Mullerian Agenesis

Müllerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome) is congenital absence or severe hypoplasia of the uterus and the upper two thirds of the vagina in a woman with a normal 46,XX karyotype, normal ovaries and normal secondary sexual characteristics. It occurs in about 1 in 4,500 female births.

Type I is isolated uterovaginal aplasia; type II (MURCS association) includes renal anomalies (unilateral renal agenesis, ectopic or horseshoe kidney in 30 to 40 percent), skeletal anomalies (cervicothoracic vertebral fusion, scoliosis in 10 to 15 percent), hearing loss and cardiac defects. Most cases are sporadic; mutations or copy number variants of WNT4, LHX1, TBX6 and the 17q12 region are implicated. Ovarian function is normal, so puberty (thelarche, pubarche) is normal, but menstruation never occurs.

• Primary amenorrhoea in a girl aged 15 to 16 years with normal breast development and normal pubic and axillary hair.
• Cyclical pelvic pain is uncommon; if present, indicates functional endometrium in a rudimentary uterine horn (found in 2 to 7 percent).
• Short blind ending vagina (usually only a dimple, 1 to 3 cm), difficulty or inability with intercourse, with normal external genitalia and a normal hymenal ring.
• Associated renal, skeletal and auditory abnormalities.
• Psychological distress at diagnosis (loss of fertility and identity) is substantial.

• Pelvic ultrasound shows absent uterus and normal ovaries; MRI of the pelvis confirms absence of the uterus and upper vagina, delineates a rudimentary horn, and locates ovaries.
• Karyotype 46,XX; serum testosterone in the normal female range (below 2.0 nmol/L; androgen insensitivity syndrome, which gives female phenotype with sparse pubic hair and male range testosterone with 46,XY, is the main differential), with normal FSH, LH and oestradiol.
• Exclude imperforate hymen and transverse vaginal septum (haematocolpos on imaging), distal vaginal agenesis with functional uterus and cervical agenesis.
• Screen for associated anomalies: renal ultrasound, spinal X-ray or MRI, audiometry, and cardiac assessment when indicated.

• Disclosure and counselling should be staged, honest and supportive, with peer support groups. Explain that ovarian function is normal and sexual function is achievable. Genetic motherhood is possible through assisted reproduction with gestational surrogacy, and uterine transplantation is now available in some centres.
• Timing of treatment: the patient decides, when psychologically ready and motivated, usually in late adolescence.
• First line vaginal creation is the Frank dilator method. The patient applies graduated dilators (acrylic, 15 to 20 mm diameter, increasing to 25 to 30 mm) to the vaginal dimple with firm pressure for 20 to 30 minutes, once or twice daily, directed posteriorly then upward.
• Success (functional vagina over 6 cm and adequate width) occurs in 80 to 90 percent over 3 to 6 months. Ongoing coitus or dilator use maintains the length.
• Surgical options when dilation fails or is declined:
  • laparoscopic Vecchietti procedure (traction device pulls the dimple upwards over 7 to 9 days, completed with dilators)
  • McIndoe vaginoplasty using a split thickness skin graft
  • peritoneal vaginoplasty (Davydov), sigmoid colon vaginoplasty or buccal mucosa graft in selected cases
• Perform surgery only after the patient is mature and committed to post-operative dilatation for months. Complications include stenosis, graft contracture, granulation tissue, fistula and rectal injury.
• Rudimentary horn with functioning endometrium and pain: laparoscopic removal.
• Fertility: ovarian stimulation, oocyte retrieval and in vitro fertilisation with a gestational carrier produce genetic children.
• Uterine transplantation from living or deceased donors is established in specialised programmes, with live births reported. It requires immunosuppression (tacrolimus, mycophenolate, prednisolone) and caesarean delivery.
• Hormone replacement is not needed as ovarian function is normal. Provide bone health, renal surveillance and psychological support.