Mullerian duct anomalies (MDAs) are a complex group of uterine anomalies that present in adolescence or later, and affect a woman’s sexual and reproductive health. Though the reported incidence is 0.1 – 3.5% in the general population, we encounter a spectrum of anomalies at the tertiary care level, some of which have been presented in previous editions of this journal. MDAs are often only diagnosed when evaluating menstrual irregularities (primary or secondary amenorrhea, dysmenorrhea, cyclical abdominal pain) or infertility. The reported incidence varies from 3 -6% in women with infertility, to as high as 5-10% in patients with bad obstetric history. The practicing gynecologist may not routinely encounter these anomalies, and should be aware of the various types and classifications, diagnosis, surgical management and psychological and sexual consequences. This article addresses the recent proposed classification system, three-dimensional ultrasonography (3D-USG) and MRI in diagnosis, and endoscopic surgical correction in selected cases.
Normal development of the female reproductive tract involves a series of complex interactions where the embryologic paired mullerian ducts originating from mesoderm, undergo dynamic processes of differentiation, migration, fusion and resorption (or canalization) to form the uterus, cervix, fallopian tubes and superior third of the vagina. MDAs can occur when there is a dysregulation or disruption in any of these normal processes. Although the urogenital sinus (UGS) arises from the endoderm, the developmental fate of both the mullerian ducts and UGS are closely linked; the lower two-thirds of vagina arise from the UGS. Concurrently, abnormalities of the urinary system and axial skeleton are associated with MDAs, and are sometimes first diagnosed when patients are evaluated for menstrual complaints or infertility.
The developmental stages when interruptions occur are well established, and defects are grouped according to the failed developmental mechanism that gives rise to a particular malformation. For easy understanding, it is practical to divide mullerian development into three sequential stages, namely development, fusion and degeneration and hence three general categories of failure, namely, nondevelopment, nonfusion, and nondegeneration.
Nondevelopment: Early arrest of development results in complete uterine agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome), concomitant agenesis or hypoplasia of cervix and vagina, or segmental vaginal atresia. If only one of the mullerian ducts develops, unicornuate uterus results; rudimentary communicating or non-communicating horn with or without functional endometrium may co-exist.
Nonfusion: Complete failure of midline fusion results in uterus didelphys, whereas incomplete fusion leads to bicornuate uterus
Nondegeneration: Arrest at the final stage of degeneration or resorption of fused margins of mullerian ducts results in uterine or longitudinal vaginal septa, or arcuate uterus. Failure of canalization of the vaginal plate results in transverse vaginal septum.
The most widely used method of classification of MDAs is the American Fertility Society (AFS) classification based on the scheme of Buttram and Gibbons, which includes seven main categories and correlates anatomic anomalies with the degree of developmental failure. These categories are: I - segmental or complete agenesis or hypoplasia; II - unicornuate uterus (with/without rudimentary horn); III - didelphys uterus; IV - bicornuate uterus (complete or partial); V - septate uterus (complete or partial); VI - arcuate uterus and VII - DES- related abnormalities. The AFS classification is merely a framework; many MDAs coexist and not all fit completely into the above categories. This classification has been criticized as being awkward and confusing, as it does not account for combinations, or for cervical and vaginal defects which remain unclassified.
Recognizing the need for standardized common terminology among clinicians and researchers, the European Society of Human Reproduction and Embryology (ESHRE) and European Society for Gynaecological Endoscopy (ESGE), established a common working group named CONUTA (CONgenital UTerine Anomalies), with the goal of developing an updated classiﬁcation system based on anatomy. Anomalies are classified separately as uterine (U), and coexistent cervical (C) and vaginal (V), according to increasing severity of the anatomical deviation with the normal variants at the beginning and more deformed types at the end.
Uterine anomalies: U0 - normal uterus; U1- dysmorphic uterus; U2 - septate uterus; U3- bicorporeal uterus; U4 - hemi-uterus; U5- aplastic uterus; U6 – unclassified malformations. These main classes are subdivided into anatomical varieties with clinical significance, such as partial, complete, rudimentary horn, etc.
Cervical anomalies: C0 – normal cervix; C1 – septate cervix; C2 – double cervix; C3 – unilateral cervical aplasia; C4 – cervical aplasia.
Vaginal anomalies: V0 – normal vagina; V1- longitudinal non- obstructing vaginal septum; V2 - longitudinal obstructing vaginal septum; V3 – transverse vaginal septum and/or imperforate hymen; V4 – vaginal aplasia.
This system was developed using scientific research, consensus assessment and consensus development; its clinical value however needs to be proved in day-to-day practice.
Traditionally, hysterosalpingography (HSG) has been used to evaluate the cervical canal, uterine cavity and fallopian tubes; it can diagnose uterine septa, intrauterine synechiae, submucous fibroids, as well as evaluate tubal patency. However, it has limited accuracy as it cannot be used in virgins, it does not image obstructed canals or the external uterine fundal contour (hence cannot differentiate between uterus didelphys and septate uterus). Ultrasonography alone has a variable sensitivity and specificity in diagnosis of MDAs, and depends on the type of transducer and skill of the sonologist. Currently, MRI is the gold standard imaging modality for MDAs because it is non-invasive, has exceptional accuracy (96-100%), does not involve ionizing radiation, has multiplanar capability, and allows excellent soft tissue characterization. MRI provides for accurate classification of the type of anomaly in the pediatric and adolescent population; it reduces the number of invasive procedures by guiding management decisions. MRI has an excellent correlation with intraoperative laparoscopic findings in predicting anatomical defects. Recently the use of 3D-USG has proven to be more sensitive and specific than MRI in categorizing specific types of MDAs, though MRI is superior for cervical and vaginal anomalies. 3D-USG has the added advantage of being cost-effective and providing immediate results, and as practitioners become more experienced in its use, it may emerge as the new reference standard. Presently however there is a lack of comparative studies between MRI and 3D-USG. MRI features of MDAs are well described elsewhere.
Regardless of whether diagnosis is by HSG, USG, MRI or a combination, management at a higher center is associated with more accurate diagnosis and a reduction in the number of inappropriate surgical interventions. After an accurate diagnosis is reached, many treatment options exist which are usually tailored to the specific anomaly. Vaginal atresia is surgically corrected by creation of a neovagina. Several vaginoplasty methods have been developed and refined; the modified McIndoe procedure remains the most common surgical approach. Various materials used to line the neovagina are skin graft, human amnion, bowel segment, and exogenous graft sources like artificial dermis and absorbable adhesion barriers. Alternate methods are the Vecchietti laparoscopic procedure.
Septate uterus is the most common MDA, and hysteroscopic septal resection is a relatively simple procedure. However, the decision to perform septal resection should be based on poor reproductive performance rather than the presence of a septum. Laparoscopy has made surgical correction of MDAs less invasive, and laparoscopic hemihysterectomy has been used successfully for the excision of a rudimentary horn. Decision to perform metroplasty for uterus didelphys or bicornuate uterus should be individualized, and the apparent benefits of this surgery are not clear. Laparoscopic-assisted uterovaginal anastomosis with placement of a silicone stent in patients with cervical agenesis along with concomitant vaginoplasty has been described; endometriosis and subsequent hysterectomy may be averted in these young girls and menstrual function restored. It should be kept in mind that a high transverse vaginal septum is one of the most difficult anomalies to treat and patients may be subjected to numerous surgical attempts. Case reports and case series from large centers continue to provide insights into novel surgical approaches and operative techniques.
In conclusion, MDAs consist of a wide range of defects, and their diagnosis and management should be individualized taking anatomical and clinical characteristics into consideration. Postoperative restoration of long term reproductive and sexual function in women with MDAs continues to remain a challenge.