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��ࡱ�>��	������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������	���Zbjbj���	.������R�������CCCCC����WWWW�,W�=�GGGGG"""Y=[=[=[=[=[=[=$�?�&B�=C�""��=CCGG��=p%p%p%�R	CGCGY=p%�Y=p%p%��5|Q7G����`D��P�WL#U6E=�=0�=g6��BL#B�B$Q7�BCQ7�"��hp%Tp�"""==�$�"""�=�������������������������������������������������������������������������B"""""""""		:	Vaginal Outlet Obstruction  - A Review of Cases

Dobanovacki Dusanka, Vuckovic Nada, Marinkovic Smiljana, Jokic Radoica, Bukarica Svetlana


Introduction
Vaginal outlet mechanism consists of undisturbed fluid passage from vagina through hymenal opening. Genital tract outflow is important for secretion and menstrual effluxion, and as a pathway in reproductive function. Congenital outflow obstruction may occur at different levels and with a different clinical presentations [1].
Embryological development of vagina results  from lower portion paramesonephric ducts fusion and regression forming the uterovaginal primordium (gives rise to the uterus and superior part of vagina). Contact of the uterovaginal primordium with urogenital sinus induces formation of paired outgrowths named sinovaginal bulbs. The sinovaginal bulbs fuse to form the vaginal plate. The cells of the fused bulbs undergo apoptosis to form the lumen of the vagina. Until late fetal life the lumen of the vagina is separated from the cavity of the urogenital sinus by a membrane � the hymen [2,3].
Misdevelopment can result in: imperforate hymen (failure of epithelial degeneration), low, mid, or high transverse septum of the vagina (incomplete unit), or  in atresia of the vagina resulting in persisting of a portion of solid cells cord.
Recently interest has focused on expression and function of the mammalian HOX genes as a possible etiology of those genital developmental abnormalities [4]. 
Despite different origin of some parts of vagina and hymen, their obstructed forms are clinically manifested as hydro(metro)colpos in neonatal period, and hemato(metro)colpos at the beginning of puberty.
In this report on our ten-year experience the importance is illustrated of early diagnosis in preventing morbidity and mortality.

Variation in hymenal development
Regular development of ringlike hymenal structure provides normal vaginal outflow. Until late fetal life, the lumen of the vagina is separated from urogenital sinus by invagination of the posterior wall forming a hymenal membrane. The hymen usually ruptures during the perinatal period and remains as a thin fold of mucous membrane circumferentialy at the entrance of the vagina [2]. 
There is a spectrum of variations in hymenal configuration, like different type of fenestration, septa etc. with more or less clinical significances. Imperforate hymen (IH), as result of failed hymen rupture, is the most important in this misdevelopment spectrum. 

Imperforate hymen 
IH is an external congenital genital anomaly when nonperforated membrane of hymenal tissue covers the entrance into vagina. Membrane composed of vaginal epithelium and epithelium of the urogenital sinus is interposed by mesoderm [5]. Imperforation of hymenal tissue may also be present in variations as microperforate, septate, stenotic or cribriform hymen.
The maternal hormones affect the reproductive tract of the female infant both in utero and during the early neonatal period, increasing secretions of uterine and cervical glands. The explanation could be that target tissue may be more sensitive to or exposed to higher levels of maternal estrogen [6]. By the age of a month vaginal secretion becomes poor and alkaline, the epithelium is thin, the individual cells small and devoid of glycogen, and the basal layer comparatively inactive [7].
If estrogenic stimulation and vaginal obstruction coexsist hydro(metro)colpos will develop. The retained fluid in hydrometrocolpos consists of vaginal and uterine secretions and may be acidic and serous or mucoid, containing large numbers of desquamated epithelial cells, leukocytes, and erytrocytes [8].
In the setting of imperforate hymen, efflux of these secretions is not possible, and the newborn may present with a whitish bulging mass filling the introitus (hydrocolpos or mucocolpos). If hydrocolpos is small or not detected at birth, secretions resorb up to the end of first months of life, and the condition may be undetected until puberty. Also, if there is a low level of maternal hormones, there is no extragenital secretion and the obstruction will usually remain unnoticed until puberty.
Hydrocolpos is the mass usually consisting of fluid-filled vagine but uterus is displaced upwards. Why the uterus is not always dilated is not known. 
Clinical presentation in neonates is a translucent bulging membrane-hymen between labia as a result of distention of the vagina and uterus due to accumulation of excessive mucous secretion. After delivery or a few days later lower abdominal mass can be palpated. Membrane can�t be seen until the abdomen is manually pressed, or    the baby cries. On close inspection, a normally positioned urethral meatus should be identifiable cephalad to the mass.
The hydro(metro)colpos  may compress the adjacent bladder and ureters, bowel, and pelvic veins, causing problems of urinary retention, constipation, and edema or cyanosis of the lower extremities [1,9]. Secondary infection of the vaginal fluid, usually with colonic organisms, is not uncommon. Others abnormalities are published as [10]. syndromatic forms of hydrometrocolpos: associated with genetic syndromes as McKusick-Kaufman syndrome [11,12] or Bardet-Biedl syndrome.

At puberty, the main factor of the accumulation is menstrual blood    clinically present as hemato(metro)colpos. The accumulated secretion evert the membrane producing a bluish-colored bulging mass at the introitus (mid and high transverse vaginal septa or vaginal atresia will not present with this characteristical interlabial mass [6]. Clinical signs at the beginning of puberty may be as follows: recurrent pelvic, lower abdominal or back pain or lower abdominal midline mass [13-15]. Severe long-standing obstruction may cause urinary retention, constipation, and hydronephrosis [16]. Pressure of the vagina on the ureters crossing the pelvic brim results in hydronephrosis and hydroureter.
Compression of the vena cava and the iliac vessels would cause cyanosis, edema, and ecchymosis of the perineum, lower extremities, and abdominal wall. The rectum is less commonly involved, but constipation may complicate hydro(metro)colpos.
Rarely reflux of endometrial tissue through the fallopian tubes (hematosalpinx) may result in secondary endometriosis [17].

Diagnosis of hydro(metro)colpos is possible by fetal ultrasound from 25th gestational week [18-20]. Hydrocolpos should be considered when an abdominopelvic cystic mass is diagnosed in a female fetus. Also, prenatally it is necessary to reveal whether there are associated anomalies [21].
In cases when pelvic mass is difficult to distinguish from other abnormalities � mother is obese, olygohydramnios or fetus is in unapropriate position � an ultrafast MRI is suggested [22-24].  MRI shows the exact location and extension of the cystic mass, the bladder or cloacal abnormalities if they exist [25]. The diferential diagnosis of a pelvic mass includes sacrococcygeal teratoma and anterior meningomyelocele.
In neonates clinical finding and pelvic ultrasound that shows a dilated vagina are sufficient for diagnosis. Abdominal ultrasonography reveals a large, sonolucent midline mass displacing the bladder forward and the rectum posteriorly (Nussbaum and Lebowitz). Associated anomalies have to be excluded. In pubertal girls CT scan or MRI demonstrate other congenital abnormalities [26].
Differential diagnosis includes vaginal atresia or agenesia, transverse vaginal septum, vaginal cyst, hymenal cyst or paraurethral cyst, cloacal malformation, etc. To distinguish an imperforate hymen from transverse vaginal septum is important because of possible influence on fertility.

Treatment of imperforate hymen can be performed in infancy, childhood, or in adolescence. Under general anesthesia hymen is incised, and after that fluid is drained. The best solution is an elliptical excision of the membrane close to the hymenal ring, with running absorbable suture along the incised edges to prevent recurrence. Local anesthetic should be applied: lidocain sol injected or lidocain gel topically. Slow evacuation of the retained material is suggested.
Puncture and drainage of hematocolpos without a definitive surgical procedure is not recommended. The fluid is viscous and may not adequately drain, which increases the risk of an ascending infection. Simple incision of the hymen may be associated with postoperative stenosis. Spontaneous rupture of the IH with hematocolpometra is described and hymenotomy may not be needed if adequate opening for menstrual discharge is warranted [27]. After decompression repeated ultrasonography is necessary for confirmation of normal vaginal outflow over the next few months. 
A complication like acute abdomen due to bilateral hematosalpinx and unilateral rupture of the hematosalpinx is published [28].

Over the last ten years (2003-2012) 15 females were admitted at the Pediatric Surgery Hospital in Novi Sad and treated for IH. 
Four of them were neonates: 
Three were full-term neonates from unremarkable pregnancies. Pediatricians from primary health care had noticed enlarged abdomen (Fig.1.A.) a few days after delivery, diagnosis was confirmed by ultrasound and operative treatmen was successful. Mild hydronephrosis in two neonates regresses after treatment. Also vascular pressure on pelvis and distal extremities (Fig.1.B.) dissapeared immediately after decompression. No other anomalies were detected. Two of them were diagnosed by fetal ultrasonography during the last week of pregnancy.
One premature infant in the 30th week of gestation was born and admitted in Intensive Therapy unit for duodenal atresia. Physical examination revealed small hymenal protrusion (Fig.2.). After duodenal surgery hymenotomy was performed but parents were informed about the local setting and necessity of observation up to the pubertal age. This has been the youngest female with hymenal incision and we are going to continue with regular control.
One was the infant aged two:
A two year female suffered recurrent urinary infection. She had a complete adhesion of the labia minora and after adhesiolysis it was expected that uroinfections would stop. Micturition urethrocystography performed for repeated infection diagnosed bilateral vesicoureteral reflux. During examination for endoscopic treatment of reflux, IH was noticed and an elliptical incision was performed during the same procedure for reflux.
Two  prepubertal girls:
A girl of 9 went to a urology consultant because her parents had at her birth been informed that she had IH though without a complication. An incision was proposed before the age of puberty. External genitalia were normally developed but hymen consisted of translucent imperforate membrane. Two years later she started to menstruate with regular cycles.
An amenorrhoic girl of 10 had an increased leucorrhoea, and in primary care vaginal outflow obstruction was noticed. There were no signs of dilated vagina, external genital examination revealed membrane instead of typical hymenal appearance. During intervention a pin-point opening in the cephalad part of the hymen was noticed. We defined it as an incomplete hymenal obstruction. An elliptical excision was performed. Ten months later menarche appeared followed by irregular cycles.
Eight were pubertal amenorrhoeic girls:
They were sent to consultation for extreme constipation, urinary retention, abdominal tumor, nodi haemorrhoidales and four for recurrent abdomino-pelvic pain. Genital examinations revealed the IH and hematocolpos, ultrasound confirmed the diagnosis and all girls underwent elliptical hymenal incision with running sutures successfully.  Regular follow-up and ultrasound confirmed a physiologic cycle of menstruation. No other anomalies were noticed.

Congenital Anomalies of Fusion in Vagina Development 
The sinovaginal bulbs  complete their growth by the 16th gestational week, forming the primitive vaginal plate. Canalisation of this plate is completed with forming of vagina by the 5th month [29]. Failure of canalisation might be present with a spectrum of anomalies that rarely cause symptoms during infancy but disturb the time of menstruation.
According  to the American Fertility Society (AFS) classification, m�llerian duct abnormalities [30,31] manifest as a wide spectrum caused by arrest in different stages of development (lateral, horizontal or longitudinal fusion disorders), or as a result of abnormal canalisation of vaginal plate or failure of fusion (disorders of vertical or transverse fusion) [32,33].
 
Transverse vaginal septa
Transverse vaginal septa (TVS) may occur at any level above the hymen. It is also caused by failure of vaginal plate canalisation. As a result high, mid or low diaphragm-like formations are present obstructing the outflow. Patients are primary amenorrheic.
Clinical presentation is rarely as hydro(metro)colpos (usually presented with low TVS) but most often as hemato(metro)colpos. Symptoms of recurrent abdominal or pelvic pain are in the patients� history data. Abdominal ultrasound and external genitalia examination lead to a diagnosis. A bulging membrane protruding through the vulva is not always an imperforate hymen. In some cases a transverse septum higher in the vagina is seen to protrude through a normally perforated hymen, membrane bulging through a normal hymen. It is possible that some patients with a protruding membrane are incorrectly diagnosed with IH.

When the obstructon is due to a very low vaginal septum, the accumulated secretion everts the membrane producing a bulging mass at the introitus. Mid and high transverse vaginal septa or vaginal atresia will not present with this interlabia mass. [6,9]. Hydro(metro)colpos from a low membrane is usually not associated  with other congenital anomalies unless the obstructed vagina is one-half of a duplicate system [34]. This is how hydro(metro)colpos differs from vaginal atresia or a mid or high transverse septum, which is almost always associated with severe and often multiple congenital anomalies of the genitourinary and gastrointestinal tract [6]. 
The diagnosis is usually made by physical and ultrasound examination. Surgery for a transverse vaginal septum depends on location and thickness. Excision of the septum and maintained vaginal patency are the main tasks. Sometimes there is indication for vaginoplasty. In cases of strictures repeated dilatation is required.
A follow-up examination 4-6 weeks after is recommended to ensure that the scar tissue has not caused a recurrence of obstruction.

Our experience includes three patients with low transverse septa:
Neonatal period � A two-day-old female newborn with enormous abdominal distension, respiratory insufficiency due to bilateral massive pneumonia and hydromineral imbalance was admitted at the hospital. A firm smooth mass occupied the lower and medium abdomen up to the costal margin. External genitalia were normal. Ultrasound revealed large fluid filled cystic mass  extending from pelvis occupying the whole abdomen,  and the displacement of the intestine cranially. At the top of the cyst a uterine like formation was noticed. Urinary tract was normal. Vaginoscopy was performed through normal hymenal aperture. At the 5 milimeters upward a blind septum was noticed bulging into vagina. An incision and insertion of small polietilen F 4 catheter was adequate to drainage 600cc of odorous mucoid fluid. General condition deteriorated  with life-threatening septic presentation and neonate died five days after the operation.
Pubertal age � Two girls of thirteen had a history of recurrent low abdomen pain lasting a few months. Ultrasound revealed a large vagina filled with menstrual blood. On examination of external genitalia a bulging but not translucent membrane obstructed the entrance of the vagina (Fig. 3.A.). Rectal examination revealed a pelvic mass. Associated anomalies were not detected. Under general anesthesia an elliptical excision was done through the septum formation. It was a few milimeters  thick and not resembling the hymen. Slowly, 300ml from one vagina and 350ml from the other one were evacuated. Running sutures were used in trying to prevent recurrence or stenosis. Microscopical analisys of tissue specimen revealed the possibility of a low transverse septum (Fig.3.B.). Both girls are now under the outpatients care of juvenile gynecologists.

Vaginal Atresia
Vagina originates from two embryonic structures: the upper part from M�llerian duct system in and the lower third from the urogenital sinus. Canalisation of the vaginal canal is complete by week 20. Misdevelopment presented as failure of fusion or canalisation of these two systems in vertical plane may be clinically present with a spectrum of m�llerian duct anomalies. Vaginal atresia (VA) is one of them. Missing portion of the vagina is replaced with fibrous tissue [17].  According to the American Society for Reproductive Medicine 1998. Classification, vaginal atresia is categorized as Type I [35]. Some authors believe that variants of VA, formerly called partial vaginal agenesis, are more correctly classified as variants of a transverse vaginal septum [17].
In VA the appearance of the external genitalia can be normal or vulva slightly retracted upwards. This is why this abnormality can not be detected without a careful examination of the genitalia.
Clinical findings vary depending on the anatomy of the vaginal outlet and the changes in the upper vagina and uterus. The upper vagina becomes enormously distended when the girl starts to menstruate, usually producing a palpable abdominal mass arising from the pelvis. The Fallopian tubes can be normal, although they may be distended allowing escape of the fluid into the peritoneum. Other anomalies are occasionally seen with hydrometrocolpos. Some other combinations of structural anomalies may be present as Mayer-Rokitansky-K�ster-Hauser syndrome, Bardet �Biedl syndrome, Frase syndrome, and Winter syndrome [36-39].
The diagnosis is usually made when symptoms of obstruction are obvious. Ultrasound and other imaging studies confirm the physical examination. Urogram would demonstrate anterior and superior displacement of bladder and, possibly, hydronephrosis and hydroureter. As mullerian agenesis can be associated with other anomalies, particularly those of kidneys and skeleton [41,41], further investigation is indicated. 

Therapy is directed to relief of the obstruction of the vaginal outlet providing normal sexual life and reproductive function. Vaginal reconstruction is required, sometimes by an abdomino-perineal approach, but stenosis and fistula formation could complicate postoperative period. 

We have the experience with only one case of VA:
Pubertal age - A twelve-year-old amenorrhoic girl was admitted as an emergency case for the symptoms and signs of acute abdomen. History taking revealed that a healthy and sport oriented girl started to suffer a lower abdominal pain six month earlier, followed by parestetic feelings on the both legs. Progressing symptoms and the lower back intensive pain after abdominal ultrasound turned attention to a large cystic mass arising from the pelvis which was suspected to be uterus didelphys in the form of hematometra (Fig. 4.A.), and also a solitary kidney on the right (Fig.4.B). CT scan confirmed the diagnosis. External genitalia appearance was normal (Fig. 4.C.). Emergency laparoscopy revealed two large masses of hemotodidelphys uterus and bilateral hematosalpinx with perforation on the left. Transabdominal drainage was performed. When general condition imroved transvaginal desobstruction and vaginoplasty were performed. Treatment involved dissection through the atretic segment with pull-through anastomosis of both proximal and distal parts. Regular dilatations were performed in the next few months, preventing the stenosis.

Conclusion
The genital tract�s expulsion function is important especially from the beginning of puberty and menstruation. The outflow obstruction may occur at different levels with variations in clinical presentation. It is also noticed that m�llerian abnormalities may be a component of a multiple malformation syndrome.  
In many patients they remain undetected until puberty, when patients reach menstrual cycle and experience the retrograde menstruation. Most patients present with the history of amenorrhea, recurrent lower abdominal cyclical pain, or lower abdominal midline mass. Severe long-standing obstruction may cause urinary retention, hydronephrosis and constipation.
Examination of the newborn and inspection of genitalia are still essential. Any suspicion of absence of vaginal outlet can be detected during this simple evaluation which may indicate further investigation. Ultrasound is essential in diagnostics but in some cases CT scan or MRI are necessary prior to surgery. Surgery of vaginal outlet obstruction depends on local anatomy. Simple excision or vaginal reconstruction can be performed. Postoperative follow-up is necessary until the normal menstrual cycle is established.


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