Polyps (AUB-P)

Polyps are categorized as either being present or absent on the basis of one or a combination of ultrasound, ideally contrast hysterosonography, and hysteroscopic imaging with or without histopathology. Although there is no distinction regarding the size or number of polyps, it is probably important to exclude polypoid-appearing endometrium from this category because such an appearance may well be a variant of normal. Although not currently included in the classification system, the clinician should describe polyp dimensions, location, number, morphology, and, following removal, the histopathology of the lesion.

Adenomyosis (AUB-A)

Whereas the role of adenomyosis in the genesis of AUB is unclear , most would consider that in at least some instances, there is a cause and effect relationship. Although 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 in hysterectomy, these criteria vary substantially and, regardless, have little value when evaluating women with AUB. Highly sensitive sonographic and magnetic resonance imaging (MRI)-based diagnostic criteria are currently in use . 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 .

As with polyps and leiomyomas, adenomyosis is a disorder that should have its own sub-classification system , and it is clear that there should be an initiative to standardize the methods of both imaging and histopathological diagnosis.

Leiomyomas (AUB-L)

Leiomyomas are extremely common benign fibromuscular tumors of the myometrium. They manifest with a spectrum of sizes, numbers, and locations (submucous, intramural, subserous, and combinations of the same), and because of their prevalence and variable relationship to symptoms, they 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 presence of leiomyomas requires only sonographic examination confirming that one or more myomas are present.

In the secondary system, the clinician is required to distinguish myomas that contact the endometrium (submucous or “sm”) from others (o) because it is generally considered that such (sm) lesions are most likely contribute to the genesis of AUB.

The tertiary system is based on the predicate Wamsteker system for submucous leiomyomas (Type 0, 1, and 2) and expanded to include tumors that just contact the endometrium without distorting 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, and 7) ( Figure 2 ). When a myoma abuts or distorts both the endometrium and serosa, it is categorized first by the sm classification and 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 useful for surgeons who perform myomectomy to facilitate the identification of situations where resectoscopic myomectomy is not appropriate.

Although not part of the system, clinicians and investigators are encouraged to include data such 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 (e.g., fundus, lower segment, cervix, and so on), and the estimated number of tumors.

Malignancy and Premalignant Conditions (AUB-M)

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

Coagulopathy (Systemic Disorders of Hemostasis) (AUB-C)

AUB, and particularly HMB, that is associated with any of the spectrum of systemic disorders of hemostasis known as coagulopathies is designated as AUB-C. There is a relatively high prevalence of these disorders in several developing and developed countries . Indeed, there is high-quality evidence that about 13% of women with HMB have a diagnosis of von Willebrand disease if adequate laboratory investigation is performed . 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 as well as counseling children and other blood relatives. Women with AUB while on therapeutic anticoagulation, formerly designated AUB-C, are now categorized as AUB-I (below).

Ovulatory Disorders (AUB-O)

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 HMB . In fact, while anovulation may result in amenorrhea, many women may 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, which appears to be associated with reduced local levels of F2α, one of the necessary ingredients for efficient endometrial hemostasis .

Particularly in the later reproductive years, there is emerging evidence that another disorder can occur in ovulatory women: the “luteal out-of-phase” event . These women ovulate but recruit follicles early in the luteal phase, a circumstance that results in high circulating levels of estradiol and related HMB.

Although 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 as well as other factors including mental stress , obesity, anorexia, weight loss, and extreme aerobic exercise . In some instances, the disorder may be iatrogenic, caused by gonadal steroids or drugs that impact dopamine metabolism such as phenothiazines and tricyclic 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 age .

Endometrial Causes (AUB-E)

When AUB occurs in the context of predictable and cyclic menstrual cycles, suggesting ovulation and particularly, but not only, when no other definable causes are identified, the mechanism is likely a primary disorder residing in the endometrium . If the symptom is HMB (previously called “menorrhagia”), a primary disorder of local endometrial hemostasis may be present. There is high-quality evidence demonstrating deficiencies in the local production of vasoconstrictors such as endothelin-1 and prostaglandin F _2α . In addition, it is evident that affected women typically have accelerated breakdown of endometrial clot secondary to excessive production of plasminogen activator and increased local production of substances that promote vasodilation such as prostaglandin E ₂ and prostacyclin (PGI ₂ ) . Unfortunately, and despite this longstanding evidence, laboratory testing for such abnormalities are not currently available to clinicians.

It is likely that there are other primary endometrial disorders that do not result in HMB, instead causing intermenstrual or prolonged menstrual bleeding. Prolonged bleeding may be a manifestation of deficiencies in the molecular mechanisms of endometrial repair . 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 . However, the role of infection and other local inflammatory disorders in the genesis of AUB is not well defined and is sometimes confounded by the normal presence of inflammatory cells in the endometrium .

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 and with no other definable cause or when it is suspected that a structural abnormality is asymptomatic (e.g., Type-6 leiomyoma).

Iatrogenic (AUB-I)

There is a spectrum of medical devices and pharmacological interventions that can cause or contribute to AUB and are collectively termed iatrogenic . These include both inert and drug-eluting intrauterine systems (IUSs) [e.g., levonorgestrel-releasing IUS (LNG-IUS)] and pharmacologic agents that directly affect 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 causes, it is categorized as AUB-I.

If combination estrogen and progestogen (E+P) formulations are administered cyclically, scheduled uterine bleeding generally occurs in conjunction with the periodic withdrawal of the steroidal agents. Unscheduled endometrial bleeding is termed “breakthrough bleeding” (BTB). Frequently, gonadal steroid preparations, including combined E+P formulations, progestogens, and rarely androgens, are administered continuously with the goal of establishing amenorrhea; any bleeding unrelated to other causes is considered to be AUB-I. There are other pharmacological interventions including selective progesterone receptor modulators and gonadotrophin-releasing hormone agonists and antagonists that are administered with a goal of attaining amenorrhea but frequently are associated with BTB.

For orally administered agents at least, many episodes of BTB are related to reduced circulating gonadal steroid levels secondary to compliance issues, resulting in reduced suppression of FSH production and subsequent follicular development and increased endogenous estradiol . Other potential causes of reduced circulating levels of estrogens and progestins include the use of anticonvulsants such as valproic acid , antibiotics such as rifampin and griseofulvin , cigarette smoking, and related enhanced hepatic metabolism of gonadal steroids . Valproic acid may also impact gonadal steroid metabolism by increasing serum androgen levels and otherwise being associated with features of PCOS .

As many as 55% of women using a 52 mg LNG-IUS can be expected to experience BTB in the first six months after placement, after which it reduces to about 15–20%. Approximately 20% become amenorrheic by the end of the second year, increasing to 50% by year five .

Another contributor to AUB-I can be pharmaceuticals used to treat depression or those that interfere with dopamine metabolism, disordered prolactin release, and resulting disorders of ovulation .

An important cause of AUB-I, in particular 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 Menstrual Disorders Committee (MDC) has determined that the rightful place for AUB related to these agents is in the AUB-I category.

Not Otherwise Classified (AUB-N)

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 and cesarean scar defects (“Isthmocele”) . In addition, other disorders that have not yet been identified and can be defined only using biochemical or molecular biological assays may exist. 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.

Overview

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 the most likely mechanism in a given patient. For girls and women with chronic AUB, these strategies include the following:

• a.
  

  Identification of the symptom type of chronic AUB—HMB, irregular uterine bleeding, IMB, or unscheduled or BTB—in the context of the use of gonadal steroids or other agents for contraception or therapy.

  
  
• b.
  

  Determination of the clinical impact of the symptom(s) on the 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 appropriately comprehensive approach based on 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 5 a–d .

  
  

  
  

  
  

  
  

  
  

  PALM-COEIN Working Matrix. This matrix can be used to guide and document the process of investigation.

  
  

Optimal management of patients with chronic AUB requires a menstrual history obtained with detail at a level rarely taught in medical school or residency training programs. This is necessary not only to distinguish among those with ovulatory cycles, ovulatory disorders, and bleeding between normal periods but also to understand the effect of AUB on the patient’s quality of life. This information is typically followed by available investigative techniques that preferably start with transvaginal ultrasonic imaging of the uterus, if possible, during the initial evaluation. In absence of immediate availability of transvaginal ultrasound (TVUS), 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.

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 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 AUB defined as that which, in the opinion of the clinician, is of sufficient severity to warrant urgent intervention , 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 hemodynamic status and stabilization as appropriate.

  
  
• b.
  

  Identification of the most likely underlying cause(s) including evaluation for the presence of pregnancy.

  
  
• c.
  

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

Once the acute AUB is successfully treated, patient counseling is undertaken based upon 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 because of a transient ovulatory disorder. However, if chronic AUB is present, appropriate investigation is indicated to identify the potential causes.

The Menstrual History

The features that distinguish normal uterine bleeding from AUB in the reproductive years have been modified by FIGO on the basis of a contemporary review of available data, and the use of a form can facilitate the determination of the status of a given patient ( Figure 1 ). Many aspects of the history are critical for optimal categorization of the causes of the bleeding. For example, cyclic and predictable menstruation is usually associated with ovulation, whereas irregular and unpredictable bleeding is a typical symptom of ovulatory disorders (AUB-O). For women who experience IMB in the context of predictable cyclic menses, a focal lesion such as an endometrial polyp is often found (AUB-P) .

For chronic AUB, it is essential that the health care provider clearly determines 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 do not consider the clots to be bleeding). For women with HMB, the presence of an underlying coagulopathy can be suggested by adding structured questions to the menstrual history ( Figure 4 ) . For those who are identified to be at high risk with this tool, appropriate investigations for coagulopathy are warranted, and a referral to a specialist with expertise in hematology may be required.

Screening for Coagulopathy.

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

It is recommended that the evaluation of AUB symptoms should be based on a patient’s reported heaviness, frequency, regularity, and duration of bleeding in conjunction with the perceived impact on quality of life and general functioning . In routine clinical practice, attempts at accurate measurement of menstrual blood loss volume are impractical and, in general, unnecessary. Although the effect of the bleeding on the levels of iron or hemoglobin are important considerations, abnormal hemoglobin is not a prerequisite for investigating AUB including HMB. The aspects of AUB, and particularly HMB, that worry women the most include the psychological irritation associated with the bleeding and the complex of accompanying symptoms, particularly pelvic pain, the failure to always contain the gushes of menstrual loss (both during the day and at night), and the modification in lifestyle behaviors that are necessary to conceal or contain menstrual flow .

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, and lifestyle factors and will be a starting guide to possible underlying causes (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 and use of “double” protection, changing menstrual protection at night, self-consciousness about odor, inability to contain “gushes” of menstrual flow, embarrassment at being unable to contain “gushes” of flow, and preparations and rituals to prevent embarrassing episodes .

Pelvic examination

For both acute and chronic AUB, the physical examination may identify potentially relevant pathologies and other features that may influence the investigational and/or treatment plan; however, most of the clinically significant contributors to the symptoms are not detected because physical examination does not provide any information about the pathology impacting the endometrial cavity. Whereas the physical examination is limited to the identification of intracavitary causes of AUB, it is of great value in evaluation of the cervix, vagina, vulva, perineum, and perianal regions and possible causes of abnormal bleeding and local tenderness.

Laboratory Assessment

Women with HMB should be, at the minimum, measured for hemoglobin and hematocrit as well as, in most instances at least, ferritin, total iron, and 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 ) . Patients determined to be at high risk for coagulopathy on the basis of this instrument should undergo evaluation, if possible in conjunction with a hematologist, where assays may be obtained for von Willebrand factor, Ristocetin co-factor, and a number of other disorders as appropriate. Other laboratory investigations are performed as appropriate depending on the history. For example, an assessment of prolactin and thyroid function should be undertaken in women with ovulatory disorders.

Evaluation of the Uterus

Evaluation of the uterus is an integral component of the evaluation of patients with chronic AUB. Manual examination is usually inadequate because palpable lesions such as leiomyomas may not contribute to the bleeding; clinically significant abnormalities are infrequently detected by this process. Conceptually, it is important to consider three components when evaluating the uterus: (1) assessment of the endometrium for the presence of hyperplasia or malignancy, (2) visualization of the endometrial cavity and cervical canal for localized lesions such as polyps and submucous leiomyomas, and (3) 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, which is sometimes a result of previous cesarean section. Because 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.

• a.
  

  The Role of Ultrasound

Currently initial imaging of the uterus is almost always undertaken using two-dimensional (2-D) TVUS, a routine component of the investigation in moderate- and high-resource settings. However, although 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 particularly 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; however, 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 the evaluation of the endometrial cavity and the relationship of myometrial abnormalities to the endometrium. Direct comparison among 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 hysterosonography is better than conventional TVUS .

Other advances in sonographic imaging include color-flow Doppler assessment to assist with the evaluation of the vascular patterns in endometrial and myometrial lesions and 3-D 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 , can help distinguish benign polyps from malignant ones , and may have some utility in differentiating between leiomyomas and leiomyosarcomas .

• b.
  

  Evaluation of the Endometrium

Blind endometrial sampling is the standard method by which women are assessed for endometrial neoplasia; however, 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 categorized as having AUB-M.

It is also apparent that there is a relationship between endometritis, most 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 .

• 
  

  Sonographic evaluation

  
  

  The single-layer thickness of the endometrium in ovulatory women fluctuates in from approximately 2 mm in the early follicular phase to approximately 6 mm in the late luteal phase . 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 (EEC). Consequently, the menstrual phase EEC is typically approximately 4 mm and increases up to approximately 12 mm 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 carcinoma. As a result, TVUS may be considered a component of initial triage of at-risk premenopausal women with AUB . A well-designed study has suggested that as long as the premenopausal EEC thickness is 12 mm or less (in premenopausal women), there is very low incidence of endometrial hyperplasia or neoplasia .

  
  
• 
  

  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, particularly if an adequate specimen is obtained for the detection of endometrial carcinomas , although sensitivity may be as low as 91% in premenopausal versus postmenopausal women (98% sensitivity) . However, insufficient tissue obtained for diagnosis has been reported in 4–29.8% of cases , and when only premenopausal women are considered, it has been reported to be approximately 25% . In 10–25% of the patients, the previous “traditional D&C” alone does not uncover existing endometrial pathology , and it is associated with adverse outcomes such as hemorrhage (0.4% of cases) and uterine perforation (0.6–1.3% of cases) . Up to 50% of polyps are missed by blind techniques, some of which may include atypical hyperplasia or carcinoma . 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 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 suggest that endometrial sampling should be considered in all women with AUB over the age of 45 years . Other investigators have provided more selective criteria considering risk factors for the presence of unopposed estrogen (such as obesity and chronic anovulation manifesting in AUB-O), a feature present in the vast majority of cases of endometrial carcinoma and one that places at risk those below the 45 years threshold. It is apparent that premenopausal individuals with AUB and BMI of 30 or more have up to fivefold increased risk of having complex and atypical endometrial hyperplasia or cancer compared with women of normal weight . Ultrasound thresholds have also been suggested: those with AUB and EEC greater than 12 mm should be sampled . A New Zealand group identified the following factors: (1) age over 45 years; (2) obesity (>90 kg); (3) a history of chronic anovulation, infertility, or diabetes; (4) a family history of endometrial cancer; and (5) prolonged exposure to unopposed estrogens or tamoxifen .

  
  
• 
  

  Women from families with Lynch syndrome (previously known as 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 between 48 and 50 years . Consequently, women with AUB of any type who are known or suspected to be from affected families should be liberally investigated 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 imaging with ultrasonographic and/or hysteroscopic techniques. In instances when vaginal access is limited (for example, virginal women and women who are very reticent about examination), evaluation with MRI may be the best option.

In skilled hands, TVUS has 96% sensitivity, 86% specificity, 91% positive predictive value, and 94% negative predictive value in the diagnosis of intrauterine abnormalities causing AUB , and the more recent introduction of high-frequency vaginal probes has further improved image quality and predictive value . In the presence of an abnormally thick endometrium, when myomas are present suspiciously close to EEC, or when abnormal bleeding occurs or persists despite a normal TVUS, contrast hysterosonography 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 . The major deficiency, compared with 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, particularly 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 .

With modern equipment and at least selective use of local anesthesia, operative hysteroscopy can also be performed by most gynecologists in the office environment to identify and, if appropriate, direct the biopsy of focal lesions . Patients with tortuous or stenotic cervices may be difficult to examine using office hysteroscopy; however, usually even difficult cases can be evaluated successfully and comfortably provided there is adequate local anesthesia .

MRI has been shown to be accurate in the evaluation of the endometrial cavity in women with AUB, particularly in selected patients in whom SIS or hysteroscopy are not feasible .

• d.
  

  Evaluation of the Myometrium

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 and documented.

Two-dimensional 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 examination. Furthermore, 2-D imaging can be challenging when the aggregate uterine and leiomyoma volume is quite large because it is difficult to adequately image and track the various lesions identified. In such instances, 3-D ultrasound or MRI is of additional value.

For the diagnosis of adenomyosis, TVUS with the application of a set of objective criteria for the diagnosis of adenomyosis has been found to be comparable with MRI, with approximately 80% sensitivity and similar specificity . These criteria include the following: a globular uterine configuration, poorly defined endometrial–myometrial junction, myometrial echogenic linear striations, thickening of the myometrium, asymmetrical anterior and posterior myometrial thickness, irregular myometrial cystic spaces, and a heterogeneous myometrial echotexture. Although there is evidence suggesting a threshold of three of these criteria for making a diagnosis , the ideal number has not been established. Similar to the case for polyps and leiomyomas, adenomyosis is a disorder that could benefit from its own sub-classification system .

Color-flow Doppler ultrasound is useful in detecting blood flow and, consequently, is valuable for the detection of arteriovenous malformations; in addition, it may also have a role in detecting atypical endometrial polyps and malignancies. However, the most important application of color Doppler is in distinguishing focal adenomyosis from leiomyomas because in the latter, myometrial vessels course around the lesion, whereas in adenomyosis, the vessel retains its vertical orientation to the endometrial cavity .

MRI has utility in at least selected women with AUB not only for the detection of adenomyosis but also 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 . There is some evidence that quantified irregularity (thinnest to thickest ≥ 4–6 mm) in MRI- or 3-D ultrasound-determined thickness of the junctional zone provides additional sensitivity for the diagnosis of adenomyosis . MRI may be superior to transvaginal sonography, contrast hysterosonography, and hysteroscopy for determining the myometrial involvement of submucous leiomyomas .

Although the use of myometrial biopsy to distinguish adenomyosis from leiomyomas has been explored, the results are somewhat disappointing. Whereas transcervical needle biopsy seems to have high specificity, it has poor sensitivity for the diagnosis of adenomyosis compared with histopathological examination of hysterectomy specimens .