Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome), also known as Müllerian agenesis, is the most common form of vaginal agenesis, and one of the most common reasons for primary amenorrhea. It is characterized by congenital absence of the vagina and uterus and occurs in roughly one in 4,000 to 5,000 people assigned female at birth, according to the National Organization for Rare Disorders.
MRKH syndrome is caused by the failure of the Müllerian ducts to develop properly during fetal development, leading to an either poorly developed or absent vagina, cervix or uterus. Patients with MRKH syndrome and Müllerian aplasia — absence of the uterus and cervix, and blockage of the top third of the vagina — may experience complete uterine factor infertility, or at minimum, trouble conceiving and bringing a pregnancy to term.
Diagnosing MRKH Syndrome
Typically, patients with MRKH syndrome present with primary amenorrhea and cyclic pelvic pain at puberty, according to a review in the International Journal of Women's Health. When physical examination suggests an absent or hypoplastic vagina, clinicians should consider the possibility of MRKH syndrome or complete androgen insensitivity syndrome.
Once these conditions are suspected, imaging studies play a critical role in diagnosing and establishing the degree of gynecologic and extra-gynecologic abnormalities, including renal or skeletal issues. Ultrasonography and MRI are the main imaging options for diagnosis.
According to Fertility and Sterility, MRI or a combination of ultrasound and clinical examination are considered equally reliable methods for an initial diagnosis. Ultrasound has the advantage of being easily available and accessible, but even a well-trained sonographer can sometimes miss underdeveloped Müllerian structures and ovaries.
An OB/GYN or reproductive specialist should also collaborate with a patient's primary care physician for further testing, since a pelvic ultrasound may fail to spot any renal or skeletal issues.
MRKH Syndrome and Infertility
Since all patients with Mayer-Rokitansky-Küster-Hauser syndrome lack a functional uterus, providers may counsel patients who wish to grow their families on options such as gestational surrogacy or adoption. Patients who qualify might even seek out a clinical trial for a uterine transplant until this option becomes more readily available.
2014 marked the first time a woman with MRKH syndrome who had undergone a uterine transplant gave birth to a child. Despite this success story, uterine transplantation is still considered experimental, and its short- and long-term risks for mothers and newborns are still being established, according to a review from Reproductive BioMedicine Online. This comprehensive review looked at 14 published studies on the reproductive potential of patients with MRKH syndrome using in vitro fertilization (IVF) with a gestational carrier or surrogate. Although IVF with surrogacy has been available in some regions for more than two decades, only a handful of studies have looked at the clinical outcomes for these patients.
How MRKH Syndrome Affects Fertility Treatments
There are several issues that fertility specialists must consider when working with patients with MRKH syndrome. Because patients lack a uterus, fertility treatment involves stimulating the ovaries with oocyte retrieval followed by in vitro fertilization, then implantation into a surrogate gestational carrier, according to the International Journal of Women's Health.
Several common issues can arise with MRKH patients undergoing fertility treatments.
Hormonal Irregularities
Patients' hormonal levels may be irregular, possibly due to lack of normal ovarian-uterine communication. As many as 60.8 percent of women with MRKH syndrome had biochemical hyperandrogenaemia, according to a review from Reproductive BioMedicine Online. This may contribute to FSH, LH, and inhibin B irregularities, which are observed in some patients.
Defining an Optimal Ovarian Stimulation Protocol
With no outflow of menstrual blood, defining an optimal ovarian stimulation protocol is also difficult. However, because of the transfer to a carrier, there is no need to coordinate transfer with the endometrial dating, so ovarian hyperstimulation may happen with random start protocols, according to research published in the International Journal of Women's Health.
Researchers have suggested several stimulation methods, including the measurement of serum progesterone levels to determine the luteal phase, beginning the pituitary downregulation using a GnRH agonist and the use of oral contraceptives to help regulate the menstrual cycle (oral contraceptives have also been successfuly used in at least one case to reduce dysmenorrhea in a patinet with MRKH). This is followed by gonadotropins to stimulate the ovaries.
Vaginal or transabdominal ultrasound is used to take follicular measurements and correlated with steroid serum level dynamics. The combination of hormonal profile and ultrasound allows the clinician to pinpoint the precise phase of the patient's cycle.
Oocyte Retrieval
Providers must also consider whether oocyte retrieval is feasible based on an individual patient's anatomy. According to the International Journal of Women's Health study, the unique anatomy of the pelvis in MRKH may require that oocytes are retrieved via a transabdominal route rather than the usual transvaginal route. However, for most patients, vaginal oocyte retrieval is possible.
Additional Factors to Consider
The patient's age and the subtype of MRKH syndrome they have may also influence the expected success rate of fertility treatments for a particular patient. Patients presenting with "typical" MRKH syndrome may yield greater success in ovarian response and embryo quality than those with an atypical subtype. However, studies have not shown a difference in pregnancy rates between the two groups.
Additional research is needed to determine the likelihood of success for IVF and surrogacy for patients with MRKH syndrome. However, based on the extremely limited data that exists, there's a chance that patients with MRKH syndrome may one day achieve a successful live birth by undergoing IVF with a gestational carrier.
