Genital Tract Outflow Obstruction

Embryologically, the reproductive system develops from all three germinal layers, starting at approximately 6 weeks' gestation and reaching completion by 14 weeks.[2] The ovaries are derived from endoderm, the internal reproductive structures from mesoderm, and the external reproductive structures from ectoderm.[3]  Because the greater part of the obstructive pathology develops during embryology, it is important to understand the steps that occur.

The female internal reproductive structures include the fallopian tubes, the uterus, the cervix, and the upper two thirds of the vagina. Before differentiation into male and female, all embryos have paired mesonephric (or wolffian) ducts that connect the kidneys to the cloaca, as well as paired paramesonephric (or müllerian) ducts.[4] Female development is the default occurrence in the absence of the SRY gene from the Y chromosome. Without SRY, the mesonephric ducts degenerate, and the paramesonephric ducts develops further into the internal reproductive structures.[3]

Failure of vertical fusion or canalization of the paired ducts in utero may result in rudimentary uterine horns, bicornuate uterus, uterus didelphys, or a longitudinal vaginal septum.[4] Often time such müllerian anomalies occur in conjunction with renal anomalies due the metanephric duct developing into the kidneys and ureters around the same time.[5]

The female external reproductive structures include the lower third of the vagina, the external genitalia, and parts of the bladder. These develop as the urogenital sinus involutes cephalad and differentiates into the sinovaginal bulb. The sinovaginal bulb ultimately meets and fuses with the vaginal plate from the distal portion of the müllerian ducts forming the hymen.[4] Normally, the hymen then perforates during embryogenesis, but if it does not, the result is an imperforate hymen. Incomplete vertical fusion of the two systems can lead to cervical atresia, transverse vaginal septa, or distal vaginal atresia.[4]

The exact etiology of such genital tract anomalies is unclear. Any defect in the normal organogenesis involving the urogenital sinus or the müllerian duct can result in genital tract anomalies. No single gene mutation has been found to be responsible for such anomalies. Mice studies have shown a variety of genes involved in normal development of the reproductive system[1] ; specifically, WNT and HOX have been found to be involved with Mayer-Rokitansky-Küster-Hauser syndrome (MRKH).[5]

Acquired outflow obstructions have also been described. They can develop in patients who have posttransplant graft-versus-host reactions, undergo radiation therapy, or have lichen sclerosis lesions that cause scarring of the vagina and vaginal agglutination.

Female genital malformations occur in 5-7% of the general population.[1] The most common of these is imperforate hymen, with an estimated incidence of 1:1000-2000.[1] Müllerian agenesis (also referred to as müllerian aplasia, MRKH, or vaginal agenesis) has an incidence of 1 per 4500-5000 females.[6] It is caused by embryologic underdevelopment of the müllerian duct, with resultant agenesis or atresia of the vagina, uterus, or both. As many as 53% of such malformations are associated with other anomalies as well, particularly anomalies of the kidneys and the skeleton.[6]

After surgery, these patients' quality of life usually improves immediately; only very rarely do any further complications arise.[7] The extent of the surgical procedure required depends on the type of anomaly found. For the most common anomalies (eg, imperforate hymen), the procedure is performed via a vaginal approach and is relatively low-risk. For some of the more complex anomalies, especially those in which with other systems are affected, an abdominal approach may be necessary, and other specialists (eg, urology) should be involved.[8]

In selected patients, menstrual suppression may be attempted as a means of delaying surgery.[8] However, complete suppression is not always achievable, and it is a therapy that would have to be maintained until menopause. Infertility rates among patients after treatment are consistent with those among the general population, aside from the unique situation of cervical agenesis that neessitates hysterectomy for treatment.[3]

If outflow obstruction is left untreated, menstrual blood will continue to accumulate just above the anomaly. Some of the blood does begin to be reabsorbed, but not rapidly enough for reabsorption to be completed before trapped menstrual blood accumulates with the next period. Once the volume of trapped blood is large enough, it can become very painful to the patient and can even lead to urinary retention and constipation.[9] These patients also have higher rates of endometriosis, which is theorized to be due to retrograde menstruation occurring as a consequence of the obstruction.[10] In most patients, the endometriosis seems to resolve after the obstruction is relieved.[11]

For patient education resources, see the NASPAG and Female Sexual Problems.  

Although some anomalies (eg, imperforate hymen) can be diagnosed upon gentle inspection with labial separation, most patients go undiagnosed until puberty. Unless the newborn develops a mucocele (a buildup of vaginal secretions that were stimulated by maternal estrogen), the obstruction is not obviously seen on physical exam.   

Once puberty occurs, patients present with history of amenorrhea, recurrent lower abdominal cyclical pain, or lower abdominal midline mass.[12] An obstructive anomaly should be part of the differential diagnosis when a patient presents with primary amenorrhea but normal secondary sexual characteristics. With normal puberty, menses is expected 2-3 years after breast bud development.[3]  A workup for primary amenorrhea is indicated in any patient with secondary sexual characteristics and no menses by age 15 years or by 3 years after breast development. 

Even when a patient presents with monthly menstrual flow, the clinician should still be suspicious for an obstructive anomaly. There are duplicate-system disorders (eg, obstructive hemivagina and ipsilateral renal agenesis [OHVIRA] syndrome [also known as Herlyn-Werner-Wunderlich syndrome] and rudimentary uterine horn) in which an obstruction causes cyclical pain while normal unobstructed menstrual flow still occurs via a separate system.

Physical examination findings vary according to the level of the obstruction (see Levels of Outflow Obstruction below). Some obstructions may not even be visualizable without imaging.

In cases involving imperforate hymen or certain transverse vaginal septa, obstructions can be seen in the office upon gentle examination. Given that these patients are young and this is usually their first vaginal examination, it is vital to ensure their comfort and give them some control over the situation. Often, they are most comfortable when placed in a frog-leg position with a sheet covering to allow them to decide when they are ready to have the sheet lifted. If menstruation has occurred and hematocolpos developed, the hymen or vaginal septum may bulge and exhibit a bluish discoloration.[1]  On occasion, it can be helpful to have the patient perform a Valsalva maneuver to enable better visualization of a bulge. 

On physical examination, it is important to differentiate an imperforate hymen from a transverse vaginal septum; the two conditions are managed differently. A transverse vaginal septum will be present cephalad to a hymenal ring. It can be found anywhere along the vaginal canal, in the lower, middle, or upper portion.[13]  A knee-chest examination position is sometimes better for visualizing the presence of a bulging septum, especially when it is in the upper third of the canal. If the patient is old enough, digital examination can help identify a septum that is difficult to see. If an obstruction cannot be visualized on examination but is suspected on the basis of the history, appropriate imaging should be ordered.  

Obstruction of menstrual flow can occur at any place between the endometrium and the hymen. To determine the necessary treatment (see Treatment), one must accurately diagnose the anomaly present. The following sections list different outflow obstructions according to the level at which the obstruction occurs, proceeding from cephalad to caudad.  

Uterus 

Rudimentary uterine horn  

Rudimentary uterine horn is a consequence of failed fusion of the paired müllerian ducts. Patients have one normal unicornuate uterus that is connected to the cervix and the vagina, along with a smaller separate rudimentary uterus. The rudimentary horn can come in various forms. Some are communicating with the functional uterus, whereas others are separated (ie, noncommunicating). Any noncommunicating rudimentary horn can be obstructive if it has a functional endometrium. These patients present with cyclical abdominal pain but normal menses. If the condition is left undiagnosed, patients will experience severe constant abdominal pain as the menstrual blood builds up in the rudimentary horn.[14]   

Mayer-Rokitansky-Küster-Hauser syndrome 

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is the congenital absence of the vagina and uterus resulting from failed fusion of the caudal portion of the müllerian ducts.[4]  It is the second most common cause of primary amenorrhea.[5]  Despite having a blind vaginal pouch, the majority of these patients do not have obstructive symptoms, because they lack an endometrium. This disorder, however, has a spectrum of manifestations, and some patients do have rudimentary müllerian structures with functional endometrium.[6]

Cervix 

Cervical agenesis

Cervical agenesis is a rare anomaly (estimated incidence, 1:80,000) in which the cervix fails to develop.[3]  It can present in a variety of forms, including partial and complete agenesis, and it may occur with or without agenesis of the vagina.[15]

Vaginal canal 

Transverse vaginal septum

Transverse vaginal septum is due either to incomplete canalization of the vaginal plate or to failure of the sinovaginal bulb fails to meet the müllerian ducts.[13]  As mentioned previously, it is vital to differentiate this condition from an imperforate hymen. Both can present with amenorrhea, bulk symptoms, or, if microperforations present, difficulty with tampon insertion or intercourse.[13]  The only means of determining which pathologic condition is present is physical examination.

For appropriate surgical planning, it is important to obtain an accurate assessment of both the location of the transverse septum and its thickness. The location of the septum is determined by measuring its distance from the vaginal introitus: Any septum less than 3 cm cephalad is considered low, and any septum more than 6 cm is considered high.[16]  As for thickness, any septum with a thickness of 1 cm or greater is considered thick for the purposes of surgical planning.

Partial vaginal agenesis

Incomplete atresia of the müllerian duct leads to a shortened vaginal canal internally (which becomes the hematocolpos) and to a blind vaginal pouch externally. On physical examination. no bulge is seen, because the anomaly does not involve the urogenital sinus. The hematocolpos may be palpated abdominally or on rectal examination.[1]

Obstructed hemivagina and ipsilateral renal agenesis syndrome

OHVIRA syndrome is defined by a specific combination of anomalies, as follows[3] :

• Duplicated reproductive system
• Obstructed hemivagina
• Ipsilateral renal anomaly (eg, duplicated ureter, renal agenesis, or dysplastic kidneys)

This syndrome is thought to be the result of faulty or arrested development in the caudal portion of the paramesonephric duct.[3]  Because of the duplicated system, these patients do not present with amenorrhea, and the diagnosis is therefore a challenging one. If OHVIRA is strongly suspected, follow-up with appropriate imaging is essential. In the past, laparoscopy was the only means of diagnosing OHVIRA, but in current practice, magnetic resonance imaging (MRI) is the gold standard.[11]

Hymen 

Imperforate hymen

Contrary to common cultural beliefs regarding the need to “break” the hymen at the time of first intercourse, perforation of the hymen occurs during embryogenesis in normal development. If this perforation does not occur, the patient will need surgical management to open the hymen and allow for menstruation.

Potential complications include the following:

• Hematocolpos
• Hematometra
• Pyohematocolpos
• Pyohematometra
• Urinary retention, hydronephrosis (rare)
• Postoperative recurrence of obstruction
• Constipation
• Abdominal mass

The history and physical examination usually suffice to establish the diagnosis. In rare cases of transverse vaginal septum with microperforation, ascending infection may lead to pyohematometra. Fluid culture is helpful in determining appropriate antibiotic therapy. 

If the patient has a blind vaginal pouch and no pubic or axillary hair, karyotyping or measurement of serum testosterone can help establish the diagnosis of androgen insensitivity syndrome. 

If the patient has müllerian agenesis with a normal karyotype, screening for other skeletal and urinary anomalies should be considered. Some 30% of these patients have associated renal anomalies, most commonly unilateral renal agenesis.[1]  

The best first step in the evaluation of these patients is pelvic ultrasonography (US). Transabdominal US usually suffices for visualization of any hematocolpos or hematometra.[17]  If this is unclear, transperineal US may be considered, but transvaginal US is not recommended in children, because it is unnecessary and can be emotionally and physically traumatizing. Three-dimensional (3D) US of the pelvis can also be beneficial to reveal additional associated congenital malformations of the uterus or cervix.[10]    

In the past, laparoscopy was thought to be the only means of diagnosing müllerian anomalies definitively. Subsequent studies showed, however, that magnetic resonance imaging (MRI) should now be considered the gold standard.[10] Laparoscopy was found to be superior only for diagnosing adnexal abnormalities,[2] but it is still done sometimes to facilitate concurrent resection for endometriosis. MRI should also be done to delineate other associated abnormalities (eg, of the urinary tract or the skeletal system).[18]  For patients undergoing surgery, full and accurate assessment of the underlying anatomy is vital; this is carried out via MRI before the operation is performed. 

Other common imaging modalities used in the gynecologic setting are saline sonohysterography (SIS) and hysterosalpingography (HSG). These studies require administration of saline or contrast through the cervix into the uterine cavity and therefore cannot be done in patients with obstructive anomalies. SIS and HSG can, however, be useful in diagnosing nonobstructive uterine anomalies—specifically, intracavitary anomalies such as a uterine septum or a bicornuate uterus.[10]  

At present, there is no universal staging system for the various reproductive anomalies. Such a system would be useful to have, especially for surgical planning and clear communication with patients.

A few classification systems have been proposed. The most widely accepted of these is the one developed by the American Society for Reproductive Medicine (ASRM)[1] ; however, because this system focuses on reproductive outcome, it does not include many of the obstructive anomalies discussed in this article, by reason of their limited impact on fertility. A better option for classifying outflow obstructions is the VCUAM (Vaginal Cervix Uterus Adnexa-associated Malformation) system, which includes all structures of the reproductive tract.[19]  

Once the diagnosis of a genital tract outflow obstruction has been established, consultation with a pediatric gynecologist or urologist who is familiar with such conditions is recommended. In determining the appropriate management approach, the age of the patient, as well as the psychological implications the condition poses for the patient, must be taken into account.[6]  The two available treatments are surgical repair and menstrual suppression.

For some younger patients who are not yet able to grasp complex medical decisions, delaying surgical treatment can be particularly beneficial. This is commonly done in cases of cervical agenesis because definitive treatment requires a hysterectomy that will render the patient infertile. Delaying surgery is also beneficial for patients who need to be compliant with vaginal dilation for a successful repair.  

Menstrual suppression can be achieved with a variety of methods, including the following[1] :

• Combined oral contraceptives
• Progesterone only
• Gonadotropin-releasing hormone agonists

Not all suppressive therapies result in complete amenorrhea. Consequently, some of these patients will not be successfully treated and will return with severe abdominal pain, in which case surgery will be the only remaining therapeutic option.  

Surgery is the only way of definitively treating genital outflow obstructions. Puncture and drainage of a hematocolpos without a definitive surgical procedure is not recommended, because of the high risk that an ascending infection will develop from lack of proper drainage. The type of surgical repair necessary is highly dependent on the anomaly found; consequently, accurate assessment of the structural anatomy is imperative before surgical intervention is initiated. Surgical treatments indicated for various obstructions are listed below on the basis of the level at which the obstruction occurs, proceeding from cephalad to caudad.  

Uterus 

Rudimentary uterine horn 

Rudimentary uterine horn is treated by means of surgical resection, which can be done by using minimally invasive techniques.[1] Resection is also recommended for a communicating nonobstructed horn to prevent pregnancy in that horn. If a pregnancy occurs in the rudimentary horn, there is a high chance of uterine rupture if it advances into the second trimester.[14]   

Mayer-Rokitansky-Küster-Hauser syndrome

Treatment of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome typically consists of surgical removal of the rudimentary structures to eliminate outflow obstruction. Patients who do not have an outflow obstruction, however, can usually avoid surgery. Vaginal elongation using only vaginal dilators has been successful 90-96% of the time.[6]  Patients in whom management with dilators fails can undergo surgical creation of a neovagina using either the McIndoe or the Vecchietti technique.[20]  

Cervix 

Cervical agenesis 

The recommended surgical procedure for relieving the obstruction caused by cervical agenesis is a total hysterectomy. The decision to undergo this procedure can be a difficult one, especially for young patients, because it renders them infertile. It may therefore be beneficial to delay surgery in order to give the patient more time to mature and become better informed before making her decision. To this end, medication can be given for menstrual suppression (see Medical Care) to delay a significant buildup of blood.[8] .

Some cases of uterovaginal anastomosis have been described, but these have been associated with significant morbidity, including pelvic inflammatory disease, endometritis, recurring obstruction and stenosis, and even death.[15]   

Vaginal canal 

Transverse vaginal septum

Although the physiology of a transverse vaginal septum may be similar to that of an imperforate hymen, there are a few important management differences. Surgical repair of a vaginal septum requires end-to-end anastomosis of vaginal epithelium, usually with sutures, to prevent stricture formation.[8]  Vaginal septa can also be found with other müllerian anomalies, most commonly a rudimentary uterine horn; accordingly, patients should be evaluated for these anomalies as well.[7] ​

For some of the higher and thicker septa (see Presentation, Levels of Outflow Obstruction), a combined abdominal and vaginal approach to surgical repair may be required.[16]  Alternatively, these septa can be managed with the help of a Foley catheter. Needle aspiration is performed to confirm the correct location of the vaginal canal. The septum is then serially dilated by advancing guide wires through the needle until there is an opening large enough to permit passage of a Foley catheter. The Foley catheter is then placed and the balloon inflated. Downward traction is applied to facilitate resection of the septum.[8]   

Partial vaginal agenesis

Surgical repair of partial vaginal agenesis requires not only relief of the obstruction but also elongation of the vagina. The procedure should be performed after there has been time for hematocolpos to build up. This buildup naturally distends the tissue, decreasing the need for grafts and enabling easier identification of the correct space.[20]  Preoperatively, the use of daily dilators can also be beneficial for decreasing the distance from the introitus to the vaginal canal.[8]

During the surgical procedure, the introitus between the urethra and the anus is incised and dissected caudally until the pouch or hematocolpos is met.[1]  This dissection can be technically difficult, being so near important structures (including the bladder and bowel); ultrasonographic (US) guidance is often helpful during this stage.[8]  The vagina is then grasped and elongated down to the perineum through a variety of pull-through procedures.[1]   

Obstructed hemivagina and ipsilateral renal agenesis syndrome

No intervention for obstructive hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome (also known as Herlyn-Werner-Wunderlich syndrome) is carried out until the patient reaches puberty, after which time vaginoplasty is performed to relieve the obstruction. In the majority of patients, this can be done via a vaginal approach.[11]  It may be beneficial to allow for a few menstrual cycles to distend the hemivagina and thin the wall and to facilitate determination of the incision site. Intraoperative US and needle aspiration can also help confirm that the surgeon is in the correct space before the incision is made.[11]   

Hymen 

Imperforate hymen

The timing of surgical treatment of imperforate hymen is controversial. Although repair is facilitated when estrogen stimulation is present, it can be performed in infancy, childhood, or adolescence.[3]  The majority of surgeons would probably recommend that it be done just after thelarche but before menarche, when the hymen is well estrogenized.

The surgical procedure involves making a cruciate or circular incision in the hymen to open it, thereby allowing for a normal menstrual flow and providing for comfort with future tampon use or intercourse.[8]  Because the cervix is often slightly dilated from the buildup of blood, irrigation of the vaginal canal is not recommended. Stenosis is rare in these cases, and therefore, postoperative dilation is not required.[8]  In the setting of microperforation, there have been cases where surgery was avoided and the condition was treated with serial dilation instead.[21]  

A follow-up examination 4-6 weeks after repair is recommended to ensure that scar tissue has not caused a recurrence of obstruction. In the majority of patients, endometriosis resolves spontaneously after the obstruction is relieved, but continued monitoring for pelvic pain is nevertheless warranted.[7]  If no stricture has formed and pelvic pain persists, laparoscopy for endometriosis resection could be considered.