1 Service of Obstetrics and Gynecology, San Juan University Hospital and 2 Department/Division of Gynecology, School of Medicine, Miguel Hernández University, Campus of San Juan, Alicante, Spain
* To whom correspondence should be addressed at: Departamento/División de Ginecología, Facultad de Medicina de la Universidad Miguel Hernández, Campus de San Juan, 03550 Alicante, Spain. Tel.: 965919524; Fax: 965919550; Email: acien{at}umh.es
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Abstract |
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Key words: blind vagina/cervico-vaginal atresia/genital malformations/renal agenesis/Rokitansky syndrome
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Introduction |
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Complex malformations of the female genital tract (and not only the uterine or Müllerian malformations) are not so common, but they do appear and are often incorrectly identified, inappropiately treated, and sometimes incorrectly reported. The main reasons for frequent diagnostic delay and/or inappropriate surgery are: (i) not considering the malformation as a cause of the patient's clinical symptoms and (ii) not considering the embryological origin of the different constituent elements of the genito-urinary tract (Acién, 1992). Many of the cases reported in the literature have not been correctly studied or interpreted and have not been given a credible diagnosis (Acién, 2001
, 2002
; Gorgojo et al., 2002
; Sadik et al., 2002
; Mulayim et al., 2003
). It is true that embryological hypotheses vary (Koff, 1933
; Gruenwald, 1941
; Muller et al., 1967
; Forsberg, 1973
; Ufelder and Robboy, 1976
; Marshall and Beisel, 1978
; Bok and Drews, 1983
; Dohr and Tarmann, 1984
; Minh et al., 1984
; Mauch et al., 1985
; Ludwig, 1998
; Lin et al., 2002
) and that the direct cause of the majority of anomalies is not known. However, the pathogenesis of the majority of them can be correctly explained and understood through the embryological hypothesis presented in Acién (1992)
and other publications by us. In this article, we present three new types of malformations not previously described as such, and revise the clinical and embryological classification also presented in Acién (1992)
.
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Materials and methods |
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Cases reported
1. Unilateral cervico-vaginal atresia (or only atretic hemivagina) with renal agenesis
A case of this type, without communication between hemiuteri, is presented:
Case 1. A 25-year-old woman came to the Emergency Unit at our Hospital with severe pains in the right illiac fossae towards the end of menstruation. The dysmenorrhea had become more intense over the last 2 years after having a laparotomy in another hospital. She had been operated on for a laparatomy and right adnexectomy because of the pain and the presence of endometriomas. At that time she was diagnosed as having a double uterus. In a posterior Computerized axial tomography (CAT) and intravenous pyelogram (IVP), renal agenesis was observed. At our hospital and after transvaginal ultrasound diagnosis of the hematometra in the right horn and absence of right blind hemivagina, we diagnosed a didelphys uterus with right cervico-vaginal atresia and right hematometra which had increased after the previous adnexectomy. We decided to carry out another laparotomy and right hemihysterectomy. During the operation we observed that the right atretic hemicervix opened into another atretic duct (see Figure 1A), and continued downwards parallel to and next to the existing normal vagina and upwards for only 1.52 cm. Right hemiuterus, atretic hemicervix and the duct suggesting right atretic hemivagina and/or mesonephric duct were removed. The posterior histological study showed that this atretic duct was lined by cylindrical epithelium with areas of squamous metaplasia in the sections which presumably corresponded to the right atretic hemivagina. The left hemiuterus was moved to the center of the lower pelvis and fixed to the right round ligament. Postoperational recovery was normal. Menstruation after the operation was normal and continues to be normal without dysmenorrhea. A diagram of the genito-urinary malformation of this patient is shown in Figure 1B.
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Case 2. A 22-year-old woman, married for 2 years, with 1 previous miscarriage. She mentions that she was in hospital at age 3 due to feverish convulsions and a urinary infection. A gammagraphy and intravenous pyelogram showed left renal agenesis at that time. Later, she had new urinary infections and 1 year ago, after recurrent pain in the right iliac fossae, her gynaecologist diagnosed a double uterus. In December 2001 she came to our hospital with metrorrhagia, and the ultrasound showed a non evolutive gestation in the left horn. A uterine curetage was carried out. The posterior hysterosalpingography (HSG) showed bicornuate uterus with communication between both hemiuteri at a low cervical level, but with the left hemicervix ending blindly (see Figure 2). The atretic left hemivagina was not identified with magnetic resonance imaging (MRI). Therefore, we believe the definitive drawing of this malformation is the one shown in Figure 2C.
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The clinical examination shows the vulva and anus as basically normal, with the cloacal correction scar. The vagina presents stenosis at 1 cm, which is not permeable to a finger. The ultrasound did not provide well defined images but the uterus seemed bicornuate or didelphys, the right side being more developed. The MRI showed unicornuate uterus, but not a proper image of the vagina. By introducing a Foley sound through the stenosis, we also managed to fill in the unicornuate uterus and normal tube shown in the image (see Figure 5A). Due to the inverted location of the radiographic identification, it was then diagnosed as left unicornuate uterus. The patient wanted surgery and to have all her symptons resolved, so she eventually had a hysterectomy as she did not want nor planned to have any children in the future. Therefore, in December 2000, we carried out a laparotomy and it was possible to observe (see Figure 5C) a non-cavitated rudimentary left hemiuterus with normal tube and ovary, as is usually observed in the Rokitansky syndrome. On the right side, we could see a properly developed unicornuate uterus, with a normal aspect and normal tube and ovary. A total hysterectomy of both hemiuteri was performed and it was possible to observe that the right hemicervix opened into a small and almost closed vaginal cavity in its middle third, as if it were a transverse vaginal septum. The final diagram of the malformation, as we understand it, is shown in Figure 5F. The right side would definitively correspond to a blind vagina and renal agenesis syndrome (vaginal stenosis must correspond to the opening of the blind vagina which gynecologists carried out when she had surgery at age 12); and the left side would be characteristic of unilateral Rokitansky syndrome, with normal tube and ovary and, likewise, normal left kidney. But this woman, as mentioned above, was also born with a cloacal anomaly; therefore, her complex malformation consisted of a combined Müllerian, Wolffian and cloacal (urogenital sinus) anomaly.
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Results |
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Discussion |
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However, as we reported in different previous publications (Acién and Armiñana, 1986; Acién et al., 1987
, 1991
; Acién, 1989
, 1992
, 2001
, 2002
), it is essential to consider the embryological origin of the different elements of the genitourinary tract in order to explain and understand the pathogenesis of any genital malformation before undertaking the best correction or therapeutical approach in each specific case. Besides, independent from the classification of the Müllerian anomalies proposed by the ASRM, we recommend a clinical embryological classification of all genital tract malformations as shown in Table 1 and Figure 6, which could lead to a better understanding and classification of complex malformations.
Indeed, it is clear that when there is absence of a whole urogenital ridge, the patient will present renal agenesis, and of all genital organs in that same side. Naturally, the absence of the hemivagina ipsilateral to the renal agenesis is not observed. Associated vertebral anomalies are sometimes observed (Acién et al., 1991).
The most complex malformations, however, tend to be those mesonephric anomalies with absence of the Wolffian duct opening to the urogenital sinus, probably due to agenesis or early and extensive lesion (from above) of the mesonephric duct. Since the ureteral bud sprouts from the mesonephric or Wolffian duct in its opening to the urogenital sinus and goes to the metanephros to form the definitive kidney, there will be renal agenesis in all distal lesions of the Wolffian duct. There will also be ipsilateral blind hemivagina, since the vagina comes from the Wolffian duct (sinuvaginal bulbs) and Müllerian tubercle (Bok and Drews, 1983; Acién, 1992
). So due to the mesonephric distal lesion, its opening to the urogenital sinus will not exist either, provoking blind hemivagina. However, there is sometimes a posterior partial reabsorption of the intervaginal septum. After careful examination a buttonhole can be seen on the anterolateral wall of the normal vagina giving access to the genital organs on the renal agenesis side, or the longitudinal vaginal septum does not usually reach the lower third of the vagina (Acién et al., 1987
). Besides this, the Wolffian duct has an inducing function on the appropriate Müllerian development (Gruenwald, 1941
; Magee et al., 1979
), so there will always be associated uterine malformations (didelphys, bicornuate-bicollis, or septate uterus, with septate cervix and/or communicating uteri).
These are the cases of renal agenesis and ipsilateral blind hemivagina syndrome (Acién and Armiñana, 1986; Acién et al., 1987
) that can appear clinically: (i) with a large unilateral hematocolpos, or (ii) with Gartner pseudocyst: Either (a) as a blind vaginal bag holding menses and secretions and behaving as if it was a Gartner cyst communicating with bicornuate uterus (HerlynWerner syndrome), or (b) as a simple cyst in the anterolateral upper third of the vagina associated to, but not communicating with, a bicornuate uterus. In these cases, it is actually a septate or bicornuate uterus with two cervices, but the hemicervix of the Gartnerian pseudocyst side is atretic and the hemiuteri are communicated, simulating a bicornuate-unicollis uterus. Evidently, if the vaginal or cervico-vaginal atresia on this side is complete we will have cases as reported in this paper in point 1: Unilateral cervico-vaginal atresia (or only atretic hemivagina) with renal agenesis (with or without communicating uteri). And, if there is also atresia or hypoplasia of the corresponding hemiuterus, we would have the cases published as uterus unicornis with rudimentary horn and ipsilateral renal agenesis (Acién, 1992
; Stolzlechner et al., 1995
; Heinonen, 1997
); at other times the rudimentary horn is cavitated, with hematometra (Shukunami et al., 2000
).
Occasionally, a duct ending in the hemicervix of the blind side can also be seen in the HSG, and this can correspond to a remnant of the mesonephric duct, and also to an atretic ectopic ureter (see Acién et al., 1991, 2004
). In other cases there is a single ectopic ureter associated to any of the previous types. In these cases there may be no agenesis but renal hypoplasia, and such an ectopic ureter may end in the blind hemivagina (Acién et al., 1990
), or the ectopic ureter ends at the top, ramified in fibrous tracts. There could even be different atretic ectopic ureters coming from the same mesonephric duct (Bhandarkar et al., 1997
). The further from the site where the ureteral bud normally sprouts, the more dysplasic the kidney formed in the metanephros and induced by the ureteral bud is; therefore the anomaly can then range from dysplasia to complete renal agenesis.
For some years, there have been reports on cases of a simple ectopic ureter opening into the Gartner duct cyst with ipsilateral renal hypoplasia and dysplasia (or agenesis) (Currarino, 1982; Gotoh and Koyanagi, 1987
), or in hydrocolpos (Constantian, 1966
), or in duplicated Müllerian ducts (Gilsanz and Cleveland, 1982
), probably with insufficient surgery and varied embryological interpretations (Borer et al., 1998
; Wu et al., 2001
; Petit et al., 2002
) and usually reported by pediatrics (Wakhlu et al., 1998
). Some of these ducts could already be a mesonephric remnant in which an atretic ectopic ureter could open.
Isolated Müllerian anomalies can also be induced by a minor mesonephric defect. In any case, such Müllerian anomalies can affect:
With regards to the anomalies of the urogenital sinus, the most common is the unperforated hymen, but we must also consider the cloacal (anusvulva) anomalies, frequently combined with other higher anomalies. Indeed, a final group, and perhaps the most complex malformations, would be those malformative combinations which associate Wolffian, Müllerian and cloacal alterations, as in Case 5.
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Conclusions |
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All lesions of the mesonephric duct are associated to unilateral renal agenesia and utero-vaginal anomalies. If the lesion is distal, blind hemivagina with hematocolpos can be observed; if it is higher, a Gartner pseudocyst can be observed in some cases, while in others, there is vaginal or complete cervico-vaginal agenesis. At the same time, both anomalies can have: (i) communicating uteri (apparently there is a bicornuate or septate uterus), or (ii) non-communicating uteri and then retrograde menstruation, endometriosis and/or unilateral hematometra (if the tube is closed) are eventually observed.
The Rokitansky syndrome would be an exclusively Müllerian anomaly of the ducts and Müller tubercle. There is no renal agenesia and it can be unilateral.
Also, there can be alternating Müllerian and Wolffian or mesonephric malformative combinations with respect to the affected side. It could be a Müllerian anomaly in one side (unilateral Rokitansky syndrome), and in the other, a mesonephric anomaly with blind hemivagina and ipsilateral renal agenesia.
Therefore, gynecologists must be aware of:
Every clinical suggestion of genital malformation. Attention to long-lasting intra- and postmenstrual dysmenorrhea which does not improve with the pill, to metrorrhagia or persistent postmenstrual spotting (occasionally very malodorous), to endometriosis, specially in youth (Acién, 1986; Acién et al., 1992
), to obstetric problems and abnormal presentations, etc.
Knowledge of the genito-urinary embryology that best explains the malformative anatomic findings, and
To make a careful clinical examination and transvaginal ultrasound.
To ask for and to carry out hysterosalpingography and i.v. pyelogram, as well as CAT, MRI and anything needed to clarify a complex malformation.
To carry out a detailed and appropiate laparoscopic or laparotomic observation when needed, and
To think about and act on the malformation according to embryological deductions, trying to correct only what is necessary to avoid present and likely clinical manifestations.
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References |
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Submitted on March 29, 2004; accepted on June 24, 2004.