Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: a comprehensive update

Abstract

Background: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian aplasia, is a congenital disorder characterized by aplasia of the uterus and upper part of the vagina in females with normal secondary sex characteristics and a normal female karyotype (46,XX).

Main body: The diagnosis is often made during adolescence following investigations for primary amenorrhea and has an estimated prevalence of 1 in 5000 live female births. MRKH syndrome is classified as type I (isolated uterovaginal aplasia) or type II (associated with extragenital manifestations). Extragenital anomalies typically include renal, skeletal, ear, or cardiac malformations. The etiology of MRKH syndrome still remains elusive, however increasing reports of familial clustering point towards genetic causes and the use of various genomic techniques has allowed the identification of promising recurrent genetic abnormalities in some patients. The psychosexual impact of having MRKH syndrome should not be underestimated and the clinical care foremost involves thorough counselling and support in careful dialogue with the patient. Vaginal agenesis therapy is available for mature patients following therapeutical counselling and education with non-invasive vaginal dilations recommended as first-line therapy or by surgery. MRKH syndrome involves absolute uterine factor infertility and until recently, the only option for the patients to achieve biological motherhood was through gestational surrogacy, which is prohibited in most countries. However, the successful clinical trial of uterus transplantation (UTx) by a Swedish team followed by the first live-birth in September, 2014 in Gothenburg, proofed the first available fertility treatment in MRKH syndrome and UTx is now being performed in other countries around the world allowing women with MRKH syndrome to carry their own child and achieve biological motherhood.

Conclusion: Several advances in research across multiple disciplines have been made in the recent years and this kaleidoscopic review provides a current status of various key aspects in MRKH syndrome and provides perspectives for future research and improved clinical care.

Keywords: 46,XX DSD; Disorders of sex development; Female genitalia; Female infertility; Genetics; MRKH syndrome; MRKHS; Müllerian aplasia; Uterus transplantation; Vaginal agenesis.

Fig. 1

a The original illustration by Carl von Rokitansky (1838) showing the uterovaginal morphology in MRKH syndrome with a shortened blind-ending vagina and two rudimentary uterine remnants. b A sagittal T2-weighted MRI showing complete uterovaginal absence in type II MRKH syndrome associated with renal agenesis and a solitary pelvic kidney. c The pelvis of a patient with MRKH syndrome during surgical preparation for uterus transplantation. The forceps is holding the fibrous uterine rudiment in the midline, while it is dissected free from the bladder. On the uterine buds, located on the pelvic sidewalls, small subserosal leiomyomas are seen on both sides. The ovaries are located medially towards the Pouch of Douglas

Fig. 2

A transplanted uterus in the pelvis of a woman with MRKH syndrome. The uterus is seen in the middle. The bladder is seen below the uterus and the rectum is above