Mullerian anomalies

Dr. Chandani Pandey

Definition
• An abnormal development of the Mullerian ducts during
embryogenesis.

• 7- 10 % of young women and girls present with reproductive tract

anomaly

• 57 % of women with uterine defect have successful fertility and

pregnancy
Mullerian Ducts

• Paired ducts derived from intermediate mesoderm.

• Known as para-mesonephric duct.

• Named after Johannes peter mullero described them in 1830.

Embryological development
• Appear between 5-6 weeks

• Derived from intermediate mesoderm lateral to wolffian duct as

invagination of dorsal coelomic epithelium.

• The site of origin of invagination remains open and forms the fimbriated
end of fallopian tube

• Depends on absence of male determining factor which is present in Y-

chromosome
Embryological development …

• Female development called Basic developmental path of the human

embryo – requires not only estrogen but the absence of testosterone
as well .

• Ambisexual period persist upto 8 weeks, thereafter one type of duct

system persist & other disappears.
 Development of Genital Ducts

• Both male and female embryos have two pairs of genital ducts

• The mesonephric ducts (wolffian ducts) - male reproductive system

• The paramesonephric ducts (Mullerian ducts) - female reproductive

system

• Till the end of sixth week, the genital system is in an indifferent state,
when both pairs of genital ducts are present
• Mullerian ducts form as buds of coelomic epithelium .

• Grows downward & lateral to corresponding Wolffian ducts.

• Turn inwards & crosses anterior to it joining its fellow from opposite side.
Consists of : -
• Upper vertical part lateral to wolffian duct - fallopian tube.

• Middle horizontal part crossing wolffian duct

- remaining part of fallopian tube.

• Lower vertical part fusing to opposite part - uterus, cervix

upper 1/3rd of vagina.

• In forming the uterus, the mullerian ducts fuses from below upwards
 Development of Vagina
• Develops in 3rd month of embryonic life.

• From lower end of uterovaginal canal (mullarian duct) & urogenital

sinus under estrogenic stimulation.

• Uterovaginal canal fuses with sinovaginal bulb (develops from

posterior aspect of urogenital sinus)forming vaginal plate.

• Later canalizes to form vaginal canal.

 Development of vagina
• Upper 1/3rd develops from Mullerian duct – mesodermal.

• Lower 2/3rd develops from vaginal plate – endodermal.

• Incomplete breakdown of the junction between the bulbs above and

the urogenital sinus proper below leaves the hymeneal membrane.

• Not derived from Mullerian ducts

Development of vagina
 Development of the Gonads
The phase of indifferent gonads (Genital Ridge):

• The germ cells (primordial germ cells) migrate to the genital ridge by the
6th week.

• The germ cells influence development of the gonad into ovary or testes.

• The covering epithelium proliferates and sends cluster of cells into the
underlying mesoderm known as the cells of the sex cords.
 Development of the Gonads

• Differentiate into testis or ovaries depending on the presence or

absence of the Y chromosome in the germ cells.

• Ovarian Differentiation
- Occur in the absence of Y chromosome and SRY protein
- Occurs two weeks later (about the 8th week)
• The cortical zone that contain the germ cells develop to a much greater
extent, while the medulla regress.
• By the fourth month:
- Each germ cell, now become as Oogonia, is surrounded by a single layer
of epithelial cells
- The oogonia are transformed into primary oocytes as they enter the 1st
meiotic division and arrest in prophase until puberty and beginning of
ovulation

- Around the 20th week of gestation the ovary contains about 5 - 7 million
germ cells.
- Degeneration and atresia begins around 20 weeks and by birth
approximately 2 million germ cells remain.
Embryonic structures and their adult
homologous
Embryonic structures and their adult
homologous
MULLERIAN DUCT ANOMALIES
Mullerian Anomalies.. classification
Mullerian Anomalies.. Classification
Class I - Dysgenesis of the Mullerian ducts

Class II - Disorder of vertical fusion of Mullerian ducts

Class III - Disorder of lateral fusion of Mullerian ducts

Class IV – Unusual configurations of vertical- lateral fusion defects

ESHRE–ESGE classification - 2013

• European society of Human Reproduction and Embryology–European

Society for Gynaecological Endoscopy.

• Proposed to eliminate the subjective diagnosis of the original ASRM

classification (Woelfer et al., 2001; Grimbizis and Campo, 2010)

• Enable differentiation between septate uterus and other similar

conditions, independent of absolute morphometric criteria
Class Uterine cavity shape External contour

U0: normal uterus Straight, curved interostial line or Normal outline or external
internal indentation,50% myometrial cleft ,50% of uterine wall
thickness thickness

U1: Dysmorphic uterus Abnormal Normal outline or external

cleft ,50% of uterine wall
A . T-shaped Narrow cavity Narrow cavity; thickened lateral walls; thickness
correlation of two-third uterine corpus
and one-third cervix
B . Infantilis Narrow cavity without wall thickening;
correlation of one-thirda uterine body
and two-third cervix
C . Others Internal indentation ,50% myometrial
thickness (?)
Class Uterine cavity shapes External contour

U2 : septate uterus Internal indentation .50% Normal outline or external cleft

a. Partial myometrial thickness 50% of uterine wall thickness
a. Division above of the internal
b. complete cervical os
b. Division up to the internal
cervical os

U3 : Bicorporeal uterus External cleft .50% myometrial

a. Partial a. Division above of the internal thickness
cervical os
b. complete b. Division up to the internal
cervical os
c. bicorporeal septate [Link] fundal indentation
(myometrial thickness at the
central point of the external
cleft) .150% uterine wall thickness
(average myometrial thickness)
Class U4: Hemi-uterus
a. With a rudimentary (functional) cavity- With communicating or non-
communicating functional contralateral horn of cavity
b. Without rudimentary (functional) cavity -Without functional
contralateral horn of cavity

Class U5: Aplastic uterus

a. With rudimentary (functional) cavity- Cavity remnant present
b. b. Without rudimentary (functional) cavity - Cavity remnants absent

Class U6: Unclassified cases

• Three main principles governs the practical approach to
Mullerian anomalies.

1. Mullerian and Wolffian ducts are so closely related

embryologically that Mullerian anomalies are commonly
associated with anomalies of kidney and ureter.

2. Development of gonads is separate from ducts so normal

ovaries are present in Mullerian anomalies.

3. Mullerian anomalies may be associated with anomalies in

sex chromosome make up of individual.
• Complete formation & differentiation of Mullerian duct into female
reproductive system depends on completion of 3 phases of
development as follows-

- Organogenesis

- Fusion

- Septal resorption
ORGANOGENESIS
• One or both mullerian duct may not develop fully-Uterine agenesis
or hypoplasia
Unicornuate uterus.

FUSION
• Lateral fusion- process during which lower segment of paired
Mullerian duct fuse
- Uterine didelphys or Bicornuate uterus
Vertical fusion-
• Fusion of ascending sino-vaginal bulb with descending Mullerian
duct –
Transverse vaginal septum

Septal resorption – after fusion central septum persist later resorbs

to form single uterocervical cavity – Septate uterus, arcuate uterus
Class I : Agenesis or hypoplasia
- Complete agenesis of uterus, fallopian tubes, cervix and upper part of
vagina

- Mayer-Rokitansky-Kuster-Hauser

- Diagnosed at the age of 15 -18 years

- WT1 , WNT4 , Pax 2, PBX1,

HOX genes has been associated
Class I : Agenesis or hypoplasia…
Vaginal Atresia :
- Urogenital sinus fails to contribute its expected caudal portion

- The lower portion of the vagina usually one fifth to one third of the
total length is replaced by 2- 3 cm of fibrous tissue

- Hymeneal ring is normal , proximal to ring only a vaginal dimple or

small pouch found

- Rectovaginal examination confirms midline organs

Cervical Agenesis :

• Commonly present with the absence of the vagina as well

• Uterus develops normally

• Cyclic abdominal or pelvic pain and primary amenorrhea

• If functional endometrium is present may present with distended

uterus and endometriosis secondary to retrograde menstrual flow
Complete Agenesis ( MRKHS )
• Congenital absence of both the uterus and vagina

• Shallow vaginal pouch of 1 to 2 cm

• Only small rudimentary Mullerian bulb with or without endometrial

cavity

• Normal ovarian functions, including ovulation

MRKHS
• Phenotypic – female

• Genotypic – female ( 46 XX karyotype )

• Frequent association of other congenital anomalies

• 15-36 % - urinary system anomalies and 12 % - Skeletal anomalies

• MURCS syndrome- Mullerian duct aplasia, renal aplasia and

cervicothoracic somite dysplasia
MRKHS .. Etiology
• Autosomal mode of inheritance

• Possible reason ( knab et al )

- Inappropriate production of Mullerian regressive factor in the female
embryonic gonads
- Regional absence or deficiency of estrogen receptors limited to lower
Mullerian ducts
- Arrest of Mullerian duct development by teratogenic agent
- Sporadic gene mutation
Class I : Agenesis or hypoplasia…

• Typical MRKH – Isolated uterovaginal aplasia/hypoplasia

Prevalence – 64%

• Atypical MRKH – Uterovaginal aplasia/hypoplasia with renal

malformation or uterovaginal aplasia/hypoplasia with ovarian
dysfunction
Prevalence – 24%
Class I : Agenesis or hypoplasia…
Laboratory studies:

• Chromosomal analysis

• Circulating levels of LH and FSH (normal in MRKH syndrome )

• Testosterone
Class I : Agenesis or hypoplasia…
Ultrasonography

• Easily depicts the upper level of the vagina and the length of its
obstruction

• Allows simultaneous assessment of the kidneys and bladder for

abnormalities and visualization of some vertebral anomalies
 Class I : Agenesis or hypoplasia…
• Other investigation
- MRI
- IVP and renal sonography
- Diagnostic Laparoscopy
Class I : Agenesis or hypoplasia…
Laparoscopy
• Used in patients who also present with abdominal pain to evaluate
and possibly resect the Mullerian horn

• Therapeutic laparoscopic surgery can also be performed in the same

setting

• Preferred procedure when uterine remnants or endometriosis cause

cyclic pelvic pain requiring excision
Treatment
• Psychological support

• Vaginal Reconstruction

• Fertility – by surrogacy

• Uterine transplant ( Ozkan 2013 )

 Class I : Agenesis or hypoplasia…

Management :
Non- invasive :
• Frank technique or perineal dilation

Invasive :
• McIndoe procedure
• Vecchietti procedure
• Williams vaginoplasty
• Autotransplant of a resected sigmoid colon ( colpoplasty )
• Davydov procedure
VAGINAL AGENESIS
• Aim:- to create a neovagina.

Non surgical
• Initial therapy.
• Frank (1938) described non surgical method to create neovagina using
sequential application of wider & longer dilator.
• Series of graduated dilator dilate vaginal space creates a functional
vagina within 3-6 months.
• Patient instructed to sit on racing type bicycle seat for at least 2 hrs/day
at interval of 15-30 min (to apply pressure by leaning forward with
dilator in place)
SURGICAL

- Indication : Failed non surgical treatment

Without use of abdominal contents-

• Without dissecting cavity-
1. Williams vulvovaginoplasty (1964)
2. Vecchietti procedure(1965)
• Dissecting cavity & lining with graft-
1. Mc Indoe operation
2. Dermis graft
3. Amnion graft
4. Flaps-Musculocutaneous, fasciocutaneous

With use of abdominal contents-

• Peritoneum
• Intestinal contents.
Mc Indoe operation
• Procedure of choice.

• Three important principles-

- Dissection of adequate space between bladder & rectum.
- Inlay a split thickness skin graft.
- Prolonged dilatation during the contractile phase of healing.
Post operative management
• Antibiotics.
• Low residue diet.
• Replacing with new form
• Removed after 7-10 days. vaginal cavity irrigated with warm saline.
- Inspection of cavity to determine the take of graft.
• New form applied.
• Applied continuously for 6 weeks except at the time of urination &
defecation.
• Next 12 months-new form applied only during night.
Williams Vulvo vaginoplasty
• Full thickness skin flap of labia majora to create a vaginal pouch.

• Advantages-
- Technique is simple.
- Less local complication.
- Early recovery.
- Operation of choice for unsatisfactory Mc Indoe operation.
- After extensive pelvic surgery or radiation therapy.
Williams Vulvo vaginoplasty
Colpoplasty
Class II : Unicornuate uterus
• Results from complete or almost complete arrest of development of 1
mullerian duct
• With rudimentary horn –
 With endometrial cavity-
-Communicating (10%)
-Non communicating (22%)
Without endometrial cavity (33%)

• Without rudimentary horn (35%)

Associated with urological anomalies-44%.

 Reproductive outcomes in Unicornuate uterus

Rackshow , 2007
• Live birth rate - 54 %

• Abortion rate - 36%

• Preterm delivery - 16%

• Others – Malpresentation , Fetal growth restriction , fetal

demise , premature rupture of membrane
 Class II : Unicornuate uterus…

• Poorest fetal survival among all mullerian anomalies because of –

• Insufficient muscular mass.
• Decreased uterine volume.
• Decreased ability to expand.

• Non communicating accessory horn having endometrial cavity- most

common & most clinically significant.
Can cause- hematometra , endometriosis
NONCOMMUNICATING RUDIMENTARY UTERINE HORN
* attached fallopian tube (arrow) was patent*
USG
• Useful for identifying rudimentary horn.
• Can identify communication with main uterine cavity.
Class II : Unicornuate uterus…
Laproscopy
• Rarely indicated.
Additional :
• IVP, Renal USG

• Indication of surgery-Presence of accessory horn with endometrium.

• Laparoscopic hemi hysterectomy of rudimentary horn is treatment of
choice.
Class III -UTERINE DIDELPHYS
• Failure of medial fusion of two mullerian ducts.
• Characterised by 2 separated uterus each with endometrial cavity , 2
cervix, vagina can be single or double.
• Each hemiuterus having one fallopian tube.
• Simultaneous pregnancy can occur in each uterus –are always dizygotic.

• Usually asymptomatic (non obstructive) – diagnosed during pelvic

examination- two cervix seen.

• Associated with best possibility of successful pregnancy after arcuate

uterus.

• May have history of recurrent second trimester abortion.

Unilateral vaginal obstruction can cause
• Hematocolpos, hemetometra , endometriosis
• Can be overlooked as there is cyclical menstruation from opposite Side.
Reproductive outcome
• Fetal survival rate – 75 %
• Preterm - 24 %
• Fetal growth restriction - 11%
HSG
• Two uterine cavity with two cervix with two vagina.
• Intercornual distance-> 4 cm.

MRI
• Two widely separated uterus.
• Two cervix, two vagina.
• Associated renal anomaly identified.
• Indication of vaginal septum resection:
- Obstructed unilateral hemivagina to preserve fertility.
- In non obstructive vagina – surgical correction is limited.(severe
dyspareunia).

- Metroplasty – Rarely indicated.

- Only in patient with repeated late trimester loses or premature
delivery with no apparent cause
Class IV- BICORNUATE UTERUS

• Incomplete fusion at the level of uterine fundus.

• Lower uterus & cervix are fused completely.

• Two separate but communicating endometrial cavity.

• Important to differentiate bicornuate uterus from septate uterus –

different reproductive outcome & treatment strategies.
• Usually don’t have reproductive associated problem.
Sub - classification : depending on septum length.
COMPLETE : Septum upto cervix.
• BICORNUATE UNICOLLIS : Septum extends to internal os.

• BICORNUATE BICOLLIS : Septum extends to external os.

PARTIAL : Septum confined to fundal region.

Complete Partial
Reproductive outcomes
• Live birth – 60 %

• Abortion – 28 %

• Preterm – 28 % ( partial )
66 % ( complete )
 Class IV : Bicornuate uterus…

USG
• Should be done in luteal phase- endometrial echo
complex is better identified.
• Not useful for distinguishing bicornuate uterus form
septate uterus.
 Class IV : Bicornuate uterus…

HSG
• Not reliable.
• Two chambered uterine cavity.
• Septal thickness is important.
MRI
• Two uterine body
• Myometrial tissue separating
two cavity has intensity identical
to that of myometrium.
Class IV : Bicornuate uterus…

• LAPROSCOPY

• Strassmann procedure –treatment of choice.

STRASSMANN METROPLASTY

• Incision given in medial side of each hemicorpus, deep enough to enter the
endometrial cavity.

• The incision extends from the superior aspect of each horn, near the
interstitial region of the fallopian tubes, to the inferior aspect of the uterus.

• The goal is to achieve a single endocervical canal.

• If 2 cervices are present, their unification is not recommended.

• Apposition of the myometrium
– After resecting the wedge, the myometrial edges naturally evert.
- Apposition of the opposing myometrium is achieved using interrupted
vertical figure-8 sutures along the posterior and anterior uterine walls.
– The final layer is closed using continuous subserosal sutures, without
exposing any suture material to the
peritoneal cavity.
– Transvaginal dilatation of the cervix is performed, assuring proper
endometrial cavity drainage.
STRASSMANN METROPLASTY
The Strassmann metroplasty with modification. A: If a rectovesical ligament is found, it should
beremoved. B: An incision is made on the medial side of each hemicorpus and carried deep
enoughto enter the uterine cavity. The edges of the myometrium will evert to face the opposite
side. Cand D: The myometrium is approximated by use of interrupted vertical figure-of-eight 3—
0polyglycolic acid sutures. One should avoid placing sutures too lose to the interstitial portion ofthe
fallopian tubes. E: A continuous 3—0 polyglycolic acid subserosal suture is used as a final layer.
Tourniquets are removed, and defects in the broad ligament are closed.
 Class V : Septate uterus
•Failure of resorption of medial septum
after complete fusion of mullerian duct

• Most common

• A complete or partial midline septum is

present within a single uterus
Classification: Septate uterus…

• Depending on septal length.

- COMPLETE : Septum up to os.( double vagina)

- PARTIAL : Septum doesn’t extend upto os.
Classification: Septate uterus…
• Fertility is not compromised yet has poorest reproductive outcome
- Decreased intrauterine space for fetal growth
- Implantation of placenta on poorly vascularized septum

• The greater the septum , greater the risk of miscarriage especially in

second trimester
Reproductive outcome
• Fetal salvage rate - 33%
Class V: Septate uterus…

HSG
• Two chambered uterine cavity.
• Length & thickness of septa should be assessed.
 Class V : Septate uterus…
LAPROSCOPY
• Best for distinguishing septate from bicornuate uterus.
• Normal fundal contour.

MRI
• Normal fundal contour with outward
convexity.
• Low signal intensity for septum.
Bicornuate vs Septate uterus
Imaging modalities Bicornuate uterus Septate uterus

HSG - >105 degree < 75 degree

Intercornual angle
MRI- > 1 cm < 1cm
Intrafundal down cleft
Class V: Septate uterus…
INDICATION FOR SURGERY
• Recurrent spontaneous abortion.
• Single second trimester abortion.
• Preterm delivery.
Class V : Septate uterus…

• Metroplasy – Abdominal
- Hysteroscopy metroplasty with concurrent laparoscopy (outcomes are
excellent)

• Pre treatment miscarriage rates without treatment : 90%

• Post treatment miscarriage rates :10%

Hysteroscopic metroplasty
Abdominal metroplasty
• Jones metroplasty
• Tompkins metroplasty

- Term pregnancy rate after metroplasty – 80-85 %

- Mode of delivery after metroplasty – elective caesarean section
Jones metroplasty
Class VI : Arcuate uterus
• Near complete resorption of uterovaginal septum

• Characterised by small intrauterine indentation <1 cm in fundal region

• Considered as mild form of bicornuate uterus

• Clinically benign
 Class VI : Arcuate uterus…

HSG
• Single uterine cavity with saddle shaped
fundal indentation

MRI
• Convex contour
• Cavity with broad & smooth indentation
similar to myometrium
Class VII : DES-related abnormalities

• T-shaped uterine cavity with or without dilated horns is

evident.

• Not associated with renal anomalies

• Fetal exposure to diethylstilbesterol

Class VII : DES-related abnormalities
• Lower conception rates

•Increased incidence of abortion : due to structural anomalies and

cervical incompetence

• Increased incidence of ectopic pregnancy : due to tubal and uterine

anomalies

• Infertility : due to cervical hypoplasia and atresia

Disorder of vertical fusion of Mullerian ducts

TRANSVERSE VAGINAL SEPTUM

• Formed when tissue between vaginal plate & caudal aspect of fused
mullerian ducts fail to reabsorb.

• Develop at all levels.

a) Superior vagina-46%
b) Mid vagina-40%
c) Inferior vagina-14%
NEONATES & INFANTS
• Rarely diagnosed in neonates & infants – hydromucocolpos.
• Unlike imperforate hymen bulging vagina is not seen with valsalva
maneuvre.
• USG is initial study
• MRI is more useful as it clearly defines the length of atretic segment
between the upper and lower vagina.

• Management : surgical excision of septum.

POST MENARCHAE
• Symptoms depends on whether septum is complete or incomplete.
• Presents with primary amenorrhea , Cyclical pelvic pain.

• O/E
Palpable central lower abdominal or pelvic mass secondary to
hematometra, hematocolpos, hematosalpinx.
• Local examination - no bulging membrane.

• Incomplete TVS allows menstrual flow to escape

periodically but hematometra, hematocolpos can later
develop.

• Chronic retrograde menstruation frequently result in pelvic

endometriosis and adhesions
Hematometra
 Complication of Mullerian anomalies
• Abortion
• Weak uterine action
• Post partum haemorrhage
• Adhesion of the placenta
• Malpresentation
• Prolonged or obstructed labour
• Uterine rupture due to its poor development
 CLINICAL OUTCOME…
Obstetrical
• Preterm labour

• Prolonged labour – due to incoordinate uterine action

• Obstructed labour – obstruction by the non-gravid horn of the

bicornuate rudimentary horn

• Retained Placenta and postpartum hemorrhage (where the placenta is

implanted over the uterine septum.)
 CLINICAL OUTCOME
Gynecological:

• Infertility and dyspareunia are often related in association with

vaginal septum

•Dysmenorrhea in bicornuate uterus or due to cryptomenorrhea

(collection of menstrual blood in rudimentary horn)

• Menorrhagia – due to increased surface area in bicornuate

uterus
References
[Link] gynecology 3rd edition

[Link] Linde’s operative gynecology 11th and 12th edition

3 A. Ludwin and I. Ludwin . Comparison of the ESHRE–ESGE and ASRM
classifications of Mullerian duct anomalies in everyday practice. Human
Reproduction, 2015 , 30;3 ;569–80.