Female genital anomalies (FGA) represent a group of inborn disorders of the reproductive tract. Frequently, FGA manifest during adolescence and, not infrequently, they affect reproductive health adversely. Early establishment of a precise diagnosis is important to decide on a treatment and to avoid complications both in the genitals and in the adjacent organs 1. Classification of Müllerian anomalies on the basis of the existing treatment opportunities seems coherent, and the inclusion of previously unclassified entities is important for the broad understanding and management of this group of disorders 2. Several treatment options for FGA have been developed and have been subjected to several refinements 2–4. The surgical approaches for the correction of Müllerian duct anomalies are individualized aiming at improving a patient’s postoperative ability to have healthy sexual relations and achieve a successful reproductive outcome 5–8.
With cumulative reporting and advances in diagnostic modalities, subclasses and sporadic cases may be found and serve as important clues for understanding its embryologic background 9,10. We proposed the present preface for an ‘adolescent-focused, treatment-based’ classification system on the basis of the general frame of the American Fertility Society (AFS) classification with some fundamental differences aimed at covering the limitations of the AFS classification. However, any disagreement with the AFS classification was discussed and supported with scientifically analyzed evidences. Finally, the present preface represents our view, which may be of interest to scientists in other countries for the formulation of an ideal updated classification system.
In women, the Wolffian ducts regress at an early stage of development, and the remnants provide a guide for the developing Müllerian ducts. This explains the frequent associations observed between Müllerian defects and renal–urinary system malformations 9–12. The original hypothesis of fusion of Müllerian ducts (in a caudal–cranial direction) has been challenged by the presence of special entities of Müllerian anomalies characterized by a septate uterus, cervical duplication, and longitudinal vaginal septum. The presence of the latter anomalies supports an alternative hypothesis in which fusion of the Müllerian ducts is segmental and bidirectional 9,10. Some of the modern experimental and observational studies 12,13 support those of the early 20th century that identified the sinovaginal bulbs as being derived from the caudal aspects of Wolffian and Müllerian ducts. The hymen is a vestige of the endodermal membrane that separates the vaginal lumen from the cavity of the urogenital sinus; it usually ruptures prenatally and remains as a thin mucous membrane 14,15.
Existing classifications of female genital anomalies
Buttram and Gibbons 16,17 reported the first comprehensive work on the classification of FGA, which was the basis for the later development of the AFS classification in 1988. The AFS classification system has been accepted widely and is currently the most widely used system.
Two other classifications are available; the first is based on the embryological origin 18, whereas the second is based on the anatomical area affected starting from the vagina, through the cervix, uterus, adnexae, and associated malformations (VCUAM). Although the VCUAM classification is more comprehensive, it does not have the same wide acceptability as the AFS classification.
However, the AFS classification has many limitations as many recognized congenital defects have not been included in the AFS classification. In addition, there is a complete lack of categories such as longitudinal fusion defects 19–26, complex septate uteri, hybrid septate uteri, obstructing uterine septa, as well as complex, asymmetrical, and obstructed uterine duplications 27–29. However, the AFS classification categorizes insignificant anomalies such as the arcuate uterus and diethylstilbosterol related anomalies into two special major classes, but does not include tubal anomalies such as accessory tube, tubal elongation, and accessory oestia. Such missed anomalies are important clinically in the diagnosis, differential diagnosis, and management of related presentations and complications.
Finally, the AFS as well as other classification systems failed to highlight the obstructive Müllerian duct anomalies, which represent a very important subclass in every major class. This is a huge limitation as an early diagnosis and prompt treatment of obstructive Müllerian anomalies is important to avoid the adverse effects of long-lasting menstrual retention.
Principals for ‘adolescent-focused, treatment-based’ classification
Over the past 3 years, the author’s group has been working on the introduction of a preface for a comprehensive classification system for FGA. After a review of the literature and reports of more than 400 cases of congenital malformation in two large referral centers in upper Egypt, several classification protocols have been proposed. Comparison of these options in the context of the need for an accurate diagnosis and prompt treatment led the working group to develop a preface for a proposal based primarily on embryological backgrounds of the defects for an in-depth understanding and ultimately to consider the treatment options available.
Our proposal is adolescent focused and user friendly as it highlights the different categories of FGA that present during adolescence, especially ‘obstructive menstrual anomalies’. Obstructive menstrual anomalies frequently cause acute pains during adolescence and are often misdiagnosed and inappropriately treated, which may adversely affect the reproductive capabilities of adolescent females later in life.
Principles for rearrangement of major classes
We rearranged six major classes on the basis of the embryological backgrounds of the defects and the treatment options available are as follows: (a) bilateral plasia/hypoplasia, (b) unilateral aplasia/hypo-plasia, (c) fusion defects, resulting in duplications, (d) failure of resorption, resulting in septate uterus, (e) communication defects, and (f) miscellaneous group of defects (Table 1 and Box 1).
Principles for arrangement of subclasses
Under each of these major classes, we arranged subclasses on the basis of two basic principles: first, according to anatomical hierarchy (AH) for simplicity and clarity. The AH was also thought for practicability and easiness. According to the AH, class I (aplasia/hypoplasia) was subdivided into four subclasses, starting with a – tubal, and then b – uterine, followed by c – uterovaginal, and ending with d – cervicovaginal aplasia (Fig. 1).
The second principle was involved management complexity hierarchy (MCH). In terms of MCH, the anomalies were arranged from the simple-to-treat to the more difficult-to-treat cases and finally the most technically complex cases. According to MCH, cases that present during adolescence and require immediate interventions because of menstrual retention were allocated to subclass d in all the major classes. A descriptive example can be seen in the arrangement of class I as uterine aplasia/hypoplasia with normal vagina currently requiring no treatment. Uterovaginal aplasia or Mayer–Rokitansky–Kuster–Hauser syndrome requires the creation of a neovagina. Isolated cervical aplasia requires endoscopic canalization or uterovaginal anastomosis. Isolated vaginal aplasia requires the creation of a neovagina and uteroneovaginal anastomosis (Fig. 1). The same principles were applied for the arrangement of other major classes.
Another descriptive example of arrangement within the context of AH and MCH is the arrangement of anomalies resulting from failures of fusion (class III) of the paired Müllerian ducts, which result in the duplication of a part or all the Müllerian duct derivatives. In terms of AH, this major class included, first affection of the uterine fundus, resulting in a bicornuate uterus, followed by extension to the uterine corpus, resulting in what was previously known as uterus didelphys unicollis or (duplicated uterine body with a single cervix), and so on until duplication of the entire genital tract. The MCH is also well evident as we started with simple anomalies that usually require no treatment and finally we included complex anomalies that require urgent and difficult surgeries (Fig. 3).
How is it different from the American Fertility Society classification and why?
The differences from the general outline of the AFS can be summarized in five main points. The first is the merging of AFS class III (didelphys) and class IV (bicornuate) into a single class in the treatment focused classfication (TFC); we called it class III or lateral fusion defects. Although this incorporation seems to be very different from the general characteristics of a well-recognized classification, there are strong justifications as well as many advantages. Both a bicornuate and a didelphys uterus arise when midline fusion of the Müllerian ducts is arrested 30. Therefore, the embryological and etiological backgrounds of the didelphys and the bicornuate uteri are common. In addition, didelphys and bicornuate uteri share a common clinical presentation as well as similar obstetric performance 31,32. Finally, both are candidates for either no treatment versus the requirement of only a cervical cerclage operation or, on rare occasions, Strassmann’s operation 33. Therefore, merging of two major classes with the same etiology, clinical/obstetrical performance, and treatment options is not only justifiable but also global, abbreviated and accurate.
The second difference is in the expansion of each major class to include all related subclasses with a special focus on those with obstruction of the menstrual outflow 34,35. These subclasses are invariably organized as an extension (subclass D) of the five major classes (Table 1 and Box 1). Such anomalies require urgent surgical interventions for the treatment of pain and to prevent complications related to prolonged menstrual retention.
The third difference is that the arcuate uterus was included in the septate class on the basis of the very same principles of incorporation of the didelphys and bicornuate uteri. This has been a subject of extensive discussion in the previous literature 1,36, and we did not categorize the arcuate uterus into a separate major class 2. In this class, we included the presence of a special variety of septate with fundal depression. Septate uterus with fundal depression is present, but if unreported, it may be misdiagnosed as bicornuate uterus with the possibility of depriving these cases from the merits of hysteroscopic metroplasty. We reported this hybrid septate variety in 17 of 339 cases of pure septate uteri (El Saman AM, Shahin AY, Nasr A, Tawfik RM, Saadeldeen HS, Othman ER, Habib DM, Abdel-Aleem MA; unpublished data). These hybrid septate/bicornuate cases may be candidates for hysteroscopic metroplasty under laparoscopic monitoring as they are susceptible to perforation; thus, they were allocated to subclasses of a septate uterus (Fig. 4).
The fourth difference is in the creation of class IV: failures of communication or longitudinal fusion defects (Fig. 5). These groups of disorders are specific to adolescence as they present mainly during this period of life. This important class has not been mentioned in the AFS classification most probably because of its somewhat different embryogenesis. However, as mentioned in the brief embryological backgrounds presented earlier in this article, experimental and observational studies identified the sinovaginal bulbs as being derived from the caudal aspects of the Wolffian ducts and the Müllerian ducts. Therefore, the Müllerian ducts are implicated in part in the embryogenesis of these groups of defects. Furthermore, the identification and incorporation of this important category is important as corrective surgeries can be performed, which should be carried out in a timely manner to avoid the adverse effects of prolonged menstrual retention, which may affect reproductive potential 2,14,15.
The final difference was renaming of the last AFS major class and including diethylstilbosterol-related anomalies as a subclass of TFC class VI (Table 1). In addition, we also included other anomalies such as other tubal anomalies (accessory tube, accessory ostia, diverticulum, elongation, etc.).
Furthermore, we kept class VI open ended to include other undescribed rare entities and complex associations (Table 1; Fig. 6). This was done because with cumulative reporting and advancements in diagnostic modalities, new classes or subclasses are unlikely to be discovered, but sporadic cases may be found and can be allocated into the appropriate subclass in the TFC (Figs 2 and 4).
Müllerian anomalies in isolation or in complex associations
One of the well-known characteristics of Müllerian anomalies is the possibility of association with other anomalies, especially those of the urinary and other systems. Each major class of the treatment focused classification included two letters indicating the possibility of such associations: I/C, where I indicates isolated genital anomalies irrespective of their complexity and C indicates the presence of combined genital and extragenital anomalies. Extragenital malformations include urinary, gastrointestinal, skeletal, or any other associated anomalies.
Treatment plan summary for Müllerian duct anomalies
Table 2 shows an updated summary of the treatment options available for Müllerian duct anomalies.
Treatment management of class I
Class Ia: Tubal
Some tubal anomalies can be corrected, but others may not. Assisted reproductive technology represents an efficient tool for uncorrectable isolated tubal anomalies such as aplasia, hypoplasia, and non canalization.
Class Ib: Uterine
In cases of isolated uterine aplasia and/or hypoplasia with an anatomically and functionally normal vagina, there is no current treatment. Gestational carrier is an option in some societies.
Patients with vaginal aplasia are offered nonsurgical use of successive dilators or the creation of a surgical space to be covered with a graft, and a mold to maintain the graft, with variable rates of success and wide range of complications 37–45. Recently, a novel treatment option was introduced by El Saman and colleagues, balloon vaginoplasty (BV), where traction is applied from the abdominal side on a silicon-coated balloon catheter, creating a natural neovagina over 1 week of time. With BV, there is a unique possibility of manipulating both the depths and the widths of the neovaginas using different schedules of catheter traction and balloon distention. The procedure has shown a high success rate, with the possibility of early onset of initiation of coital activities, and minimal complications 2–5,46–49.
Endoscopically monitored canalization of isolated cervical aplasia is a recent procedure in which a special inserter can be used to pass a silicon drain attached to its caudal end across the uterine fundus to the vaginal pouch, which is then fixed securely for three months 3. Other methods include uterovestibular anastomosis or vaginoplasty and uteroneovaginal anastomosis. However, the logical management plan should involve the creation of a neovagina using any of the aforementioned techniques, followed by uteroneovaginal anastomosis 2. Because BV represents the fastest way to create a functional neovagina, it is the first choice of treatment in patients with isolated vaginal aplasia 3,50.
Treatment of class II
Class IIa, class IIb, and class IIc
Women with unicornuate uterus subclasses IIa, IIb, and IIc (Fig. 2) are not normally considered for reconstruction metroplasty 14,51. The main indication for surgery is the presence of a functioning endometrium in the accessory horn. Laparoscopic hemihysterectomy of the rudimentary horn is the treatment of choice 52–53. Hysteroscopic endometrial ablation of the accessory horn endometrium as well as hysteroscopic drainage of a hematometra in a noncommunicating accessory horn have been reported 54,55.
We reported one case with a communicating hypoplastic hemiuterus leading to a normal vagina and a noncommunicating well-developed functioning horn. The patients had presented with primary amenorrhea and cyclic pain. We were able to perform a procedure to establish communication of the functioning horn with the existing vagina. Normal menstruation was established after surgery.
Management of class III
Strassmann’s metroplasty of the partial or the complete bicornuate uterus is very rarely required. Transabdominal metroplasty can considerably improve the reproductive performance of women who have a history of recurrent spontaneous abortions, midtrimester loss, and premature birth, and in whom no other etiologic factor has been identified 33,51,56.
The didelphys uterus has extraordinary capacity, intercourse is often possible in both vaginas, and simultaneous pregnancies in each uterus can occur 57–59. Cervical unification is technically difficult and can result in cervical stenosis or incompetence 33,55.
The management of a nonobstructing longitudinal septum is simple and appears to be associated with improvement in fecundability. Excision of the septum allows the simultaneous insemination of both hemiuteri during a single act of coitus. Both cold knife/scissor excision and diathermy excision have been reported to yield similar outcomes 40,60.
The obstructed unilateral vagina is a clear indication for resection of the vaginal septum, followed by a laparoscopic treatment of associated endometriosis and/or adhesions 40,61.
Treatment of class IV
The arcuate uterus is the most commonly observed uterine anomaly detected by HSG 62,63. It is a clinically benign anomaly; adverse obstetric outcomes are rare and it may not affect reproductive outcomes 63,64. Women with recurrent spontaneous abortions or histories of preterm delivery are considered candidates for 65,66 hysteroscopic metroplasty, which is a state-of-the-art treatment plan 3,52,60,67,68.
The depth of the groove and the length of the uterine septum in the adult uterus depend on the length of the incompletely fused Müllerian ducts in the fetus. Failure of resorption in the remaining part results in the down prolongation of the dividing septum. On laparoscopy, a shallow fundal depression not correlating with the depth of the internal division may be seen. Thus, it is important to consider the results of other investigations (MRI, US, and HSG) with the laparoscopic procedure. Symptomatic patients with this disorder are candidates for hysteroscopic metroplasty but there is a greater risk of perforation. Laparoscopy helps reduce the risk of uterine perforation and aids the diagnosis of associated pelvic pathology 10,52.
Excision of the vaginal septum is carried out either by cold knife/scissor division or diathermy resection, followed by hysteroscopic metroplasty 60.
An obstructed unilateral vagina is a clear indication for resection of the vaginal septum 40,61,69. This is followed by definitive resection of the cervicouterine extension of the septum 60.
Treatment of class V
This important class represents a group of defects that are not classified by the AFS system 1,2. Appropriate timely diagnosis and management will help prevent irreversible damage of the pelvic organs. Fortunately, this group of defects is amenable to complete surgical correction.
Early diagnosis of an imperforate hymen and timely optimized interventions are very important 25,70–73. Premenarchal asymptomatic girls are best treated conservatively until puberty, except in those presenting with mucolpos or hydrocolpos 74–76. An imperforate hymen is treated by two perpendicular or X-shaped hymenotomy incisions, followed by complete excision. However, procedures that spare the integrity of the hymen are strongly preferred by patients and families in many societies 38,77–79.
Incomplete transverse vaginal septum (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 or soft tissue dystocia 80,81. Dilation under anesthesia, followed by regular dilation or definitive resection may be required. Asymptomatic cases may manifest themselves during delivery, where a generous episiotomy may be needed for low-seated vaginal septa. High-seated and thick septa, especially those involving a long segment of the upper third of the vagina, can be managed by a cesarean section with a definitive management at a later time 82,83.
The management of a TVS is technically difficult; because most of these septa are located in the superior vagina, management should be in a tertiary-care center with a qualified surgical team. A TVS may be found concurrently with an imperforate hymen 24,84. Patients presenting with acute pain can be treated with laparoscopic drainage, providing pain relief without compromising the success of definitive surgery that can be performed at a later date 85.
Excision of the septum should be performed under transabdominal or transrectal ultrasound guidance. The widest possible excision should be made with a careful approximation of edges 86. Patients with cyclical hematuria require reconstruction using a transvaginal and transabdominal approach 87.
Segmental atresia usually requires reconstructive surgery to cover the raw area created from the excision of long atretic segments 88,89. In extreme cases of segmental vaginal atresia, retropubic BV may be required 3,48. Other techniques used for the creation of neovaginas could be used for the treatment of this rare condition. We have described a successful pull-down BV technique for patients presenting with segmental atresia of the middle or lower one-third in association with upper hematocolpos.
Treatment of class VI
In this class, treatment is individualized according to the presentation of the cases. In addition, in all classes/subclasses, it is important to pay attention to any associated extragenital anomalies or complications of long-standing obstructions.
The current proposal represents a model for a logical and updatable classification of Müllerian duct anomalies. It has the advantages of being uniform, being based on embryologic backgrounds, and following anatomical, management complexity hierarchies, and may be potentially user friendly.
Conflicts of interest
There are no conflicts of interest.
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