Mullerian ducts anomaly of 2 divergent uterine horns with cervicovaginal hypoplasia: Is it considered unclassified or under the spectrum of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome?

A 25-year-old woman with a history of primary amenorrhea went to the OB/GYN outpatient clinic in 2017 and had a transabdominal US ( Fig. 1 ) and pelvic MRI, which revealed MDA. However, she reported 2 episodes of blood spotting/menstruation at the age of menarche, around 13 years old. Fig. 1 Transabdominal ultrasound in 2017 and 2023 done for the patient demonstrating similar findings. (A) show widely separated 2 uterine horns with normal myometrial echogenicity and central thin echogenic endometrial stripe on either side (White arrows). (B) On the longitudinal view, no cervix or upper vagina could be seen. (C) show bilateral normal appearing ovaries containing physiological follicles (White arrows). No abnormal pelvic masses. Fig 1 Transabdominal ultrasound in 2017 and 2023 done for the patient demonstrating similar findings. (A) show widely separated 2 uterine horns with normal myometrial echogenicity and central thin echogenic endometrial stripe on either side (White arrows). (B) On the longitudinal view, no cervix or upper vagina could be seen. (C) show bilateral normal appearing ovaries containing physiological follicles (White arrows). No abnormal pelvic masses. Then, she returned to the obstetric clinic in 2022, married for the second time since 2019 with a history of primary infertility and seeking pregnancy. On examination, the patient is skinny and has normally developed secondary sex characteristics with normal breast tissue, normal hair growth, and marked body acne. There were no palpable abdominal masses. Local and vaginal speculum examination show normal external genitalia, blind vagina, and normal vaginal length with a small cervical dimple on the left posterior wall of the vagina. During the bimanual exam, the uterus was not palpable. The patient has had regular sexual intercourse without any issues and was medically free. There was no significant past surgical history apart from a diagnostic laparoscopy in the USA in 2019. This laparoscopy revealed no cervix, blind vagina, separated didelphys uterus, hypoplastic/absent cervix, and stage 1 endometriosis. She also had 3 trials of IVF, which failed twice in 2019 through trans-tubal ET and once in 2020 through transvaginal trans-myometrium ET. She has had normal laboratory investigations, including TSH, LH, FSH, estradiol, progesterone, and testosterone levels. In January 2023, the patient had another pelvic US and MRI ( Fig. 2 ), demonstrating the same findings in 2017 of 2 widely separated noncommunicating uterine horns with preserved normal zonal anatomy and a normally appearing endometrial cavity. There is a rudimentary tissue or band of low signal intensity in T2 and T1 located in the midline converging between the uterine horns and extends along the expected location of the cervix and upper two-thirds of the vagina representing the hypoplastic cervix and upper vagina. The lower one-third of the vagina and ovaries are normal. The kidneys are in their normal location, with no identifiable renal anomalies. Fig. 2 Magnetic resonance imaging of the pelvis confirming the ultrasound findings with additional details. Non-fat sat axial T2 weighted images (A, B). (A) show 2 widely separated uterine horns (White circles) with well appreciated normal zonal anatomy and normally appearing non-communicating endometrial cavities of high signal intensity. (B) At lower level there is a dark signal intensity band/tissue at expected location of the lower uterine segment and cervix (Yellow arrow) and normal lower one-third of the vagina (White arrow). (C) Non-fat sat sagittal T2 weighted image shows the poor anatomical differentiation and development of the cervix/upper vagina (Yellow arrow) and the present lower vagina (White arrow). A thin dark T2 signal intensity fibrous band between the 2 horns converging into midline was seen (not shown here). (D) Coronal fat sat T2 weighted image shows bilateral normal ovaries with multiple physiologic follicles. (E) Non-fat sat coronal T2 HASTE shows normal kidneys are present in its anatomical position. Fig 2 Magnetic resonance imaging of the pelvis confirming the ultrasound findings with additional details. Non-fat sat axial T2 weighted images (A, B). (A) show 2 widely separated uterine horns (White circles) with well appreciated normal zonal anatomy and normally appearing non-communicating endometrial cavities of high signal intensity. (B) At lower level there is a dark signal intensity band/tissue at expected location of the lower uterine segment and cervix (Yellow arrow) and normal lower one-third of the vagina (White arrow). (C) Non-fat sat sagittal T2 weighted image shows the poor anatomical differentiation and development of the cervix/upper vagina (Yellow arrow) and the present lower vagina (White arrow). A thin dark T2 signal intensity fibrous band between the 2 horns converging into midline was seen (not shown here). (D) Coronal fat sat T2 weighted image shows bilateral normal ovaries with multiple physiologic follicles. (E) Non-fat sat coronal T2 HASTE shows normal kidneys are present in its anatomical position.

Written informed consent for the publication of this case report was obtained from the patient.

MDA is widely variable and complex, with similar reported cases having identical findings described and classified differently by the authors. Thus, if the classification is uncertain using the known systems or a combined anomaly exists, it is better to give descriptive anatomical details of the abnormality rather than submitting single or multiple classes. Diagnostic imaging is essential for complete characterization and directs gynecologists’ management plan, especially MRI.

Depending on the present classification systems, we proposed that our case can be classified by the ASRM ( Table 1 and Fig. 3 ) into (class Ie), considering the presence of combined cervical and vaginal hypoplasia with no specific class could be assigned for the divergent uterine horns [ 1 , 3 , 4 ]. By the ESHRE/ESGE ( Table 2 and Fig. 4 ), we classify it as (U5a/b, C4, and V0/4) [ 1 , 3 ]. Table 1 American Society for Reproductive Medicine classification [3] . Table 1 Class Classification Class I Agenesis or hypoplasia – (a–e) (vaginal or cervical or fundal or tubal or combined) Class II Unicornuate – (a–d) (communicating horn or non-communicating horn or no cavity or no horn) Class III Uterine didelphys Class IV Bicornuate uterus (a and b – Complete or partial) Class V Septate uterus (a and b – Complete or partial) Class VI Arcuate uterus Class VII Diethylstilboestrol related Fig. 3 American Society for Reproductive Medicine classification [3] . Fig 3 Table 2 The European Society of Human Reproduction and Embryology and European Society for Gynecological Endoscopy classification (U, uterine; C, cervical; V, vaginal) [3] . Table 2 Uterine anomaly Cervical/Vaginal anomaly Main class Sub-class Coexistent class U0 Normal uterus U1 Dysmorphic uterus U1a - T-shaped uterus C0 Normal Cervix U1b - uterus infantile C1 Septate U1c - others C2 Double “normal” U2 Septate uterus U2a - partial septate uterus C3 Unilater aplasia or dysplasia U2b - complete septate C4 Aplasia or dysplasia U3 Bicorporeal uterus U3a - partial bicorporeal U3b - complete bicorporeal U3c - bicorporeal septate uterus V0 Normal vagina U4 Hemi-uterus U4a - – hemi-uterus with a rudimentary (functional) cavity V1 Longitudinal nonobstructing vaginal septum U4b - – hemi-uterus without a rudimentary (functional) cavity V2 Longitudinal obstructing vaginal septum U5 Aplastic uterus U5a - aplastic uterus with rudimentary (functional) cavity V3 Transverse vaginal septum or imperforate hymen U5b - aplastic uterus without rudimentary (functional) cavity V4 Vaginal aplasia U6 Unclassified cases Fig. 4 . The European Society of Human Reproduction and Embryology and European Society for Gynecological Endoscopy classification [3] . Fig 4 American Society for Reproductive Medicine classification [3] . American Society for Reproductive Medicine classification [3] . The European Society of Human Reproduction and Embryology and European Society for Gynecological Endoscopy classification (U, uterine; C, cervical; V, vaginal) [3] . . The European Society of Human Reproduction and Embryology and European Society for Gynecological Endoscopy classification [3] . While reviewing the literature, we found that some published cases had findings like ours. Although the images are identical in some cases, there was wide variability in describing and classifying the anomalies. Mahdavi et al. [6] published the most similar cases, describing them as uterus dysplasia associated with cervicovaginal agenesis, and the patient was in (class I) of the ASRM and categorized as (U5a/C4/V4) in the ESHRE/ESGE classification [6] . Jegannathan et al. [3] classified a similar anomaly as (U6 – a mix of U3b, U4a, and U5a with C4 and V1/V3) according to the ESHRE/ESGE and (unclassified – Ie, IIb, and III mixed) according to the ASRM. Chandak et al. [7] state that our case could not be categorized into a specific category by the ASRM classification but could easily be categorized using the ESHRE/ESGE classification, which described as (U5a/C4/V4) [7] . Slightly different cases of 2 uterine horns, right rudimentary and left hematometra, with cervical atresia and blind short vaginal pouch, were reported by Dwivedi et al. [2] and classified as (U6/C4/V4) according to the ESHRE/ESGE without a proposed ASRM class. Others, like Bakri et al. [8] and Goluda et al. [9] , described the anomaly as bicornuate, nonfused, separate rudimentary blind uterine horns with functioning endometria and complete cervicovaginal atresia or agenesis [ 8 , 9 ], where they could not assign it to any group of ASRM. Some cases show vaginal or cervicovaginal atresia or agenesis with a normal uterine corpus or bulky uterus containing hemorrhagic endometrial collection and hematocervicometra with an absent vaginal opening [ 5 , 10 ]. Finally, published studies by Boruah et al. [11] and Sugi et al. [1] described similar cases under the spectrum of MRKH syndromes. They noted that most of these patients (92%) have unilateral or bilateral rudimentary uteri, with varying sizes and degrees of differentiation into 3 layers (ie, myometrium, junctional zone, and endometrium) [1] . As in our case, at T2WI, a low signal intensity fibrous band between the 2 horns was seen converging into the midline in these cases [ 1 , 11 ]. Considering this and our proposed classification for our case under (class Ie), according to ASRM, it might be under the broad spectrum of MRKH syndrome. A comparison between these studies revealed that most authors easily and efficiently used the ESHRE/ESGE classification with similarity in the submitted class to their cases. Simultaneously, there was variability in the assigned ASRM classification, and some found it challenging to assign a specific class with this system. Worth mentioning is that some, like Jegannathan et al. and Chandak et al. [ 3 , 7 ], distinctly highlighted the superiority and simplicity of the ESHRE/ESGE classification, which is anatomical and embryological based and includes cervical and vaginal anomalies separately. Mahdavi et al. [6] added that more research projects on the pathophysiological and genetic aspects of these anomalies are required to unify MDA classification. Another point of agreement among all researchers was that MRI had become a crucial and excellent diagnostic tool for those patients which accurately correlated with the surgical findings during exploratory laparotomies and laparoscopies as documented by Bakri et al., Sharma et al. and Boruah et al. [ 8 , 10 , 11 ].

Mullerian duct anomaly (MDA) is a unique entity with a widely variable and complex spectrum of abnormalities. Its prevalence varies substantially according to the population under study, with mean prevalence in the general population up to 7% [ 1 , 2 ] and 25% in women with a history of infertility and miscarriage [1] . There are multiple classification systems in the literature. The most widely used system was published in 1988 by the American Society for Reproductive Medicine (ASRM); it includes seven classes [3] and was updated in 2016 [1] . The other was founded by the European Society of Human Reproduction and Embryology and the European Society for Gynaecologic Endoscopy (ESHRE/ESGE) in 2013, which is anatomy-based, classifying the anomalies according to the morphology of the uterus, cervix, and vagina, independently [3] . Knowledge of the embryology and formation mechanism of the female reproductive system is essential in understanding the pathophysiology of MDA. It originates from different structures; the paired Mullerian ducts give rise to the uterus, fallopian tubes, cervix, and upper two-thirds of the vagina [4] , which undergo specific processes of development, fusion, and resorption. Any failure in the process will lead to MDA. The ovaries and distal one-third of the vagina originate from the primitive yolk sac and sinovaginal bud, respectively [4] . Therefore, MDA is not associated with anomalies of the external genitalia or ovarian development [4] . It can be isolated or associated with different anomalies, especially renal ones. Patients often present with primary amenorrhea, infertility, obstetric complications, and endometriosis [4] . They may also present with obstructive symptoms such as hematometra, hematocolpos, and cyclic lower abdominal pain or may be asymptomatic, depending on the functional status of the endometrium [2] . Imaging has a vital role in the detection, diagnosis, and complete characterization of MDA. Transabdominal and endovaginal US are the first-line modalities [1] . The MRI is the imaging standard of reference because it is noninvasive, does not involve ionizing radiation, has multiplanar capability, allows excellent soft-tissue characterization, and permits a greater interrogation field than ultrasound [ 4 , 5 ]. It enables a detailed anatomical description of the uterus, cervix, vagina, and ovaries [3] in addition to detection of possible associated urological anomalies. MRI has a reported accuracy of up to 100% in evaluating MDA [2] . Hysterosalpingography (HSG) remains the standard modality for evaluating fallopian tube patency in patients with infertility [1] but has a limited role in fully evaluating MDA.