ARTICLE IN PRESS

A Review of Mullerian Anomalies and

Their Urologic Associations
Charlotte Q. Wu, Krista J. Childress, Elizabeth J. Traore, and Edwin A. Smith
Structural anomalies of the female reproductive tract, known as Mullerian anomalies, can occur in isolation or in associa-
tion with anomalies of other organ systems. Due to shared embryology, the most common association in up to 40% of
patients is with renal, ureteral, and bladder anomalies. Affected girls can have a wide range of genitourinary symptoms
with urologists playing an integral role in their diagnosis and treatment. To facilitate the recognition and management of
these conditions, we provide a review of Mullerian anomalies including the embryology, classifications, syndromes, evalu-
ation, and treatments with attention to their urologic applicability. UROLOGY 00: 1−9, 2020. © 2020 Elsevier Inc.

M
ullerian duct anomalies (MDAs) are deviations
from normal anatomy involving the fallopian
tubes, uterus, and/or vagina, which embryologi-
cally are derived from the paramesonephric (Mullerian)
ducts. The terminology is used interchangeably with “con-
genital anomalies of the female genital tract” or “congeni-
tal uterine anomalies.” Due to the interlinked embryology
of the paramesonephric ducts, mesonephric ducts, and
urogenital sinus, coexisting renal, ureteral, and bladder
anomalies occur in up to 40% of these patients.1 The uro-
logic and gynecologic manifestations are often interre-
lated, and pediatric urologists maintain an integral role in
their diagnosis and treatment.
Mullerian anomalies may affect a single portion or mul-
tiple portions of the paramesonephric ducts, with or with-
out associated malformations of other organ systems
depending on the embryologic aberrancy.2,3 Some women
with MDAs are asymptomatic, while others have variable
symptomatology with problems that may present at any
age.3 In those with isolated MDAs, the initial presenta-
tion commonly occurs at puberty with primary amenor-
rhea or dysmenorrhea. In the prepubertal girl with multi-
organ anomalies, the initial presentation may instead be
urologic, with urinary incontinence or retention, pelvic
pain, pelvic mass, or infection among the most commonly
described.1,4-6
The reported prevalence of MDAs in the general popu-
lation is between 4% and 7%.7-9 While conditions arising
from disorders of sex determination and differentiation
(DSD) can affect Mullerian anatomy, primary DSD
cases occurring from alterations in chromosomes, gonado-
genesis, or steroidogenesis have historically been excluded
from the classification.3 Primary cloacal anomalies in girls,
Financial Disclosure: The authors declare that they have no relevant financial
interests.
From the Division of Pediatric Urology, Children’s Healthcare of Atlanta; Emory Uni-
versity School of Medicine, Atlanta, GA; and the Division of Gynecologic Specialties,
Department of Gynecology and Obstetrics, Emory University School of Medicine; Divi-
sions of Pediatric Surgery and Pediatrics, Children’s Healthcare of Atlanta, Atlanta, GA
Address correspondence to: Charlotte Q. Wu, M.D., Georgia Pediatric Urology,
Emory University School of Medicine/Children’s Healthcare of Atlanta, 5730 Glenridge
Drive, Suite 200, Atlanta, GA 30328 E-mail: qiaqia.charlotte.wu@emory.edu
Submitted: March 6, 2020, accepted (with revisions): April 22, 2020
© 2020 Elsevier Inc.
All rights reserved.
which coexist with MDAs in 30% of cases, have also been
classified separately.10
Herein we provide a review of Mullerian anomalies
including the embryology, classifications, syndromes, eval-
uation, and treatments with particular attention to their
urologic applicability.
FEMALE GENITOURINARY EMBRYOLOGY
A series of highly coordinated and interrelated events
allow for the normal development of the female genitouri-
nary tract. The paramesonephric and mesonephric (Wolf-
fian) ducts first arise during indifferent fetal development
at the 5th-6th week of gestation. Development of the
mesonephric ducts occurs first. The transient primitive
kidney (pronephros) initially drains via the mesonephric
ducts into the cloaca. Close to its attachment to the clo-
aca, the mesonephric duct develops an epithelial out-
growth, the ureteric bud, which extends to meet
intermediate mesoderm. Through continuous reciprocal
interactions, the ureteric bud and mesoderm (metaneph-
rogenicblastema) become the collecting system and renal
tubules of the definitive kidney, respectively.
The developmental fate of the indifferent parameso-
nephric and mesonephric ducts subsequently depends on
gonadal identity and function.11 In the presence of an
ovary and with a relative paucity of androgens, regression
of the mesonephric ducts occurs. Provided Mullerian
inhibiting substance (MIS) levels remain low, develop-
ment of the paramesonephric duct follows with direct
influence from the regressing mesonephric ducts.12,13 The
cranial portions of the paramesonephric ducts become the
fallopian tubes, while the caudal ends fuse at the urogeni-
tal ridge to become the uterus. Resorption of the fused
wall ensues.3 At the contact point of the fused ducts and
dorsal urogenital sinus, the uterovaginal plate develops.
Canalization of the plate forms the vaginal lumen around
week 20. It is hypothesized that the fused paramesonephric
ducts also form the cervical os and upper portion of the
vagina, while epithelial tissue from the uterovaginal
plate along with the urogenital sinus form the lower
https://doi.org/10.1016/j.urology.2020.04.088 1
0090-4295
 ARTICLE IN PRESS
portion.13 The different embryologic origins of the upper
reproductive tract and lower vagina can explain some of
the discordant pathologies observed proximally versus
distally.
Simultaneously, during the 5th-8th weeks of gestation,
the cloaca is divided by the urorectal septum into the uro-
genital sinus and the rectum. As the dorsal urogenital
sinus forms the uterovaginal plate, the ventral urogenital
sinus expands with the base of the allantois to form the
bladder, which incorporates the mesonephric ducts and
ureteric buds as it grows.
The process of female genitourinary development relies
on a complex system of signal transduction pathways. The
involvement of Wnt and Hox genes, bone morphogenetic
protein concentration gradients, and Wilms’ Tumor
(WT-1) suppressor gene have been implicated in key
roles.11,13,14 In effect, the mesonephric ducts and their
timely interactions with the urogenital sinus both induce
the proper development of the paramesonephric ducts
and determine their anatomic relationship to the urinary
system. The disruption of this phenomenon accounts for
the large number of renal, ureteral, and bladder anomalies
that coexist with Mullerian anomalies.
CLASSIFICATION OF MULLERIAN DUCT
ANOMALIES
Despite newer, more comprehensive classification systems
for Mullerian anomalies, the most established remains the
American Fertility Society (AFS; now American Society
of Reproductive Medicine) guidelines, which stratifies the
clinical findings into categories based on the major uterine
defect (Table 1).15-17 A limitation of the AFS system is its
simplicity relative to the wide spectrum of MDAs that can
occur, and it therefore does not account for all MDAs,
particularly rare types.18,19 Its simplicity, however, has
also made it widely applicable and easy to use.
The uterine defects described in the AFS system typi-
cally result from one of 3 main types of embryologic prob-
lems − Mullerian duct agenesis/hypoplasia (class I-II),
failure of Mullerian duct fusion (class III-IV), or incom-
plete resorption of the uterovaginal septum (class V-
VI).20 Given the heterogeneity of published series and
variations in clinical relevancy, the incidence of specific
Mullerian anomalies occurring alongside urinary tract
anomalies is difficult to ascertain; however, note is made
herein of specific incidences and patterns that have been
established in the literature.
Class I anomalies account for 3%-16% of MDAs and
represent segmental Mullerian agenesis resulting in a spec-
trum of uterovaginal hypoplasia affecting the uterine fun-
dus, fallopian tubes, cervix, and/or vagina.12,16 The
ovaries in these cases are normal. The most extreme form
is known as Mayer-Rokitansky-Kuster-Hauser (MRKH)
Syndrome, characterized by absence of the fallopian tubes,
uterus, cervix, and proximal vagina. Class I anomalies also
include partial or complete vaginal and uterine agenesis,
2 UROLOGY 00 (00), 2020
which often occur in association due to failure of the ute-
rovaginal plate (Fig. 1).16 In cases of segmental agenesis,
urinary anomalies have been reported at lower rates than
with other MDAs.21 When urinary tract anomalies are
present, the most commonly observed are unilateral renal
agenesis (URA), horseshoe kidney, pelvic kidney, or a
renal duplex collecting system, which are often detected
incidentally.20,21
Class II anomalies account for approximately 9%-10%
of MDAs and are characterized by a unicornuate uterus
with or without a rudimentary horn resulting from agenesis
or hypoplasia of one of the Mullerian ducts.12,16 The uni-
cornuate uterus is curved and elongated with a narrowed,
off-midline fundus, while the horn can have a communi-
cating or non-communicating endometrial cavity, can
have no cavity, or can be absent. The unicornuate uterus
may function normally, but the horn can be obstructed
depending on its configuration. Class II anomalies are
commonly associated with renal anomalies, particularly
renal agenesis or renal dysplasia ipsilateral to the side of
the horn, which occurs in 30%-40% in most series.1,22
Other anomalies include pelvic kidney and malrotation.21
Class III anomalies include the spectrum of uterus
didelphys, characterized by complete or partial duplication
of the uterus, cervix, and vagina, which results from non-
fusion of the Mullerian ducts. These account for approxi-
mately 5%-10% of all MDAs.12,16,23 In most cases, the
duplicate vagina involves at minimum the proximal two
thirds, and less commonly extends down to the perineum
to form a complete duplication separated by a longitudinal
septum. In cases of complete uterine and vaginal duplica-
tion, the patient can remain asymptomatic from a gyneco-
logic standpoint but have obstetric complications such as
spontaneous abortion, premature birth, or avulsion of the
vaginal septum at birth.23 When the uterine duplication
is complete and vaginal duplication is incomplete, such as
in Obstructed Hemivagina and Ipsilateral Renal Agenesis/
Anomaly (OHVIRA), one side features a transverse hemi-
vaginal septum, which obstructs the outflow of the ipsilat-
eral hemiuterus. Affected patients typically present at
menarche with dysmenorrhea or pelvic mass due to
obstruction of the hemiuterus.20 Other complications of
obstructive Mullerian anomalies such as a non-communi-
cating uterine horn or obstructive vaginal septum include
hematosalpinx or endometriosis related to retrograde
menstruation. Left undiagnosed, the long-term sequelae
include pelvic inflammatory disease, chronic pelvic pain,
and infertility.19 Uterine didelphys is reported to have
one of the highest associations with urinary anomalies
with unilateral renal agenesis being most common.16,21 In
many patients, a pelvic ureteric remnant has been
observed, whereby a stump is seen ectopically inserting
into the cervix or hemivagina.1
Class IV anomalies are characterized by a bicornuate
uterus resulting from incomplete Mullerian duct fusion
and represent 8%-26% of MDAs.12,16 Typically, there are
2 divergent uterine horns fused caudally at the lower uter-
ine segment, with (“bicollis”) or without (“unicollis”)
UROLOGY 00 (00), 2020

Table 1. AFS classification of congenital Mullerian duct anomalies (Class I-VI only; Modified from AFS Classification, 198814) *Most common associations are listed.
Embryologic Corresponding
Class Uterine Anomaly Figure Description Process Syndromes
I Agenesis/ Agenesis and/or hypoplasia Agenesis/ MRKH I, MRKH II,
Hypoplasia involving tubes, uterus, cervix, Hypoplasia MURCS, ARM
vagina, or combination

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II Unicornuate One Mullerian tube develops Agenesis/
normally with variations in Hypoplasia
development of the other
“rudimentary horn”

III Didelphys Complete or partial duplication of Failure of fusion OHVIRA, ARM,

the uterus, cervix, and/or OEIS
vagina
IV Bicornuate Partial duplication of the uterus Failure of fusion OHVIRA (in bicollis
with single cervix and vagina. subtype only),
Endometrial cavities are ARM
separate but communicate.

V Septate Presence of partial or complete Incomplete Septal ARM

fibrous septum dividing cavity of Resorption
single uterus

VI Arcuate Small septal indentation at the Incomplete Septal

fundus Resorption

MRKH, Mayer RokitanskyKuster Hauser; MURCS, Mullerian-Renal-Cervicothoracic-Somite abnormalities; OHVIRA, Obstructed HemivaginaIpsilateral Renal Agenesis/Anomaly; ARM, anorectal malforma-
tion; OEIS, omphalocele, exstrophy of the bladder and rectum, imperforate anus, and spinal defects (cloacalexstrophy).
3
 ARTICLE IN PRESS
Figure 1. Vaginal agenesis on pelvic exam. A patulous ure-
thra (arrow) is a common finding. (Color version available
online.)
duplication of the cervix. These anomalies are felt to be a
milder form of uterus didelphys.24 Most women are asymp-
tomatic from a gynecologic standpoint, but have higher
risks for obstetric complications.23 Coexisting urinary
tract anomalies can occur but have been less commonly
described.1,25 One series cites 15% renal anomaly, pre-
dominantly renal agenesis, among 33 patients with
bicornuate uterus.21 Bicornuate bicollis subtype can also
be seen in OHVIRA but is uncommon.26
Class V and VI anomalies develop when the fibrous
septum between the Mullerian ducts fails to fully resorb.
Together, these are the most common MDAs (50%-
60%) and also the mildest.12,16 Class V refers to a sep-
tated uterus characterized by persistence of a fibrous
uterine septum, and class VI is an arcuate uterus charac-
terized by a mild indentation of the endometrium at the
fundus resulting from near complete septum resorption.
Arcuate uterus has been described as a variant of nor-
mal anatomy. Both classes are associated more com-
monly with obstetric complications such as miscarriage,
Figure 2. Coronal and Sagittal MRI of the pelvis in a girl with primary amenorrrhea and cyclic pelvic pain. Imaging reveals
hematocolpos associated with a bicornuate uterus with cervical and vaginal agenesis. LH, left horn; LUS, lower uterine seg-
ment; RH, right horn. (Color version available online.)
4 UROLOGY 00 (00), 2020
premature birth, fetal malpresentation, and intrauterine
growth restriction than with gynecologic complica-
tions.23 Both classes are associated to lesser degrees
with urinary tract anomalies.25 One series cites an inci-
dence of 14% renal tract anomaly in women with sep-
tate uterus, and only 3.8% among those with partial
bicornuate, subseptate, or arcuate uterus.21
SYNDROMES FEATURING PRIMARY
MULLERIAN DUCT ANOMALIES
MRKH Syndrome
MRKH is characterized by congenital absence of the fallo-
pian tubes, uterus, and/or vagina in genotypic (46, XX)
females. Isolated cases of MRKH that do not involve
other organ systems are classified as the typical form or
Type I MRKH. Girls with MRKH Type I most commonly
present in adolescence with primary amenorrhea despite
normal pubertal development.27 While many have com-
plete aplasia of all Mullerian structures, in approximately
50% of patients, there will be some remnant uterine tissue
with functional endometrium. This can cause cyclic pel-
vic pain similar to other obstructive MDAs (Fig. 2).28
Atypical MRKH are those associated with extra-Muller-
ian anomalies, the most common of which are urinary
anomalies (32%-34%), skeletal anomalies (12%), and car-
diac anomalies (1%).29 Atypical MRKH is also called Type
II MRKH.30 The most heterogeneous and poorly defined
category associated with Mullerian agenesis is known
as Mullerian-renal-cervicothoracic-somite abnormalities
(MURCS).27 MURCS has been described in some litera-
ture as a separate entity from MRKH Types I and II, and in
others as the most severe form of MRKH Type II.11,30,31
Patients with MURCS have any combination of uterovagi-
nal aplasia with skeletal, muscular, cardiac, lung, ear and
eye anomalies, with or without renal anomalies.
The embryopathy of MURCS has long been speculated
to result from a different process than typical MRKH, per-
haps by an insult in fetal development at the fourth week
of gestation, when the cervicothoracic somites, arm buds,
and pronephric ducts are in close proximity.32 In rare
cases, MURCS overlaps with VACTERL (vertebral
anomalies, anal atresia, cardiovascular anomalies,
 ARTICLE IN PRESS
esophageal atresia, renal anomalies, limb anomalies) and
with TAR (thrombocytopenia absent radius) syn-
drome.27,29 Urologic manifestations of Type II MRKH or
MURCS are varied depending on the anatomy, which
may involve renal agenesis, renal ectopia, renal hypopla-
sia, horseshoe kidney, and/or hydronephrosis of one or
both kidneys.11
For Mullerian duct aplasia, it is essential to differentiate
the diagnosis of MRKH and its variants from other condi-
tions that present similarly. Complete androgen insensi-
tivity syndrome (CAIS) is a DSD characterized by a
defective androgen receptor in 46, XY individuals.33
Patients with CAIS, and less commonly partial androgen
insensitivity syndrome (PAIS), present as phenotypically
normal females due to the absence of androgen action on
their development. Because of absent androgen effect,
there is scant or no axillary and pubic hair development
after puberty in CAIS patients, and this remains one clini-
cal distinction from MRKH. Otherwise, the most com-
mon presentation in CAIS, like in MRKH, is primary
amenorrhea resulting from absent Mullerian duct deriva-
tives. In CAIS, Mullerian agenesis is due to intact MIS
production by testis gonadal tissue. The diagnosis can be
ascertained by karyotype and hormone profiles, which
demonstrate elevated testosterone and male-range MIS.33
OHVIRA Syndrome
OHVIRA (also Herlyn-Werner-Wunderlich Syndrome) is
seen in association with uterine duplication defects such as
uterus didelphys and less commonly bicornuate bicollis,
where there is an outflow obstruction of one hemiuterus at
the level of the vagina. Classically, the presentation is an ado-
lescent girl who soon after menarche reports regular menses
via the communicating hemiuterus but experiences progres-
sive pelvic pain or dysmenorrhea. Exam reveals a vaginal
bulge as a manifestation of the obstructed hemivagina, and
imaging reveals a solitary kidney, with the absent kidney ipsi-
lateral to the obstructed hemivagina.34 Another familiar sce-
nario is a woman who, after menarche, develops a
microperforation in the vaginal septum, allowing menstrua-
tion to occur but with retained products that serve as a nidus
for infection. These women can present initially with ipsilat-
eral tubo-ovarian abscess, pyocolpos, or pelvic inflammatory
disease.35
While the vast majority of patients are diagnosed fol-
lowing a gynecologic presentation, more recent literature
attests to the heterogeneous ways in which OHVIRA can
manifest. There is mounting evidence that the absence of
a kidney on the side of the Mullerian obstruction results
not from agenesis but from dysplasia.6 Several case series
describe OHVIRA patients who become symptomatic
from a dysplastic atrophic kidney, presenting with abdom-
inal pain, urinary retention, renal failure, or urinary
incontinence due to the presence of an ectopic ureter to
an unroofed obstructed hemivagina.6,36 Other series
describe the association of obstructed hemivagina with
various ipsilateral urologic anomalies including duplicated
collecting system and polycystic kidney.34 Some girls
UROLOGY 00 (00), 2020
diagnosed classically with OHVIRA in adolescence also
report a history of infant nephrectomy, presumably for
symptoms related initially to renal dysplasia.34 Familiarity
with these aforementioned presentations, while generally
rare for OHVIRA, is particularly relevant for the evaluat-
ing urologist who may be treating the urologic problems
prior to any gynecologic manifestations.37
ASSOCIATED SYNDROMES
Anorectal Malformations
Anorectal malformations (ARM), including cloacal
anomalies and various types of imperforate anus or anal
atresia in girls, are associated with genitourinary anomalies
in 40%-50% of cases.38,39 ARMs are disorders primarily of
the urogenital sinus or cloaca rather than the Mullerian
ducts, though their closely linked embryology accounts for
the high incidence of MDA with ARM. Both vaginal and
uterine anomalies are observed, with the most common
configuration being a uterus didelphys or septated uterus
with or without a longitudinal vaginal septum or vaginal
agenesis.38 In cloacal anomalies, the incidence of a com-
plete uterus didelphys with 2 hemiuteri and 2 hemivaginas
is 40%.40 Associated urologic anomalies include hydro-
nephrosis, vesicoureteral reflux, horseshoe kidney, mega-
ureter, and ectopic ureter.40 Neurogenic bladder can also
occur from coinciding spinal anomalies or from pelvic sur-
gery.39 The extent of Mullerian and urinary anomalies are
generally more severe in more complex cases of ARM.
The presentation of a MDA that coexists with ARM is
variable given the range of anomalies that can occur. The
most concerning in the neonatal period is the presence of
hydrocolpos, which is a dilated vagina filled with fluid,
urine, and/or mucous. This structure is seen in 30% of clo-
acal anomaly patients, and most girls with hydrocolpos
have a Mullerian duplication.40 The hydrocolpos may ini-
tially present as an abdominal mass or it may be identified
first on ultrasound. When hydrocolpos is large, secondary
urinary tract obstruction can occur due to compression of
the trigone and ureterovesical junction obstruction result-
ing from mass effect. Ultrasound is, therefore, typically
obtained within the first 24 hours of life.40 The presence
of hydrocolpos and hydroureteronephrosis could signify a
potentially life-threatening urinary tract obstruction that
must be addressed early. The treatment of choice is a vagi-
nostomy or vaginostomy tube, performed at the time of
colostomy creation.41 Drainage of the hydrocolpos should
always be performed prior to urological diversions such as
ureterostomy or vesicostomy as the urinary obstruction
often resolves with vaginostomy alone. In select cases
where the child has vesicoureteral reflux and/or poor blad-
der emptying due to a long common channel, a vesicos-
tomy may also be necessary.40
Outside of the neonatal period, if the MDA is not ini-
tially apparent, the presentation may be similar to other
obstructive or nonobstructive Mullerian anomalies, mani-
festing after puberty when menarche should occur. To
5
 ARTICLE IN PRESS
prevent the adverse sequelae of a delayed presentation after
puberty, a comprehensive initial assessment of the reproduc-
tive anatomy followed by surveillance is advised for all girls
with ARMs. During initial ARM diagnosis and prior to
reconstruction, vaginoscopy should be performed, evaluating
for presence and number of cervices. When the child is taken
for other necessary abdominal or pelvic surgeries, an exam of
the uterus should be performed, taking note of its contour.
Surveillance abdomino-pelvic ultrasound is then recom-
mended 6 months after the start of puberty (Tanner II breast
development) while the uterus enlarges under estrogen stimu-
lation and should continue every 6-9 months through menar-
che.41 Other diagnostic tools and interventions that apply
generally to all MDAs are summarized in the next section.
Cloacal Exstrophy
Otherwise known as OEIS Syndrome for omphalocele, exs-
trophy of the bladder and rectum, imperforate anus, and
spinal defects, cloacal exstrophy is considered a complex
sub-type of ARM.38 It is associated with the most profound
MDAs often involving the uterus, cervix, and vagina. Most
but not all girls with OEIS have MDAs.42 Uterus didelphys
associated with double cervices and double vagina is fre-
quently observed, though other combinations featuring
aplasia/hypoplasia or persistent septa (longitudinal and
transverse) are also seen. Urinary tract anomalies in OEIS
are similarly complex with the possibility of multiple over-
lapping anomalies. As with other syndromes, a comprehen-
sive assessment and anatomic survey of the genitourinary
system in OEIS is critical for optimal management, particu-
larly as these patients undergo surgeries across a range of
organ systems and types of reconstruction may be more lim-
ited due to less tissue availability.42
DIAGNOSIS AND EVALUATION
Adequate diagnosis and proper assessment of the anatomy
is imperative to appropriate treatment. Initial laboratory
testing such as hormone profiles and karyotyping are useful
when a differential diagnosis of DSD must be excluded, as
with uterine aplasia. A combination of imaging modalities
or diagnostic procedures can then be pursued. In the prepu-
bertal and adolescent population (without ARM), the
most appropriate initial evaluation is an ultrasound. If fur-
ther imaging is needed, the gold standard is magnetic reso-
nance imaging, which can provide intricate detail
regarding uterovaginal anatomy with accuracy up to
100%.18,19,25,43 T1-weighted images allow for detection of
blood products, as seen in obstructed uterine remnants or
hematometrocolpos, while T2-weighted allows differentia-
tion of the uterine tissue layers.25,44 The role for computer-
ized tomography scan is very limited. Cystoscopy,
vaginoscopy/hysteroscopy, and diagnostic laparoscopy are
other means to evaluate the anatomy, though these are not
typically pursued prior to imaging or for diagnostic purposes
alone, except in complex anomalies like ARM when the
child is already undergoing anesthesia for other reasons.
6 UROLOGY 00 (00), 2020
With any type of anatomic assessment in prepubertal
girls, it is important to acknowledge the limitations of
attempting to characterize the still immature reproductive
structures. Assessment at puberty, when the uterus begins
to grow under estrogen stimulation, is most appropriate in
the majority of cases, though this guideline is not firmly
established. Specific to the diagnosis of URA, which
remains the most consistently reported urinary tract
anomaly among all girls with MDAs, it has been recom-
mended that families receive early counseling for potential
obstructive Mullerian anomalies when the diagnosis of
URA is made. At puberty, an initial pelvic ultrasound is
recommended, followed by magnetic resonance imaging if
any abnormal findings are seen.37
Except in girls with URA or ARM, a clear surveillance
protocol for Mullerian anomalies has yet to be established.
Early diagnosis can predict and sometimes prevent later
gynecologic, obstetric, or urologic complications. It more-
over allows for adequate counseling and preparedness;
however, the risks of overscreening, such as cost and emo-
tional toll, for an overall rare condition are not to be min-
imized.37 Only patients in whom there is a reasonably
high suspicion of a coexisting, clinically relevant Muller-
ian anomaly should be screened; Table 2 serves as a frame
of reference but is not meant to be inclusive of all scenar-
ios. Ultimately, the basis for which we have to decide if a
girl is “at-risk” remains somewhat limited and continues
to evolve as we learn more about the embryologic pro-
cesses and clinical manifestations. In practice, the deci-
sion to offer screening and surveillance is at the provider’s
discretion, often with shared decision-making between
the provider, parent, and patient.
TREATMENT
The mainstay of treatment is preservation of sexual func-
tion, preservation of natural fertility when possible, and
alleviation of the presenting gynecologic or urologic
symptoms. For nonobstructive anomalies of aplasia such
as MRKH, treatments are typically geared toward estab-
lishing sexual function, first with vaginal dilation to create
a neovagina, then surgical creation if necessary due to
failed dilation.45 Native childbearing is not possible; how-
ever, uterine transplantation as an experimental proce-
dure has recently proven successful, resulting in live births
from cesarean delivery.46 More commonly, fertility can be
achieved through surrogacy with egg retrieval from the
patient if genetic children are desired.
Treatments for nonobstructive, non-aplasia MDAs that
generally have subtle or no gynecologic symptoms may
only be applicable at the time of reproduction. These
women generally have a higher risk of miscarriage, pre-
term rupture of membranes, fetal malpresentation, and
intrauterine growth restriction. Surgical management is
only indicated when there is a septum that contributes to
the aforementioned risks. Removal of the septum can be
achieved by hysteroscopy.33
 ARTICLE IN PRESS
Table 2. Summary of gynecologic, obstetric, and urologic associations by AFS Class
Gynecologic Reproductive/Obstetric
Class Presentation Associations Urinary Tract Associations Urologic Considerations
I Primary amenorrhea Fertility by IVF and MRKH I: None Rule out DSD (CAIS)
Cyclic pain with uterine surrogacy Others: URA, horseshoe
remnant (50%) Unable to carry pregnancy kidney, pelvic kidney,
duplicated collecting system
II Asymptomatic Miscarriage URA or renal dysplasia
Dysmenorrhea Preterm labor ipsilateral to rudiment
IUGR Pelvic kidney
Uterine rupture (if Malrotation
pregnancy occurs in
rudiment)
III Asymptomatic Normal pregnancy URA ipsilateral to obstructed Renal anomaly may
Dysmenorrhea Miscarriage hemiuterus manifest prior to
Tubo-ovarian abscess, Preterm labor Other ipsilateral renal anomaly gynecologic symptoms
PID IUGR (MCDK, ectopic ureter) ARM/ cloaca:
Fetal malpresentation Ureterocele Hydrocolpos in the
Ruptured vaginal septum VUR neonate must be
diagnosed and drained
before urinary
diversion
IV Asymptomatic Miscarriage No urinary anomaly
Tubo-ovarian abscess, Preterm labor URA
PID (obstructed IUGR
bicollis; rare) Fetal malpresentation
V-VI Asymptomatic Miscarriage No urinary anomaly
Preterm labor URA
IUGR Duplicated collecting system
Fetal malpresentation (Class V)
Bolded: most common and/or well established.
CAIS, complete androgen insensitivity syndrome; DSD, disorders of sex differentiation; IVF, in vitro fertilization; IUGR, intrauterine growth
restriction; MCDK, multicystic dysplastic kidney; MRKH, Mayer Rokitansky Kuster Hauser;; PID, pelvic inflammatory disease; URA, unilat-
eral renal agenesis; VUR, vesicoureteral reflux.

Figure 3. Hysterectomy specimen of patient depicted in Figure 2 with vaginal agenesis, cervical agenesis, and bicornuate
uterus. This patient also has a kidney transplant related to renal failure from congenital hydroureteronephrosis secondary to
bilateral ectopic ureters, congenital absence of the pericardium and left pleura, coarctation of the aorta, and scoliosis. LH,
left horn; LUS, lower uterine segment; RH, right horn. (Color version available online.)

UROLOGY 00 (00), 2020 7

 ARTICLE IN PRESS
In obstructive MDAs, when there is functional endo-
metrium in obstructed uteri, surgical resection or men-
strual suppression may be offered. Suppression can be
achieved with combination estrogen-progestin or proges-
tin-only therapy and should be sought if delaying surgical
management is appropriate at the time of initial diagnosis,
as in young girls who cannot perform vaginal dilation
postoperatively, or when there are other medical comor-
bidities.19 Surgical management is variable depending on
the exact anomaly. For noncommunicating uterine horns
or symptomatic communicating horns, removal is typi-
cally indicated and can be done by laparoscopy or robotic
surgery.19 In cases of more distal obstruction at the level
of the vagina, such as OHVIRA, a vaginoplasty is per-
formed by excising the occluding septum and re-approxi-
mating the vaginal mucosal edges.34 In patient with poor
reproductive potential who has an obstructive or other
symptomatic pathology, hysterectomy may be offered after
extensive counseling (Fig. 3).
Given the wide spectrum of anomalies, most cases will
need to be approached in an individualized manner. A mul-
tidisciplinary team with involvement of pediatric gynecol-
ogy, pediatric urology, and pediatric surgery is invaluable.
CONCLUSION
Improved recognition of Mullerian anomalies and their
urologic associations in the last few decades has broadened
our understanding of the complexity and heterogeneity of
these conditions; however, due to many overlapping fea-
tures they remain difficult to classify and challenging to
accurately diagnose. Since the urologic and gynecologic
manifestations may be clinically significant at different
time points in a child’s life, the pertinent history can often
be missed. A better understanding of these associations
will help urologists, gynecologists, and other care pro-
viders recognize the clinically relevant patterns and syn-
dromes, which can facilitate comprehensive, timely
assessment and treatment of all affected girls.
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