Mullerian Anomalies By Elizabeth Diaz. Mullerian Anomalies. Introduction Embryology and Development Anomalies of the Female Ductal System Clinical Presentation, Diagnosis and Treatment. Introduction.
1. Gonads ovaries or testes
2. Genital Duct Systems
Paramesonephric and Mesonephric Ducts
3. External Genitalia
5th week of pregnancy
Swellings on either side of the dorsal mesentery
Intermediate mesoderm forms the urogenital ridge.
Gonad develops from somatic and germ cells.
Somatic cells derived from mesonephric cellsFormation and Differentitation of the Gonads
Coelomic epithelium and underlying mesoderm of the urogenital ridge proliferate to form the gonadal ridge
Germ cells arrive in gonadal region, stimulate coelomic epithelium and mesonephros to form primitive sex cordsFormation and Differentiation of Gonads
Primary sex cords develop from the gonadal ridge and incorporate primordial germ cells (XX or XY genotype) which migrate into the gonad from the wall of the yolk sac.
Sex cords and germ cells essential for normal developmentGonad
Y c’some: TDF ( testis determing factor), SRY (sex determining region), crucial for differentiation
Primary sex cords form seminiferous cords, tubuli recti, and rete testes.
Somatic cells of primary sex cords form sertoli cells and germ cells form spermatogonia
Seminiferous cords: spermatogonia and sertoli cells, which secrete Anti-Mullerian Hormone (AMH) or MIS, and ABP (androgen binding protein).
Mesoderm b/w seminiferous cords gives rise to Leydig cells, which secrete testosterone. Leydig cells have receptors for HCG, induced by HY antigen.Development of Testes
Secondary sex cords develop and incorporate primordial germ cells
Secondary sex cords break apart and form primordial follicles, which contain primary oocytes surrounded by a layer of follicular (granulosa) cells.
Primary oocyte stage maintained until adulthoodFormation of the Ovary
Sertoli cells produce anti-mullerian hormone
- TDF cortical sex cords differentiate into oocytes and follicular cells
Lack of sertoli cells no AMH
Genetic males have testis determining factor on the sex determining region SRY of the Y chromosome. Genetic males produce Testis Determing Factor in the sex cords
6 degenerate.th week, two pairs of genital ducts.
Mesonephric Duct extending from the mesonephros (Wolff’s body) to the cloaca (urogenital sinus) referred to as the Wolffian system
Second duct arises as a longitudinal invagination of coelomic epithelium on the anterolateral surface of the urogenital ridge, known as Paramesonephric or Mullerian Duct.Genital Duct Development
Cranial uterine tubes degenerate.
Caudal portions fuse and form the uterovaginal primordium and bring together two peritoneal folds, the broad ligament.
Initially they remain separated by a septum but later they fuse to form the uterus.Paramesonephric Duct
Paramesonephric ducts do not make contact with the urogenital sinus.
Paramesonephric ducts fuse with the medial wall of the mesonephric ducts.
Below the caudal tip of the uterine primordium and above the dorsal wall of the urogenital sinus, with the mesoneprhic ducts lying laterally, a collection of paramesonephric cells forms constituting the Mullerian tubercle.Paramesonephric Duct
Ureteral Buds urogenital sinus. :Mesonephric ducts open caudally in urogenital sinus. At caudal tip ureteral bud sprouts. Grows laterally, anteriorly and cranially becomes metanephros to form the definitive kidney
Testis forms, the testosterone produced by leydig cells and is carried along the tubules by ABP stimulates the development of the mesonephric ducts to form the efferent ductules, epididymis, ductus deferens, and seminal vesicles. The AMH produced in Sertoli cells inhibits paramesonephric duct development.Male Genital Duct Formation
In ovary the absence of testosterone inhibits the development of the mesonephric ducts.
The atretic remains form the epoophoron, paraoophoron and Gartner’s ducts.
In absence of AMH, paramesonephric ducts form the female internal genital tract.Female Genital Duct Formation
Mullerian tubercle cellular condensation b/w inferior part of fused paramesonephric ducts and urogenital sinus.
Sinovaginal bulbs develop, constitute vaginal plate.
Cavity formed lined with paramesonephric epithelium, opens into the urogenital sinus and the metaplastic induction to polystratified plain epiithelium would produce the vagina.Theory of Mullerian Tubercle.
Studies show sinovaginal bulbs are caudal segments of mesonephric ducts.
Between these bulbs and caudally to the paramesonephric ducts, a solid epithelial structure is located contacting the dorsal wall of the urogenital sinus…the mullerian tubercle.Inductor role of mesoneprhic duct on vagina
Paramesonephric ducts form uterus to external cervical os and adequate formation is induced by mesonephric ducts.
Mesonephric ducts regress cranially but at cervical os, they enlarge and form the sinovaginal bulbs.
The paramesonephric cellular condensation (mullerian tubercle ) incorporates itself in the vaginal plate formed by fusion of the two bulbs.
Cavitation allows the paramesonephric cells to line the primitive vaginal cavity with paramesonephric epithelium.Mesonephric duct induction
As ureteral bud sprouts from the opening of the mesonephric ducts in the urogenital sinus, the absence or distal agenesis of a mesonephric duct would result in an absence of its opening to the sinus ( the origin of the blind vagina) and in an absence of the ureteral bud on that side. Thus, the definitive kidney would fail to develop (ipsilateral renal agenesis)Agenesis of mesonephric duct
3. Anomalies urogenital sinus urogenital membrane (imperforate hymen).
Hox-9, 10, 11, 13 are expressed along the length of mullerian ducts. Alteration of HOX genes may give rise to mullerian anomalies
Surgical: Create neovagina
1. McIndoe operation: Skin graft between
2. Sigmoid vaginoplasty:
3. Vecchietti operation: transabdominal approach.
Cyclic pelvic pain due to hematocolpos hematometria, or hematosalpinx
Bulging hymeneal membrane or a blind-ending pouch on exam.
Pelvic/Rectal exam, U/S, MRI
Rarely urologic anomalies.
Tx: Cruciate incisionImperforate Hymen: Diagnosis/ Treatment
Obstructive Defect of Lateral Fusion: hematosalpinxFailure of lateral fusion of two mullerian ducts and failure of one duct to communicate with the outside, thus unilateral obstruction. Uterus didelphys with obstructed hemivagina with ipsilateral renal agenesis
Inductor role of mesonephric duct hematosalpinx
Absence of ureteric bud, no ureter/kidney
Distal agenesis, no opening into urogenital sinus, therefore blind vaginaAgenesis of Mesonephric Duct
Dysmenorrhea, abd pain, vaginal masses, intermittent foul odor, mucopurulent discharge, endometriosis
IVP generally shows renal agenesis on obstructed side.
Dx is difficult: U/S, HSG, MRI
Tx: excision of septum or excise obstructed uterine horn to prevent endometriosis or pregnancy in rudimentary hornObstructed Lateral Fusion: Presentation/Dx/Tx.
Generally limited to uterus and cervix (uterine didelphys and bicollis (two cervices), although duplication of vulva, bladder, urethra, vagina and anus may also occur
Generally have good reproductive outcomes.
A septated vagina may occur in 75% of cases and may cause difficulty with intercourse or vaginal delivery.Uterine didelphys
Obstructed hemivagina and ipsilateral renal agenesis will have regular menses, but pain.Uterine didelphys with complete vaginal septum
1. Unicornuate with uterine horn (no endometrial cavity) fused to unicornuate uterus 2. Unicornuate uterus with noncommunicating horn containing endometrial cavity not fused
Bicornuate: fused to unicornuate uterus 2. Unicornuate uterus with noncommunicating horn containing endometrial cavity not fused
Partial fusion of mullerian ducts
Variable degree of separation of uterine horns that can be complete, partial or minimal
HSG won’t dx, need laparoscopy
Minimal reproductive problems, however can have pregnancy loss, PTL, etc.
Normal external surface, need laparoscopy to dx
Defect in canalization or resorption of midline septum between mullerian ducts.
Septum can cause infertility, recurrent midtrimester loss
Tx: resection of septum hysteroscopically or hysteroscopic metroplastyBicornuate and Septate Uteri