Müllerian Duct Anomalies: Clinical Concepts
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1 Müllerian Duct Anomalies: Clinical Concepts Elyan A, MD* and Saeed M, MD** Müllerian duct anomalies MDAs occur in 2-3% of all women but can be as high as 10-15% in women with recurrent abortions. Because the reproductive consequences of this group of anomaly vary widely - from nearly normal reproductive life to sterility and even the need for hysterectomy- the gynecologist should have clear knowledge about the types, diagnosis, surgical management if any, and the consequences (reproductive and psychological) of the disease and its management. Embryologic Background The müllerian ducts and the urogenital sinus (UGS) are embryologic structures that differentiate to form the female reproductive tract. The müllerian ducts are mesodermal in origin, while the UGS is of endodermal origin. Disruption of local mesoderm development and its contiguous somites accounts for some associated axial skeletal abnormalities. The developing urinary system is also closely related to the reproductive tract. Kidney and other urinary tract abnormalities are often associated with defects in the reproductive system. Development of the fallopian tubes, uterus, and uterine cervix At 6 weeks of development, both female and male embryos have 2 sets of paired genital ducts: the paramesonephric (müllerian) ducts (PMDs) and the mesonephric (wolffian) ducts (MDs). The development of the MDs precedes PMD development. 26 In the female fetus, the MDs degenerate in the absence of antimüllerian hormone. 40 At the same time, the PMDs develop bidirectionally along the lateral aspects of the gonads. This early, shared connection between the PMDs and urinary tract structures explains the frequent association observed between MDAs and renal-urinary system malformation. The PMDs originate as longitudinal invaginations of coelomic epithelium on the anterolateral surface of the urogenital ridge. 26 Their edges approach each other and fuse. 26 Initially, 3 recognizable regions of the PMD are identified: a cranial vertical portion, a *Professor and Head of the Obstetrics & Gynecology Department, Ain-Shams University. **Lecturer, Department of Obstetrics & Gynecology, Ain-Shams University. Correspondence to: Prof. Aly Elyan, Department of Obstetrics and Gynecology, Ain Shams University. editor@asjog.org horizontal portion, and a caudal vertical portion. 26 The funnel-shaped cranial region of the PMDs opens directly into the early peritoneal cavity. These ducts remain separated and eventually form the fallopian tubes. The horizontal region crosses ventrally, and extends in a caudomedial direction. The caudalvertical region comes into contact with the PMD from the opposite side at the median plane of the future pelvis. These paired PMDs, initially separated by a septum, fuse and form a single Y-shaped tubular structure, the uterovaginal primordium (UVP). 26 The UVP consists of a uterine segment and a vaginal segment; these form the uterus and superior vagina, respectively. 40 The uterus is initially bicornuate, but soon undergoes a process of fusion with subsequent canalization of the intervening septum. Uterine septum regression may be mediated through the mechanism of apoptosis (programmed cell death), which is regulated by the bcl-2 gene. 21 By week 12, the fundus rises and the uterus assumes its mature morphological shape. The endometrium is derived from the lining of the fused müllerian ducts, and the endometrial stroma and myometrium are derived from adjacent mesenchyme. 26 This entire process is completed by the 22nd week of development and results in a uterus, cervix, and single uterine cavity. 40 Development of the vagina and hymen Normal vaginal development involves fusion of 2 different embryological structures: the mesodermal PMDs and the endodermal UGS. The caudal tip of the UVP inserts into the dorsal wall of the UGS, creating the müllerian or sinus tubercle. This process also induces the formation of the sinovaginal bulbs at the distal aspect of the sinus tubercle. These bulbs are paired endodermal solid evaginations that extend from the UGS to the caudal aspect of the UVP and fuse, forming the vaginal plate. The vaginal plate canalizes in a caudad to cephalad manner to form the vaginal canal. The precise boundary between the UVP and UGS and their individual contributions to the vagina is still controversial. Some authors claim that the superior third of the vaginal epithelium is derived from the UVP and the inferior two thirds is derived from the UGS. Most other experts consider the entire vaginal lining to be derived from the vaginal plate of the UGS. 26 The vaginal fibromuscular wall develops from the surrounding mesenchyme. The hymen is formed by expansion of the caudal aspect of the vagina with the subsequent invagination of the posterior wall of the UGS. 11,26 The hymen initially serves to separate the lumen of the vagina ASJOG Volume 1 January
2 from the UGS cavity until late in fetal development. It usually ruptures perinatally and remains as a thin mucous membrane. 1 Classification of Müllerian Duct Anomalies The 1988 American Fertility Society (AFS) classification of müllerian anomalies 2 (Table 1 and figure 1) is based on the degree of uterine anomalies that are grouped according to similarities of clinical manifestations, treatment, and reproductive prognosis. AFS classification system is concerned with lateral fusion disorders and does not include associated vaginal anomalies (anomalies involving the vagina, tubes, and urinary tract are described as associated malformations). Table1. American Fertility Society Classification of Müllerian Duct Anomalies* Classification Anomaly Description Class I Class II Segmental A. Vaginal B. Cervical C. Fundal D. Tubal E. Combined anomalies Unicornuate A. Communicating B. Non-communicating C. No cavity D. No horn Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is the most common example in this category. If horn is present, this class is subdivided into communicating (continuity with the main uterine cavity is evident) and noncommunicating (no continuity with the main uterine cavity). The non-communicating type is further subdivided based on whether an endometrial cavity is present within the rudimentary horn. These malformations have previously been classified under asymmetric lateral fusion defects. The significance of this is that they are invariably accompanied by ipsilateral renal and ureter agenesis. 1,7 Class III Didelphus Complete or partial duplication of the vagina, cervix, and uterus characterizes this anomaly. Class IV Class V Bicornuate A. Complete B. Partial Septate A. Complete B. Partial Complete bicornuate uterus is characterized by a uterine septum that extends from the fundus to the cervical os. The partial bicornuate uterus demonstrates a septum, which is located at the fundus. In both variants, the vagina and cervix each have a single chamber. A complete (septum to internal os) or partial midline septum is present within a single uterus. Class VI Arcuate A small septate indentation is present at the fundus. Class VII Diethylstilbestrol related A T-shaped uterine cavity with or without dilated horns is evident. Anomalies of the vagina, cervix, tubes (right, left) and kidneys (right, left) are described as associated variations (*Adapted from the American Fertility Society. Classification of Müllerian anomalies. Fertil Steril 1988, 49:944). Associated Problems Urinary Tract and Skeletal Abnormalities Abnormal development in one of the urinary or the reproductive systems is a strong indication to search for anomalies involving the other system. The incidence rate of associated urologic anomalies discovered with vaginal agenesis varies from 15-40%; skeletal anomalies, such as congenital fusion or absence of vertebra, occur in 12-50% of cases. 13 An association between MRKH syndrome and Klippel- Feil syndrome has been reported. This syndrome is 12 ASJOG Volume 1 January
3 characterized by congenital fusion of the cervical spine, short neck, a low posterior hairline, and limited range of motion in the cervical spine. 46 The MURCS association (ie, müllerian, renal, cervicothoracic somite abnormalities), characterized by müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia, has also been associated with MRKH syndrome. 22 Endometriosis Presence of patent tubes, a functioning endometrium, and an outflow obstruction is associated with a high incidence (up to 77%) of endometriosis. 38 Clinical Symptoms Congenital uterine abnormalities are commonly associated with second trimester loss because of limited intrauterine space and an associated incompetent cervix. An intrauterine septum may have poor blood supply to the septum resulting in poor implantation, poor placental growth, and early or mid trimester pregnancy loss (Spontaneous abortion rates of 67% have been noted, with a live birth rate of 15-28%). 9 Premature labor and abnormal fetal presentation are also common problems associated with intrauterine anomalies that limit intrauterine space. The spontaneous abortion rate (40%) is high. 31 A non-communicating rudimentary horn with functional endometrium may present as recurrent abdominal pain or hematometra. Many patients with müllerian system anomalies have cervical incompetence. Vaginal septums may present as dyspareunia or obstruct a normal vaginal delivery. Some patients with severe outflow obstruction present with hydrocolpos or hematocolpos (Table 2). Table 2. Conditions associated with uterovaginal anomalies Obstetric problems High presenting part Abnormal presentation, breech Retained placenta Premature birth Dystocia Still Birth Intrauterine growth retardation Gynecologic problems Recurrent first trimester loss Ssecond trimester loss Incompetent cervix Dyspareunia, penetration problems Ectopic pregnancy Primary amenorrhea with cyclic abdominal pain, mass Gynecologic examination findings Broad uterus or fundal notch noted on examination Presence of vaginal or cervical anomalies Two separate cornua on bimanual exam Ultrasound findings Two-lobed contour of uterus with asymmetric shape of fundus off-center amniotic sac Hysterosalpingogram findings Oblong-shaped cavity instead of a normal triangular shape V-shaped endometrial cavity Duplicated cavity Figure 1. Classification of müllerian anomalies developed by the American Fertility Society. DES: diethylstilbestrol. ASJOG Volume 1 January
4 Class I - Vaginal agenesis Vaginal agenesis is characterized by an absence or hypoplasia of the uterus, proximal vagina, and, in some cases, the fallopian tubes. It is a rare anomaly and occurs in an estimated 1 in 5000 newborn females. 35 Multiple variants, some with complicated associated anomalies, have been reported. In 7-10% of women with vaginal agenesis, a normal but obstructed uterus or a rudimentary uterus with functional endometrium is present. 39 Diagnosis of vaginal agenesis Vaginal agenesis is usually diagnosed at puberty when patients present to the gynecologist with primary amenorrhea. It is the second most common cause of primary amenorrhea in adolescents. 30 Physical examination reveals normal growth with the presence of age-appropriate secondary sexual characteristics. External genitalia are normal. Pelvic examination often reveals a patulous urethra. 3,18 The vagina may be completely absent, short vaginal pouch, or short vaginal dimple 1-2 cm superior to the hymenal ring. Uterus is not palpated upon rectal examination. A smooth band, representing a uterosacral ligament remnant, can sometimes be palpated. 18 Ultrasonography findings can support clinical findings of an absent uterus and normal ovaries. MRI is extremely useful; lack of visualization of the vagina and uterus indicates agenesis or hypoplasia. 25 Laparoscopy is not usually indicated unless the diagnosis cannot be determined based on findings from other studies or if a concern exists regarding the presence of a functioning uterus or rudimentary uterine tissue. These patients are not candidates for hysterosalpingography (HSG). Cervical Agenesis Congenital absence of the cervix with functioning endometrial tissue is extremely rare. Primary amenorrhea and cyclic abdominal pain is the usual presentation. Creation of a functional cervix is difficult due to a lack of cervical mucus production. Infection, stenosis, and re-operation are common. 38 Tubal Agenesis Diagnosis of congenital tubal anomalies is made during infertility workup. Microscopic tubal unification may be possible in cases of segmental tubal agenesis. 38 Combined Uterovaginal Agenesis: The most severe vaginal anomaly results from an unexplained inhibition in growth of the müllerian ducts at a very early stage. Vaginal agenesis associated with absence of the uterus is called Mayer-Kokitansky-Kuster- Hauser syndrome and occurs in 1 out of 5000 female births. 11 The ovaries are are normal. The tubes are either rudimentary or fairly well developed, and are 14 usually connected near the midline to a small bulb of fibrous or muscular tissue located between the bladder peritoneum and the rectosigmoid. Occasionally (8%), this bulb of tissue contains a small amount of endometrial tissue and occult menstruation may occur. Complete vaginal agenesis is usual, but about 25% of patients will have at least a short vaginal pouch. 11 MRI can demonstrate ovaries, müllerian and vaginal remnants, and renal agenesis. Treatment is usually directed at the creation of a functional vagina. If a rudimentary uterine anlage is symptomatic, it should be removed. Palpation of a partially descended testis, presence of scant public hair, or failure to identify ovaries is an indication for karyotype testing. Androgen insensitivity syndrome (testicular feminization) has a 46,XY karyotype with high incidence of seminomas (testes need to be removed after puberty). 38 Class II - Unicornuate uterus The unicornuate uterus is formed when one müllerian duct fails to elongate while the other develops normally. Unicornuate uterus accounts for 13% of all MDAs. 7 Diagnosis of Unicornuate uterus HSG is not useful for diagnosing a noncommunicating rudimentary horn. MRI findings can diagnose unicornuate uterus and presence of a noncommunicating horn, which is not opacified if the endometrium is absent. 10,25 High-resolution ultrasonography is helpful for identifying rudimentary horns and are more reliable than those of laparoscopy for helping determine whether the horn is communicating. Laparoscopy is rarely indicated in the workup of an obstructed, non-communicating horn. 8 Additional studies should include an IVP or renal ultrasound to diagnose ipsilateral renal agenesis, horseshoe kidney, and ipsilateral pelvic kidney. 14 Class III - Uterus didelphus It is a rare congenital anomaly and is a consequence of unilateral or bilateral müllerian duct duplication. This müllerian defect is composed of 2 separate, normal-sized uteri and endocervical canals with cervices that are fused at the lower uterine segment. Vaginal duplication is frequent and is characterized by a longitudinal septum extending either completely or partially from the cervices to the introitus. A complete longitudinal vaginal septum occurs in 75%, although septa can also coexist with other MDAs. 33 These septa are usually sagittal, but, in some cases, obstructing transverse septa are found. ASJOG Volume 1 January
5 Diagnosis of uterine didelphus Nonobstructive uterus didelphus is asymptomatic till accidental discovery occurs. Uterine didelphus is often diagnosed during the patient s initial pelvic examination, when 2 cervices are identified. Women with uterine didelphus and unilateral vaginal obstruction experience cyclic pain even though menstrual flow may be present. Their clinical presentation is similar to patients with unicornuate uterus with a non-communicating functional horn. 41 Ipsilateral renal agenesis frequently accompanies both of these conditions. 41 Pelvic examination shows 2 cervices and a paravaginal cystic mass that can usually be palpated. Preoperative diagnostic workup is similar to that used for unicornuate uterus. Workup should include HSG, MRI, and an IVP for associated urinary tract anomalies. Ultrasound may be valuable. 10,25,29 Class IV - Bicornuate uterus When the müllerian ducts fuse incompletely at the level of the uterine fundus, a bicornuate uterus is formed. The lower uterus and cervix are completely fused, resulting in 2 separate but communicating endometrial cavities with a single cervix and vagina. A muscular uterine septum is also present, and classification depends on the extent of this septum. When it extends to internal os, the anomaly is considered complete; this is known as a bicornuate unicollis uterus. Another variant of the complete form of bicornuate uterus is the bicornuate bicollis uterus, in which the septum extends to the external os. When the septum is confined to the fundal region, it is considered a partial bicornuate uterus. The presence of a septum corresponds to a sagittal groove identified on the external uterine surface at the fundal region. The depth of the groove and septum length depend on the length of the incompletely fused müllerian ducts. 31 Diagnosis of bicornuate uterus Distinguishing a bicornuate uterus from a septate uterus is extremely important. Bicornuate uterus results in minimal reproductive problems, but septate uterus has a high association with reproductive failure. Evaluation of bicornuate uterus should begin with ultrasound during the luteal phase of the menstrual cycle, when the endometrial echo complex is better identified. 10 Sonography is not always accurate for distinguishing a septate uterus from a bicornuate uterus. MRI findings can distinguish a bicornuate uterus from a septate uterus. 43 HSG is usually the cornerstone of the workup of most uterine structural anomalies; however, it is not reliable in distinguishing bicornuate uterus from septate uterus because it can demonstrate similar uterine cavity images 10,25,29 Class V - Septate uterus Reviews Septate uterus is the most common structural abnormality of all müllerian duct defects. It results from incomplete resorption of the medial septum after complete fusion of the müllerian ducts has occurred. The septum, which is located in the midline fundal region, is composed of poorly vascularized fibromuscular tissue. 32 Numerous septal variations exist. The septum is considered complete if it extends to the internal os, thus dividing the endometrial cavity, and partial if it does not. In addition, septa may be segmental, which results in partial communication between the endometrial cavities. 8 Diagnosis of the septate uterus HSG is essential in diagnosing and planning surgery. A 2-chambered uterus and the length and thickness of the septum can be assessed using this method. It also permits concomitant assessment of tubal patency. 17 Transvaginal ultrasound is useful in diagnosing septate uterus, with one study demonstrating a sensitivity of 100% and a specificity of 80%. 29 Wu and colleagues published a prospective study of 40 women with history of recurrent miscarriage.47 In this study, physician interpretation of 3-dimensional ultrasound had an accuracy of 92% for the diagnosis of septate uterus. 47 MRI provides excellent tissue characterization and can differentiate between septate and bicornuate uteri. 10 Class VI - Arcuate uterus Arcuate uterus is characterized by a small septate indentation at the superior aspect of the uterine cavity in the fundus. It is the most commonly observed uterine anomaly detected on HSG findings. 23 Classification of this anomaly has been problematic. In the classification system of Buttram and Gibbons, it was considered a mild form of bicornuate uterus. 7 The AFS created a separate class for this anomaly because it can be distinguished from septate uterus based on its external unification. 2 The arcuate uterus is clinically benign despite an infrequent association with adverse obstetrical outcomes. 15 Diagnosis and management of arcuate uterus The literature regarding the diagnosis, management, and reproductive outcomes for arcuate uterus is limited. HSG demonstrates a single uterine cavity with a saddle-shaped fundus. MRI depicts normal fundal contour with a minimal indentation of the fundus. 23 Usually, no treatment is needed for arcuate uterus. Class VII - DES-related anomalies DES is a synthetic estrogen that was prescribed to women for recurrent miscarriage and premature delivery during the late 1940s to early 1970s. Its use ASJOG Volume 1 January
6 during pregnancy was banned in 1971 after in utero exposure was found to be associated with vaginal clear cell adenocarcinoma and various benign vaginal and cervical abnormalities. 16 In utero exposure was also discovered to be associated with characteristic uterine, cervical, and vaginal structural abnormalities. DES-related uterine anomalies are quite common in women with a history of in utero DES exposure. In one study, 69% of 267 women exposed to DES in utero demonstrated uterine abnormalities identified based on HSG.20 Uterine anomalies include a widened lower uterine segment, a T-shaped endometrial cavity, mid-fundal constrictions, endometrial filling defects, irregular margins, and a hypoplastic uterus. 28 Cervical anomalies (in 44%) include hypoplasia, an anterior ridge, a collar, and pseudopolyps. Vaginal adenosis and constrictions are associated abnormalities. 20,28 DES exposure has been shown to be a significant risk factor in poor obstetric outcome. Studies have suggested an increased rate of spontaneous abortion and ectopic pregnancy. 12 Other studies have indicated that cervical incompetence may be an associated factor in these women. 12 No specific DES-related anomaly has been associated with any form of adverse obstetric outcome, which has led some experts to speculate that other factors may be involved. 20,28 Diagnosis of DES-related anomalies HSG is the primary modality used for diagnosing intrauterine contour abnormalities associated with DES. Ultrasound and MRI are useful if additional imaging is required. 10,25,29 DES-related anomalies have not been associated with urinary-renal system problems. Defects not classified by the American Fertility Society Imperforate Hymen Hymenal anomalies represent UGS malformations. Familial occurrences have been reported. 6 An imperforate, and occasional microperforate, hymen may present as an obstructive anomaly. It can be identified during a newborn physical examination with a bulging introitus. A mucocolpos may develop due to stimulation of mucus production from maternal estradiol in utero. If not diagnosed in infancy, the mucus will resorb. Adolescent may present with cyclic pain, amenorrhea (imperforate hymen), menstrual irregularities (microperforate hymen) or difficult urination. After menarche, a pelvic or abdominal mass may be present (hematocolpos); this may be detected on abdominal or rectoabdominal examination. A bluish bulge is seen at the introitus (blood distends hymenal tissue) Transverse vaginal septum Incomplete vertical fusion between müllerian tubercle and sinovaginal bulbs or canalization failure of vaginal plate results in formation of a transverse vaginal septum (TVS) which can divide vagina into 2 segments and reduces its functional length. TVS can be perforate or imperforate, and can develop at nearly all levels in the vagina. Most are located in the superior vagina at the putative junction between the vaginal plate and caudal aspect of the UVP (46%). Other locations are mid-vagina (40%), and inferior vagina (14%).34 TVS is very rare (1/70,000 females). 24,42 Diagnosis of TVS - Fetuses, neonates, and infants TVS is rarely diagnosed in the neonate or infant unless the obstruction causes a significant hydromucocolpos. In rare cases, copious amounts of fluid may collect in the vagina above the obstructing septum and create a mass effect in which the surrounding organs are compressed causing serious consequences if not promptly diagnosed and treated.18 Hydromucocolpos can be diagnosed in utero during a third-trimester transabdominal ultrasound which reveals fetal abdominal distension. 5 Hydromucocolpos in the neonate and infant presents as a large mass palpated in the lower abdomen, but, unlike an imperforate hymen, the obstruction is well within the vagina and a bulging septum is not noted. Initial studies should include a pelvic ultrasound. 37 MRI should also be performed to make a definitive diagnosis. MRI can also be useful to depict pelvic anatomy and determine the thickness of the vaginal septum. Proper imaging studies frequently eliminate the need for laparoscopy or laparotomy. 24 Diagnosis of TVS Postmenarche: In general, TVS remains undetected until the time of menarche. Postmenarchal presentation depends on whether the septum is complete or incomplete. If the TVS is complete, the patient commonly presents with primary amenorrhea and cyclic pelvic pain. Like an imperforate hymen, symptoms are caused by obstructed menstrual flow with retention of mucus, blood, or both. Physical examination frequently reveals a palpable central pelvi-abdominal mass secondary to hematocolpos, hematometra, hematosalpinx, and even hemoperitoneum. However, unlike an imperforate hymen, examination of the genitalia reveals no evidence of bulging at the introitus. Incomplete TVS allows menstrual flow to escape periodically, but hematocolpos and hematometra often develop over time. Complaints include foul-smelling vaginal discharge, dyspareunia secondary to a short vagina, and infertility. TVS can cause soft tissue dystocia in patients who eventually become pregnant. 42 ASJOG Volume 1 January
7 Vaginal atresia Vaginal atresia occurs when the UGS fails to contribute to inferior portion of vagina. Müllerian structures are usually normal, but lower portion of the vagina is replaced by fibrous tissue. Vaginal atresia clinically mimics vaginal agenesis and imperforate hymen. Surgically, it is managed similarly to vaginal agenesis. Most cases of vaginal atresia occur sporadically. Some authors have described vaginal atresia as a component of a syndrome that demonstrates autosomal recessive inheritance and includes middle ear ossicle anomalies and renal dysgenesis. 45 Diagnosis of vaginal atresia Young women with vaginal atresia usually present to the gynecologist with primary amenorrhea. Physical examination reveals age-appropriate development with normal secondary sexual characters. A midline pelvic mass can often be palpated on abdominal-rectal examination. Pelvic examination reveals findings of normal external genitalia; however, a vaginal dimple is present at the introitus. Transperineal ultrasound reveals the presence of ovaries, a uterus, a cervix, and an obstructed blindending superior vagina. All of these features distinguish vaginal atresia from vaginal agenesis. 36 MRI aids in detecting the presence of a cervix, which should distinguish this anomaly from cervical agenesis. This modality can establish the presence of a functioning endometrium. 44 Diagnostic Modalities Once MDAs are suggested based on evidence from the patient s history and physical examination, clinician may opt for imaging workup for distinguishing forms of uterine anomalies which are based on the configuration of endometrial cavity and uterine fundus. The first examination ordered is a pelvic ultrasound (US). MDAs may be suggested on transvaginal 2- dimensional (2D) sonographic imaging but may not be excluded on the basis of negative US findings. Newer 3-dimensional (3D) sonographic techniques offer higher sensitivity and specificity. 43 HSG allows evaluation of uterine cavity and tubal patency. Anomalies may be suggested but positive findings often are nonspecific for precise diagnosis. 43 MRI is considered the criterion standard for imaging uterine anomalies. MRI provides highresolution images of the uterine body, fundus, and internal structure. In addition, it can help evaluate the urinary tract for concomitant anomalies (intravenous urography can be used for this purpose). Most types of uterine anomalies can be diagnosed confidently using pelvic MRI. 43 Limitations of Techniques US is the first imaging modality chosen because of its availability, short scan time, and low cost. Image quality from transabdominal and transvaginal examinations is operator dependent. Overlying bowel gas can confound transabdominal imaging. Transvaginal imaging, although superior to the transabdominal approach, may not always be possible, as in patients with vaginal septa. 43 HSG is the only imaging modality providing highresolution imaging of the uterine cavity and tubes, but it is limited to imaging only the endoluminal contour. Visualization of 2 uterine cavities on HSG does not aid in distinguishing septate, didelphus, and bicornuate uteri. MRI provides high-resolution images of the uterine cavity, the configuration of the uterus (body and fundus), and the ovaries. MRI is limited by motion artifact (patient movement, bowel peristalsis) and other features that degrade image quality (eg, metal prostheses, clips, filters) and cannot be performed in some patients (eg, patients who are claustrophobic, have pacemakers, or are obese). X-Ray A common finding is separation of the uterine cavity into right and left compartments. A divided uterine cavity can result from septate, bicornuate, or didelphus uterus. Certain criteria are used to increase confidence in diagnosing 1 of the 3 entities: 43 Intercornual distance: If the distance between the distal ends of the horns (ends that are continuous with fallopian tubes) is <2 cm, the likelihood of septate uterus is increased. If the distance is > 4 cm, the likelihood of didelphus uterus is increased. Measurements of 2-4 cm (typical distance in a normal uterus) were indeterminate in an abnormal cavity configuration. Intercornual angle: This is the angle formed by the most medial aspects of the 2 uterine hemicavities. If the angle is < 60, septate uterus is more likely. For larger angles, the anomaly is more likely to be a bicornuate uterus. T-shaped cavity: A hypoplastic, irregular, T- shaped uterine cavity is pathognomonic for in utero DES exposure. The only anomaly in which HSG plays a significant role is DES uterus (AFS class VII). The abnormal uterine cavity can be depicted clearly on HSG but often is visualized as only uterine hypoplasia on US or MRI. MRI MRI of the uterus (in benign conditions such as congenital anomalies or fibroid evaluation) is performed at the author's institution following ASJOG Volume 1 January
8 administration of 1.0 mg IM of glucagon to decrease motion artifacts associated with bowel peristalsis. MRI appearance of müllerian anomalies (AFS classification system) 43 Class I (hypoplasia/agenesis) In uterine agenesis, no identifiable uterine tissue is noted. Partial agenesis of müllerian duct derivatives also can be visualized. In uterine hypoplasia, the endometrial cavity is small, with a reduced intercornual distance (<2 cm). Class II (unicornuate uterus) Appears banana shaped without the usual rounded fundal contour and triangular appearance of the uterus. Uterine zonal anatomy is normal. A rudimentary horn can be observed as a soft tissue mass. If obstructed, a rudimentary horn with functioning endometrium may be distended by blood. Class III (Didelphus uterus) Two separate normal-sized uteri and cervices are seen. A septum is visualized extending into the upper vagina. The 2 uterine horns are widely splayed and endometrial and myometrial zonal widths are preserved. Class IV (bicornuate uterus) Two uterine cavities are seen with normal endometrium and a concave fundus with a fundal cleft >1 cm (distinguishing bicornuate uterus from septate uterus). Increased intercornual distance (>4 cm) is observed. Class V (septate uterus) The outer fundal contour is convex, flattened, or mildly concave (fundal cleft <1 cm). The intercornual distance is usually normal (<4 cm) and each uterine cavity is usually small. Class VI (arcuate uterus) MRI may detect this abnormality. Class VII (DES related) MRI may detect this abnormality as a hypoplastic uterus. MRI has high sensitivity and specificity in evaluating uterine anomalies. It has 100% accuracy compared to 92% by endovaginal sonography (EVS). 29 For anomalies requiring surgery MRI demonstrated 100% sensitivity and specificity compared to 67% sensitivity and 100% specificity of EVS. 29 For nonsurgical lesions, both MRI and EVS had 100% sensitivity and specificity. MRI had the advantage of detecting other incidental abnormalities, as a dermoid and submucosal leiomyoma, found on 18 EVS to be indeterminate and nonvisualized, respectively 29. Ultrasound Transabdominal 2D imaging offers reduced sensitivity and specificity. 3D sonography is superior in detecting uterine anomalies. Image quality for all techniques is highly operator dependent. US appearance of müllerian anomalies (AFS classification system) 43 Class I (hypoplasia/agenesis) Findings of agenesis include absence of the cervix and/or uterus with a blind-ending vagina. In uterine agenesis, no uterine tissue is present. Partial agenesis of PMD also can be observed. In uterine hypoplasia, the endometrial cavity is small with intercornual distance <2 cm. Class II (Unicornuate uterus) Appears banana shaped without the usual rounded fundal contour and triangular appearance of the fundal cavity. Uterine zonal anatomy is normal. A rudimentary horn is observed as a soft tissue mass. If obstructed, a rudimentary horn with functioning endometrium is shown as a complex hemorrhagic cystic structure. Class III (Didelphus uterus) Two separate normal-sized uteri and cervices are observed. A vaginal septum is difficult to be visualized. The 2 uterine horns are widely splayed and endometrial and myometrial zonal widths are preserved. Class IV (bicornuate uterus) Two uterine cavities with normal endometrium and a concave fundus with a cleft >1 cm is shown (distinguishing bicornuate from septate uteri). 3D US is more useful. An increased intercornual distance (>4 cm) is observed. The septum separating the 2 horns demonstrates echogenicity identical to myometrium. Class V (septate uterus) Appears as convex or flattened fundal contour with normal or decreased (<4 cm) intercornual distance and each uterine cavity is small. Class VI (arcuate uterus) Can be detected by US but, it is not clinically significant. ASJOG Volume 1 January
9 Class VII (DES related) US may detect the abnormality as uterine hypoplasia. Typically, DES-related uterus is diagnosed confidently using HSG. 3D US is sensitive (100%) and specific (100%) in diagnosing müllerian anomalies. 19 2D transvaginal sonography is effective (75-100% sensitivity and 95% specificity). 3D scanning has higher positive predictive value (100%) compared to 2D scanning (50%).27 In a study by Raga et al, 3D US detected 12 Table 3. Available treatments 38 IA Vaginal dilators, vaginal anastomosis, McIndoe procedure IB Surgery unwarranted in most cases IC Removal of uterine remnants if functional endometrium ID Tubal unification if segmental tubal agenesis IE II III IV V VI Dilator therapy, McIndoe procedure Cervical cerclage, removal of horn when functional endometrium causes clinical problem Cervical cerclage, value of metroplasty unclear, removal of vaginal septum Cervical cerclage, value of metroplasty unclear Hystroscopic resection, metroplasty No treatment needed VII Cervical cerclage of 12 congenital uterine anomalies and correctly classified the anomalies according to AFS class in 11 of 12 patients. One false-negative result involved bicornuate uterus misdiagnosed as septate uterus because of a leiomyoma that caused the fundal contour to appear convex. Treatment Treatment options for the disorders covered in this chapter are listed in table 3. Operative laparoscopy. Micro-surgical techniques, and advanced reproductive technologies are now available to minimize operative morbidity and increase successful reproductive outcome. Conclusion Müllerian duct anomalies are uncommon but often treatable. Patients with MDAs are known to have a higher incidence of infertility, repeated first trimester spontaneous abortions, IUGR, fetal malposition, preterm labor, and retained placenta. The role of imaging is to detect, diagnose, and distinguish surgically correctable forms of MDAs from inoperable forms. References Reviews 1. Acien P. Embryological observations on the female genital tract. Hum Reprod 1992; 7: American Fertility Society. The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, mullerian anomalies and intrauterine adhesions. Fertil Steril 1988; 49: Amesse L, Yen FF, Weisskopf B, Hertweck SP. Vaginal uterine agenesis associated with amastia in a phenotypic female with a de novo 46,XX,t(8;13)(q22.1;q32.1) translocation. Clin Genet 1999; 55: Amesse L. Surgical management of müllerian duct anomalies. obstetrics-gynecology.htm last updated: Feb. 19, 2003, accessed on Nov. 11, Banerjee AK, Clarke O, MacDonald LM. Sonographic detection of neonatal hydrometrocolpos. Br J Radiol 1992; 65: Breech LL, Laufer MR. Obstructive anomalies of the female reproductive tract. J Repro Med 1999, 44: Buttram VC Jr, Gibbons WE. Mullerian anomalies: a proposed classification. (An analysis of 144 cases). Fertil Steril 1979; 32: Candiani GB, Fedele L, Zamberletti D, et al. Endometrial patterns in malformed uteri. Acta Eur Fertil 1983; 14: Daly DC, Walters CA, Soto-Albors CE, Riddick DH. Hysteroscopic metroplasty: surgical technique and obstetric outcome. Fertil Steril 1983; 39: Forstner R, Hricak H. Congenital malformations of uterus and vagina. 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In: Rock JA, Murphy AA, Jones HW, eds. Female Reproductive Surgery. Baltimore, Md: Lippincott Williams & Wilkins; 1992: : Jurkovic D, Geipel A, Gruboeck K, et al. Three-dimensional ultrasound for the assessment of uterine anatomy and detection of congenital anomalies: a comparison with hysterosalpingography and two-dimensional sonography. Ultrasound Obstet Gynecol 1995; 5: Kaufman RH, Adam E, Binder GL, Gerthoffer E. Upper genital tract changes and pregnancy outcome in offspring exposed in utero to diethylstilbestrol. Am J Obstet Gynecol ; 137: Lee DM, Osathanondh R, Yeh J. Localization of Bcl-2 in the human fetal mullerian tract. Fertil Steril 1998; 70: Lyons JK. MURCS association: müllerian duct, renal and cervical vertebral defects. In: Smith s Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, Pa: WB Saunders; 1997: Maneschi F, Zupi E, Marconi D, et al. Hysteroscopically detected asymptomatic mullerian anomalies. Prevalence and reproductive implications. 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10 applications of magnetic resonance imaging. Top Magn Reson Imaging 1995; 7: Moore KL, Persaud TV. The urogenital system: the development of the genital system. In: The Developing Human: Clinically Oriented Embryology. 6th ed. Philadelphia, Pa: WB Saunders Co; 1998: Nicolini U, Bellotti M, Bonazzi B, et al. Can ultrasound be used to screen uterine malformations? Fertil Steril 1987; 47: Patton PE, Novy MJ. Reproductive potential of the anomalous uterus. Sem Reprod Endocrinol 1988; 6: Pellerito JS, McCarthy SM, Doyle MB. Diagnosis of uterine anomalies: relative accuracy of MR imaging, endovaginal sonography, and hysterosalpingography. Radiology 1992; 183: Petrozza JC, Gray MR, Davis AJ, Reindollar RH. Congenital absence of the uterus and vagina is not commonly transmitted as a dominant genetic trait: outcomes of surrogate pregnancies. Fertil Steril 1997; 67: Propst AM, Hill JA 3 rd. Anatomic factors associated with recurrent pregnancy loss. Semin Reprod Med 2000; 18: Raga F, Bonilla-Musoles F, Blanes J, Osborne NG. Congenital Mullerian anomalies: diagnostic accuracy of threedimensional ultrasound. Fertil Steril 1996; 65: Rock JA, Schlaff WD. The obstetric consequences of uterovaginal anomalies. Fertil Steril 1985; 43: Rock JA, Zacur HA, Dlugi AM, et al. Pregnancy success following surgical correction of imperforate hymen and complete transverse vaginal septum. Obstet Gynecol 1982; 59: Rock JA. Surgery for anomalies of the mullerian ducts. In: Tompson JD, Rock JA, eds. TeLinde s Operative Gynecology. 7th ed. Philadelphia, Pa: JB Lippincott; 1992: Scanlan KA, Pozniak MA, Fagerholm M, Shapiro S. Value of transperineal sonography in the assessment of vaginal atresia. AJR Am J Roentgenol 1990; 154: Shatzkes DR, Haller JO, Velcek FT. Imaging of uterovaginal anomalies in the pediatric patient. Urol Radiol 1991; 13: Shoupe D. Uterovaginal anomalies: Management. In Mishell DR, Goodwin TM, Brenner PF, (eds. ), Management of Common problems in obstetrics and gynecology, 4 th edition. Massachusetts, Blackwell Publishing; 2002: Singh J, Devi YL. Pregnancy following surgical correction of nonfused mullerian bulbs and absent vagina. Obstet Gynecol 1983; 61: Speroff L, Glass RH, Kase NG. Development of the mullerian system. In: Mitchell C, ed. Clinical Gynecologic Endocrinology and Infertility. 6th ed. Baltimore, Md: Lippincott Williams & Wilkins; 1998: Stassart JP, Nagel TC, Prem KA, Phipps WR. Uterus didelphus, obstructed hemivagina, and ipsilateral renal agenesis: the University of Minnesota experience. Fertil Steril 1992; 57: Suidan FG, Azoury RS. The transverse vaginal septum: a clinicopathologic evaluation. Obstet Gynecol 1979; 54: Syed I. Uterus, müllerian duct abnormalities. last updated: Aug. 13, 2002, accessed on Nov. 11, Tolhurst DE, van der Helm TW. The treatment of vaginal atresia. Surg Gynecol Obstet 1991; 172: Turner G. A second family with renal, vaginal, and middle ear anomalies. J Pediatr 1970; 76: Willemsen WN. Combination of the Mayer-Rokitansky- Kuster and Klippel-Feil syndrome-a case report and literature review. Eur J Obstet Gynecol Reprod Biol 1982; 13: Wu MH, Hsu CC, Huang KE. Detection of congenital müllerian duct anomalies using three-dimensional ultrasound. J Clin Ultrasound 1997; 25: ASJOG Volume 1 January
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