Congenital Abnormalities of the Female Reproductive Tract by Ekaterina Tchmoutina R1 3/11/2015

Female Reproductive Tract Embryology XX – barr body (X inactivation), lack of SRY gene (development of ovary) Wollfian – mesonephric – remnants in female Mullerian - paramesonephric ovary – genital ridge + primordial germ cells Tubes, Uterus, Cervix, upper 1/3 vagina – paramesonephric ducts fuse Lower 2/3 Vagina – sinovaginal bulb (from urogenital sinus) meets paramesonephric duct

Hermaphrodites true hermaphrodite – ovotestes, ambiguous external genitalia; 70% XX; pseudohermaphrodite – genetic sex opposite of phenotypic CAH – masculinized females Androgen Insensitivity – feminized males

Genetic Syndromes Swyer Syndrome = XY gonadal dysgenesis – point mutation of SRY gene – no oocytes/testes – phenotypic female w/o ovulation & menses and secondary sex characteristics Turner Syndrome – 45 X0 – increased oocyte loss  streak ovary, short stature, webbed neck, renal & cardiac (coarctation of Ao) anomalies

Female Reproductive Tract Embryology - 2 Mesonephric Remnants – epoophoron, paraophoron, Gartner’s cyst

External Genitalia Development genital tubercle – clitoris urogenital sinus – vestibule + lower 2/3 vagina urethral fold – labia minora genital swelling – labia majora

Clitoral Anomalies normal clitoris – 1-1.5 cm long, 0.5 cm wide enlarged +/- partial development of penile urethra +/- labial fusion = androgen stimulation in utero (female) or androgen insensitivity (male) bifid +/- anterior rotation & shortening of vagina + vaginal fusion – extrophy of bladder

CAH Pathway

CAH Pathway

CAH Treatment

Labial Fusion exposure to exogenous androgens CAH – 22-hydroxylase, 11-hydroxylase, 3-βhydroxysteroid dehydrogenase deficiencies Tx dexamethasone qd

Imperforate Hymen hymen = junction of sinovaginal bulbs with urogenital sinus becomes perforate in utero 1 : 1000 types: imcomplete, septate, cribriform, microperforate Sg/Sx: bulging membrane at introitus, amenorrhea, hydro/muco/hematocolpos, hematometra Tx: cruciate, triangular, oval incision

Mullerian agenesis = Mayer-Rokitansky-Kuster-Hauser syndrome absence of vagina and uterus (+/- rudimentary uterine horns) 1/4,000 – 10,000 75 % no vagina, 25% short vagina ovaries normal, Fallopian tubes present 50% w/ urinary tract anomalies: 12% skeletal abnormalities Sx/Sg: primary amenorrhea, vaginal agenesis Tx: vaginal dilators, vaginal reconstruction (Abbe-McIndoe), neovagina (labial skin graft)

Androgen insensitivity syndrome = Testicular Feminization 46 XY faulty testosterone R’s Mullerian structures Vaginal agenesis no pubic hair Tx: remove testes after growth spurt to avoid gonadoblastoma

Transverse Vaginal Septum Mullerian tubercle = joining of mullerian ducts w/ sinovaginal bulbs incomplete canalization at mullerian tubercle (at junction of upper 1/3 and lower 2/3 of vagina) 1-2 cm thick 1/75,000 associated w/ DES Sx/Sg: mucocolpos, mucometrium, hematocolpos/metrium, foul smelling discharge Tx: dilatation/excision

Vaginal Adenosis poor demarkation of mullerian vs sinovaginal junction invasion of mullerian ducts into sinovaginal area  adenosis (submucosal) DES exposure

Mullerian Development from clefts b/w mesonephros & gonads caudal & lateral to mesonephric ducts grow caudally and meet in midline at Mullerian tubercle (junction with sinovaginal bulbs) Stage 1 (wk 10) – medial aspects of caudal portions fuse (starting in middle & proceeding in both dir’ns)  septum Stage 2 (wk 10-13) – rapid midline cell proliferation  thick upper septum; lower portion on the median septum resorbed rostrally to caudally Stage 3 (wk 13-20) – degeneration of upper uterine septum

Vaginal Development from sinovaginal bulbs (outgrowth of urogenital sinus) cord  canalization beginning at hymen and ending at cervix canalization ends at wk 21

Associated Abnormalities depends on timing of teratogenesis specific to stage of development uterine didelphys – after mesonephric development – no renal anomalies communicating uteri w/ atretic hemivagina or w/ hemicervix  ipsilateral renal agenesis

Mullerian Fusion Abnormalities polygenic/multifactorial 37% - bicornuate 28% - arcuate 11% - didelphys 9% - complete septum 4% - unicornuate

Mullerian Fusion Abnormalities

Mullerian Fusion Abnormalities - 2 Sx/Sg: tampons do not obstruct uterine flow cyclic abdominal pain w/ fluid/mass in vagina/abdomen recurrent miscarriage – esp early 2nd trimester abnormal uterine activity in labor abnormal fetal presentation Dx: SOH, HSG, Hysteroscopy, US (not diagnostic), MRI concurrent evaluation of urinary tract is indicated

Absent Uterus & Cervix +/- Fallopian tubes & some fibrous tissue 50 % associated w/ urinary tract anomalies

Unicornuate Uterus from destruction of Mullerian duct on one side absence of kidney/ureter on same side fallopian tube on the present side ovary on the opposite side Sg/Sx: recurrent prego loss

Mullerian Fusion Abnormalities - 3 Tx (goal to improve fertility) Metroplasty – laparotomy wedge resection of septum with uterine reaproximation Hysteroscopic septal resection +/- concurrent laparoscopy (avoids adhesions  infertility) post op IUD for 30 ds +/- 1.25 mcg/day conjugated E evaluation for cervical competency in pregnancy

Ovarian Abnormalities Accessory Ovary 1/93,000 excess tissue near and connected to normal ovary Supernumerary Ovary 1/29,000 omentum, retroperitoneal dermoid cysts Ovotestes true hermaphrodite testes – malignant transformation, closer to groin  remove at puberty ovaries – gonadoblastoma, dysgerminoma

References Lentz, GM. 2012. Comprehensive Gynecology. Sixth Edition. Chapter 11 – Congenital Abnormalities of the Female Reproductive Tract. Mosby, Elsevier Inc.; 187-198. Yin, Aidi. Med School Embryology Lecture