Congenital anomalies of the uterus may be asymptomatic and unrecognized, or present clinically during puberty due to amenorrhea or childbearing years due to infertility or recurrent miscarriage. The Obstetrician/Gynecologist evaluating a patient in either clinical scenario takes a detailed history, performs a pelvic examination, and orders laboratory tests including a comprehensive hormonal profile. Imaging modalities available for evaluation include ultrasound and Hysterosalpingogram (HSG), but ultimately, the non-invasive diagnostic gold standard, especially for complex cases, is Magnetic Resonance Imaging (MRI) [1] because of its superior level of soft tissue detail.

If a congenital anomaly is present, the primary goal of MRI is to classify the malformation into one of the seven classes (I-VII) of Mullerian Duct Anomalies (MDA) outlined in 1988 by the American Fertility Society (Figure 1) [2], because classification directs treatment. Occam’s razor, the idea that simplest explanation is usually the correct one, is an important idea in medicine. However, the cases presented in this pictorial review run counter to this cherished principle and provide a useful reminder that classification, in some cases, may be impossible.

Figure 1: Classification system of mullerian duct anomalies developed by the American Fertility Society (now the American Society of Reproductive Medicine) [2].

Robins et al. have described the embryologic development of the mullerian ducts as a three-stage process, which is completed by week twelve of gestation [3]; first, ductal development, with errors and/or interruptions during this phase yielding class I MDAs; second, ductal fusion, with errors and/or interruptions during this phase yielding class II-IV MDAs; and third, septal reabsorption, with errors and/ or interruptions during this phase yielding class V and VI MDAs. Specifically, the bidirectional theory of septal regression posits that septal resorption progresses in both the cranial and caudal directions simultaneously, thus providing a possible embryological mechanism to explain some of the more complex mullerian duct anomalies presented in this pictorial review [4]. Maternal ingestion of Diethylstilbestrol (DES) (late 1940s-1971) during first trimester of pregnancy led to birth of daughters with class VII MDAs, among other problems [5].

Mullerian duct anomalies are associated with other congenital anomalies, such as abnormalities of the renal and skeletal system. Renal anomalies include agenesis, duplication, ectopia, fusion, hypoplasia, and malrotation [6]. Reported skeletal anomalies include spina bifida and vertebral body abnormalities [7]. In addition to such associated anomalies, which have their own set of complications, patients with mullerian duct anomalies may suffer not only from obstetrical complications such as recurrent miscarriage, but an also chronic issue such as endometriosis, as Figure 4 demonstrates.

While the true incidence of mullerian duct anomalies is difficult to determine, it is estimated that they occur in 2-4% of fertile women with normal reproductive outcomes, but with a higher incidence among women with infertility (range, 5-25%) [4,8]. For example, in a recent analysis of 94 observational studies including nearly 90,000 women all together, Chan et al report the prevalence of uterine anomalies in the general asymptomatic population to be 5.5%, in contrast to 8.0% in a population of infertile women, 13.3% in women with a history of miscarriage and 24.5% in those with miscarriage and infertility [9]. However, a small percentage of MDA anomalies seemingly appear defy classification into the traditional I-VII categories, as this pictorial review will now go on to demonstrate.

Cases 1-4: diagnosis in the teenage years

A 17 year-old female was referred to our institution with primary amenorrhea. MRI (Figure 2) demonstrates absence of the uterus and upper two thirds of the vagina; only a small undifferentiated soft tissue remnant within the lower third of the vagina above the introitus is present, consistent with a vestigial sinovaginal bulb. The kidneys were normal in size and location. Thus, this patient has aspects of both a class Ia (vaginal hypoplasia/agenesis) and class Ic (uterine agenesis) MDA. In conjunction with a normal female phenotype and karyotype, these findings are compatible with Mayer Rokitansky Kuster Hauser (MRKH) Syndrome, a rare disorder characterized by congenital aplasia of the uterus and upper two thirds of the vagina in 46 XX phenotypically normal females. MRKH type I demonstrates isolated aplasia of the uterus and upper part of the vagina, as in this case, but is more frequently associated with renal, vertebral, and, to a lesser extent, auditory and cardiac defects (MRKH type II) [10-12]. For this patient, surgical creation of a neovagina is a possibility.

Figure 2: 17 year-old female with primary amenorrhea. a) Sagittal T2-weight MR image demonstrates no evidence of a uterine corpus with only a vestigial cervix (short arrow) and absent vagina (long arrow) evident. b) Axial T2-weight MR image shows a small undifferentiated soft tissue remnant within the lower third of the vagina above the introitus (arrow), consistent with a vestigial sinovaginal bulb.

In contrast, MRKH II is demonstrated in Figure 3, images from a 13 year-old amenorrheic female with prenatal history of left-sided hydronephrosis, diagnosed postnatally as a nonfunctioning left ectopic pelvic kidney. MRI demonstrates two divergent uterine converging in the midline but not communicating. In the anticipated site of the cervix, only undifferentiated soft tissue is seen, and the upper vagina is atretic. Thus, this patient had elements of a class Ia and Ib (hypoplasia/agenesis involving both the vagina and cervix) and class IVa (bicornuate, complete) MDA. In conjunction with the history of a nonfunctioning left ectopic pelvic kidney, these findings are most consistent with MRKH, type II variant [10-12].

Figure 3: 13 year-old female with primary amenorrhea and prior left nephrectomy for a nonfunctioning pelvic kidney. a) Axial oblique MR image demonstrates bilateral divergent uterine horns with noncommunicating endometrial segments (double arrow) with undifferentiated soft tissue at the anticipated site of the cervix (single arrow). b) Axial T2 weighted-MRI image demonstrates an atretic upper vagina (arrow) as well.

Another 13 year-old female with primary amenorrhea was referred to our institution and evaluated with MRI. Figure 4 demonstrate a blind-ending unicornuate configuration with hematometra, with the lower uterine segment abutting the medial wall of the cervix without communication. A rudimentary horn with noncommunicating endometrial segment distended with blood is also present. The cervix is normal in configuration with the superficial margin ending blindly at the level of the internal os. Thus, this patient had elements primarily of a class IIb (unicornuate, noncommunicating) MDA, but the dissociation of the uterine corpus from the uterine cervix with no communication of the endometrial and endocervical cavities was beyond classification, and surgically-proven.

Figure 4: 13 year-old female with primary amenorrhea. a) Coronal oblique T2-weighted and b) axial T2-weighted MR images demonstrates a unicornuate uterine configuration (thin arrows) with an associated obstructed rudimentary horn with a non-communicating endometrial segment (thick arrows); there is dissociation of the uterine corpus from the uterine cervix (dotted arrow) with no communication of the endometrial and endocervical cavities. A hematosalpinx (dashed arrow) is also present.

Hematometra secondary to outflow track obstruction is also seen in Figure 5, however in this case due to a complex congenital anomaly involving vaginal agenesis. This was also a young female (11 years-old) with primary amenorrhea, with MRI demonstrating a right unicornuate uterus with large associated hematometros. A left rudimentary horn with endometrial segment is present but does not communicate with right unicornuate uterus. Agenesis of the vagina without soft tissue remnant was identified. Thus, this patient had elements of both a class Ia (vaginal agenesis) and a class IIb (unicornuate, noncommunicating) MDA. The patient was initially treated medically with the Gonadotropin-releasing hormone agonist Lupron, with the goal of suppressing the menstrual cycle to prevent retrograde menstruation and the development of endometriosis; she was then lost to follow-up.

Figure 5: 11 year-old female with primary amenorrhea. a) Short axis T2 oblique and b) axial T2-weighted MR images demonstrates an obstructed right unicornuate uterus secondary to an atretic/absent upper vagina (long thinner arrows); a rudimentary horn is also present, with noncommunicating endometrial segment displaced anteriorly (short thick arrow). c) Axial T2 weighted MR image demonstrates a Foley catheter in the urinary bladder, with arrow pointing to anticipated site of the vagina, which is atretic/absent.

Cases 5 and 6: diagnosis during infertility workup

A 26 year-old female with multiple failed IVF cycles and ultrasound suggesting a uterine anomaly was referred for MRI (Figure 6), which demonstrates the uterus to have a complete septum as well as focal duplication of the cervix at the level of the external os. In addition, a blind-ending, tubular left Wolffian duct remnant extending to the level of the atretic/absent vagina along the left pelvic sidewall is seen. Thus, this patient had elements of both a class Va (septate, complete) and class III (didelphus) MDA; the wolffian duct remnant was beyond classification, but confirmed surgically when reunification of uterine cavity space with septal resection was attempted.

Figure 6: 26 year-old female status post multiple failed IVF cycles. a) Short axis T2 oblique and b) axial T2-weighted MR images demonstrates an obstructed right unicornuate uterus secondary to an atretic/absent upper vagina (long thinner arrows); a rudimentary horn is also present, with noncommunicating endometrial segment displaced anteriorly (short thick arrow). c) Axial T2 weighted MR image demonstrates a Foley catheter in the urinary bladder, with arrow pointing to anticipated site of the vagina, which is atretic/absent.

Detection of a mullerian duct anomaly, straightforward or complex, does not necessarily preclude the possibility of future successful pregnancy. The 29 year-old female with unexplained infertility in Figure 7 had an MRI demonstrating a right unicornuate configuration (volume = 50 cc) with evidence of a small rudimentary horn without an associated endometrial segment. The rudimentary horn is in continuity with an undifferentiated mullerian duct remnant which tracks laterally up the left pelvic sidewall. Thus, this patient had elements of a class IIc (unicornuate, no cavity) MDA as well as an undifferentiated mullerian duct remnant which defies classification. However, the uterine volume was considered potentially sufficient for pregnancy, and the patient is pursuing IVF.

Figure 7: 29 year-old female with unexplained infertility. A) Oblique and b) coronal T2-weighted MR images demonstrate a right unicornuate uterine configuration (short arrows) and an associated undifferentiated mullerian duct remnant tracking up the left pelvic sidewall (long arrow).

In conclusion, when the complex mullerian duct anomalies presented here are considered together, they provide the important reminder that classification, in some cases, is impossible. As Behr et al. write in their recent review, “even with today’s state-of-the-art imaging techniques, classification of MDAs may be challenging; when a specific designation cannot be made, it is best to describe the anatomy rather than to force the MDA into a category” [1]. In such clinical scenarios, albeit rare, a careful description of morphology, in conjunction with an interdisciplinary review of the actual images, may be the best course of action in order to optimize the care of these complex patients.