely underlying cause(s) including evaluation for the
presence of a pregnancy.
ACCEPTED MANUSCRIPT
c. Initiation of immediate intervention(s) designed to promptly reduce or stop the

bleeding.
Once the acute AUB is successfully treated, patient counselling is undertaken based upon
the previous history. Those with no prior history of chronic AUB may be considered for expectant
management as long as no clinically significant finding has been obtained – many, if not most, of
these patients have experienced acute bleeding as a result of a transient ovulatory disorder.
PT
However, if there exists chronic AUB, appropriate investigation is indicated to identify the
potential causes.
2. The Menstrual History
RI
The features that distinguish normal from abnormal uterine bleeding in the reproductive
years have been modified by FIGO based upon a contemporary review of available data, and the
use of a form can facilitate determination of the status of a given patient (Figure 1). Many aspects
SC
of the history are critical for optimal categorization of the causes of the bleeding. For example,
cyclical, predictable menstruation is usually associated with ovulation, while irregular and
unpredictable bleeding is a typical symptom of ovulatory disorders (AUB-O). For those women
who experience intermenstrual bleeding (IMB) in the context of predictable cyclic menses, a focal
U
lesion such as an endometrial polyp is often found (AUB-P)(53).
AN
For chronic AUB, it is essential that the provider clearly determine the duration of the
clinical problem in months or years as well as the cycle length in days, the predictability of onset
of bleeding, and the duration and rate of the bleeding episodes, including the number of heavy
days, and the passage of clots – some women don’t consider the clots to be bleeding. For women
M
with the symptom of HMB, the presence of an underlying coagulopathy can be suggested by
adding structured questions to the menstrual history (Figure 4) (24). For those who are identified
at high risk with this tool, appropriate investigations for coagulopathy are warranted and a referral
to a specialist with expertise in haematology may be required.
D
TE
3. Determination of the Extent of Blood Loss and Impact on Quality of Life

It is recommended that evaluation of AUB symptoms should be based on a patient’s
reported heaviness, frequency, regularity and duration of bleeding (6, 54) in conjunction with the
perceived impact on quality of life and general functioning (8, 55, 56). In routine clinical practice,
EP
attempts at accurate measurement of menstrual blood loss volume are impractical and, in general,
unnecessary. While the impact of the bleeding on the levels of iron or haemoglobin are important
considerations, abnormal haemoglobin is not a prerequisite for investigating AUB including the
symptom of HMB. The aspects of AUB, and especially HMB, that worry women most, include
C
the psychological irritation associated with the bleeding and the complex of accompanying
symptoms, especially pelvic pain, the failure to always contain the gushes of menstrual loss (both
AC
during the day and at night) and the modification in lifestyle behaviours that are necessary to
conceal or contain menstrual flow (56, 57).
Work is ongoing to develop a simple structured menstrual questionnaire for use in
clinical practice, which will assist with assessment of blood loss, total menstrual fluid loss,
lifestyle factors and starting guide to possible underlying causes(58) . (Internal Reference
Matteson). For the present, it is recommended that a series of simple questions be asked, which
encompass as many of the following as practicable: Frequency of changing “menstrual
protection” items, use of ‘double” protection; changing menstrual protection at night; self-
consciousness about odour; inability to contain “gushes” of menstrual flow; embarrassment at
being unable to contain “gushes” of flow and preparations and rituals to prevent embarrassing
ACCEPTED MANUSCRIPT
episodes (8, 57, 58).
4. Pelvic examination
For both acute and chronic AUB, the physical examination may identify potentially
relevant pathology and other features that may influence the investigational and/or treatment plan
most of the clinically significant contributors to the symptoms are not detected as it does not
provide any information about pathology impacting the endometrial cavity. Whereas the physical
PT
examination is limited for the identification of intracavitary causes of AUB, it is of great value in
evaluation of the cervix, vagina, vulva, perineum and perianal regions, possible causes of
abnormal bleeding and local tenderness.
RI
5. Laboratory Assessment
Women with the symptom of HMB should have, at the minimum, a measure of
haemoglobin and haematocrit, and in most instances at least, evaluation of ferritin, total iron and
SC
iron saturation. Testing for coagulation disorders should be performed in women who are
identified by validated instruments such as the questionnaire described previously (Figure 4) (24-
26, 59). Patients determined to be at high risk for coagulopathy based on this instrument should
undergo evaluation, if possible in conjunction with a haematologist, where assays may be
U
obtained for von Willebrand factor, Ristocetin co-factor and a number of other disorders as
appropriate. Other laboratory investigation is performed as appropriate depending on the history.
AN
For example, an assessment of prolactin and thyroid function should be undertaken in women
with ovulatory disorders.
6. Evaluation of the Uterus

M
Evaluation of the uterus is an integral component of the evaluation of patients with chronic
AUB; manual examination is usually inadequate since palpable lesions such as leiomyomas may
not contribute to the bleeding; clinically significant abnormalities are infrequently detected by this
D
process. Conceptually, it is important to consider three components when evaluating the uterus:
(a) assessment of the endometrium for the presence of hyperplasia or malignancy; (b)
TE
visualization of the endometrial cavity and cervical canal for localised lesions such as polyps and
submucous leiomyomas; and (c) evaluation of the myometrium for adenomyosis, leiomyomas,
and, more rarely, arteriovenous malformations. The endocervical epithelium and cervical stroma
should also be assessed considering polyps, malignancy, and abnormalities such as the isthmocele
EP
– a sometime result of previous Caesarean section. Since it is not necessary to evaluate all
components in every patient, it is important to apply these investigative approaches judiciously
considering the age of the patient, existing risk factors, and the previous response, if any, to
medical or surgical interventions.
C
a. The Role of Ultrasound

AC
Currently initial imaging of the uterus is almost always undertaken with two dimensional
(2-D) transvaginal ultrasound (TVUS), a routine component of the investigation in
moderate and high resource settings. However, while most primary care, and many
specialist physicians uncritically accept the printed report describing the findings as an
accurate depiction of the anatomical situation, the quality of the assessment, and
especially the interpretation, are highly dependent on the skill and experience of the
ultrasound operator.
Several developments have improved our ability to detect and define certain structural
lesions, but none are more accessible than contrast hysterosonography performed with the
simultaneous injection of sonographic contrast solutions such as saline or gel, a
circumstance that facilitates evaluation of the endometrial cavity, and the relationship of
ACCEPTED MANUSCRIPT
myometrial abnormalities to the endometrium. Direct comparison between TVUS,

contrast hysterosonography, and hysteroscopy suggests that diagnostic hysteroscopy is
significantly better than the other two techniques at detecting endometrial and
intracavitary lesions, and that contrast sonography is better than conventional TVUS
(60, 61).
Other advances in sonographic imaging include color-flow Doppler assessment to
PT
assist with evaluation of the vascular patterns in endometrial and myometrial lesions and
3D imaging, a technique that may well largely replace MRI for more detailed evaluation
of the uterus. Doppler assessment is particularly useful in the identification of AV
malformations (62), can help distinguish benign from malignant polyps (63, 64), and may
RI
have some utility in differentiating between leiomyomas and leiomyosarcomas (65).
b. Evaluation of the Endometrium
SC
Blind endometrial sampling is the standard method by which women are
assessed for endometrial neoplasia, but there is an emerging role for both sonographic
and hysteroscopic imaging. When atypical endometrial hyperplasia (endometrial
intraepithelial neoplasia) or endometrial cancer or sarcomas are identified, the patient is
U
categorized as having AUB-M.
It is also apparent that there exists a relationship between endometritis, most
AN
notably chlamydial infection of the endometrium and AUB (AUB-E). Consequently, it
may be prudent to consider evaluating for the organism in the endometrium in
symptomatic patients (66).
M
i. Sonographic evaluation
The single-layer thickness of the endometrium in ovulatory women fluctuates in
thickness from about two mm in the early follicular phase to about six mm in the
D
late luteal phase(67). At least in normal sized uteri, the two adjacent layers of
endometrium – in essence, a double thickness – can be readily imaged; a
measurement termed the endometrial echo complex or EEC. Consequently, the
TE
menstrual phase EEC is typically about four mm and increases up to about 12mm
in the late luteal phase. In the presence of ovulatory disorders, absent exposure to
progesterone, the EEC is frequently much greater in thickness - a feature shared by
the great majority of instances of endometrial hyperplasia and endometrial
EP
carcinoma. As a result, TVUS may be considered a component of initial triage of

at-risk premenopausal women with AUB (68). A well-designed study has
suggested that as long as the premenopausal EEC thickness is 12 mm or less (in
C
premenopausal women), there is a very low incidence of endometrial hyperplasia

or neoplasia (69).
AC
ii. Endometrial sampling

Histological assessment of the endometrium requires that a sample (curettage or,
preferably, catheter-based biopsy) be obtained to evaluate for endometrial
hyperplasia or malignancy. Office endometrial sampling has a reasonably high
accuracy and, if an adequate specimen is obtained for the detection of endometrial
carcinomas (70, 71), although sensitivity may be as low as 91% (compared to 98)
in premenopausal versus postmenopausal women(70). However, insufficient tissue
obtained for diagnosis has been reported in 4-29.8% of cases (72-75), and when
only premenopausal women are considered it has been reported to be about 25%
(74). In 10- 25% of patients the previous “traditional D&C” alone does not
uncover existing endometrial pathology (76) and it is associated with adverse
ACCEPTED MANUSCRIPT
outcomes such as haemorrhage (0.4% of cases) and uterine perforation (0.6 –

1.3%) (76). Up to 50% of polyps are missed by blind techniques, some of which
may include atypical hyperplasia or carcinoma(70). Consequently, even if
satisfactory and reassuring blind endometrial sampling is performed, should
symptoms persist, the ideal approach is hysteroscopy with targeted sampling or
excision of polyps or other identified lesions.
There is inconsistency in the medical literature regarding the appropriate selection
PT
criteria for endometrial sampling in premenopausal women. Guidelines such as
those of the New Zealand Guidelines Group and the UK’s National Institute for
Health and Care Excellence (NICE) suggest that endometrial sampling should be
RI
considered in all women with AUB over the age of 45 years (8, 77). Other
investigators have provided more selective criteria considering risk factors for the
presence of unopposed oestrogen (such as obesity and chronic anovulation
manifesting in AUB-O), a feature present in the vast majority of cases of
SC
endometrial carcinoma and one that places at risk those below the 45 year
threshold. It is apparent that premenopausal individuals with AUB and a BMI of
30 or more have up to a fivefold increased risk of having complex, atypical
endometrial hyperplasia or cancer compared with women of normal weight (78-
U
81). Ultrasound thresholds have also been suggested - those with AUB and an EEC
greater than 12 mm should be sampled (69). A New Zealand group identified the
AN
following factors: (1) age over 45 years; (2) obesity (>90kg); (3) a history of
chronic anovulation, infertility, or diabetes; (4) a family history of endometrial
cancer; and (5) prolonged exposure to unopposed oestrogens or tamoxifen(82, 83).
M
iii. Women from families with Lynch syndrome (previously called HNPCC, or
hereditary nonpolyposis colorectal cancer) have a lifetime risk of developing
endometrial cancer that may be as high as 60%, with a mean age of diagnosis
D
between 48 and 50 (84). Consequently, women with AUB of any type who are
known or suspected to be from affected families should be liberally investigated
TE
with endometrial sampling, regardless of age.
c. Assessment for Focal Endometrial and Endocervical Pathology

Accurate structural evaluation of the endometrial cavity and cervical canal requires
EP
imaging with ultrasonographic and/or hysteroscopic techniques. In instances when

vaginal access is limited (for example virginal women, those women very reticent about
examination) evaluation with MRI may be the best option.
In skilled hands TVUS has 96% sensitivity, 86% specificity, 91% positive
C
predictive value and 94% negative predictive value in the diagnosis of intrauterine
abnormalities causing AUB (85) and more recent introduction of high frequency vaginal
AC
probes has further improved image quality and predictive value.(86). In the presence of an
abnormally thick endometrium, when myomas exist suspiciously close to the EEC, or
when abnormal bleeding occurs or persists despite a normal TVUS, contrast sonography
or hysteroscopy is indicated. Contrast hysterosonography with saline or gel infusion
sonography is comparable to hysteroscopy in its sensitivity for the diagnosis of
intracavitary polyps and submucous leiomyomas (60, 61, 87, 88). The major deficiency,
when compared to hysteroscopy, is limited evaluation of the endocervical canal and the
inability to concurrently remove selected lesions unless additional instrumentation is
performed. Endometrial carcinoma and endometrial hyperplasia, especially those arising
as a field defect, may not always be clearly recognizable by endoscopy alone, making
catheter-based endometrial sampling a necessary adjunct to targeted biopsy (89).
ACCEPTED MANUSCRIPT
With modern equipment and at least selective use of local anaesthesia, even
operative hysteroscopy can be performed by most gynaecologists in the office
environment to identify and, if appropriate, direct the biopsy of focal lesions (90-95).
Patients with tortuous or stenotic cervices may be difficult to examine with office
hysteroscopy, but usually even difficult cases can be performed successfully and
comfortably provided there is adequate local anaesthesia (94).
Magnetic resonance imaging has been shown to be accurate in the evaluation of the
endometrial cavity in women with AUB, especially in selected patients in whom SIS or
PT
hysteroscopy are not feasible (96).
d. Evaluation of the Myometrium
RI
The purpose of myometrial assessment is generally to identify and characterize
adenomyosis, adenomyomas, and leiomyomas as well as other abnormalities such as AV
malformations and the uterine isthmocele that may contribute to the genesis of AUB. For
leiomyomas, the number, location, size(s), and FIGO classification should be determined
SC
and documented.
Two-dimensional (2-D) TVUS (and sometimes abdominal ultrasound) is a useful
primary technique for the detection and evaluation of myomas in the myometrium,
although variations in echogenicity and body habitus can reduce the sensitivity of the
U
examination. Furthermore 2-D imaging can be challenging when the aggregate uterine
and leiomyoma volume is quite large, as it is difficult to adequately image and track the
AN
various lesions identified. In such instances, 3-D ultrasound or MRI are of additional
value.
For the diagnosis of adenomyosis, transvaginal ultrasound with the application of
a set of objective criteria for the diagnosis of adenomyosis has been found to be
M
comparable to MRI with approximately 80 per cent sensitivity and similar specificity (97,
98). These criteria include the following: a globular uterine configuration; poorly defined
endometrial-myometrial junction; myometrial echogenic linear striations; thickening of
D
the myometrium; asymmetry of the anterior and posterior myometrial thickness; irregular
myometrial cystic spaces; and a heterogeneous myometrial echotexture. While there is
TE
evidence suggesting a threshold of three of these criteria for making a diagnosis (16), the
ideal number has not been established. As is the case for polyps and leiomyomas,
adenomyosis is a disorder that could benefit from its own sub-classification system(17).
Colour flow Doppler ultrasound is useful in detecting blood flow and,
EP
consequently, is valuable for the detection of arteriovenous malformations and may also
have a role in detecting atypical endometrial polyps and malignancies. However, the most
important application of colour Doppler is in distinguishing focal adenomyosis from
leiomyomas, as myometrial vessels course around the lesion, while in adenomyosis the
C
vessel retains its vertical orientation to the endometrial cavity(99, 100).

AC
MRI has utility in at least selected women with AUB, not only for the detection of
adenomyosis(101) but to distinguish adenomyomas from leiomyomas. For adenomyosis,
although other criteria exist, a measured “junctional zone” thickness of greater than 12
mm correlates well with a histopathological diagnosis of adenomyosis (14, 102). There is
some evidence that quantified irregularity (thinnest to thickest ≥ 4-6 mmm) in the MRI or
3-D ultrasound determined thickness of the junctional zone provides additional sensitivity
for the diagnosis of adenomyosis (16, 103). MRI may be superior to any of transvaginal
sonography, contrast hysterosonography and hysteroscopy for determining the myometrial
involvement of submucous leiomyomas (96).
While the use of myometrial biopsy to distinguish adenomyosis from leiomyomas has
been explored the results are somewhat disappointing. Whereas transcervical needle
ACCEPTED MANUSCRIPT
biopsy seems to have high specificity, it has poor sensitivity for the diagnosis of
adenomyosis when compared to histopathological examination of hysterectomy specimens
(104, 105).
V. IMPLEMENTATION AND INTEGRATION OF RESULTS

There are a number of practical considerations for clinicians who deal with women with
PT
AUB in the reproductive years. The exact order and comprehensiveness of the investigation may
appropriately vary depending upon the clinical situation. It is also important to remember that the
evaluation may reveal more than one potential contributor to the genesis of the AUB, and that,
frequently, identified structural lesions such as adenomyosis, some polyps, and leiomyomas,
RI
especially ≥ Type 3, may be asymptomatic. In these circumstances, clinical judgment should be
applied with trials of therapy utilized, if appropriate and desired by the patient, to address the
symptom(s) and, in the process, assist with the determination of the clinical relevance of
SC
potentially asymptomatic findings.
1. When can the evaluation be abbreviated?
There are a number of situations where all of the investigations described above will not be
necessary, at least initially. This requires that the clinician seek to identify individuals at low
U
risk for malignancy or structural abnormalities. For example the thin 19 year old with apparent
AUB-O manifesting in irregular but light or normal volume menstrual bleeding and a normal
AN
physical examination will not usually require imaging, laboratory assessment or endometrial
sampling. She may be offered expectant management, or, for example, cyclically administered
combination oestrogen and progestogen containing pills, rings or patch contraceptive
formulations to provide regular and predictable withdrawal bleeding, or, used continuously,
M
for suppression of bleeding as desired. A similar situation exists when a young, previously
untreated patient has the symptom of HMB and likely AUB-E, understanding that there may
exist uncommon features – submucous leiomyomas (AUB-Lsm), adenomyosis (AUB-A) not
D
recognizable by physical examination. However, endometrial sampling will be unnecessary if

simple medical therapy is effective, and acceptable to the patient, it may be reasonable to
TE
defer additional imaging evaluation pending the response to a trial of therapy. For women
with the symptom of HMB, it is still necessary to at least measure haemoglobin and
haematocrit, as, while many women with “normal bleeding” are normal in this regard, others
may have existing iron deficiency and iron deficiency anaemia (IDA).
EP
Who should have more extensive and complete evaluation?

A number of features of the initial assessment, including the menstrual history and
physical examination, can be useful in identifying patients who require a more complete
C
evaluation. The first group are those who have an increased risk of endometrial neoplasia.
The criteria for routine endometrial sampling may vary across jurisdictions, but when
AC
ovulatory dysfunction is suggested by the presence of prolonged irregular, unpredictable

bleeding in a woman over the age of 40, evaluation of the endometrium is generally
necessary. And age isn’t the only criterion. For example, the obese 28 year old with a BMI
of 42 and a long history of apparent AUB-O should undergo endometrial sampling for she
could also have EIN (atypical endometrial hyperplasia) or endometrial carcinoma. Another
group are those who have intermenstrual bleeding, a typical manifestation of endometrial
polyps. For others, including women who fail initial therapy, further investigation is
almost always warranted.
VI. CASE STUDIES
Figure 5a
ACCEPTED MANUSCRIPT
a) AUB-LSM
This 32-year-old nulliparous patient has the symptom of heavy menstrual bleeding
- her menstrual pattern suggests ovulation (30-day cycle – range 27 to 33 days, with a
menstrual duration of 9 days and heavy with clots. Although her bimanual examination
demonstrates a normally sized uterus, ultrasound and contrast hysterosonography
demonstrate a FIGO Type 2 leiomyoma. Her haemoglobin level was 10.9 and serum
ferritin and iron saturation all suggested iron deficiency. Since the patient wished to
PT
preserve fertility, she selected a hysteroscopic resection of her leiomyoma after treating her
anaemia and iron deficiency with oral iron.
Figure 5b
RI
b) AUB LO, -O
This 25-year-old para 0000 presents with a nine-month history of irregular
menstrual bleeding, every 14 to 60 days with variable duration and heaviness of
SC
flow – 2 to 11 days. She has a BMI of 33 but no other abnormalities on her general
examination. While manual examination of the uterus is limited, transvaginal
ultrasound demonstrates a 2.5 cm diameter FIGO Type 6 leiomyoma. It is correct to
assume that the leiomyoma is not responsible for the AUB, and that the symptoms
U
are related to an ovulatory disorder. The patient’s thyroid function was normal but
her haemoglobin was 9.3 with red cell indices suggesting iron deficiency anaemia.
AN
Because she didn’t wish pregnancy at this time, she selected cyclically administered
combined contraceptive pills, oral iron replacement, and a weight loss program.
M
Figure 5c
c) AUB-P, -LO
D
This 38-year-old para 2002 presented with a 6-month history of light intermenstrual
bleeding. Her menses were unchanged with a cycle length of 31 +/- 3 days, and a
TE
normal duration of 4 days with normal volume. Examination demonstrated normal

vulva, vagina and cervix – no lesions. Her manual examination suggested a slightly
enlarged uterine corpus. Transvaginal ultrasound demonstrated 3 cm FIGO Type 4
and a 4 cm FIGO type 5 leiomyomas, however, contrast sonohysterogram revealed
EP
a 1.2 cm long by 8 mm wide endometrial polyp. She underwent hysteroscopic

polypectomy and her symptoms resolved. The leiomyomas were clinically
insignificant.
C
Figure 5d
d) AUB-A, -C
AC
This 35 year old nulligravida presented with a lifelong history of the symptom of
heavy menstrual bleeding. Her menses were always cyclic and predictable but long
and heavy with clots. She has fought anaemia all of her life. Over the past several
years, she has experienced progressively worsening dysmenorrhoea, which extends
through the entire period, and, the volume of bleeding and clots is increasing. It is
more difficult to maintain her haemoglobin levels even with 185 mg of elemental
iron every day. She has unexplained bruising on her arms and legs – a lifelong
experience, but more recently she is experiencing bleeding with flossing and
brushing her teeth.
Examination demonstrates a normal appearing woman with some bruising on arms

and legs. Her BMI is 25. The vulva, vagina and cervix are normal, but the uterine
ACCEPTED MANUSCRIPT
corpus is symmetrically enlarged and slightly tender. Transvaginal ultrasound

reveals a globally enlarged uterine corpus with thickened heterogenous
myometrium, a pattern of striae, and a blurred endomyometrial junction. Because
she “failed” the screening test of a coagulopathy, blood assays were obtained
revealing evidence of von Willebrand disease. A haematology consultation was
sought. Ultimately, because she didn’t wish to conceive in the foreseeable future,
she selected a LNG-IUS releasing 20 µg of levonorgestrel per day for therapy.
PT
VII. SUMMARY
The exact usage of the techniques described will be greatly dependent on access to local
RI
technologies, the skills to use and interpret them, and on the ways in which this information may
influence management. However, there are few components of a FIGO based investigation that
are unavailable to most clinicians throughout the world. A structured history, generally simple
SC
laboratory tests, and transvaginal ultrasound with and without contrast can be used to completely
evaluate women with chronic AUB. Clinical judgement and trials of therapy remain as critical
components of the investigation and management pathway.
U
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT
Practice Points
• Many terms and definitions that, heretofore, have been used to describe the
symptoms of abnormal uterine bleeding, and even abnormal bleeding-related
diagnoses, have been poorly defined, leading to inconsistent communication
between and among members of the research, clinical, and patient communities.
• The first FIGO system has been designed to create terms and definitions of normal
PT
and abnormal uterine bleeding in the reproductive years that minimize ambiguity.
Clinicians are encouraged to use these terms and definitions when evaluating
patients.
RI
• While seemingly mundane, a meticulously obtained menstrual history, past and
present, is critical to the understanding of both the quality of life impact of
menstrual symptoms on the patient, and of the potential causes of the AUB
SC
problem itself.
• Many women have excessive menstrual loss that they feel is normal and which
they minimize, while others have comparatively little blood loss that, by virtue of
U
unpredictability, is disruptive. The clinician should seek to uncover the individual
suffering in silence, and respect the capacity of a spectrum of abnormal bleeding
AN
patterns to adversely impact quality of life.
• The second FIGO system, called the PALM-COEIN system, is designed to assist
clinicians, educators, and basic, translational and clinical investigators in
M
identifying the potential causes of AUB in a given patient.
• Complete investigation of women with AUB in the reproductive years frequently

D
requires that the endometrial cavity be evaluated. This is best performed by the
clinician with either diagnostic hysteroscopy or office-based contrast
TE
hysterosonography.
• Investigation may identify one or more potential “PALM-COEIN” contributors to

the patient’s symptoms.
EP
• Whereas many of the mechanisms underlying the symptom of heavy menstrual

bleeding secondary to AUB-E have been determined, there is as yet no available
clinical test for this diagnosis. Consequently, AUB-E can be suspected in any
C
apparently ovulatory individual with the symptom of HMB and no other

identifiable cause such as a submucous leiomyoma.
AC
• All involved – clinician, trainee, patient, and, if appropriate, investigator – should

understand that many findings may indeed not contribute to the symptoms in a
given patient. Examples of findings that may have no relevance in the AUB of a
given patient include adenomyosis, endometrial polyps, Type 4 through 8
leiomyomas and Type 1 von Willebrand disease.
Research Agenda
ACCEPTED MANUSCRIPT
The two FIGO systems have been designed as both clinical and research tools. All types of
investigators are invited and encouraged to use the system(s) to help them identify
homogenous groups of patients to help them advance their own research agendas.
Possible applications include the following:
PT
• Determine the role of Type 3 uterine leiomyomas on the genesis of the symptom of
RI
heavy menstrual bleeding
SC
• Distinguish between the endometrial molecular manifestations in women with HMB
with and without adenomyosis and absent any other potential contributor to the
symptom such as coagulopathy or submucous leiomyoma.
U
• Evaluate the impact of tranexamic acid on HMB in women with isolated Type 1, 2, 3,
or 4 leiomyomas AN
• Compare AUB-Related QoL in women with AUB-E and AUB-O
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT
Figure 1.
FIGO System 1. Definitions and Nomenclature for Normal and Abnormal Uterine Bleeding
in the Reproductive Years
This worksheet can guide evaluation of the patient’s menstrual bleeding and AUB
symptoms. The top panel describes the four parameters – the white section represents normal as
defined by the 5th to 95th percentiles from large-scale epidemiological studies. The definition of
PT
regularity has been changed from the original version to reflect reanalysis of the data and the
exclusion of longest and shortest cycles. The middle and lower panels are new; the middle used to
describe the presence or absence of intermenstrual bleeding while the lower panel is for
description of unscheduled bleeding while using gonadal steroid medication, most often
RI
progestogen or oestrogen and progestogen-containing preparations.
SC
Figure 2
FIGO System 2. The PALM-COEIN Classification of Causes of Abnormal Uterine
Bleeding in the Reproductive Years.
U
The categories on the left (PALM) reflect structural abnormalities that can be defined by
AN
some combination of appropriate imaging and histopathological evaluation. The COEI
categories all reflect some sort of physiological dysfunction that requires a disciplined,
careful history, in some instances coupled with laboratory evaluation such as demonstration
of a coagulopathy (AUB-C) or absence of ovulatory levels of progesterone (AUB-O. Patients
M
with AUB-E have evidence of normal ovulatory function, but have abnormal bleeding – such
as the symptom of heavy menstrual bleeding – related to local endometrial factors. The “N”
group comprises entities that are rare, of questionable relationship to the genesis of AUB, or
D
which are otherwise not classified.
The leiomyoma subclassification system first divides leiomyomas into submucous or “other”
TE
fibroids that are not in contact with the endometrium. The subclassification system is based
upon the original Wamsteker (18) version (Types 0, 1 & 2) but with additional
categorization intramural myomas that touch (Type 3) or do not contact the endometrium
(Type 4).
C EP
Figure 3
AC
PALM-COEIN Working Matrix
This matrix can be used to guide and document the process of investigation.
Figure 4. Screening for Coagulopathy

ACCEPTED MANUSCRIPT
References
1. *Munro MG, Critchley HO, Broder MS, Fraser IS. The FIGO Classification System
(“PALM-COEIN”) for causes of Abnormal Uterine Bleeding in Non-gravid Women in
the Reproductive Years, Including Guidelines for Clinical Investigation. International
journal of gynaecology and obstetrics: the official organ of the International Federation
PT
of Gynaecology and Obstetrics. 2011;113:3-13.
2. Cote I, Jacobs P, Cumming DC. Use of health services associated with increased
menstrual loss in the United States. American journal of obstetrics and gynecology.
2003;188:343-8.
RI
3. Frick KD, Clark MA, Steinwachs DM, Langenberg P, Stovall D, Munro MG, et al.
Financial and quality-of-life burden of dysfunctional uterine bleeding among women
agreeing to obtain surgical treatment. Women's health issues : official publication of the
SC
Jacobs Institute of Women's Health. 2009;19:70-8.
4. Khaskheli MN, Baloch S, Sheeba A, Baloch S, Khaskheli FK. Iron deficiency anaemia is
still a major killer of pregnant women. Pak J Med Sci. 2016;32:630-4.
5. Maswime S, Buchmann E. Causes and avoidable factors in maternal death due to
U
cesarean-related hemorrhage in South Africa. International journal of gynaecology and
obstetrics: the official organ of the International Federation of Gynaecology and
6.
Obstetrics. 2016. AN
*Fraser IS, Critchley HO, Munro MG, Broder M. A process designed to lead to
international agreement on terminologies and definitions used to describe
abnormalities of menstrual bleeding. Fertility and sterility. 2007;87:466-76.
M
7. *Fraser IS, Critchley HO, Munro MG, Broder M. Can we achieve international
agreement on terminologies and definitions used to describe abnormalities of
menstrual bleeding? Human reproduction. 2007;22:635-43.
D
8. Heavy menstrual bleeding. In: Excellence NIfHaC, editor. United Kingdom: National
Institute for Health and Clinical Excellence; 2007.
TE
9. Munro MG. Abnormal Uterine Bleeding. Cambridge: Cambridge University Press; 2010.
10. Weiss G, Maseelall P, Schott LL, Brockwell SE, Schocken M, Johnston JM. Adenomyosis
a variant, not a disease? Evidence from hysterectomized menopausal women in the
Study of Women's Health Across the Nation (SWAN). Fertility and sterility.
EP
2009;91:201-6.
11. Naftalin J, Hoo W, Pateman K, Mavrelos D, Foo X, Jurkovic D. Is adenomyosis
associated with menorrhagia? Human reproduction. 2014;29:473-9.
12. Dueholm M. Transvaginal ultrasound for diagnosis of adenomyosis: a review. Best
C
Pract Res Clin Obstet Gynaecol. 2006;20:569-82.

13. Reinhold C, McCarthy S, Bret PM, Mehio A, Atri M, Zakarian R, et al. Diffuse
AC
adenomyosis: comparison of endovaginal US and MR imaging with histopathologic

correlation. Radiology. 1996;199:151-8.
14. Bazot M, Cortez A, Darai E, Rouger J, Chopier J, Antoine JM, et al. Ultrasonography
compared with magnetic resonance imaging for the diagnosis of adenomyosis:
correlation with histopathology. Human reproduction. 2001;16:2427-33.
15. Champaneria R, Abedin P, Daniels J, Balogun M, Khan KS. Ultrasound scan and
magnetic resonance imaging for the diagnosis of adenomyosis: systematic review
comparing test accuracy. Acta obstetricia et gynecologica Scandinavica. 2010;89:1374-
84.
16. Dueholm M, Lundorf E, Hansen ES, Sorensen JS, Ledertoug S, Olesen F. Magnetic
resonance imaging and transvaginal ultrasonography for the diagnosis of
adenomyosis. Fertility and sterility. 2001;76:588-94.
ACCEPTED MANUSCRIPT
17. Gordts S, Brosens JJ, Fusi L, Benagiano G, Brosens I. Uterine adenomyosis: a need for
uniform terminology and consensus classification. Reprod Biomed Online.
2008;17:244-8.
18. Wamsteker K, Emanuel MH, de Kruif JH. Transcervical hysteroscopic resection of
submucous fibroids for abnormal uterine bleeding: results regarding the degree of
intramural extension. Obstetrics and gynecology. 1993;82:736-40.
19. Parkash V, Fadare O, Tornos C, McCluggage WG. Committee Opinion No. 631:
Endometrial Intraepithelial Neoplasia. Obstetrics and gynecology. 2015;126:897.
PT
20. Tavassoli FA, Devilee P. World Health Organization Classification of Tumors: Pathology
and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARC Press;
2003.
RI
21. Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, Benedet JL, et al.
Carcinoma of the corpus uteri. FIGO 6th Annual Report on the Results of Treatment in
Gynecological Cancer. International journal of gynaecology and obstetrics: the official
SC
organ of the International Federation of Gynaecology and Obstetrics. 2006;95 Suppl
1:S105-43.
22. Trasi SA, Pathare AV, Shetty SD, Ghosh K, Salvi V, Mohanty D. The spectrum of
bleeding disorders in women with menorrhagia: a report from Western India. Ann
U
Hematol. 2005;84:339-42.
23. Saxena R, Gupta M, Gupta PK, Kashyap R, Choudhry VP, Bhargava M. Inherited
AN
bleeding disorders in Indian women with menorrhagia. Haemophilia : the official
journal of the World Federation of Hemophilia. 2003;9:193-6.
24. Kouides PA, Conard J, Peyvandi F, Lukes A, Kadir R. Hemostasis and menstruation:
appropriate investigation for underlying disorders of hemostasis in women with
M
excessive menstrual bleeding. Fertility and sterility. 2005;84:1345-51.
25. Kadir RA, Chi C. Women and von Willebrand disease: controversies in diagnosis and
management. Semin Thromb Hemost. 2006;32:605-15.
D
26. James AH, Kouides PA, Abdul-Kadir R, Edlund M, Federici AB, Halimeh S, et al. Von
Willebrand disease and other bleeding disorders in women: consensus on diagnosis
and management from an international expert panel. American journal of obstetrics
TE
and gynecology. 2009;201:12 e1-8.

27. Shankar M, Lee CA, Sabin CA, Economides DL, Kadir RA. von Willebrand disease in
women with menorrhagia: a systematic review. BJOG : an international journal of
EP
obstetrics and gynaecology. 2004;111:734-40.

28. Hale GE, Hughes CL, Burger HG, Robertson DM, Fraser IS. Atypical estradiol secretion
and ovulation patterns caused by luteal out-of-phase (LOOP) events underlying
irregular ovulatory menstrual cycles in the menopausal transition. Menopause.
C
2009;16:50-9.
29. Smith SK, Abel MH, Kelly RW, Baird DT. The synthesis of prostaglandins from
AC
persistent proliferative endometrium. The Journal of clinical endocrinology and

metabolism. 1982;55:284-9.
30. Brink HV, Chizen D, Hale G, Baerwald A. Age-related changes in major ovarian
follicular wave dynamics during the human menstrual cycle. Menopause.
2013;20:1243-54.
31. Schliep KC, Mumford SL, Vladutiu CJ, Ahrens KA, Perkins NJ, Sjaarda LA, et al.
Perceived stress, reproductive hormones, and ovulatory function: a prospective
cohort study. Epidemiology. 2015;26:177-84.
32. De Souza MJ, Toombs RJ, Scheid JL, O'Donnell E, West SL, Williams NI. High prevalence
of subtle and severe menstrual disturbances in exercising women: confirmation using
daily hormone measures. Human reproduction. 2010;25:491-503.
ACCEPTED MANUSCRIPT
33. Meczekalski B, Katulski K, Czyzyk A, Podfigurna-Stopa A, Maciejewska-Jeske M.

Functional hypothalamic amenorrhea and its influence on women's health. Journal of
endocrinological investigation. 2014;37:1049-56.
34. Rosenfield RL. Clinical review: Adolescent anovulation: maturational mechanisms and
implications. The Journal of clinical endocrinology and metabolism. 2013;98:3572-83.
35. Burger HG, Hale GE, Dennerstein L, Robertson DM. Cycle and hormone changes during
perimenopause: the key role of ovarian function. Menopause. 2008;15:603-12.
36. *Critchley HO, Maybin JA. Molecular and cellular causes of abnormal uterine bleeding
PT
of endometrial origin. Seminars in Reproductive Medicine. 2011;29:400-9.
37. Salamonsen LA, Marsh MM, Findlay JK. Endometrial endothelin: regulator of uterine
bleeding and endometrial repair. Clin Exp Pharmacol Physiol. 1999;26:154-7.
RI
38. Smith SK, Abel MH, Kelly RW, Baird DT. Prostaglandin synthesis in the endometrium
of women with ovular dysfunctional uterine bleeding. British journal of obstetrics and
gynaecology. 1981;88:434-42.
SC
39. Maybin JA, Critchley HO. Menstrual physiology: implications for endometrial
pathology and beyond. Hum Reprod Update. 2015;21:748-61.
40. Gleeson NC. Cyclic changes in endometrial tissue plasminogen activator and
plasminogen activator inhibitor type 1 in women with normal menstruation and
U
essential menorrhagia. American journal of obstetrics and gynecology. 1994;171:178-
83.
AN
41. Smith SK, Abel MH, Kelly RW, Baird DT. A role for prostacyclin (PGi2) in excessive
menstrual bleeding. Lancet. 1981;1:522-4.
42. Maybin JA, Critchley HO, Jabbour HN. Inflammatory pathways in endometrial
disorders. Molecular and cellular endocrinology. 2011;335:42-51.
M
43. Endrikat J, Gerlinger C, Plettig K, Wessel J, Schmidt W, Grubb G, et al. A meta-analysis
on the correlation between ovarian activity and the incidence of intermenstrual
bleeding during low-dose oral contraceptive use. Gynecol Endocrinol. 2003;17:107-14.
D
44. Morrell MJ, Hayes FJ, Sluss PM, Adams JM, Bhatt M, Ozkara C, et al. Hyperandrogenism,
ovulatory dysfunction, and polycystic ovary syndrome with valproate versus
lamotrigine. Ann Neurol. 2008;64:200-11.
TE
45. Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. Interaction of St. John's Wort with oral
contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl
estradiol, ovarian activity and breakthrough bleeding. Contraception. 2005;71:402-8.
EP
46. Rosenberg MJ, Waugh MS, Stevens CM. Smoking and cycle control among oral
contraceptive users. American journal of obstetrics and gynecology. 1996;174:628-32.
47. Irvine GA, Campbell-Brown MB, Lumsden MA, Heikkila A, Walker JJ, Cameron IT.
Randomised comparative trial of the levonorgestrel intrauterine system and
C
norethisterone for treatment of idiopathic menorrhagia. British journal of obstetrics

and gynaecology. 1998;105:592-8.
AC
48. Uguz F, Sahingoz M, Kose SA, Ozbebit O, Sengul C, Selvi Y, et al. Antidepressants and
menstruation disorders in women: a cross-sectional study in three centers. Gen Hosp
Psychiatry. 2012;34:529-33.
49. Haddad PM, Wieck A. Antipsychotic-induced hyperprolactinaemia: mechanisms,
clinical features and management. Drugs. 2004;64:2291-314.
50. Narang HK, Puri M, Patra S, Trivedi SS. Arterio-venous malformations of uterus -
diagnostic and management dilemmas. J Obstet Gynaecol. 2015;35:632-7.
51. Tower AM, Frishman GN. Cesarean scar defects: an underrecognized cause of
abnormal uterine bleeding and other gynecologic complications. J Minim Invasive
Gynecol. 2013;20:562-72.
ACCEPTED MANUSCRIPT
52. *Madhra M, Fraser IS, Munro MG, Critchley HO. Abnormal uterine bleeding:
advantages of formal classification to patients, clinicians and researchers. Acta
obstetricia et gynecologica Scandinavica. 2014.
53. Lieng M, Istre O, Sandvik L, Engh V, Qvigstad E. Clinical effectiveness of transcervical
polyp resection in women with endometrial polyps: randomized controlled trial. J
Minim Invasive Gynecol. 2010;17:351-7.
54. Rahn DD, Abed H, Sung VW, Matteson KA, Rogers RG, Morrill MY, et al. Systematic
review highlights difficulty interpreting diverse clinical outcomes in abnormal uterine
PT
bleeding trials. J Clin Epidemiol. 2010.
55. Warner PE, Critchley HO, Lumsden MA, Campbell-Brown M, Douglas A, Murray GD.
Menorrhagia II: is the 80-mL blood loss criterion useful in management of complaint
RI
of menorrhagia? American journal of obstetrics and gynecology. 2004;190:1224-9.
56. *Santer M, Wyke S, Warner P. What aspects of periods are most bothersome for
women reporting heavy menstrual bleeding? Community survey and qualitative
SC
study. BMC Womens Health. 2007;7:8.
57. *Matteson KA, Clark MA. Questioning our questions: do frequently asked questions
adequately cover the aspects of women's lives most affected by abnormal uterine
bleeding? Opinions of women with abnormal uterine bleeding participating in focus
U
group discussions. Women Health. 2010;50:195-211.
58. Matteson KA, Munro MG, Fraser IS. The structured menstrual history: developing a
Medicine. 2011;29:423-35.
AN
tool to facilitate diagnosis and aid in symptom management. Seminars in Reproductive
59. Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA. Frequency of inherited bleeding
disorders in women with menorrhagia. Lancet. 1998;351:485-9.
M
60. Farquhar C, Ekeroma A, Furness S, Arroll B. A systematic review of transvaginal
ultrasonography, sonohysterography and hysteroscopy for the investigation of
abnormal uterine bleeding in premenopausal women. Acta obstetricia et gynecologica
D
Scandinavica. 2003;82:493-504.
61. *Grimbizis GF, Tsolakidis D, Mikos T, Anagnostou E, Asimakopoulos E, Stamatopoulos
P, et al. A prospective comparison of transvaginal ultrasound, saline infusion
TE
sonohysterography, and diagnostic hysteroscopy in the evaluation of endometrial

pathology. Fertility and sterility. 2010;94:2720-5.
62. Timor-Tritsch IE, Haynes MC, Monteagudo A, Khatib N, Kovacs S. Ultrasound diagnosis
EP
and management of acquired uterine enhanced myometrial vascularity/arteriovenous

malformations. American journal of obstetrics and gynecology. 2016;214:731 e1- e10.
63. Hosny IA, Elghawabit HS, Mosaad MM. The Role of 2D, 3D ultrasound and color
doppler in the diagnosis of benign and malignant endometrial lesions. J Egypt Natl
C
Canc Inst. 2007;19:275-81.

64. Lieng M, Qvigstad E, Dahl GF, Istre O. Flow differences between endometrial polyps
AC
and cancer: a prospective study using intravenous contrast-enhanced transvaginal

color flow Doppler and three-dimensional power Doppler ultrasound. Ultrasound in
obstetrics & gynecology : the official journal of the International Society of Ultrasound in
Obstetrics and Gynecology. 2008;32:935-40.
65. Exacoustos C, Romanini ME, Amadio A, Amoroso C, Szabolcs B, Zupi E, et al. Can gray-
scale and color Doppler sonography differentiate between uterine leiomyosarcoma
and leiomyoma? J Clin Ultrasound. 2007;35:449-57.
66. Toth M, Patton DL, Esquenazi B, Shevchuk M, Thaler H, Divon M. Association between
Chlamydia trachomatis and abnormal uterine bleeding. Am J Reprod Immunol.
2007;57:361-6.
67. Baerwald AR, Pierson RA. Endometrial development in association with ovarian
follicular waves during the menstrual cycle. Ultrasound in obstetrics & gynecology : the
ACCEPTED MANUSCRIPT
official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

2004;24:453-60.
68. Emanuel MH, Verdel MJ, Wamsteker K, Lammes FB. A prospective comparison of
transvaginal ultrasonography and diagnostic hysteroscopy in the evaluation of
patients with abnormal uterine bleeding: clinical implications. American journal of
obstetrics and gynecology. 1995;172:547-52.
69. Schwarzler P, Concin H, Bosch H, Berlinger A, Wohlgenannt K, Collins WP, et al. An
evaluation of sonohysterography and diagnostic hysteroscopy for the assessment of
PT
intrauterine pathology. Ultrasound in obstetrics & gynecology : the official journal of the
International Society of Ultrasound in Obstetrics and Gynecology. 1998;11:337-42.
70. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The accuracy of endometrial
RI
sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a
meta-analysis. Cancer. 2000;89:1765-72.
71. Clark TJ, Mann CH, Shah N, Khan KS, Song F, Gupta JK. Accuracy of outpatient
SC
endometrial biopsy in the diagnosis of endometrial cancer: a systematic quantitative
review. BJOG : an international journal of obstetrics and gynaecology. 2002;109:313-
21.
72. Stovall TG, Ling FW, Morgan PL. A prospective, randomized comparison of the Pipelle
U
endometrial sampling device with the Novak curette. American journal of obstetrics
and gynecology. 1991;165:1287-90.
73.
74.
AN
Ben-Baruch G, Seidman DS, Schiff E, Moran O, Menczer J. Outpatient endometrial
sampling with the Pipelle curette. Gynecol Obstet Invest. 1994;37:260-2.
Williams AR, Brechin S, Porter AJ, Warner P, Critchley HO. Factors affecting adequacy
of Pipelle and Tao Brush endometrial sampling. BJOG : an international journal of
M
75. Visser NC, Breijer MC, Herman MC, Bekkers RL, Veersema S, Opmeer BC, et al. Factors
attributing to the failure of endometrial sampling in women with postmenopausal
D
bleeding. Acta obstetricia et gynecologica Scandinavica. 2013;92:1216-22.

76. Grimes DA. Diagnostic dilation and curettage: a reappraisal. American journal of
obstetrics and gynecology. 1982;142:1-6.
TE
77. An evidence-based guideline for the management of heavy menstrual bleeding.

Working Party for Guidelines for the Management of Heavy Menstrual Bleeding. N Z
Med J. 1999;112:174-7.
EP
78. Aune D, Navarro Rosenblatt DA, Chan DS, Vingeliene S, Abar L, Vieira AR, et al.
Anthropometric factors and endometrial cancer risk: a systematic review and dose-
response meta-analysis of prospective studies. Ann Oncol. 2015;26:1635-48.
79. Gao Y, Dai X, Chen L, Lee AC, Tong M, Wise M, et al. Body Mass Index Is Positively
C
Associated with Endometrial Cancer in Chinese Women, Especially Prior to

Menopause. J Cancer. 2016;7:1169-73.
AC
80. *Wise MR, Gill P, Lensen S, Thompson JM, Farquhar CM. Body mass index trumps age
in decision for endometrial biopsy: cohort study of symptomatic premenopausal
women. American journal of obstetrics and gynecology. 2016.
81. Wise MR, Jordan V, Lagas A, Showell M, Wong N, Lensen S, et al. Obesity and
endometrial hyperplasia and cancer in premenopausal women: A systematic review.
American journal of obstetrics and gynecology. 2016;214:689 e1- e17.
82. Farquhar CM, Lethaby A, Sowter M, Verry J, Baranyai J. An evaluation of risk factors
for endometrial hyperplasia in premenopausal women with abnormal menstrual
bleeding. American journal of obstetrics and gynecology. 1999;181:525-9.
83. Morgan RW. Risk of endometrial cancer after tamoxifen treatment. Oncology
(Williston Park). 1997;11:25-33.
ACCEPTED MANUSCRIPT
84. Lu KH, Dinh M, Kohlmann W, Watson P, Green J, Syngal S, et al. Gynecologic cancer as a
"sentinel cancer" for women with hereditary nonpolyposis colorectal cancer
syndrome. Obstetrics and gynecology. 2005;105:569-74.
85. Vercellini P, Cortesi I, Oldani S, Moschetta M, De Giorgi O, Crosignani PG. The role of
transvaginal ultrasonography and outpatient diagnostic hysteroscopy in the
evaluation of patients with menorrhagia. Human reproduction. 1997;12:1768-71.
86. Clark TJ. Outpatient hysteroscopy and ultrasonography in the management of
endometrial disease. Current opinion in obstetrics & gynecology. 2004;16:305-11.
PT
87. Krampl E, Bourne T, Hurlen-Solbakken H, Istre O. Transvaginal ultrasonography
sonohysterography and operative hysteroscopy for the evaluation of abnormal
uterine bleeding. Acta obstetricia et gynecologica Scandinavica. 2001;80:616-22.
RI
88. Ossola MW, Bertulessi C, Iasi L, Bianchini B, Hanozet F, E G, et al. Comparison of saline
infusion sonography to transvaginal echography and hysteroscopy in the diagnostic
evaluation of abnormal uterine bleeding. It J Gynaecol Obstet. 1999;4:147-52.
SC
89. Huang GS, Gebb JS, Einstein MH, Shahabi S, Novetsky AP, Goldberg GL. Accuracy of
preoperative endometrial sampling for the detection of high-grade endometrial
tumors. American journal of obstetrics and gynecology. 2007;196:243 e1-5.
90. Abu JI, Habiba MA, Baker R, Halligan AW, Naftalin NJ, Hsu R, et al. Quantitative and
U
qualitative assessment of women's experience of a one-stop menstrual clinic in
comparison with traditional gynaecology clinics. BJOG : an international journal of
AN
91. Munro MG, Brooks PG. Use of local anesthesia for office diagnostic and operative
hysteroscopy. J Minim Invasive Gynecol. 2010;17:709-18.
92. Garuti G, Centinaio G, Luerti M. Outpatient hysteroscopic polypectomy in
M
postmenopausal women: a comparison between mechanical and electrosurgical
resection. J Minim Invasive Gynecol. 2008;15:595-600.
93. Penketh RJ, Bruen EM, White J, Griffiths AN, Patwardhan A, Lindsay P, et al. Feasibility
D
of resectoscopic operative hysteroscopy in a UK outpatient clinic using local

anesthetic and traditional reusable equipment, with patient experiences and
comparative cost analysis. J Minim Invasive Gynecol. 2014;21:830-6.
TE
94. Keyhan S, Munro MG. Office Diagnostic and Operative Hysteroscopy Using Local
Anesthesia Only: An Analysis of Patient Reported Pain and Other Procedural
Outcomes. Journal of Minimally Invasive Gynecology. 2014.
EP
95. Dealberti D, Riboni F, Cosma S, Pisani C, Montella F, Saitta S, et al. Feasibility and
Acceptability of Office-Based Polypectomy With a 16F Mini-Resectoscope: A
Multicenter Clinical Study. J Minim Invasive Gynecol. 2016;23:418-24.
96. *Dueholm M, Lundorf E, Hansen ES, Ledertoug S, Olesen F. Evaluation of the uterine
C
cavity with magnetic resonance imaging, transvaginal sonography,

hysterosonographic examination, and diagnostic hysteroscopy. Fertility and sterility.
AC
2001;76:350-7.
97. Champaneria R, Abedin P, Daniels J, Balogun M, Khan KS. Ultrasound scan and
magnetic resonance imaging for the diagnosis of adenomyosis: systematic review
comparing test accuracy. Acta obstetricia et gynecologica Scandinavica. 2010;89:1374-
84.
98. Maheshwari A, Gurunath S, Fatima F, Bhattacharya S. Adenomyosis and subfertility: a
systematic review of prevalence, diagnosis, treatment and fertility outcomes. Human
reproduction update. 2012.
99. Chiang CH, Chang MY, Hsu JJ, Chiu TH, Lee KF, Hsieh TT, et al. Tumor vascular pattern
and blood flow impedance in the differential diagnosis of leiomyoma and
adenomyosis by color Doppler sonography. J Assist Reprod Genet. 1999;16:268-75.
ACCEPTED MANUSCRIPT
100. Perrot N, Frey I, Mergui JL, Bazot M, Uzan M, Uzan S. Picture of the month.
Adenomyosis: power Doppler findings. Ultrasound in obstetrics & gynecology : the
official journal of the International Society of Ultrasound in Obstetrics and Gynecology.
2001;17:177-8.
101. Mark AS, Hricak H, Heinrichs LW, Hendrickson MR, Winkler ML, Bachica JA, et al.
Adenomyosis and leiomyoma: differential diagnosis with MR imaging. Radiology.
1987;163:527-9.
102. Novellas S, Chassang M, Delotte J, Toullalan O, Chevallier A, Bouaziz J, et al. MRI
PT
characteristics of the uterine junctional zone: from normal to the diagnosis of
adenomyosis. AJR American journal of roentgenology. 2011;196:1206-13.
103. Exacoustos C, Brienza L, Di Giovanni A, Szabolcs B, Romanini ME, Zupi E, et al.
RI
Adenomyosis: three-dimensional sonographic findings of the junctional zone and
correlation with histology. Ultrasound in obstetrics & gynecology : the official journal of
the International Society of Ultrasound in Obstetrics and Gynecology. 2011;37:471-9.
SC
104. Vercellini P, Cortesi I, De Giorgi O, Merlo D, Carinelli SG, Crosignani PG. Transvaginal
ultrasonography versus uterine needle biopsy in the diagnosis of diffuse adenomyosis.
Human reproduction. 1998;13:2884-7.
105. Popp LW, Schwiedessen JP, Gaetje R. Myometrial biopsy in the diagnosis of
U
adenomyosis uteri. American journal of obstetrics and gynecology. 1993;169:546-9.
AN
M
D
TE
C EP
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
PT
RI
U SC
AN
M
D
TE
EP
C
AC
ACCEPTED MANUSCRIPT
Highlights
I can’t find any instructions for this process or component
PT
RI
U SC
AN
M
D
TE
C EP
AC

Aub 1

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Aub 1

Uploaded by

Copyright:

Available Formats

Accepted Manuscript

Malcolm G. Munro, MD, FACOG, FRCS(c)

Received Date: 15 September 2016

Accepted Date: 23 September 2016

Departments of Obstetrics and Gynecology, David Geffen School of Medicine, University of

Station 3-B, 4900 Sunset Boulevard

The author has no disclosures related to the content of this manuscript.

Key elements of successful therapy include identification of the potential contributors to

complete evaluation for the potential causes or contributors to the symptoms.

II. The SYSTEM for DEFINITION of NORMAL MENSTRUAL BLEEDING and

ultrasound, ideally, contrast hysterosonography, and hysteroscopic imaging with or without

of both imaging and histopathological diagnosis.

myomectomy to facilitate the identification of situations where resectoscopic myomectomy is not

etc), and the estimated number of tumors.

4. Malignancy and Premalignant Conditions (AUB-M)

5. Coagulopathy (Systemic Disorders of Haemostasis)(AUB-C)

6. Ovulatory Disorders (AUB-O)

7. Endometrial Causes (AUB-E)

by the normal presence of inflammatory cells in the endometrium (39).

If combination oestrogen and progestogen (E+P) formulations are administered cyclically,

androgen levels and otherwise being associated with features of PCOS(44).

As many as 55 per cent of women using a 52 mg levonorgestrel-releasing intrauterine system

9. Not Otherwise Classified (AUB-N)

a. Identification of the symptom-type of chronic AUB - HMB, irregular uterine bleeding,

c. Initiation of immediate intervention(s) designed to promptly reduce or stop the

2. The Menstrual History

3. Determination of the Extent of Blood Loss and Impact on Quality of Life

episodes (8, 57, 58).

6. Evaluation of the Uterus

a. The Role of Ultrasound

myometrial abnormalities to the endometrium. Direct comparison between TVUS,

Other advances in sonographic imaging include color-flow Doppler assessment to

b. Evaluation of the Endometrium

carcinoma. As a result, TVUS may be considered a component of initial triage of

premenopausal women), there is a very low incidence of endometrial hyperplasia

ii. Endometrial sampling

outcomes such as haemorrhage (0.4% of cases) and uterine perforation (0.6 –

There is inconsistency in the medical literature regarding the appropriate selection

with endometrial sampling, regardless of age.

c. Assessment for Focal Endometrial and Endocervical Pathology

imaging with ultrasonographic and/or hysteroscopic techniques. In instances when

d. Evaluation of the Myometrium

vessel retains its vertical orientation to the endometrial cavity(99, 100).

V. IMPLEMENTATION AND INTEGRATION OF RESULTS

recognizable by physical examination. However, endometrial sampling will be unnecessary if

Who should have more extensive and complete evaluation?

ovulatory dysfunction is suggested by the presence of prolonged irregular, unpredictable

VI. CASE STUDIES

normal duration of 4 days with normal volume. Examination demonstrated normal

a 1.2 cm long by 8 mm wide endometrial polyp. She underwent hysteroscopic

Examination demonstrates a normal appearing woman with some bruising on arms

corpus is symmetrically enlarged and slightly tender. Transvaginal ultrasound

• Complete investigation of women with AUB in the reproductive years frequently

• Investigation may identify one or more potential “PALM-COEIN” contributors to

• Whereas many of the mechanisms underlying the symptom of heavy menstrual

apparently ovulatory individual with the symptom of HMB and no other

• All involved – clinician, trainee, patient, and, if appropriate, investigator – should

Possible applications include the following:

which are otherwise not classified.

PALM-COEIN Working Matrix

Figure 4. Screening for Coagulopathy

Pract Res Clin Obstet Gynaecol. 2006;20:569-82.

adenomyosis: comparison of endovaginal US and MR imaging with histopathologic