Mullerian duct Abnormalities N.Cem FICICIOGLU, MD, Ph.D,.AA, MBA Prof in OB&GYN

the development of paramesonephric (müllerian) ducts The differentiation of the gonad- Y chromosome, SRY gene Gonad is not testis- the absence of antimüllerian hormone-the development of paramesonephric (müllerian) ducts The formation, fusion and resorption of müllerian ducts In the normal absence of the Y chromosome or the sexdetermining region of the Y chromosome (SRY gene) the somatic sex cords of the indifferent gonad do not produce TDF. In the absence of TDF, differentiation of the gonad into a testis and its subsequent production of antimüllerian hormone and testosterone do not occur.The indifferent gonad becomes an ovary. Complete ovarian differentiation seems to require two X chromosomes (XO females exhibit ovarian dysgenesis, in which ovaries have precociously degenerated germ cells and no follicles and are present as gonadal “streaks”). The first recognition of a developing ovary around weeks 9–10 is based on the temporal absence of testicular-associated features (most prominently, the tunica albuginea) and on the presence of early meiotic activity in the germ cells

the development of paramesonephric (müllerian) ducts Sertoli cell Leydig cell AMH Testosteron 5 α reductase DHT The regression of mullerian duct The development of mesonephric Ducts The differantion of external genitalia

the development of paramesonephric (müllerian) ducts Both ducts, paramesonephric (müllerian) ducts and mesonephric ducts in fetus, up to eight weeks; bipotent period One of them disappears in 12th week The differantion occurs by AMH secreted by sertoli cell and testosterone secreted by leydig cell In the absence of AMH, uterus, fallopian tubes and 1/3 upper vagina develop from müllerian ducts The uterine tubes are derivatives of the cranial segments of the paramesonephric (müllerian) ducts, which differentiate in the urogenital ridge between the sixth and ninth weeks

the development of paramesonephric (müllerian) ducts Fetal yaşamın 6. haftasına kadar mezonefrik ve paramezonefrik olmak üzere iki kanal bulunur. Y kromozomu ve testis varlığında ve dolayısıyla mıf varlığında mezonefrik kanal ve erkek genitaller gelişir. Mıf yoksa paramezonefrik kanal gelişir ve yaklaşık 12. haftadan itibaremn artık tek kanal vardır Sequential development of the reproductive tract explains the variation in observed anomalies.The paramesonephric ducts arise laterally to the mesonephric or Wolffian duct system. Without suppression from the SRY gene, development of the paramesonephric or Mu¨ llerian duct system is stimulated. These ducts migrate caudally and medially. Canalization of the Mu¨ llerian ducts, with a cranial lumen opening into the peritoneal cavity, results in the formation of the lateral fallopian tubes. Fusion of the caudal ducts in the midline, followed by regression of medial aspects, yields a single uterine cavity and cervix Normal development of the female reproductive tract involves a series of complex processes characterized by the differentiation, migration, fusion, and subsequent canalization of theMu¨ llerian system13. Uterine anomalies result when these processes are interrupted. Mu¨ llerian agenesis, characterized by a failure of the Mu¨ llerian ducts to develop, results in inability to conceive. The m€ullerian ducts arise from the urogenital ridge of the embryo as an invagination of the celomic epithelium at about 5 to 6 weeks of embryonic life. The ducts grow downward immediately to fuse in the midline at about 9 weeks and then are united with the endodermal bulbs of the urogenital sinus to form the remainder of the vagina. This process is completed by 12 to 14 weeks of gestation, and reabsorption of the septum is completed by week 19 to 20 embryonic life. In the absence of m€ullerian inhibiting factor produced by the testes, the paramesonephric m€ullerian ducts progress to normal female development.

the development of paramesonephric (müllerian) ducts

Mullerian duct Abnormalities Sporadic abnormalities Multifactoriel, Poligenic Familial Uriner system abnormalities accompany with vagina, cervix, fallopian tubes The different stages of arrest in mullerian ducts differentiation are manifested in various clinical entities. Unilateral absence of a mullerian duct results in a unicornuate uterus, and medial absence of the ducts results in absence of the uterus. Lack of fusion at various stages results in a didelphic uterus with a double cervix and septate vagina. Failure of reabsorption of the medial septum in the uterus results in a septate uterus

Prevalance %5,5, in selected population %8, in infertile population %13,3, pregnancy loss %24,5, reccurent pregnancy loss

Mullerian duct Abnormalities Congenital Acquired Myomas Polyps Intrauterine adhesions

Classification of Mullerian duct Abnormalities The different stages of arrest in mullerian ducts differentiation are manifested in various clinical entities. Unilateral absence of a mullerian duct results in a unicornuate uterus, and medial absence of the ducts results in absence of the uterus. Lack of fusion at various stages results in a didelphic uterus with a double cervix and septate vagina. Failure of reabsorption of the medial septum in the uterus results in a septate uterus

AFS Classification of Mullerian duct Abnormalities

AFS Classification of Mullerian duct Abnormalities

uterus didelphys Complete failure of fusion of the paired Mullerian ducts results in duplication of the uterine corpus and cervix called uterus didelphys. A longitudinal vaginal septum is present in most women with a didelphys uterus, and may facilitate the early diagnosis when identified on routine speculum examination

bicornuate uterus A results from failure of the Mullerian ducts to completely fuse. The central myometrium may extend to the level of the internal cervical os (bicornuate unicollis) or external cervical os (bicornuate bicollis). The latter is distinguished from uterus didelphys because it demonstrate some degree of fusion between the two horns, whereas in classic uterus didelphys the two horns and cervices are separated completely.

Septate uterus The partition between the ducts is thought to resorb in a caudal to cranial direction Failure of complete resorption results in a fibromuscular septum that can be partial or complete—dividing the uterine cavity and cervical canal into two parts The partition between the ducts is thought to resorb in a caudal to cranial direction. Failure of complete resorption results in a fibromuscular septum that can be partial or complete—dividing the uterine cavity and cervical canal into two parts. Recent reports have described anomalies that do not fit this model such as women with a septate uterus with cervical duplication and a longitudinal vaginal septum and a woman with a double cervix and vagina with a normal uterus and blind cervical pouch. In 1967, Musset suggested that fusion occurs at the level of the uterine isthmus and simultaneously proceeds in both directions. According to this hypothesis, the dual cervix and vagina could be explained by the failed fusion of the Mullerian ducts in the caudal direction, beginning at the uterine isthmus.

Septate uterus

Differantial diagnosis of bicornuat and septate uterus Fundal eksternal konturun tubal ostiumlardan geçen düz çizginin altında ise veya bu mesafe <5 mm ise BİKORNUAT UTERUS Apeks bu çizginin 5 mm ve üzerinde ise UTERİN SEPTUM

Unicornuat uterus A unicornuate uterus represents a uterine malformation where the uterus is formed from one only of the paired Mullerian ducts while the other Mullerian duct does not develop or only in a rudimentary fashion. The sometimes called hemi-uterus has a single horn linked to the ipsilateral fallopian tubes that faces its ovary

diagnosis Physical examination Ultrasonography, 2D and 3D HSG MRI Laparoscopy

Diagnosis of septate uterus

Clinical outcomes Symptoms depend on the severity and type of the defect Dysmenorrhea, chronic pelvic pain, dyspareunia, hematocolpos, hematometra in adolescent Treccurent pregnancy loss Preterm labor Abnormal fetal presentation Infertility