Genital tract anomalies

Three steps that build the female tract

• Müllerian (paramesonephric) ducts form lateral to the mesonephric ducts, then their caudal parts fuse in the midline to make the uterus, cervix and upper vagina; finally the midline septum is resorbed to leave a single cavity.
• The vaginal plate (from the sinovaginal bulbs of the urogenital sinus) canalises to form the lower vagina; the hymen is the thin membrane left where the plate meets the sinus.
• The gonad decides the hormonal environment: AMH from Sertoli cells removes the Müllerian ducts, and testosterone (and dihydrotestosterone) builds Wolffian ducts and masculinises the external genitalia.
• Ask which step failed and every clinical feature follows.

Uterine (Müllerian) malformations

• The outer fundal contour separates septate (smooth) from bicornuate (notched) on 3D ultrasound or MRI; hysterosalpingography shows only the cavity and cannot tell them apart.
• The septum is poorly vascularised, so implantation on it fails: septate uterus has the strongest link with recurrent miscarriage, and it is the one treated by hysteroscopic resection.
• Other obstetric effects: preterm labour, malpresentation (breech, transverse lie), retained placenta, and rupture of a pregnancy in a rudimentary horn.
• The Müllerian duct depends on the mesonephric duct, which also gives the ureteric bud, so renal anomalies (agenesis, pelvic kidney) accompany Müllerian defects; image the kidneys.

Müllerian agenesis (MRKH syndrome)

• 46,XX woman with primary amenorrhoea, normal breasts and normal pubic and axillary hair.
• Uterus and upper vagina absent; a short blind vaginal pouch remains, formed by the sinovaginal bulbs (urogenital sinus).
• Ovaries are normal and ovulate, because they arise from the genital ridge, not the Müllerian ducts; secondary sexual characteristics and hormone levels are normal.
• Renal and skeletal (cervical spine) anomalies may coexist.
• After Turner syndrome (gonadal dysgenesis) it is the second commonest cause of primary amenorrhoea.

Vaginal and hymenal obstruction

• Where the blood collects (haematocolpos, then haematometra, then haematosalpinx) shows the level of the block.
• An imperforate hymen is the commonest obstructive cause of primary amenorrhoea and is cured by a simple cruciate incision; the anatomy above it is normal.

Diethylstilboestrol (DES)

• DES is a synthetic non-steroidal oestrogen once given in pregnancy to prevent miscarriage.
• It is a teratogen of the Müllerian system in female offspring: T-shaped uterine cavity, cervical hoods and collars, vaginal adenosis (glandular Müllerian epithelium persisting in the upper vagina) and a later risk of clear cell adenocarcinoma of the vagina and cervix.
• It does not virilise; it is an oestrogen, not an androgen.

External genitalia and their homologues

• Androgen exposure of a female fetus fuses the labioscrotal swellings into a rugose scrotum-like sac; fusion of the urethral folds would instead close a penile urethra.
• Fusion only happens before about 12 weeks; androgen exposure after that enlarges the clitoris alone.
• Causes of a virilised 46,XX baby: congenital adrenal hyperplasia (commonest), maternal androgenic progestogens or danazol, maternal androgen-secreting tumours, and placental aromatase deficiency.

Disorders of sex development: reasoning

• Three questions: what is the gonad, did it make AMH, did it make testosterone (and could tissues respond)?
• AMH absent: uterus present. Androgen absent or not acting: female external genitalia and no Wolffian ducts.
• Hormones act locally on the duct on their own side, so a testis on one side and a streak on the other gives asymmetric internal organs.
• A 46,XX baby with ambiguous genitalia is CAH until proven otherwise; the commonest cause of an undervirilised 46,XY individual (old term male pseudohermaphroditism) is androgen insensitivity.

Key syndromes compared

• In Swyer syndrome the uterus is present for one reason: the streak gonads made no AMH. Breasts are absent because there is no ovarian oestrogen either.

Congenital adrenal hyperplasia: enzymes

• Low cortisol removes negative feedback, ACTH rises and the adrenals become hyperplastic, pushing precursors into the open androgen pathway.
• The 21-hydroxylase form is the one that does not cause hypertension.

Turner syndrome

• Karyotype 45,X (written 45,XO in older papers); about half are mosaics or have a structural X (for example isochromosome Xq).
• No Barr body in classic 45,X, because there is no second X to inactivate. A Barr body in a Turner phenotype points to mosaicism (45,X/46,XX) or a structurally abnormal second X.
• Features: short stature, webbed neck, low posterior hairline, shield chest, cubitus valgus, lymphoedema of hands and feet at birth (cystic hygroma in utero), coarctation of the aorta and bicuspid aortic valve, horseshoe kidney, primary amenorrhoea with high FSH; intelligence usually normal.
• Germ cells reach the ovary but oocytes are lost by accelerated atresia, leaving fibrous streaks. Turner is the commonest cause of primary amenorrhoea overall.
• A boy with short webbed neck, low hairline and fused cervical vertebrae has Klippel–Feil anomaly or Noonan syndrome, not Turner, because Turner occurs only in phenotypic females.

Remember Breasts tell you about oestrogen, pubic hair tells you about androgen action, and a uterus tells you about AMH.

Exam trap MRKH and androgen insensitivity both have breasts, a blind vagina and no uterus; normal pubic hair and 46,XX mean MRKH.

Exam trap The uterus is absent in androgen insensitivity because AMH worked, not because of androgen; in Swyer syndrome the uterus is present because AMH was never made.

How FCPS asks about this

• Bicornuate uterus is due to: incomplete fusion of the paramesonephric ducts; septate uterus is failed septal resorption.
• 46,XX with ambiguous genitalia: congenital adrenal hyperplasia, usually 21-hydroxylase deficiency with raised 17-hydroxyprogesterone.
• CAH enzyme that does not cause hypertension: 21-hydroxylase; 11-beta and 17-alpha deficiencies raise deoxycorticosterone and cause hypertension.
• Turner karyotype and Barr body: 45,X with no Barr body; a Barr body suggests 45,X/46,XX mosaicism.
• 46,XY female with no breasts and a uterus: Swyer syndrome; streak gonads made no AMH.
• Virilised 46,XX baby with scrotum-like labia: fused labioscrotal swellings from androgen exposure before 12 weeks.
• T-shaped uterus and vaginal adenosis: diethylstilboestrol in utero; risk of clear cell adenocarcinoma.