Müllerian duct anomalies and renal malformations: from clinical suspicion to advanced diagnostic strategies

Introduction

Müllerian duct anomalies cover a broad spectrum of faulty development, fusion, or incomplete septal resorption during fetal life. The Müllerian (or paramesonephric) ducts are the primary components of the female genital tract, which comprise the fallopian tubes, uterus, cervix, and the upper two-thirds of the vagina. Given the vagina’s dual origin, the upper two-thirds arise independently from the Müllerian ducts, while the lower third comes from the urogenital sinus⁽¹⁾. Uncertainty surrounds the prevalence of Müllerian duct anomalies, which range from 1.5 to 6.7% of the general population to 24.5% of infertile patients or those with a history of spontaneous abortion.

Diagnosis

There are several methods for diagnosing Müllerian anomalies. Clinical history and examination can raise suspicions. Obstructive Müllerian anomalies may present in newborns as a palpable pelvic mass or at menarche with cyclic pelvic pain, a pelvic mass, and primary amenorrhea. Complications include hematocolpos, hematometra, hematosalpinx, endometriosis (due to retrograde menstruation), pelvic adhesive disease, and acute urinary retention⁽²⁾. Imaging exams like pelvic ultrasound, which can only evaluate the vagina and cervix and identify a rudimentary horn in a unicornuate uterus, can complement these. Hysteroscopy and laparoscopy have been considered the gold standard for final diagnosis, but they are invasive methods, so it is recommended to replace them with magnetic resonance imaging (MRI), especially in patients who are not sexually active, with a reported diagnostic accuracy of nearly 100%. Recent advances in pediatric pelvic MRI imaging include faster sequences, isotropic volumetric image acquisition, and higher field strengths (3 Tesla)⁽³⁾.

Patients with Müllerian anomalies should have their kidneys and renal collecting systems evaluated, as up to 40% present with concomitant renal anomalies. Common associated anomalies include unilateral agenesis, ectopia, renal hypoplasia, multicystic dysplastic kidney, and hydronephrosis. A rapid spin-echo sequence, which provides a large field of view in the coronal plane and captures the renal fossae, ureters and bladder, can perform such evaluation. We also discuss and illustrate a variety of Müllerian anomalies and mimics in pediatric patients in terms of clinical features, imaging, and management, as defined by the American Society for Reproductive Medicine⁽⁴⁾.

Classification

There is considerable controversy regarding the classification and nomenclature of Müllerian anomalies. The American Fertility Society (AFS) developed the most widely accepted classification system in 1988. The American Fertility Society groups anomalies are based on their similar uterine anatomy and their impact on pregnancy outcome and fetal survival. This system classifies anomalies into seven major types of uterine anatomy, with additional subdivisions. Given the absence of standardized terminology, it is crucial for surgeons and radiologists to communicate and conduct common case reviews to make appropriate clinical decisions and prevent terminological inconsistencies from leading to incorrect decisions or management differences. However, critics point out that the AFS classification primarily focuses on uterine anomalies, excluding those of the vagina and cervix, lacks clear diagnostic criteria, and fails to classify complex malformations. Consequently, Müllerian anomalies may remain undiagnosed for extended periods, receive inadequate surgical interventions, and result in persistent issues such as pain or loss of reproductive function. To design a new classification, the American Society for Reproductive Medicine formed the Task Force on Müllerian Anomaly Classification. The AFS classification no longer uses numbers to identify the categories, instead using descriptive terminology in nine major categories⁽⁵⁾. We present hereinafter the most frequent Müllerian anomalies in children.

Class 1: Uterine agenesis/hypoplasia

The failure of the Müllerian ducts to develop around 5 weeks of gestation causes uterine agenesis or hypoplasia, which results in varying degrees of agenesis or hypoplasia of the upper two-thirds of the vagina, cervix, or uterus⁽⁶⁾.

Mayer-Rokitansky-Küster-Hauster (MRKH) type 1: this severe form of the anomaly involves complete agenesis of the uterus, cervix, and proximal two-thirds of the vagina. Because normal ovaries are usually present, this disorder is characterized by a normal female phenotype, but with primary amenorrhea during adolescence⁽⁶⁾. The presence or absence of functional uterine remnants determines the symptoms. During puberty, primary amenorrhea is a sign of complete agenesis. On the other hand, primary amenorrhea and severe cyclic abdominal pain due to cryptomenorrhea and hematometra are signs of a functional remnant⁽²⁾.

The therapeutic management consists of correcting the anatomical anomaly, along with patient and parental counseling. Some patients with MRKH choose to create a vagina, with vaginal dilation being the preferred method. Whether a functional Müllerian remnant is “communicating” or not, one can initiate medical suppression of menstruation, followed by laparoscopic removal of the hypoplastic remnant. The surgical management is mandatory due to the potential for pregnancy in the rudimentary horn, which can have catastrophic consequences⁽²⁾.

Class 2: Unicornuate uterus

The unicornuate uterus accounts for 20% of all uterine anomalies and results from incomplete or absent development of one of the paired Müllerian ducts. In 40% of patients, this type of abnormality is linked to renal abnormalities, especially ipsilateral renal agenesis of the rudimentary or absent horn⁽⁶⁾.

The symptoms depend on the presence or absence of a noncommunicating functional rudimentary horn. If a noncommunicating functional rudimentary horn is absent, the diagnosis is usually incidental or made during the investigation of infertility or surgical interventions (e.g., caesarean section). If present, symptoms generally appear at menarche, with adolescents presenting with dysmenorrhea and hematometra. Some gynecological problems that can happen with a unicornuate uterus are ectopic pregnancy (when sperm moves through the peritoneum) and endometriosis (when periods move backwards). Obstetric complications frequently include abnormal fetal positioning, intrauterine growth restriction, and preterm birth⁽²⁾.

Management: a unicornuate uterus with a nonfunctional rudimentary horn does not require surgical intervention. People who have a functional horn that doesn’t communicate are thought to have the rudimentary horn cut out using laparoscopy or laparotomy (pregnancy can happen in a unicornuate uterus no matter what the communicating status is⁽²⁾.

Class 3: Uterus didelphys

Uterus didelphys happens when the Müllerian ducts don’t fuse. It appears in about 5% of cases and is marked by having two uterine cavities that don’t connect to each other and two openings⁽⁶⁾. It is not uncommon for some of these patients to present with an obstructed hemivagina and associated ipsilateral renal agenesis, known as the OHVIRA syndrome or Herlyn-Werner-Wunderlich syndrome (HWW)⁽⁷⁾.

The presence of an obstruction causes the symptoms. Nonobstructive uterine didelphys is typically asymptomatic, being diagnosed incidentally. People who have an obstructed uterus didelphys and a hemivagina start to have symptoms at puberty. They have cyclic pelvic pain (dysmenorrhea), which happens at the same time as their period from the side that isn’t blocked. This obstruction can cause retrograde menstrual flow, explaining the increased prevalence of endometriosis and pelvic adhesions in affected patients. Obstructive anomalies with a vaginal septum present as a bulging mass in the vagina on digital vaginal examination or speculum use. This condition is linked to a spontaneous abortion rate of 23%⁽²⁾.

The management depends on the presence or absence of an obstruction. It is preferable to surgically remove the vaginal septum to alleviate an obstruction. You can also remove a nonobstructive vaginal septum, which typically doesn’t interfere with sexual activity or childbirth. Patients with uterus didelphys and a hypoplastic cervix can benefit from a simple and effective laparoscopic hemihysterectomy, but it’s still advisable to avoid it due to the equal incidence of pregnancies in both uterine cavities. We recommend ipsilateral hysterectomy in cases of cervical atresia complications, as septum resection will not relieve obstructive symptoms⁽⁸⁾.

Class 4: Bicornuate uterus

A bicornuate uterus accounts for approximately 10% of uterine anomalies and can present with or without cervical duplication⁽⁶⁾.

Clinical characteristics: women with a bicornuate uterus have a higher prevalence of pregnancy loss but are asymptomatic. Because these women have fewer reproductive issues than those with other anomalies, the pathological condition may remain undiagnosed until caesarean delivery. Imaging for other indications may also incidentally identify it. Spontaneous abortion rates range from 28% to 35%, and preterm birth rates range from 14% to 23%⁽²⁾.

Management: a bicornuate uterus does not require surgical intervention⁽²⁾.

Class 5: septate uterus

The septate uterus represents the most common type of uterine anomaly, accounting for more than 50% of cases. The fibrous, or fibromuscular, septum can be partial or complete⁽⁶⁾.

Clinical characteristics: higher prevalence of pregnancy loss; otherwise, generally asymptomatic. Patients with a complete septum may present with unilateral obstruction, dysmenorrhea, normal menstruation, and an increased risk of endometriosis. A septate uterus is often associated with poor reproductive outcomes. Fetal survival rates range from 10% to 75%, preterm birth rates range from 9% to 33%, and spontaneous abortion rates range from 26% to 94%⁽²⁾.

Hysteroscopic resection of the septum can effectively treat this condition, resulting in improved obstetric outcomes. According to Homer, the percentage of full-term births increased from 3% before septum resection to 80% after the procedure⁽²⁾.

Results

The study included 16 patients, aged between 7 and 15 years old (mean age: 12.2 years old). Of these, the ACS classified five patients as having MRKH syndrome (Class 1), 10 patients as having HWW syndrome (Class 3), and a single patient as belonging to Class 4. Clinical manifestations were evident in only 11 of the patients, and associated malformations included renal anomalies (16/16 patients), skeletal anomalies (3/16 patients), and other anomalies (3/16 patients). Ten out of 16 patients underwent surgical treatment, while only four patients received psychological counselling either before or after the diagnosis (Tables 1 and 2).
 

Conclusions

Understanding genitourinary embryology is critical for the comprehension, study, diagnosis, and subsequent treatment of genital malformations, particularly the complex ones that lead to gynecological and reproductive issues, especially in young patients. We should consider all the current concepts regarding imaging and therapeutic management, and it may be time to unify all these efforts and knowledge to find a therapeutic management plan that satisfies all prerequisites, both in the short and long term.

We recommend imaging investigations like MRI to characterize Müllerian anomalies and evaluate the possibility of vaginal anomalies, thereby defining their type to inform management strategies and preoperative planning. The 3D Tesla MRI model is an additional cost-effective software tool that enhances the surgeon’s capability to achieve a more accurate diagnosis of pelvic anatomical structures compared to MRI alone. Obtaining a more precise description of pelvic anatomy allows for better planning of the necessary corrective procedure and preoperative evaluation of the expected prognosis.

Because the paramesonephric and mesonephric ducts are so close to each other in embryology, renal tract problems are linked to Müllerian anomalies in up to 30% of cases. Therefore, it is imperative to investigate the renal system in all patients presenting with Müllerian anomalies. Renal agenesis is the anomaly most commonly associated with Müllerian anomalies, but reports also include reno-pyelo-ureteral duplications, horseshoe kidneys, crossed renal ectopia, and cystic renal dysplasia.

Finally, we must not forget the psychological, cognitive, and psychosocial impact on patients as they progress through psychoemotional maturity. 

Autor corespondent: Ovidiu Bîcă E-mail: ovidiu-daniel-c-bica@umfiasi.ro

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

This work is permanently accessible online free of charge and published under the CC-BY.