The VCUAM (Vagina Cervix Uterus Adnex associated Malformation) Classification: a new classification for genital malformations
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1 The VCUAM (Vagina Cervix Uterus Adnex associated Malformation) Classification: a new classification for genital malformations Peter Oppelt, M.D., a Stefan P. Renner, M.D., a Sara Brucker, M.D., b Pamela L. Strissel, Ph.D., a Reiner Strick, Ph.D., a Patricia G. Oppelt, M.D., a Hellmuth G. Doerr, M.D., c Guenther E. Schott, M.D., d Juergen Hucke, M.D., e Diethelm Wallwiener, M.D., b and Matthias W. Beckmann, M.D. a a Department of Gynecology and Obstetrics, c Department of Pediatrics, and d Department of Children s Urology, University Hospital, Erlangen; b Department of Gynecology and Obstetrics, University Hospital, Tübingen; and e Department of Gynecology and Obstetrics, Bethesda Hospital, Wuppertal, Germany Objective: With an incidence of up to 5% in the general population, genital malformations are a frequent clinical occurrence. However, using the existing published classifications of malformations, difficulties arise in classifying genital malformations appropriately. The aim of the present study was to produce a simple, systematic, and reproducible classification system. Design: A systematic arrangement of genital and associated malformaltions, using a structure similar to that in the TNM classification of oncological tumors, was developed and validated. Setting: Patients with genital malformations in a university hospital. Patient(s): Ninty-nine premenopausal patients with genital malformations. Intervention(s): Patients were diagnosed for genital malformation using laparoscopy or magnetic resonance imaging. Main Outcome Measure(s): A new classification (VCUAM) is presented to evaluate patients with different genital malformations. Result(s): The external and internal female genital organs were divided into the following subgroups in accordance with the anatomy: vagina (V), cervix (C), uterus (U), and adnexa (A). Associated malformations were assigned to a subgroup (M) relative to each specific organ. The classification was validated in a group of 99 patients with genital malformations. Conclusion(s): The VCUAM classification for the first time makes it possible to reflect even complex malformations in a precise and individual fashion, taking associated malformations into account. The classification makes it easier to provide appropriate clinical care for the affected patients. (Fertil Steril 2005;84: by American Society for Reproductive Medicine.) Key Words: Genital malformation, genital classification, MRKH-syndrome, uterus subseptus, uterus didelphius, cervix duplex, associated malformation, uterine malformation Genital malformations have an incidence of 0.1% to 5% in the general female population (1 4). A higher incidence of 3.5% to 6.5% has been observed in the diagnosis of groups of patients with infertility (1, 2). The highest rate, with up to 38% of women having abnormalities in the müllerian ducts (5), was observed in a group of patients with recurrent abortions. In addition to uterine malformations, vaginal and cervical abnormalities and malformations of the adnexa are observed, as well as malformations of other organs and systems such as the kidneys and skeleton. Adequate classification of complex malformations of this type for example, in Mayer- Rokitansky-Küster-Hauser (MRKH) syndrome has not so far been possible (6). Received January 11, 2005; revised and accepted May 10, Reprint requests: Peter Oppelt, M.D., Department of Gynecology and Obstetrics, University Hospital, Universitätsstrasse 21 23, D Erlangen, Germany (FAX: ; peter.oppelt@ gyn.imed.uni-erlangen.de). In 1907, to include various forms of genital malformation, Strassmann (7) for the first time introduced systematic subdivisions into describing septate uterus (uterus bilocularis, bipartite uterus, subseptate uterus) and bicornate uterus (uterus bicornis, bifid uterus, didelphic uterus). Using this broad classification limited to the uterus alone, it was not possible to classify many malformations. In 1979, Buttram and Gibbons (8) proposed a classification arranged into six subgroups. This was revised in 1988 by the American Fertility Society (AFS) (6). In the latter scheme, the main difference from the Buttram and Gibbons (8) classification is that arcuate uterus is separated into its own subgroup, distinct from subseptate uterus. The limitations of the current AFS classification lie in the impossibility of assigning variations of a malformation to precise organ subgroups. All of the current classifications are primarily limited to the uterus and vagina, disregarding malformations of the adnexa. Associated malformations, which are present in up to 30% of /05/$30.00 Fertility and Sterility Vol. 84, No. 5, November 2005 doi: /j.fertnstert Copyright 2005 American Society for Reproductive Medicine, Published by Elsevier Inc. 1493
2 TABLE 1 Description of the individual malformations relative to the organ. Vagina (V) 0 Normal 1a Partial hymenal atresia 1b Complete hymenal atresia 2a Incomplete septate vagina 50% 2b Complete septate vagina 3 Stenosis of the introitus 4 Hypoplasia 5a Unilateral atresia 5b Complete atresia S1 Sinus urogenitalis (deep confluence) S2 Sinus urogenitalis (middle confluence) S3 Sinus urogenitalis (high confluence) C Cloacae Cervix (C) 0 Normal 1 Duplex cervix 2a Unilateral atresia/aplasia 2b Bilateral atresia/aplasia Uterus (U) 0 Normal 1a Arcuate 1b Septate 50% of the uterine cavity 1c Septate 50% of the uterine cavity 2 Bicornate 3 Hypoplastic uterus 4a Unilaterally rudimentary or aplastic 4b Bilaterally rudimentary or aplastic Adnexa (A) 0 Normal 1a Unilateral tubal malformation, ovaries normal 1b Bilateral tubal malformation, ovaries normal 2a Unilateral hypoplasia/gonadal streak (including tubal malformation if appropriate) 2b Bilateral hypoplasia/gonadal streak (including tubal malformation if appropriate) 3a Unilateral aplasia 3b Bilateral aplasia associated Malformation (M) 0 None R Renal system S Skeleton C Cardiac N Neurologic 1494 Oppelt et al. VCUAM classification Vol. 84, No. 5, November 2005
3 FIGURE 1 VCUAM classification of uterus septus: V0, C0, U1b, A0, M0. (A) Hysteroscopic view. (B) Intraoperative view. cases depending on the genital malformation, are also not taken into account. MATERIALS AND METHODS The structure of the system used to reflect oncologic tumors in the TNM classification (9) served as the basis for establishing a new classification of genital malformations. Because no underlying molecular-genetic alterations have so far been identified for any of the existing malformations (1, 10, 11), the intention was that the classification should be oriented toward anatomic variations in the external and internal female genital organs. The aim of the classification is to provide a description of malformations that is both as individual and as precise as possible. The description should be reproducible and clinically practicable. The classification of malformations presented here was tested in a group of 99 patients: 28 with typical MRKH syndrome 11 with atypical MRKH syndrome FIGURE 2 VCUAM classification of uterus didelphys: V2b, C1, U2, A0, M0. (A) Vagina. (B) Intraoperative view. Fertility and Sterility 1495
4 FIGURE 3 VCUAM classification of atypical Mayer-Rokitansky-Küster-Hauser syndrome: V5b, C2b, U4b, A0, MR. (A) Vagina. (B) Intraoperative view. 17 with müllerian aplasia, renal aplasia, and cervicothoracic somite dysostosis (MURCS) association 19 with subseptate uterus 18 with bicornate uterus, including 7 with single bicornate uterus (uterus bicornis unicollis) and 11 with double bicornate uterus (uterus bicornis bicollis) 2 with testicular feminization 2 with didelphic uterus 1 with duplex cervix with a vaginal septum 1 with adrenogenital syndrome All handling and examination of patients were done according to an approved ethics vote of the Department of Medicine, University of Erlangen, Germany (Approval Number 3074). This classification was used according to the anatomy of internal and external genitalia for each of the presented malformations listed in Table 1. The validation of the malformation in its complexity was then performed. RESULTS The external and internal female genital organs are divided into the following groups, in accordance with the anatomy: vagina (V), cervix (C), and uterus (U). Because the ovular transport mechanism plays a fairly minor role in the context of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the tube and ovary are combined under the heading of adnexa (A). Systematic subclassification of the possible organ changes was carried out in each group. The number 0 was selected to indicate the lack of any pathologic features. The more strongly marked the malformation was, the higher the numerical classification assigned to it. The highest number in each group was assigned to atresia or aplasia (see Table 1). Other associated malformations often occur along with malformations of the müllerian ducts. These were included in the classification in a separate subgroup, associated malformations (M). Because of the large number of possible variations, precise classification of associated malformations was avoided. Instead, only the affected organ group, such as the renal system (R) or skeleton (S), is noted. Multiple descriptions are possible in group M (see Table 1). When an alteration cannot be accounted for with the available classification, it should be documented with a plus symbol ( ). When a malformation is not fully clarified, the subgroup concerned is assigned a hash mark (#). Three examples are given in Figures 1 through 3. All of the patients in the group (n 99) could be described in detail and in full using this new classification. DISCUSSION In the current AFS classification of genital malformations (6), the specific term for the malformation (e.g., subseptate uterus) is primarily used rather than a group classification (as in group V septate ). Problems arise due to the fact that complex malformations in particular, such as those in group I (hypoplasia/agenesis), cannot be classified individually and precisely. The classification is also based mainly on the description of uterine changes. Accompanying malformations such as duplex vagina, which often occurs in association with bicornate uterus (AFS group IV), cannot be recorded in the AFS classification. The same applies to the adnexa; although only described rarely, hypoplasia or aplasia of the adnexal region can occur in combination with müllerian aplasia, renal aplasia, and cervicothoracic somite dysostosis (MURCS) association (AFS group I) (12) or unicorn 1496 Oppelt et al. VCUAM classification Vol. 84, No. 5, November 2005
5 uterus, but it is not possible to describe and record such malformations. Associated malformations such as those of the renal system or skeletal system are not taken into account at all in any of the current classifications. Depending on the individual malformation, changes in the renal system are diagnosed in 11% to 30% of cases and changes in the skeletal system in up to 12% of cases (13). This information, which is important for the patient, has not been reflected by any of the classification schemes. Other classification systems, such as the revised version presented by Acien et al. (14), are mainly based on embryologic development. Although this includes changes in the vagina, adnexa, and renal system in addition to those in the uterus, it is extremely complex for use in clinical practice, and assignment to specific classes is difficult. In addition, the question arises of whether genital malformations need to be assigned to as many subgroups as those presented in the AFS classification. The primary criterion for the assessment of a complete genital malformation should be to provide a precise and comprehensible description, and this is not possible when groups are assigned in relation to the uterus. The main concern in the development of the vagina cervix uterus adnex associated malformation (VCUAM) classification system proposed here is to provide a simple, systematic, clinical classification in addition to providing a precise reflection of the entire malformation. In the same way as patients with breast cancer are described using the TNM classification, the VCUAM classification can be used to supplement the descriptive term for the malformation (as in the previous examples). Using this precise structural assignment of the anomaly concerned, it is possible to obtain a descriptive picture at any time of the extent of the condition and its associated malformations. REFERENCES 1. Nahum GG. Uterine anomalies: how common are they, and what is their distribution among subtypes? J Reprod Med 1998;43: Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simon C, Pellicer A. Reproductive impact of congenital müllerian anomalies. Hum Reprod 1997;12: Byrne J, Nussbaum-Blask A, Taylor WS, Rubin A, Hill M, O Donnell R, et al. Prevalence of müllerian duct anomalies detected at ultrasound. Am J Med Genet 2000;94: Marten K, Vosshenrich R, Funke M, Obenauer S, Baum F, Grabbe E. MRI in the evaluation of müllerian duct anomalies. Clin Imaging 2003;27: Salim R, Regan L, Woelfer B, Backos M, Jurkovic D. A comparative study of the morphology of congenital uterine anomalies in women with and without a history of recurrent first trimester miscarriage. Hum Reprod 2003;18: American Fertility Society. The American Fertility Society classifications of adnexal adhesions, distal tubal occlusion secondary due to tubal ligation, tubal pregnancies, müllerian anomalies and intrauterine adhesions. Fertil Steril 1988;49: Strassmann P. Die operative Vereinigung eines doppelten Uterus. Zentralbl Gynakol 1907;43: Buttram VC, Gibbons WE. Müllerian anomalies: a proposed classification. Fertil Steril 1979;32: Wittekind C, Greene FL, Hutter RVP, Klimpfinger M, Sobin LH, eds. TNM atlas: illustrated guide to the TNM/pTNM classification of malignant tumours. 5th ed. Heidelberg: Springer, Oppelt P, Strissel PL, Kellermann A, Seeber S, Humeny A, Beckmann MW, et al. Correlation of DNA sequence variations of the entire anti-müllerian hormone (AMH) gene promoter and AMH protein expression with the Mayer-Rokitansky-Küster-Hauser syndrome. Hum Reprod 2004;20: Simpson JL. Genetics of the female reproductive ducts. Am J Med Genet 1999;89: Duncan PA, Shapiro LR, Stangel JJ, Klein RM, Addonizio JC. The MURCS association: müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia. J Pediatr 1979;95: Stein AL, March CM. Pregnancy outcome in women with müllerian duct anomalies. J Reprod Med 1990;35: Acien P, Acien M, Sánchez-Ferrer M. Complex malformation of the female genital tract: new types and revision of classification. Hum Reprod 2004;19: Fertility and Sterility 1497
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