Mu¨ llerian Agenesis

Mu¨ llerian agenesis (Mayer-Rokitansky-Ku¨ ster-Hauser syndrome) involves

agenesis of the uterus and upper two thirds of the vagina; it has been
observed in 1 in 5000 females. This diagnosis is typically considered
when the patient presents during her mid to late teens with a complaint
of primary amenorrhea. After gonadal dysgenesis, it is the second most
common cause of primary amenorrhea. Since their ovaries function normally,
these patients progress through all normal pubertal phases except
menarche. Pain is an infrequent complaint. Since the hypothalamic-pituitary-ovarian axis remains unaffected,
their cycles are ovulatory and thus they may experience mittelschmerz pain. If functioning endometrialtissue is
present in the mu¨ llerian remnants, the patient may rarely complainof severe cyclic pain. Associated renal
anomalies are noted in 40%of patients. Abnormalities may include the absence or malposition of the kidney.
Spine, limb, and rib anomalies are noted in 12% of the patients, and congenital deafness has also been
reported. On physical examination, patients with vaginal agenesis have fully developedsecondary sexual
characteristics. The external genitalia appearnormal, but only a vaginal dimple or blind ending vaginal pouch is
noted.A hymenal fringe is frequently seen. Rectal examination usually fails to demonstrate any obstructive
pathology or mu¨ llerian structures. The pathogenesis of mu¨ llerian agenesis is unknown. Although
someinvestigators consider this entity to be inherited in a multifactorial mode,most believe that it is sporadic in
origin. No mu¨ llerian anomalies havebeen noted in female infants born to mothers with mu¨ llerian agenesis
via surrogacy and in vitro fertilization.Once the history and physical examination raise suspicion of mu¨
llerianagenesis, imaging of the pelvis must be performed. In most cases, ultrasoundprovides enough
information, but communication with the radiologistmust occur. Many times, a small remnant of mu¨ llerian
tissue will incorrectly be read a uterus, unless the radiologist is made aware ofpatient’s postpubertal status.
Ovaries appear normal, although they maybe located somewhat higher in the pelvis. MRI is the best modality
for detecting functioning endometrium within the mu¨ llerian remnants. Laparoscopyis usually not necessary to
make the diagnosis of mu¨ llerian agenesis.However, if the patient is experiencing pain and the radiologic
findings are inconsistent, laparoscopy may be considered.The presentation of mu¨ llerian agenesis is very
similar to complete androgen insensitivity syndrome (AIS) and must be differentiated from it.Table 9-1
summarizes the similarities and differences between these entities.After gonadal dysgenesis and mu¨ llerian
agenesis, AIS is the third mostcommon cause of primary amenorrhea. Patients with AIS have a 46XY
karyotype and produce normal male quantities of androgens. However, adefect in the androgen receptor leads
to a physiologic inability to detect androgens and a lack ofmale development of the external genitalia.
Although close inspection of the external genitalia in patients with AIS may revealunderdeveloped labia
minora and sparse or lack of pubic hair, the generalphenotypic appearance is of a normal female. These
patients commonly have a blind-ending vaginal pouch and breast development, which on close inspection may
reveal a subtle abnormality of the areola. Their sexual identity is female, and thus great care must be taken to
use an appropriate choice of words when describing the disorder. Because of their Y chromosome and risk for
development of gonadal tumors, a gonadectomy must be performed, followed by subsequent hormone
replacement therapy. Dilation, a nonsurgical mode of vaginoplasty, has a chance of success greater than 80%.
Since the complication rate is almost nonexistent, this is the preferred method of vaginoplasty in patients with
mu¨ llerian agenesis or complete AIS. RT Frank originally presented the concept of active dilation of the
vagina in 1938. Several decades later, JM Ingram proposed passive dilation of the vagina. Graduated Lucite
dilators are placed against the vaginal dimple for 30 min/day. Once one dilator fits completely, the patient
moves on to the next size dilator. In this fashion, a vagina may be created over a 3-month time span.
Encouragement and emotional support provided through frequent follow-up visits leads to high success rates.
If vaginal dilation fails or is not attempted, surgical construction of thevagina can be performed. Vaginal
construction is usually performed on patients between the ages of 16 and 22 years to ensure the presence of
endogenous estrogen and the mental maturity of maintaining the vagina after its creation. Many surgical
techniques have been devised for the formation of the vagina. In most cases, an opening is created in the area
of the vaginal vestibule between the urethra and rectum, followed by placement of a tissue such as skin graft,
amnion, bowel, or peritoneum in the neovagina. The most commonly used surgical mode of vaginoplasty is the
McIndoe procedure, first described in 1938. After a transverse incision is made in the space between the
urethra and rectum, the areolar tissue is dissected up to the peritoneal cavity. The created cavity is then lined
with a skin graft that has been wrapped around a mold. The stent is kept in the neovagina for a duration of 1
week, during which the patient is hospitalized and administered antibiotics, an indwelling urinary catheter,
strict bed rest, and a low-residue diet. Upon return to the operating room, the mold is removed and the tissue
lining the cavity is evaluated for adherence and viability. Excess tissue is trimmed, and another vaginal dilator
is placed inside the newly created vagina. The patient must be prepared to wear this dilator continually for 3
months. In the subsequent 6 months, she may switch to wearing the dilator just at night, unless she is sexually
active. Failure to comply with postoperative dilator use will lead to vaginal stenosis. Very high success rates
are reported in compliant patients.The diagnosis of mu¨ llerian agenesis or AIS must be presented with extreme
sensitivity and tact to the patient and her parents. Many times, the young patient cannot voice her fears
regarding the long-term implications of this diagnosis. The normal appearance of the external genitalia and
ability to have normal intercourse with creation of the neovagina must be stressed. Indeed, long-term studies
indicate a high sense of satisfaction with sexual function. Most couples’ sense of disappointment stems from
their inability to bear children. In vitro fertilization and surrogacy can provide a means of overcoming the lack
of a uterus in patients withmu¨ llerian agenesis. These options should be articulated to the adolescent and her
parents.

Congenital and Developmental Anomalies

Table 9-1
Differentiating
Mu¨ llerian Agenesis
From Androgen
Insensitivity
Syndrome

Characteristics
Mu¨ llerian
Agenesis
Androgen Insensitivity
Syndrome
Primary amenorrhea Yes Yes
Female external genitalia Yes Yes
Breasts Yes Yes
Blind-ending vaginal pouch/dimple Yes Yes
Normal axillary and pubic hair Yes Variable
Gonads Ovaries Testicles
Karyotype 46XX 46XY