Müllerian agenesis

Overview

Müllerian agenesis, also known as Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, is a congenital disorder characterized by the absence or underdevelopment of the uterus and the upper part of the vagina in individuals with a typical 46,XX female karyotype. Despite these internal anomalies, affected individuals have normal ovarian function, external genitalia, and secondary sexual characteristics, such as breast development and pubic hair.

Müllerian agenesis affects approximately 1 in 4,500 to 5,000 female births and is typically diagnosed during adolescence when the individual presents with primary amenorrhea (failure to start menstruation). The condition can occur in isolation (type I) or be associated with renal, skeletal, and auditory anomalies (type II).

Causes

Müllerian agenesis is caused by the improper development of the Müllerian ducts during fetal development. The Müllerian ducts normally give rise to the uterus, fallopian tubes, cervix, and the upper portion of the vagina. When these structures fail to form, the result is MRKH syndrome.

Genetic Factors

• Most cases are sporadic with no clear familial pattern, but familial clustering has been reported.

• A polygenic or multifactorial mode of inheritance is suspected in some cases.

• Mutations in certain genes (e.g., WNT4, LHX1, and HNF1B) have been implicated in rare cases, especially when associated with extra-genital anomalies.

Environmental factors during pregnancy have not been definitively linked to the condition, and in most instances, the precise cause remains unknown.

Symptoms

The primary symptom of Müllerian agenesis is the absence of menstruation during adolescence (primary amenorrhea), despite otherwise normal puberty. Other symptoms depend on the type of MRKH syndrome and whether other systems are involved.

1. Reproductive System

• Primary amenorrhea (absence of first menstrual period by age 15–16)

• Underdeveloped or absent uterus and upper two-thirds of the vagina

• Normal external genitalia

• Fully functional ovaries (normal hormone levels and ovulation)

2. Secondary Sexual Characteristics

• Normal breast development

• Normal distribution of pubic and axillary hair

3. Associated Anomalies (Type II MRKH)

• Renal anomalies (e.g., unilateral renal agenesis, ectopic kidneys, horseshoe kidney)

• Skeletal anomalies (especially spinal and rib malformations)

• Hearing defects in some individuals

Most individuals do not experience pelvic pain unless there are associated functional remnants of Müllerian structures (e.g., obstructed uterine rudiments).

Diagnosis

Diagnosis of Müllerian agenesis is typically made during the evaluation of primary amenorrhea. A thorough clinical assessment, imaging studies, and laboratory tests are essential for accurate diagnosis and to differentiate MRKH from other causes of absent menstruation.

Diagnostic Steps

• Physical examination: Normal external genitalia; shortened or absent vaginal canal

• Pelvic ultrasound: To assess presence or absence of the uterus and ovaries

• MRI of the pelvis: Provides detailed imaging of reproductive anatomy

• Karyotyping: Confirms 46,XX female chromosome pattern

• Hormonal assays: Normal levels of FSH, LH, estrogen, and testosterone

Differential Diagnosis

• Androgen insensitivity syndrome (46,XY karyotype with absent uterus and testes)

• Transverse vaginal septum or imperforate hymen (obstructive causes of amenorrhea)

Identification of associated renal or skeletal anomalies is important and may require renal ultrasound and spinal imaging.

Treatment

Treatment of Müllerian agenesis focuses on creating a functional vagina to allow for normal sexual activity and addressing the emotional and psychological impact of the diagnosis. Fertility options and management of associated anomalies are also key components of care.

1. Vaginal Reconstruction

• Non-surgical dilation: First-line treatment; involves using vaginal dilators to gradually create a neovagina

• Surgical vaginoplasty: Options include McIndoe, Vecchietti, or Davydov procedures, typically reserved for those who do not succeed with dilation

2. Psychological Support

• Counseling to address body image, sexual identity, and infertility-related distress

• Support groups or therapy for adolescents and their families

3. Fertility Considerations

• Women with MRKH have functional ovaries and can have biological children via assisted reproductive technologies (ART) such as IVF with a gestational carrier (surrogate)

• Oocyte retrieval is possible for use in surrogacy

4. Management of Associated Anomalies

• Urologic intervention for renal anomalies

• Orthopedic evaluation for spinal abnormalities

• Audiological support for hearing defects

Multidisciplinary care is essential, involving gynecologists, psychologists, fertility specialists, and other relevant subspecialties.

Prognosis

The prognosis for individuals with Müllerian agenesis is generally excellent with appropriate treatment and support. Most affected individuals lead normal, healthy lives with intact sexual function and the potential for biological parenthood through assisted reproduction.

Favorable Outcomes

• Successful vaginal reconstruction allows for normal sexual intercourse

• Fertility preserved through ART and surrogacy options

• No increased risk for other gynecological cancers

Challenges

• Emotional and psychological distress related to infertility and sexual identity

• Delayed diagnosis or misdiagnosis in some cases

• Management of associated congenital anomalies

With comprehensive care and early intervention, individuals with Müllerian agenesis can thrive both physically and emotionally. Awareness, education, and ongoing research are essential to support those affected by this condition.