What Is MRKH Syndrome?
Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, medically known as Mullerian Aplasia, is a congenital disorder due to agenesis or aplasia of the uterus and the upper part of the vagina in females. This syndrome is characterized by the absence or underdeveloped reproductive organs of the females, that is, the vagina and the uterus.
These females have a normal chromosomal karyotype (46, XX). But due to the underdeveloped reproductive structures or their absence in some cases, they are prone to ovarian failure and the absence of normal menstrual cycles or periods (amenorrhea). In the major number of clinical cases suffering from this congenital syndrome, the first sign or symptom of this condition that prompts a clinical diagnosis during early or late adolescence is that there is no menstruation even till the age of 16 years. However, normal secondary sexual characteristics with normal external genitalia in these females will not pose a problem to ART (Assisted Reproductive Technology) as their functioning ovaries can still be utilized to achieve biological motherhood.
How Is MRKH Syndrome Classified?
MRKH is mainly classified into two types:
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Type 1 MRKH: A form of uterovaginal aplasia (isolated agenesis or aplasia with MO extragenital malformations).
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Type 2 MRKH: Extragenital manifestations or malformations are associated with this type.
Type1 MRKH patients remain unaffected by renal abnormalities, and the fallopian tubes are near normal in these cases. But the vaginal depth remains reduced from only 2 to 7 cm maximum. However, type 2 patients suffer a combination of renal, skeletal, and immune abnormalities that result in impaired defense and healing. Though not very common, other valvular abnormalities of the heart or cardiac defects may be present in some patients.
What Is VACTERL Association?
In a limited number of uncommon but possible cases, MRKH syndrome is associated with a series of defects, and isolated malformations called the VACTERL phenomenon: The characteristics of this phenomenon include,
V - Vertebral defect.
A - Anal atresia (congenital abnormality characterized by missing anus).
C - Cardiac defects.
T - Tracheoesophageal fistula.
E - Esophageal atresia.
R - Renal defect.
L - Limb defect.
What Is the Etiology of MRKH Syndrome?
The main cause of either of these types being detected by the physician or the gynecologist is amenorrhea (absence of menstrual bleeding or periods). The prevalence rate of this condition is approximately in the range of 1 female in 5000 live female births.
Though the etiology of this syndrome remains elusive or unclear, studies have evidently elaborated genetic causes over the years that may range from genetic, chemicals, and mechanical force etiologies.
Familial occurrence of MRKH syndrome is a common finding that indicates a genetic etiology more often than other risk factors. Chromosomal microarrays, overexpression of the AMH (Anti-Mullerian Hormone) or the AMH receptors in embryo, the familial transmission of genetic traits (renal and MRKH abnormalities) are all proposed but not an altogether proven hypothesis by research.
According to medical literature, in the first few weeks of embryonic growth, disturbances to the urogenital tract or genetic malformations occur (via the genetic component inherited) because of the interaction of the Wolffian and Mullerian ducts. Also, during the development of the ovaries, disturbances in the estrogen metabolism are known to interfere with bone metabolism as well as impact the development of secondary sexual characteristics (although it is deemed almost normal in most cases).
Interference in bone metabolism: This leads to skeletal abnormalities, especially of the jaw, the vertebrae, or the ribs, and are common. Skeletal and dental abnormalities or defects accompanied by dysmorphia may be additional findings for diagnosis.
How Is MRKH Syndrome Diagnosed?
Gold Standard for Diagnosis:
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Examination of external genitalia by the pediatric or adolescent gynecologist or DSD (disorder in sex development ) specialist.
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MRI (magnetic resonance imaging) of the internal reproductive tract or the genitalia. This is the main gold standard for the detection of uterovaginal agenesis. Also, an MRI offers a superior view for the elaborate examination of the female genitalia. MRI plays an important role in the detection of renal abnormalities as well in this syndrome.
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CT (computed tomography) scanning.
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Laparoscopy for surgical planning.
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Transperineal or transabdominal ultrasonography (that reveals the absence of the uterus and detects ovarian presence and functionality).
What Management Measures Help MRKH Syndrome?
Along with the management of skeletal, maxillofacial and dental anomalies, renal, auditory, and reproductive abnormalities that are a part of the females suffering from this syndrome, psychological support, and physician counseling are essential adjuncts to addressing the emotional and mental needs of these patients. Mental health issues ranging from body distortions to anxiety, depression, or psychological distress should be paid attention to by the healthcare provider apart from treatment planning by the gynecologist.
The American College of Obstetricians and Gynecologists (ACOG) recommends vaginal dilation therapy as the first line of treatment (even though many surgical experts may not recommend this procedure). Vaginal reconstruction procedures remain efficacious only dependent on the individual female’s anatomy and her fertility potential that should be assessed by an expert gynecologist.
The goal of the long-term modality for solving the fertility and sexual needs of these patients is to create a neovaginal canal that can possess adequate axial direction, length, lubrication, and depth to achieve both needs. Vaginal reconstruction methods with the sigmoid colon currently have replaced age-old methods like Williams vaginoplasty. With the advent of the ART’s (Assisted Reproductive Technologies), biologic conception and fulfillment of the dream of motherhood are indeed possible for these patients depending on psychosomatic factors, ovarian functionality, and the individual potential to treatment strategies. Studies have been documented for IVF (in vitro fertilization) success rates and via surrogacy to achieve motherhood in females suffering from MRKH syndrome. This indicates the possibility of successful conception in these individuals through IVF and surrogacy.
Gestational surrogacy: In the affected female, controlled ovarian hyperstimulation (COH) along with subcutaneous administration of gonadotropins or recombinant preparations followed by oocyte retrieval and ICSI (intracytoplasmic sperm injection)/IVF procedure for these patients is done. The embryos are then transferred to the surrogate’s uterus (multiple embryos may be transferred to achieve a higher success rate for pregnancy). The option of surrogacy is preferred over uterine transplantation directly in these individuals by some gynecologists. Uterine transplantation (of a donor uterus), even if possible, needs immunosuppressive therapy additionally along with a considerable waiting period before implementing IVF.
Conclusion:
The address of mental health is crucial for boosting the psychological support of an MRKH individual alongside the current strategic interventions of vaginal reconstruction and ART procedures suited to the individual’s needs that indeed make motherhood possible or offer hope of motherhood via surrogacy.
