Mayer-Rokitansky-Kuster-Hauser Syndrome 

Updated: Aug 11, 2020
Author: Andrew J Kirsch, MD, FAAP, FACS; Chief Editor: Andrea L Zuckerman, MD 

Overview

Practice Essentials

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (also referred to as Mayer-Rokitansky syndrome or Rokitansky-Küster-Hauser syndrome) consists of vaginal aplasia with other müllerian (ie, paramesonephric) duct abnormalities.[1]  Type I MRKH syndrome is characterized by variable underdevelopment of the vagina and uterus. Type II MRKH also incorporates extragenital/extramüllerian malformations, including vertebral, cardiac, urologic (upper tract), and otologic anomalies.[2] Surgical correction of the vaginal anomaly permits normal sexual function and, possibly, reproduction with assisted techniques.

Signs and symptoms

The following may be observed in patients with MRKH syndrome:

  • The patient undergoes puberty with normal thelarche and adrenarche; however, menses do not begin (ie, primary amenorrhea)
  • Patients may report cyclic abdominal pain due to cyclic endometrial shedding without a patent drainage pathway
  • Because ovarian function is normal, patients experience all bodily changes associated with menstruation
  • Infertility
  • Difficulty with intercourse
  • Voiding difficulties, urinary incontinence, or recurrent urinary tract infections (UTIs)
  • Vertebral anomalies (most commonly scoliosis)

The degree of vaginal aplasia can vary from complete absence to a blind pouch. The more shallow the canal, the greater the likelihood that the patient will have dyspareunia or will be unable to have intercourse.

Physical examination findings are as follows:

  • Normal secondary female sexual characteristics are present after puberty
  • Height is normal
  • Speculum examination of the vagina may be impossible or difficult because of the degree of vaginal agenesis
  • The vulva, labia majora, labia minora, and clitoris are normal
  • A palpable sling of tissue may be present at the level of the peritoneal reflection

See Presentation for more detail.

Diagnosis

Laboratory studies include the following:

  • Chromosomal analysis to exclude karyotypic abnormalities of the X chromosome and androgen insensitivity syndrome (AIS); individuals with complete AIS have female external genitalia but a 46,XY karyotype
  • Circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which are normal in MRKH syndrome, indicating appropriate ovarian function
  • Testosterone levels can be assayed and are in the normal female range

Imaging modalities used for MRKH syndrome include the following:

  • Ultrasonography (US)
  • Magnetic resonance imaging (MRI)
  • Laparoscopy
  • Pyelography

Ultrasonography

  • Easily depicts the upper level of the vagina and the length of its obstruction
  • Can also be used to identify uterine duplications and tubal obstruction
  • Allows simultaneous assessment of the kidneys and bladder for abnormalities and visualization of some vertebral anomalies

MRI

  • Provides excellent images of superficial and deep tissue planes
  • Can clarify inconclusive US results concerning cavitation of the uterus
  • Improves assessment of subperitoneal structures and detects the presence of a cervix
  • Can be used to image the spine if vertebral anomalies are suspected (as can plain films)
  • Magnetic resonance urography (MRU) is an excellent imaging modality for visualization of both the reproductive and the urinary anatomy, as well as for function

Laparoscopy

  • Used in patients who also present with abdominal pain to evaluate and possibly resect the müllerian horn
  • Therapeutic laparoscopic surgery can also be performed in the same setting
  • Laparoscopy is the preferred procedure when uterine remnants or endometriosis cause cyclic pelvic pain requiring excision

Pyelography

  • Perform intravenous pyelography to assess renal structure
  • Retrograde pyelography can be used to assess the renal collecting system, and it does not require intravenous contrast injection but does require cystoscopy

See Workup for more detail.

Management

There is no consensus across specialities between nonsurgical versus surgical management for vaginal agenesis.[3]  The goal of surgical treatment is to provide the patient with an unscarred vagina that allows sexual functioning. Excision of uterine anlage can also prevent endometriosis and resultant ovarian function impairment.[4, 5]

Frank procedure or Ingram modification 

  • The only nonsurgical option
  • The patient creates a neovagina by applying progressive pressure to the perineum, using a bicycle-seat stool to hold a dilator in place  [6]
  • The technique is self-administered and requires time and patient motivation
  • Compliance may be poor in patients with a vaginal dimple or no vagina, because these patients may experience discomfort and abandon the dilator

McIndoe technique

  • The most common surgical procedure used for vaginal reconstruction
  • A split-thickness skin graft is the most popular tissue for vaginal replacement, with the thigh or buttocks preferable as a graft donor site
  • The surgeon uses blunt dissection to create a pocket between the urethra and rectum; a cylindrical stent covered with the skin graft is placed into the potential space, and the graft is fixed into place by attaching cut edges of the skin incision to recreate the introitus; the labia majora are then sutured loosely together to hold in the mold.
  • The stent is removed about 1 week later, and the patient uses a mold or dilator in the neovagina every day and night for 3 months, followed by nightly insertion for 3 more months to prevent contraction
  • Disadvantages of this procedure include scarring at the donor site, neovaginal stenosis, and the need for long-term dilation

Williams vaginoplasty

  • Uses a vulval flap to make a vaginal tube
  • Although this simple procedure does not damage the urethra or rectum, dilation is needed for a lengthy period, and the neovagina has a physiologically abnormal angle

Rotational flap procedures

  • Use the pudendal thigh, gracilis myocutaneous, labia minora, and other fasciocutaneous flaps
  • Disadvantages of these techniques include extensive skin scarring at the donor graft site and the need for patient diligence in postsurgical dilation

Intestinal neovagina

  • This technique uses an isolated segment of bowel for vagina
  • The isolated segment retains its vascular supply via intact mesentery
  • Sigmoid is generally the preferred bowel segment, as it can most easily be mobilized to the perineum in a tension-free manner [7] ; patients who have undergone this reconstructive technique report a high degree of satisfaction [8]

Vecchietti technique

  • Exerts continuous progressive pressure by an acrylic olive passed through the potential neovaginal space and the abdominal wall
  • A traction device is placed into the peritoneal cavity and gradually draws the olive upward over a period of days to weeks; this gradually lengthens the vaginal vault
  • This technique is now performed laparoscopically [9, 10]

Wharton-Sheares-George method

  • A minimally invasive neovaginoplasty that is relatively simple to perform [11]

See Treatment for more detail.

Background

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (also referred to as Mayer-Rokitansky syndrome or Rokitansky-Küster-Hauser syndrome) consists of vaginal aplasia with other müllerian (ie, paramesonephric) duct abnormalities.[1] Its penetrance varies, as does the involvement of other organ systems. Type I MRKH syndrome is characterized by variable underdevelopment of the vagina and uterus. Type II MRKH also incorporates extragenital/extramüllerian malformations; these include vertebral, cardiac, urologic (upper tract), and otologic anomalies.[2]

In both types, the extent of vaginal aplasia varies, ranging from virtually absent (dimple or less) to virtually inconsequential. Patients may have complete uterine aplasia or, more commonly, a bilateral rudimentary uterus. These can be large and may in rare cases contain functioning endometrium. Despite any functioning endometrium, however, the uterus remains rudimentary, and the cervix is absent. Patients with MRKH therefore do not menstruate and cannot carry a pregnancy. Normal ovarian function is intact, though the ovaries may be in an ectopic pelvic location.[12, 13]

MRKH syndrome usually remains undetected until the patient presents with primary amenorrhea despite normal female sexual development. MRKH syndrome is the second most common cause of primary amenorrhea.

MRKH syndrome has psychological consequences, but its physiologic defects are surgically treatable. Surgical correction permits normal sexual function and, possibly, reproduction with assisted techniques.

Pathophysiology

At approximately 5 weeks' gestation, the müllerian ducts stop developing. The skeleton, which is derived from the embryonic mesoderm, is vulnerable to developmental disturbances at this time. The uterus, the cervix, and the upper two thirds of the vagina form from the fused caudal ends of the müllerian ducts. Fallopian tubes develop from the unfused upper ends; the renal system simultaneously develops from the wolffian (ie, mesonephric) ducts. Ovarian function is preserved because the ovaries originate within the primitive ectoderm, independent of the mesonephros.

Etiology

A postulation is that the müllerian duct system ceases development during gestational days 44-48, for reasons yet to be fully elucidated. MRKH syndrome was previously thought to be a sporadic anomaly, but familial cases support the hypothesis of a genetic etiology and are receiving increased attention. Although the precise gene has not yet been identified, MRKH syndrome appears to be transmitted in an autosomal dominant fashion, with incomplete penetrance and variable expressivity.[2, 14]  It has been suggested that the pathogenesis of the condition may be multifactorial.[15]

Epidemiology

The incidence of congenital absence of the vagina is 1 per 4000-5000 female births.[16] As noted, MRKH syndrome has generally been thought to be a sporadic condition, and female relatives of the patient apparently have no increased risk; however, familial clustering is reported with increasing frequency.

MRKH syndrome is a congenital disorder that is present at birth but may remain undiagnosed until adolescence or early adulthood. It affects only females, and no racial predisposition has been identified.

Prognosis

The patient may have normal sexual functioning after surgical reconstruction. However, surgical vaginal reconstruction does not establish the ability to conceive through natural means. Conception cannot occur without the aid of assisted reproductive techniques.

There is interest in the possibility of uterine transplantation for women with uterine factor infertility (UFI), including those with UFI from MRKH syndrome.[17, 18]

Patient Education

To achieve optimal results, stress compliance with a home dilation schedule.

Thoroughly discuss the embryonic development of the reproductive system with the patient if the patient is interested and is able to use the information.

Because the ovaries in a patient with MRKH syndrome are normal, genetic offspring are possible through the use of a gestational carrier.

If indicated, refer the patient for psychological counseling to explore gender identity issues.

For patient education resources, see the Women's Health Center, as well as Amenorrhea and Female Sexual Problems.

 

Presentation

History

The following may be observed in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (also referred to as Mayer-Rokitansky syndrome or Rokitansky-Küster-Hauser syndrome).

Primary amenorrhea and possible cyclic abdominal pain

These symptoms are common in individuals with MRKH syndrome. The patient undergoes puberty with normal thelarche and adrenarche; however, menses do not begin. Patients may report cyclic abdominal pain due to cyclic endometrial shedding without a patent drainage pathway. Because ovarian function is normal, patients experience all bodily changes associated with menstruation and puberty.

Infertility

Patients who do not undergo evaluation for primary amenorrhea often seek clinical attention for infertility. However, patients rarely proceed to infertility evaluation without ever having had menses because of MRKH syndrome. Although the ovaries function normally, the fallopian tubes may be closed, and the uterus is often anomalous.

Inability to have intercourse

The degree of vaginal aplasia can vary from complete absence to a blind pouch. The more shallow the canal, the greater the likelihood of the patient having dyspareunia.

Renal malformations

Absence or ectopia of the kidneys is common. Diagnosis can lead to discovery of renal anomalies. Some patients present with a history of voiding difficulties, urinary incontinence, or recurrent urinary tract infections (UTIs).

Vertebral anomalies

Skeletal findings range in severity and clinical importance. Scoliosis is the most common of the skeletal anomalies.

Physical Examination

Normal secondary female sexual characteristics are present after puberty. Height is normal.

Speculum examination of the vagina may be impossible or difficult because of the degree of vaginal agenesis. The vulva, labia majora, labia minora, and clitoris are normal. A palpable sling of tissue may be present at the level of the peritoneal reflection.

 

DDx

Diagnostic Considerations

In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following:

  • Müllerian-inhibiting substance (MIS) deficiency
  • Müllerian aplasia
  • Androgen insensitivity
  • Low-lying transverse vaginal septum
  • Imperforate hymen

Differential Diagnoses

 

Workup

Laboratory Studies

In the workup for possible Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (also referred to as Mayer-Rokitansky syndrome or Rokitansky-Küster-Hauser syndrome), chromosomal analysis is essential to exclude karyotypic abnormalities of the X chromosome (eg, Turner syndrome, which does not cause MRKH syndrome but can cause primary amenorrhea). Chromosome analysis can rule out complete androgen insensitivity syndrome (AIS); these individuals have female external genitalia but a 46,XY karyotype.

Normal circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) indicate appropriate ovarian function. Human chorionic gonadotropin (hCG) levels are negative and are not checked. Testosterone levels can be assayed and are in the normal female range for MRKH syndrome and in the normal male range for AIS.

Imaging Studies

Ultrasonography

Ultrasonography (US) is an excellent imaging modality for MRKH syndrome, in that it requires no radiation and is both noninvasive and inexpensive. US easily depicts the upper level of the vagina and the length of its obstruction. It can also be used to identify uterine duplications and tubal obstruction. It simultaneously allows assessment of the kidneys and bladder for abnormalities and visualization of some vertebral anomalies.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) provides excellent images of superficial and deep tissue planes.[12] It can clarify inconclusive US results concerning cavitation of the uterus. In addition, it improves assessment of subperitoneal structures and detects the presence of a cervix. MRI can be used to image the spine if vertebral anomalies are suspected, as can plain films. Magnetic resonance urography (MRU) is an excellent imaging modality for visualization of both the reproductive and the urinary anatomy, as well as for function.

Laparoscopy

Laparoscopy provides only indirect assessment of uterine cavitation. Hysteroscopy (examining inside the endometrial cavity) confirms cavitation; however, MRI is also excellent for this. Laparoscopy is used in patients who also present with abdominal pain to evaluate and possibly resect the müllerian horn. Therapeutic laparoscopic surgery can also be performed in the same setting. Laparoscopy is the preferred procedure when uterine remnants or endometriosis causes cyclic pelvic pain necessitating excision.

Pyelography

Intravenous pyelography (IVP) is warranted for assessment of renal structure. Retrograde pyelography can be used to assess the renal collecting system and does not require intravenous contrast injection. This technique requires cystoscopy.

Histologic Findings

The uterine anlage may have unilaterally functioning endometrial tissue; bilateral function is rare. Hematometra develops and may lead to endometriosis. The myometrium appears thinner than usual.

 

Treatment

Approach Considerations

Although Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (also referred to as Mayer-Rokitansky syndrome or Rokitansky-Küster-Hauser syndrome) has psychologically devastating consequences, its physiologic defects can be surgically treated. Following diagnosis, surgical intervention allows patients to have normal sexual function. Reproduction may be possible with assisted techniques. There is interest in the possibility of uterine transplantation for women with uterine factor infertility (UFI), including those with UFI from MRKH syndrome.[17, 18]

Medical Care

Evaluation of patients with MRKH syndrome can be performed on an outpatient basis; however, surgical repair requires admission. Medical and surgical care are essential for capacity for sexual intercourse, as well as for genital appearance. In rare cases, fertility may be possible. Using assisted reproductive techniques, women with MRKH syndrome can become pregnant by having oocytes harvested, fertilized, and implanted in a surrogate; however, outcome data in the literature are less than optimal.[19]

Surgical Care

There is no consensus across specialities between nonsurgical versus surgical management for vaginal agenesis.[3]  The ideal repair provides the patient with an unscarred vagina that allows sexual functioning. There is no unanimity on which procedure is preferred in which circumstances, but Torres-de la Roche et al published an evidence-based expert opinion paper on the decision-making process.[20]

Excision of uterine anlage can also prevent endometriosis and resultant ovarian function impairment.[4, 5]  Removal of the rudimentary uterus is suggested if hematometra develops.

Frank technique or Ingram modification

The only nonoperative option, this technique is successful in motivated patients who are willing to spend time to create a neovagina using the molds. Patients apply progressive pressure to the perineum using a bicycle-seat stool to hold a dilator in place.[6] They need to be frequently examined to be sure they are dilating the vagina and not the urethra.

Because this technique is self-administered, compliance may be poor in patients with a vaginal dimple or no vagina because these patients may experience discomfort and abandon the dilator. However, this is often an indication of future compliance with vaginal dilators and molds in the postoperative period.

McIndoe technique

The surgical procedure most commonly employed for vaginal reconstruction is the McIndoe technique. A split-thickness skin graft is the most popular tissue for vaginal replacement. Skin from the thigh or buttocks is preferable. Sometimes, knowing the patient's tan lines is helpful in hiding the donor graft site.

With blunt dissection, a pocket is created between the urethra and the rectum. A cylindrical stent is covered with the skin graft and then placed into the potential space. The graft is fixed in place by attaching cut edges of the skin incision to recreate the introitus. The labia majora are then sutured loosely together to hold in the mold. A Foley catheter is placed, and the patient is given a low-residue diet and placed on modified bed rest.

About 1 week later, the stent is removed. The neovagina is irrigated, and any areas of granulation tissue are cauterized with silver nitrate sticks. The patient is instructed to use a mold or dilator in the neovagina every day and night for 3 months, then nightly for an additional 3 months to prevent contraction.

Disadvantages of this procedure include scarring at the donor site, neovaginal stenosis, and the need for long-term dilation.

Williams vaginoplasty

In a Williams vaginoplasty, a vulval flap is used to make a vaginal tube. Although this simple procedure does not damage the urethra or the rectum, dilation is needed for a lengthy period, and the neovagina has a physiologically abnormal angle.

Rotational flap procedures

Rotational flap procedures use pudendal thigh, gracilis myocutaneous, labia minora, and other fasciocutaneous flaps. Disadvantages of these techniques include extensive skin scarring at the donor graft site and the need for patient diligence in postoperative dilation.

Intestinal neovagina

This technique uses an isolated segment of bowel to create a neovagina. The isolated segment retains its vascular supply via an intact mesentery. Sigmoid is generally the preferred bowel segment because it can most easily be mobilized to the perineum in a tension-free manner.[7] Patients who have undergone this reconstructive technique report a high degree of satisfaction.[8]

Vecchietti technique

This procedure exerts continuous progressive pressure through passage of an acrylic olive through the potential neovaginal space and the abdominal wall. A traction device is placed into the peritoneal cavity and gradually draws the olive upward over a period of days to weeks. This gradually lengthens the vaginal vault. This technique is now performed laparoscopically.[9, 21, 10]

Wharton-Sheares-George method

The Wharton-Sheares-George neovaginoplasty has been suggested as a a simple and effective minimally invasive surgical approach to the creation of a neovagina.[11]  In this procedure, the müllerian ducts are dilated incrementally by pushing dilators in the direction of the pelvic axis,  the median raphe is intersected, and a a vaginal mold is inserted into the newly created cavity and held in position by two sutures. No allogenic or autologous transplants are used, nor is there a requirement for traction devices or specialized surgical equipment.

Complications

Potential complications of surgical treatment of MRKH syndrome include the following:

  • Excessive skin scarring at the donor graft site
  • Postoperative rectovaginal and urethrovaginal fistulas
  • Vaginal discharge and dyspareunia
  • Vaginal stenosis
  • Inadequate vaginal lubrication
  • Poor patient compliance with the postoperative dilation schedule

Consultations

The following consultations may be helpful:

  • Endocrinologist - A reproductive endocrinologist is best in this case; alternatively, a pediatric and adolescent gynecologist may be consulted
  • Geneticist
  • Orthopedic specialist
  • Urologist
  • Psychiatrist
  • Audiologist

Long-Term Monitoring

Monitor how well patients comply with postoperative dilation regimens.

Recommend condoms to help prevent human papillomavirus (HPV) infection.[22]

Regularly examine patients to assess for stenosis.