CLINICAL OBSTETRICS AND GYNECOLOGY
Volume 51, Number 1, 214–222
Müllerian Anomalies
LEE P. SHULMAN, MD
The Anna Ross Lapham Professor in Obstetrics and Gynecology,
Department of Obstetrics and Gynecology, Feinberg School of
Medicine, Northwestern University, NMH/Prentice Women’s
Hospital, Chicago, Illinois
Abstract: Müllerian anomalies are a relatively uncom-
mon occurrence with implications for adolescents and
adults as they may result in specific gynecologic,
fertility, and obstetrical issues. The exact incidence
of Müllerian anomalies is difficult to ascertain. How-
ever, clinicians should be suspicious for Müllerian
anomalies in cases of primary amenorrhea, pelvic
pain, repetitive pregnancy loss, and certain adverse
obstetrical outcomes. While for many women a good
reproductive outcome can be achieved, counseling,
and in particular psychologic counseling, may be
needed for some women, especially those with lesions
that preclude childbearing and affect normal sexual
function.
Key words: Müllerian, anomalies, didelphys, recurrent
miscarriage
Introduction
The normal development of the female
reproductive tract involves a complex in-
tegrative series of events involving genet-
ic, hormonal, and epigenetic factors
leading to the normal differentiation and
development of the Müllerian, or para-
mesonephric, ducts, Wolffian, or meso-
nephric, ducts, and urogenital sinus.
Accordingly, any one of numerous altera-
tions in this process can lead to abnorm-
Correspondence: Lee P. Shulman, MD, 250 East
Superior Street, Room 05-2174, Chicago, IL 60611.
E-mail: lshulman@nmh.org
CLINICAL OBSTETRICS AND GYNECOLOGY
214
r 2008, Lippincott Williams & Wilkins
alities of the uterus, cervix, fallopian
tubes, or vagina. Depending on the spe-
cific abnormality, affected women may
experience gynecologic, fertility, or obste-
trical problems. Nonetheless, the true
incidence of Müllerian anomalies is diffi-
cult, if not impossible, to determine be-
cause of the considerable variation in
presentation. Some anomalies may lead
to clinical problems in childhood, whereas
other anomalies may only be detected
serendipitously at the time of a clinical
evaluation or surgical procedure for an-
other medical condition. In addition,
although most cases of Müllerian anoma-
lies occur in an isolated fashion, some
anomalies are components of congenital
syndromes.
Most women with Müllerian anomalies
demonstrate no problems with menstrua-
tion or conception. However, women
with Müllerian anomalies do present with
higher rates of spontaneous abortion,
premature delivery, abnormal fetal posi-
tion, and dystocia.1 Accordingly, an over-
view of Müllerian anomalies is important
for a more complete understanding of
female sexual development and of those
clinical gynecologic and obstetrical issues
that do require intervention during the
pediatric, adolescent, and reproductive
years.
/ VOLUME 51 / NUMBER 2 / JUNE 2008

Embryology
Male (Wolffian or mesonephric) and
female (Müllerian or paramesonephric)
duct systems are indistinguishable in fe-
tuses at or before 6 weeks of development.
The absence of a Y chromosome, in most
of the cases, results in the development of
ovaries. Without testosterone, the Wolf-
fian ducts regress and permit the develop-
ment of the Müllerian ducts. Conversely,
regression of the Müllerian ducts requires
the presence of a protein (MIS or Müller-
ian-inhibiting substance) that is secreted
by the testis. In the absence of MIS, the
Müllerian ducts develop on the lateral
surface of the mesonephric ducts, with
the superior portions going on to form
the fallopian tubes whereas the posterior
portions fuse into a Y-shaped structure
that develops into the uterus, cervix, and
superior portion of the vagina.2 Indeed,
alterations of this process at any stage
can lead to Müllerian anomalies that can
impact normal female development and
sexual function.
Epidemiology
Because of the wide variation of clinical
presentation of Müllerian anomalies, as-
sessment of prevalence is challenging
insofar as some anomalies are detected
at an early age whereas others are only
detected as a result of evaluation or treat-
ment for nonrelated medical conditions.
Accordingly, the reported prevalence has
ranged from 0.16% to 10%.1 However,
the actual ascertainment of the anomaly is
a critical determinant of the reported
frequency of the anomaly. For example,
Stampe Sorensen3 reported a prevalence
of 8% to 10% among infertile women
undergoing hysterosalpingography (HSG)
whereas Byrne and colleagues4 reported
an incidence of 0.4% in women under-
going ultrasound examinations for
nonobstetrical indications. As expected,
evaluation of an unselected population
usually results in a considerably lower
Müllerian Anomalies 215
frequency of Müllerian anomalies than
the evaluation of a specific cohort identi-
fied as result of a condition (eg, infertility)
that has been associated with Müllerian
anomalies.
Classification and Clinical
Effects
Most clinicians use the classification sys-
tem devised by Buttram and Gibbons in
1979,5 as this scheme categorized the var-
ious anomalies based on clinical presenta-
tion. Although some of the conditions
within each class may originate from dif-
ferent embryologic embarrassments, this
system does provide a useful clinical tool
for determining intervention and prog-
nosis (Fig. 1).
Class I: segmental agenesis and various
degrees of uterovaginal hypoplasia. This
group includes Müllerian agenesis and
vaginal agenesis.
Class II: unicornuate uterus.
Class III: uterus didelphys.
Class IV: bicornuate uterus and varying
degrees of incomplete fusion of the supe-
rior segments of the uterovaginal canal.
Class V: varying degrees of septate uterus.
Class VI: varying degrees of arcuate uterus.
Class VII: sequela of DES exposure.
The most common Müllerian anomaly is
the septate uterus (Class V), comprising
over 50% of all reported Müllerian anoma-
lies. This condition is the result of partial or
incomplete failure of the resorption of the
uterovaginal septum after the fusion of the
paramesonephric ducts. Among those Mül-
lerian anomalies that permit pregnancy,
Class V anomalies are associated with a
marked reduction in the ability to maintain
a pregnancy. Troiano and McCarthy1 re-
port that pooled data show the prevalence
of septa in women with recurrent sponta-
neous pregnancy losses ranges from 26% to
94%. In addition, septate uteri are also
associated with adverse obstetrical out-
comes, with preterm birth rates in women
216 Shulman
FIGURE 1. Uterine fusion anomalies: I, Septate uterus; II, bicor-
nuate uterus; III, unicornuate uterus; IV, uterus didelphys; V, normal
uterus; VI, arcuate uterus.
with septate uteri ranging from 9% to 30%
and a commensurate reduction in fetal
survivability.
The differentiation between the septate
uterus and the Class IV anomalies (bicor-
nuate uterus) is based on the external
appearance of the uterus. Although these
2 classes of anomalies result from differ-
ent embryologic processes—the bicornu-
ate uterus, the second most common
Müllerian anomaly making up approxi-
mately 10% of all such abnormalities, is
the result of incomplete fusion of the
uterovaginal horns. This differentiation
is critical as the interventions for these 2
classes are widely different. Septate uterus
is usually amenable to hysteroscopic
resection whereas the bicornuate uterus
usually does not require intervention
except in those who have experienced
multiple late-term pregnancy losses. In
those cases, the Strassman metroplasty is
still used to unify the 2 cavities and restore
the contour of the external uterus.
Uterus didelphys (Class III) accounts
for approximately 5% of Müllerian
anomalies and is the result of nearly com-
plete failure of the fusion of the parame-
sonephric ducts. Indeed, this anomaly
represents a more complete embarrass-
ment in the embryologic process that
unites the 2 paramesonephric ducts. In
such cases, each duct develops into an
almost separate uterine hemicavity either
sharing a cervix or, in some cases, with its
own cervix. Without obstruction, uterus
didelphys is asymptomatic. However,
many cases can be associated with ob-
struction by vaginal septa and thus
present with progressive menarchal dys-
menorrhea that can lead to endometriosis
and pelvic adhesive disease.
Unicornuate uterus results from the
failure of 1 of the 2 paramesonephric
ducts to develop. Surprisingly, the Class
II anomalies account for almost 1/5 of all
Müllerian anomalies. Unicornuate uterus
may present as a totally isolated anomaly,
but usually (approximately 2/3 of all such
cases) presents in concert with a rudimen-
tary horn. Approximately half of such
rudimentary horns have some endome-
trial tissues whereas half do not. Interest-
ingly, most unicornuate uteri are present
on the right side, a phenomenon that has
yet to be explained.
This anomaly is associated with an
increased risk for spontaneous loss and

preterm labor, apparently associated with
the reduction in available uterine muscle
mass and deformation of the available
endometrial cavity. Our group6 has re-
cently reported on the successful use of
multifetal pregnancy reduction for those
women carrying more than 1 fetus in a
unicornuate uterus. In addition, in those
women with a noncommunicating rudi-
mentary horn with endometrial tissue,
initial presentation may occur at me-
narche with progressive dysmenorrhea.
The Class I anomalies represent the
most severe interruption of gynecologic
function and account for 8% to 10%
of Müllerian anomalies. However, both
forms of Class I Müllerian anomalies
present with no obvious phenotypic ab-
normalities at birth and only are detected
at menarche. Müllerian agenesis, also
known as Mayer-Rokitansky-Kuster-
Hauser syndrome, presents with primary
amenorrhea with normal secondary sex-
ual development. Vaginal agenesis also
presents with normal secondary sexual
development but with increasing dysme-
norrhea as this condition usually does
not preclude the development of more
superior positioned, and thus endome-
trial-containing tissues, that have no com-
munication with the vagina and thus lead
to the progressive dysmenorrhea asso-
ciated with other obstructive conditions.
Müllerian aplasia may also be a compo-
nent of syndromes involving nonpelvic
organs, the most common being Müller-
ian renal cervical spine. As such condi-
tions preclude reproduction, it is difficult
to assess the exact genetic or epigenetic
mechanisms responsible for this condi-
tion. Nonetheless, this grouping of Mül-
lerian aplasia, renal anomalies such
as horseshoe kidney, and cervical spine
abnormalities including fused vertebra,
rudimentary vertebral bodies, and Klip-
pel-Feil anomalad (cervical vertebral
fusion, reduced range of motion, low hair-
line) may occur in almost 10% of women
with Müllerian aplasia. Although most
Müllerian Anomalies 217
individuals with Müllerian anomalies do
not have chromosome abnormalities, a
few females with Müllerian anomalies
have been found to have chromosome
abnormalities including mosaic sex com-
plements (45,X/46,XX) and autosomal
deletions. In addition, our group7 has
reported on an individual with Müllerian
renal cervical spine and other associated
nongynecologic structural abnormalities,
providing evidence of the potential for
genetic, epigenetic, and environmental
factors in the abnormal development of
the female reproductive tract.
Symptoms are dependent on the pre-
sence or absence of functional endome-
trium. With no symptoms of progressive
dysmenorrhea, intervention can be de-
layed until the commencement of sexual
activity. Although specific symptoms may
lead to specific interventions, a nonsurgi-
cal approach known as Frank’s vaginal
dilation is commonly used and is consid-
ered to be the initial treatment of choice.
This approach uses serial dilation of the
rudimentary vagina with dilators. The
most commonly used surgical approach
is the Abbe-McIndoe approach and
involves the construction of a neovagina
by careful dissection of the tissue between
the urethral opening and the posterior
fourchette. In case of vaginal agenesis,
removal of the endometrial-containing
tissue is now readily accomplished by a
laparoscopic approach.
Because of the profound sexual and
fertility implications of these Class I
anomalies, referral for more detailed and
extensive counseling should be strongly
considered. Indeed, referral to a psychol-
ogist or psychiatrist is warranted for those
girls or women and their families when
finding out that they are unable to con-
ceive and will need some intervention for
normal sexual function. At our center,
such a referral is a routine part of the
diagnostic and therapeutic process for
all who are found to have such Müllerian
anomalies.
218 Shulman

FIGURE 2. Transverse vaginal septa. X points to

most common site of occurrence.

In addition to the obstructive condi- obstructive conditions. Longitudinal sep-

tions described above, vaginal septa can
present with partial or complete obstruc-
tion. Such septa are the result of late
fusion defects: vertical fusion defects lead
to transverse septa whereas lateral fusion
defects lead to longitudinal septa (Figs. 2, 3).
The transverse septum is more likely to
lead to symptoms at the time of menarche,
as such obstructions are more likely to
block the flow of menstruum and lead
to the symptoms associated with other
ta are less likely to lead to obstruction,
and may not be found until the initiation
of sexual activity or pelvic examinations.
Obstructive septa can be excised by vagi-
nal resection of the septum; nonobstruc-
tive septa may need no intervention if
such tissue does not complicate menstrua-
tion, sexual activity, pelvic examination,
or obstetrical processes.
The Class VI anomalies represent the
anomalies that are least likely to result in

FIGURE 3. Longitudinal vaginal septum.


adverse developmental, fertility or obste-
trical outcomes. The arcuate uterus is
characterized by a fundal indentation of
the endometrium resulting from a mini-
mally incomplete resorption of the uter-
ovaginal septum. Indeed, some believe
that the arcuate uterus represent a normal
variant rather than an actual anomaly.
Although there are data that support and
refute an adverse clinical impact of the
arcuate uterus, the only indication to
pursue intervention would be recurrent
pregnancy loss and the approach would
be a hysteroscopic resection of prominent
fundal tissue detected by HSG or some
other imaging technique.
Those Müllerian anomalies (Class VII)
attributed to in-utero DES exposure are
decreasing in frequency with the cessation
of the use of DES by pregnant women by
the beginning of the 1980s. A full review
of the diagnosis, implications and man-
agement of DES progeny is beyond the
scope of this chapter.
Diagnosis
Diagnosis of Müllerian anomalies is pri-
marily based on the clinical presentation,
including the temporal nature of the in-
itial presentation, the nature of the pre-
senting symptoms, and the particular
portion(s) of the pelvis that may be af-
fected by the Müllerian anomaly. Accord-
ingly, a detailed history, including family
history, and a physical examination in-
cluding assessment of the pelvic structures
is a necessary first step in assessing the
potential causes of the presenting symp-
toms and suggesting possible interven-
tions. A very small percentage of females
with Müllerian anomalies are found to
have a Mendelian disorder such as the
autosomal dominant hand-foot-uterus
syndrome, the autosomal recessive
Fraser syndrome and the X-linked
uterine-hernia syndrome.2 However, such
individuals will present with the pro-
found clinical findings of the Mendelian
Müllerian Anomalies 219
disorder and be found to have Müllerian
anomalies as part of the secondary eva-
luation. Nonetheless, women’s healthcare
providers may be called upon to consult in
the evaluation of certain gynecologic con-
ditions in such affected girls and women;
consideration of Müllerian anomalies in
such cases is strongly warranted and the
appropriate cytogenetic and imaging eva-
luation should be provided as in females
who do not present with concomitant
Mendelian disorders.
In most cases of Müllerian anomalies,
affected individuals present with normal
secondary sexual development. Although
some presentations are suggestive of
a potential chromosomal abnormality
(almost always involving the sex chromo-
somes), most Müllerian anomalies are not
associated with autosomal or sex chromo-
some abnormalities. Nonetheless, some
clinical presentations involving possible
abnormalities in sexual development, fer-
tility, and maintenance of pregnancy may
involve chromosome abnormalities and
consideration of such testing is warranted
in many, but not in all, such cases.
The use of other laboratory tests such
as serum sex steroid levels and other
assays are usually not indicated as a gen-
eral or universal assessment, except in the
presence of specific clinical symptoms. As
such, clinicians should avoid the routine
use of laboratory tests that are unlikely to
provide any useful information in the
evaluation of affected girls or women.
Primary amenorrhea is perhaps one of
the most important and noticeable initial
presenting symptoms, strongly suggestive
of an obstructive anomaly. More so than
other clinical signs, primary amenorrhea
can be representative of a variety of etiol-
ogies, including cytogenetic abnormal-
ities, Mendelian disorders, and isolated
Müllerian anomalies.
The most important initial assay to
obtain in such individuals is a karyotypic
analysis. Finding a 46,XY complement
should lead the clinician to consider one
220 Shulman
of the conditions affecting normal testo-
sterone function, including abnormalities
in receptor function or 5-a reductase
abnormalities. In these cases, there is no
concern regarding Müllerian anomalies
as the testes still produce MIS and there
are usually no normal Müllerian struc-
tures. A concern for such females, as well
as those found to have mosaic comple-
ments with Y-bearing chromosome lines,
is the potential for the development
of gonadal malignancies. The timing of
gonadal extirpation, which is needed to
prevent the development of gonadal
malignancy, will vary depending on the
particular abnormality.
In cases of 46 XX, an assessment of
pelvic organs is critical in determining the
cause of the amenorrhea. Finding a blind-
ending and shortened vagina (with no
visible cervix) should lead the clinician
to consider a Class I anomaly, which can
be evaluated by ultrasound or magnetic
resonance imaging (MRI).1,8–12 However,
some cases may require intra-abdominal
assessment, and in such cases, laparo-
scopy can provide diagnostic and thera-
peutic interventions in selected cases.13
As most affected females with primary
amenorrhea go through normal second-
ary sexual development save for the
absence of menstruation, the diagnosis
of Müllerian anomalies leading to pri-
mary amenorrhea or any other clinical
presentation is frequently accomplished
during adolescence.14 The presence of
pelvic pain, especially progressive in nat-
ure, at a time usually associated with the
onset of menses, provides important in-
formation to the clinician. Such cases are
clearly associated with functioning endo-
metrium, and the assessment again de-
pends on the findings of the physical
examination (eg, presence or absence of
a cervix). In such cases, ultrasound and
MRI provide important critical informa-
tion. Dyspareunia is also associated with
vaginal septa; however, most such cases
are not associated with primary amenor-
rhea and are unlikely to represent a totally
obstructive lesion such as the transverse
septum that completely obstructs the
outflow of menstruum. Indeed, like
other cases characterized by obstructive
anomalies with intact endometrial tissue,
females with such lesions are likely to
present with primary amenorrhea and
progressive pelvic pain rather than dys-
pareunia at a later time in their lives.
Most women with Müllerian anomalies
do not present with primary amenorrhea,
and as such, assessment of the reasons for
presentation weigh heavily in determining
the appropriate assessment. In women
presenting with repetitive pregnancy loss,
an HSG has been the conventional ima-
ging technology used for determining the
presence of Müllerian anomalies. In
women with progressive pain, or dys-
pareunia, or some chronic pelvic pain,
a combination of imaging technologies
(including HSG, MRI, and ultrasound)
and laparoscopy may be needed to evalu-
ate and possibly treat such conditions.
For some conditions such as intrauterine
septa, hysteroscopy may be needed to
confirm the diagnosis and provide the
necessary approach for resection and
treatment.15
Pain and primary amenorrhea are
important clinical signs associated with
Müllerian anomalies. However, most
women with Müllerian anomalies will
experience neither amenorrhea nor pain
as a result of having Müllerian anomaly.
Infertility, repetitive pregnancy loss,
repetitive poor obstetrical outcomes
(occurrences of preterm labor or second/
third trimester loss), chronic pelvic pain,
and dyspareunia may also indicate
the presence of Müllerian anomalies.
Depending on the presentation, imaging
technologies such as HSG, ultrasound
(2D and 3D) and MRI, laparoscopy
and hysteroscopy may be needed to prop-
erly evaluate the pelvic structures and
determine the presence of Müllerian
anomaly.

Treatment for Müllerian anomalies
is highly specific to the anomaly detected
and the desired clinical outcome. Depend-
ing on the specific anomaly, hystero-
scopy, laparoscopy and, in uncommon
or somewhat complex clinical presenta-
tions, laparotomy may be needed to
relieve the obstruction, reform the af-
fected organ and provide for a salutary
clinical outcome. For women who present
with infertility or poor obstetrical out-
comes, surgery may be needed to relieve
the malformation leading to the adverse
outcomes. However, management of these
anomalies remains controversial with few
rigorous scientific trials to provide robust
information for clinicians and women
seeking improved reproductive outcomes.
In general, surgical intervention is usually
indicated for women with Müllerian
anomalies who present with obstructive
anomalies, pelvic pain (especially when
it’s progressive in nature), endometriosis,
repetitive pregnancy loss, and repetitive
adverse obstetrical outcomes.16
Conclusions
Müllerian anomalies are a relatively un-
common occurrence with implications for
adolescents and adults with specific gyne-
cologic, fertility, and obstetrical issues.
Certain anomalies are more likely to pre-
sent in the adolescent years, whereas
others are more likely to present during
the reproductive years. Clinicians should
be suspicious for Müllerian anomalies in
cases of primary amenorrhea, pelvic pain,
repetitive pregnancy loss, and certain ad-
verse obstetrical outcomes. Imaging tech-
nologies, laparoscopy, and hysteroscopy
are the major diagnostic tools; however,
critical information is always obtained by
a thorough history and physical. Inter-
ventions are usually determined by the
actual anomaly, the clinical presentation,
and the desired clinical outcome and
usually involve laparoscopy and hystero-
scopy, although laparotomy may be
Müllerian Anomalies 221
needed in a small number of select cases.
Although good clinical outcomes can
be achieved, many such anomalies, even
when treated in optimal fashion, may not
provide the desired fertility obstetrical
outcomes. Counseling, and in particular
psychologic counseling, may be needed
for some women, especially those with
Class I lesions that invariably preclude
childbearing and affect normal sexual
function.
References
1. Troiano RN, McCarthy SM. Müllerian
duct anomalies: imaging and clinical
issues. Radiology. 2004;233:19–34.
2. Shulman LP, Elias S. Developmental ab-
normalities of the female reproductive
tract: pathogenesis and nosology. Adolesc
Pediatr Gynecol. 1988;1:230–238.
3. Stampe Sorensen S. Estimated prevalence
of mullerian anomalies. Acta Obstet
Gynecol Scand. 1988;67:237–240.
4. Byrne J, Nussbaum-Black A, Taylor WS,
et al. Prevalence of Mullerian duct
anomalies detected at ultrasound. Am
J Med Genet. 2000;94:9–12.
5. Buttram VC Jr, Gibbons WE. Mullerian
anomalies: a proposed classification.
Fertil Steril. 1979;32:40–46.
6. Shulman LP, Ginsberg NA, Dungan JS,
et al. Fetal reduction I cases of maternal
uterine anomalies. Presented at the An-
nual Meeting of the Central Association
of Obstetricians and Gynecologists, Chi-
cago, IL, 2007.
7. Gilliam M, Shulman LP, Scommegna A.
Tetrology of fallot, imperforate anus, Mül-
lerian, renal and cervical spine (MURCS)
anomalies in a 15-year-old girl. J Pediatr
Adolesc Gynecol. 2002;15:231–233.
8. Lindenman E, Shepard MK, Pescovitz
OH. Müllerian agenesis: an update.
Obstet Gynecol. 1997;90:307–312.
9. Folch M, Pigem I, Konje JC. Müllerian
agenesis: etiology, diagnosis and manage-
ment. Obstet Gynecol Surv. 2000;55:
644–649.
10. Lin PC. Reproductive outcomes in
women with uterine anomalies. J Womens
Health. 2004;13:33–41.
222 Shulman
11. Mueller GC, Hussain HK, Smith YR,
et al. Müllerian duct anomalies: com-
parison of MRI diagnosis and clinical
diagnosis. AJR. 2007;189:1294–1302.
12. Wu M-H, Hsu C-C, Huang K-H. Detec-
tion of congenital Müllerian duct anoma-
lies using three-dimensional ultrasound.
J Clin Ultrasound. 1997;25:487–492.
13. Strawbridge LC, Crouch NS, Cutner AS,
et al. Obstructive Müllerian anomalies
and modern laparoscopic management. J
Pediatr Adolesc Gynecol. 2007;20:195–200.
14. Spence JE. Vaginal and uterine anoma-
lies in the pediatric and adolescent
patient. J Pediatr Adolesc Gynecol. 1998;
11:3–11.
15. Di Spiezio SA, Guida M, Bettocchi S,
et al. Role of hysteroscopy in evaluating
chronic pelvic pain. Fertil Steril. Epub
Sept 17, 2007.
16. Rackow BW, Arici A. Reproductive
performance of women with Müllerian
anomalies. Curr Opin Obstet Gynecol.
2007;19:229–237.