Introduction, prevalence, and epidemiology
Approximately 7% of those born with female anatomy will have differences in the formation of the reproductive tract, resulting in varying degrees of vaginal, uterine, or cervical development. These variations can either lead to an obstructive outflow tract, which causes pain, or a nonobstructive outflow tract, which is not usually associated with pain. Nonobstructive reproductive tract anomalies can present with variations at the level of the hymen, vagina, cervix, or uterus. The exact cause of these anomalies is unknown but is likely multifactorial, including both genetic and environmental factors. Nonobstructive anomalies can present at various times throughout life, including during childhood, after menarche, during an infertility workup, during prenatal or antepartum care, or during evaluation of another anatomic system or syndrome. ,
Pathophysiology of disease and embryology
At 4 weeks’ gestational age, intermediate mesoderm is present and the mesonephros and paramesonephros begin their differentiation into müllerian and Wolffian ducts based on the presence or absence of the SRY gene and exposure to androgens. In the absence of the SRY gene, female anatomy develops. During gestational weeks 5 to 6, the mesonephros, metanephric ducts, and genital ridge form. Gestational weeks 7 to 8 are focused on cloacal division, further development of the paramesonephric ducts, and gonadal differentiation (ovary versus testis). The müllerian ducts fuse starting around 6 to 7 weeks and continue through the 14th week. The fused müllerian ducts interact with the urogenital sinus to form the sinovaginal bulb. Remnants of the Wolffian system may persist and result in broad ligament cysts, hydatids of Morgagni, paratubal cysts, and Gartner duct cysts. The genetic mechanism for differences in the development of müllerian ducts is not well understood in humans. Any defects in migration or fusion of these structures can lead to reproductive tract anomalies along with anomalies of other associated organ systems such as the renal system ( Fig. 26.1 ).
Classification systems
There are multiple classification systems of müllerian anomalies, including the American Fertility Society (AFS) from 1979, which focused mostly on uterine anomalies; VCUAM classification (Vagina, Cervix, Uterus, Adnexa, associated Malformations), which was developed to be more precise and describe associated anomalies; and the European Society of Human Reproduction (ESHRE) and Embryology-European Society for Gynaecological Endoscopy (ESGE), which classified uterine anomalies separately from cervical and vaginal anomalies. More recently, the American Society for Reproductive Medicine (ASRM) Task Force for Müllerian Anomaly Classification recognized the need for a more thorough classification system to improve how we describe müllerian anomalies. 
This new system allows for standard communication between providers and results in improved clinical care. It has been published as the Müllerian Anomalies Classification 2021 (MAC2021), the main classification system used in the United States today. An interactive tutorial can be found at https://connect.asrm.org/education/asrm-mac-2021/asrm-mac-2021?ssopc=1 .
General clinical presentation/evaluation
Nonobstructive anomalies of the reproductive tract are usually asymptomatic and are incidentally discovered on imaging for a gynecologic complaint, evaluation of another organ system, or during an infertility evaluation. They are not usually diagnosed on routine physical examination, as the external genitalia appear typical. Nonobstructive anomalies may present with a range of symptoms, including difficulty with tampon placement or pain with intercourse in the setting of a vaginal septum, recurrent pregnancy loss or other pregnancy complications, or even primary amenorrhea in the setting of müllerian agenesis. , Box 26.1 demonstrates the non-obstructive reproductive tract anomalies.
Müllerian agenesis/MRKH
Unicornuate uterus
Uterine didelphys
Bicornuate uterus
Septate uterus
Arcuate/normal uterus
Longitudinal vaginal septum
Relevant testing for nonobstructive reproductive tract anomalies
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Pelvic ultrasound (US)
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3D US
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Pelvic magnetic resonance imaging (MRI)
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Hysterosalpingogram (HSG)
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Hysteroscopy
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Laparoscopy
Definitions and clinical presentation
Müllerian agenesis
This congenital anomaly presents with the absence of a uterus and cervix along with most or all of the upper vagina. The ovaries are typically normal because they have a different embryologic origin. Variations of müllerian agenesis can include absence of a functional uterus but presence of unilateral or bilateral underdeveloped uterine remnants with no functional endometrium and thus no pain symptoms. There can also be functional endometrium in these structures (7%–10% of uterine remnants) leading to symptoms, most notably cyclic pain (see Chapter 27 ). Müllerian agenesis is sometimes more commonly known as Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome ( Fig. 26.2 ).
Prevalence and epidemiology :
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General population: 0.1%
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Müllerian anomalies: 5% to 10%
Manifestations of the disease:
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Normal pubertal breast development
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Primary amenorrhea and no pelvic pain
Clinical presentation and examination: Patients are likely to present during evaluation for primary amenorrhea. Physical examination will be notable for a shortened vaginal canal (dimple to several centimeters long) and no palpable cervix or uterus on vaginal or rectal examination. Rudimentary uterine horns may be seen on imaging.
Differential diagnosis:
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Androgen insensitivity syndrome
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Distal vaginal agenesis
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Transverse vaginal septum
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Imperforate hymen
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Cervical agenesis
Testing/imaging relevant to condition:
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Chromosome analysis to confirm 46,XX
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Pelvic US and MRI to confirm no functional uterus
Management/treatment options: Patients born with agenesis of the uterus and vagina have important reproductive considerations:
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No uterus: These patients will be unable to carry a pregnancy. They do have ovaries and therefore can undergo oocyte retrieval and then have a surrogate carry the pregnancy. Though successful uterine transplantation followed by pregnancy and delivery have been reported, this is still experimental, very high risk, and currently not standard of care.
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Vaginal creation : Multiple techniques are available for vaginal creation to allow for receptive intercourse:
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Vaginal dilation: Sequential dilation to lengthen the native vaginal tissue to a satisfactory length.
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Recommended first option
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99% effective
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Patient-facing resource addressing vaginal dilation in teens: https://www.dsdteens.org/taking-the-wheel/dilation-a-step-by-step-guide/ .
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Surgical:
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Simple reconstruction with insertion of a graft (i.e., McIndoe vaginoplasty with skin graft, buccal mucosa, peritoneum or Davydov procedure, artificial grafts, amnion)
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Surgical traction (i.e., Vecchietti procedure)
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Balloon
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Vulvovaginoplasty (i.e., Williams procedure)
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Bowel vaginoplasty
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Other key clinical considerations:
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Screening for spinal stenosis (spine series)
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Screen for auditory deficits
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Always screen for renal anomalies/absence
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Consider peer support groups: https://www.beautifulyoumrkh.org/
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Offer referral for psychological support for patient and family
Essentials of diagnosis and key treatment considerations:
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Clinical presentation with primary amenorrhea and no pain.
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Examination reveals dimple or shortened blind-ending vagina and pubic hair, which differentiates müllerian agenesis from androgen insensitivity syndrome.
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Atrophic uterine remnants without functional endometrium that are not causing symptoms do not need to be removed.
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Pelvic MRI and chromosome analysis can confirm the diagnosis.
Unicornuate uterus
Müllerian anomaly that manifests in a single hemiuterus, cervix, and vagina on either the right or left side of the pelvis. The other müllerian duct does not develop or presents as rudimentary (uterine remnant) with no functional endometrium (no pain) or functional endometrium (see Chapter 27 ). The uterine remnant can be located near or far from the well-developed unicornuate system. Contralateral uterine remnants (both functional and nonfunctional) are associated with unicornuate uterus approximately 70% of the time. This müllerian variant is also the most common one associated with renal anomalies (40%) ( Fig. 26.3 ).
Variants:
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Unicornuate uterus with distal atrophic uterine remnant: Unilateral hemiuterus and contralateral uterine remnant without functional endometrium, separate and distinct from the patent unicornuate uterus.
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Unicornuate uterus with associated atrophic uterine remnant: Unilateral hemiuterus and contralateral uterine remnant without functional endometrium separate but adjacent and touching the patent unicornuate uterus.
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Unicornuate uterus with uterine horn communicating at the level of the uterus or cervix: Unilateral hemiuterus with contralateral uterine remnant with functional endometrium and communicating with the unilateral hemiuterus via a tract allowing menstrual egress.
Prevalence and epidemiology :
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General population: 0.03% to 0.1%
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Müllerian anomalies: 5% to 20%
Manifestations of the disease:
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Normal pubertal breast development
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Normal menstruation from patent unicornuate uterus
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Pregnancy risks: preterm labor, malpresentation, pregnancy loss
Testing relevant to condition: Pelvic US, 3D US, pelvic MRI, HSG
Clinical presentation and examination: Patients with a variant of a unicornuate uterus without obstructed uterine remnants are not likely to present with symptoms during their adolescent years. Physical examination will show a normal vagina and cervix and a relatively smaller uterine body deviated toward one side. The contralateral uterine remnant may be diagnosed as an ovarian or other adnexal mass on US; therefore pelvic MRI can be valuable to clarify the anatomy. Unicornuate variants can also be diagnosed during pregnancy and lead to preterm labor, malpresentation (i.e., breech presentation), and recurrent pregnancy loss.
Differential diagnosis:
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Uterus didelphys with obstructing longitudinal vaginal septum (obstructed hemivagina and ipsilateral renal anomaly [OHVIRA])
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Bicornuate uterus with two cervices (bicollis) with obstructing longitudinal vaginal septum
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Complete septate uterus with obstructing longitudinal vaginal septum
Management/treatment options:
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Renal US (40% association of renal anomalies with unicornuate uterus)
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Surgical resection of the noncommunicating uterine remnant without functional endometrium is not necessary in asymptomatic patients
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Surgical resection of small functional communicating uterine remnant may be necessary to prevent pregnancy complications in the rudimentary structure
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Surgical resection or menstrual suppression in the setting of a symptomatic functional uterine remnant (see Chapter 27 )
Essentials of diagnosis and key treatment considerations:
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Asymptomatic clinical presentation in adolescents and young adults with regular menses given no obstructive symptoms.
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Can lead to pregnancy complications, including preterm labor, malpresentation, and recurrent pregnancy loss.
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Associated contralateral uterine remnants do not need to be surgically removed unless symptomatic or concern for pregnancy complications.
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Pelvic MRI or 3D US is important to determine the exact anatomy notable for solitary hemiuterus, cervix, and vagina.
