When the Müllerian ducts don’t regress: A case series on persistent Müllerian duct syndrome

INTRODUCTION

Persistent Müllerian duct syndrome (PMDS) is a rare form of internal male pseudohermaphroditism characterized by the presence of Müllerian duct derivatives – such as the uterus, fallopian tubes, and upper vagina in individuals who are genetically (46, XY) and phenotypically male. It is a congenital autosomal recessive disorder caused by either a deficiency or dysfunction of anti-Müllerian hormone (AMH), also known as Müllerian inhibiting hormone, or mutations affecting the AMH receptor. These abnormalities impair the regression of the Müllerian ducts during fetal development.

Despite having normal male external genitalia and complete virilization, individuals with PMDS retain internal female reproductive structures alongside fully developed Wolffian duct derivatives (e.g., vas deferens, seminal vesicles). Importantly, these patients typically exhibit normal development of secondary sexual characteristics at puberty, and the condition often goes undiagnosed until imaging or surgical exploration is performed for related issues, such as cryptorchidism or inguinal hernia.^[1,2] PMDS usually presents as cryptorchidism or inguinal hernia in a phenotypically normal male. Its significance lies in the risk of infertility, increased malignancy risk, and surgical complexity. This case report highlights the radiological features of PMDS in a virilized male and underscores the importance of imaging in its diagnosis and management.

CASE SERIES

Case 1

A couple, married for 1 year, presented with infertility. Both partners underwent evaluation with blood tests and imaging. All investigations for the female partner were normal. The 27-year-old male was referred to the andrology department. Clinical examination revealed a palpable mass in the left inguinal canal. Both testes were absent from the scrotum, and the scrotal sac was underdeveloped. The penis was normally developed. Hormonal tests showed low testosterone with elevated follicle-stimulating hormone and luteinizing hormone (FSH and LH). Semen analysis revealed azoospermia. Karyotyping confirmed a 46, XY genotype. Pelvic magnetic resonance imaging (MRI) showed a left inguinal hernia containing a uterus-like structure. A homogeneous, ovoid structure, which is isointense on T1 and hyperintense on short tau inversion recovery, consistent with testes, was seen. The findings were consistent with PMDS, specifically the hernia uteri inguinalis type with unilateral absence of testes. The patient underwent excision of Müllerian remnants, gonadectomy, and left inguinal hernia repair. He was started on androgen replacement therapy postoperatively [Figure 1].

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Figure 1:

(a-d) Axial T2 , T1 images, and Axial STIR images of the pelvis show a tubular structure resembling the uterus (yellow arrows) extending into the left inguinal canal, with a T2/STIR hyperintense area in the center corresponding to the endometrium. (e) Ultrasound image of the left inguinal region demonstrates a uterus-like structure with central anechoic content (yellow arrow). (f-g) Axial STIR and T1 images of the pelvis reveal a hyperintense ovoid structure in the pelvis, with no evidence of follicles or mass lesion, consistent with testes (yellow arrows). These imaging findings are suggestive of the male form of PMDS, with a left inguinal hernia containing the uterus and unilateral gonadal agenesis. STIR: Short tau inversion recovery.

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Case 2

A couple married for 2 years presented with infertility. All investigations for the female were within normal limits. The 31-year-old male was investigated in the andrology department. On examination, palpable mass was noted in the bilateral inguinal canals. There are no palpable testes in the scrotum. Penis is normal in size. On further investigation, his testosterone levels were low, and FSH and LH levels were high. Semen analysis showed azoospermia. Karyotyping confirmed 46, XY genotype. On pelvic MRI, a uterus-like structure was noted posterior to the urinary bladder and anterior to the rectum. Bilateral inguinal canals contained small, oval-shaped, homogeneously T2 isointense structures consistent with testicular tissue. Imaging findings were suggestive of female-type PMDS with B/L inguinal hernia containing testes. The patient underwent persistent Mullerian duct remnant excision and B/L gonadectomy, followed by androgen replacement [Figure 2].

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Figure 2:

(a-c) Axial T2 images of the pelvis and Sagittal T2 image of the pelvis show a tubular structure resembling the uterus (yellow arrows) located posterior to the urinary bladder and anterior to the rectum, with central hyperintense content corresponding to the endometrium. (d-e) Axial and coronal T2 images of the pelvis reveal ovoid-shaped, homogeneously T2 hyperintense structures in the bilateral inguinal canals (yellow arrows), with no evidence of follicles or mass lesions, consistent with testes. These imaging findings suggest the female form of PMDS, with bilateral inguinal hernias containing undescended testes. PMDS: Persistent mullerian duct syndrome.

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Case 3

A couple, married for 2 years, presented with an inability to conceive. Both partners were evaluated by blood and imaging. All investigations for females were within normal limits. The 29-year-old male was evaluated in the andrology department. On examination, the penis is normal in size, but no palpable testes in the scrotum. Pubic hairs are sparse. Hormonal evaluation revealed low serum testosterone with elevated FSH and LH levels. Semen analysis showed azoospermia. Karyotyping confirmed a 46, XY genotype. On pelvic MRI, a midline uterus-like structure was seen posterior to the urinary bladder and anterior to the rectum. Bilateral tubular structures, consistent with fallopian tubes, were noted extending laterally from the uterine horn. Bilateral ovoid soft tissue structures, consistent with testes, were seen in the parauterine region; no evidence of follicle-like structure, mass, or altered signal intensity was noted. He underwent persistent Mullerian duct remnant excision, B/L gonadectomy, and androgen replacement therapy [Figure 3].

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Figure 3:

(a-c) Axial T2 image , Sagittal and coronal STIR images of the pelvis show a tubular structure resembling the uterus, with a T2 hyperintense area within, consistent with endometrium, located anterior to the rectum and posterior to the urinary bladder (yellow arrows). (d) Axial T2 image of the pelvis reveals small, ovoid, homogeneously T2 hyperintense structures in the bilateral parauterine region (yellow arrows), with no evidence of follicles or mass lesions. These imaging findings are suggestive of the female form of PMDS. (e) Postoperative gross specimen shows a hypoplastic uterus and bilateral gonadal tissue. PMDS: Persistent mullerian duct syndrome, STIR: Short tau inversion recovery.

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DISCUSSION

PMDS is an uncommon disorder of sexual development where individuals with a male karyotype (46, XY) and normal male external genitalia retain internal female reproductive structures such as the uterus, fallopian tubes, and the upper vagina. This condition results from a failure in the production or action of AMH, which normally induces regression of Müllerian ducts during male embryogenesis. Mutations in the AMH gene (located on chromosome 19) or in the AMH receptor gene (AMHR2 on chromosome 12) are responsible for PMDS, which is most commonly inherited in an autosomal recessive pattern [Figure 4].

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Figure 4:

The flowchart provides an overview of the pathogenesis of persistent Müllerian duct syndrome, where either AMH deficiency or an AMH receptor defect leads to the persistence of Müllerian duct structures such as the uterus, fallopian tubes, and proximal vagina. This also affects the normal descent of testes, resulting in bilateral cryptorchidism. Meanwhile, the presence of testosterone promotes the development of male internal and external genitalia. PMDS: Persistent mullerian duct syndrome.

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PMDS is broadly classified into two anatomical variants: The male type, more frequently observed, typically involves one descended testis with the presence of Müllerian structures in an inguinal hernia sac (hernia uteri inguinalis) or the presence of both testes and Müllerian remnants is located in the same hernial sac (transverse testicular ectopia). In contrast, the female type is less common and features bilateral undescended testes and a uterus that remains fixed within the pelvis.^[2]

MRI serves as a crucial tool in diagnosing PMDS, particularly in cases of undescended testes and infertility. The hallmark imaging finding is a midline soft tissue structure resembling a uterus located between the bladder and rectum, often accompanied by fallopian tube-like structures. Testes may appear small, atrophic and are commonly located in the pelvis or inguinal canals. MRI allows accurate localization of these structures and helps differentiate PMDS from other intersex conditions.^[3-5]

In the three cases discussed, all patients presented with primary infertility, absent testes in the scrotum, low serum testosterone, elevated gonadotropins, and azoospermia. Imaging findings were consistent with PMDS. Case 1 showed features of the male variant with herniation of Müllerian remnants and testicular tissue. Cases 2 and 3 demonstrated features more in line with the female variant, including bilateral cryptorchidism and a midline uterus. One case showed bilateral inguinal testes, while another showed parauterine positioning.

Treatment strategy involves surgical removal of Müllerian remnants to reduce the risk of malignancy, which can occur in approximately 18% of patients, particularly in undescended or atrophic testes. Gonadectomy is often performed in adults with non-functional testes, followed by hormone replacement therapy. Fertility potential is usually poor due to testicular dysfunction and azoospermia.^[6]

Although PMDS is rare and likely underdiagnosed, especially in asymptomatic individuals, awareness among clinicians and radiologists is essential. Early diagnosis through imaging, particularly MRI, can aid in appropriate surgical planning and long-term management.

CONCLUSION

Although PMDS is a rare cause of infertility in phenotypic males with bilateral cryptorchidism or inguinal hernia, its recognition is of utmost importance for deciding treatment options. The disruption of the AMH signaling pathway during embryogenesis is identified to be the cause leading failure of regression of Müllerian duct structures. Thus, radiologists should be aware of characteristic imaging findings when evaluating a male with non-palpable testes and azoospermia. This case series highlights the pivotal role of MRI in accurately identifying Müllerian structures and undescended testes, thereby facilitating a definitive diagnosis and guiding appropriate surgical management. This case series highlights the pivotal role of MRI in accurately identifying Müllerian structures and undescended testes, thereby facilitating definitive diagnosis and guiding appropriate surgical management. The role of a radiologist goes further not only in recognizing this condition but also in detecting complications such as malignancy, torsion of retained gonadal tissue. A multidisciplinary approach involving radiologists, urologists, endocrinologists, and surgeons is critical for optimal patient outcomes.

TEACHING POINTS

1. Recognition of Müllerian structures in a phenotypic male

   • Ultrasound, CT, or MRI may unexpectedly reveal a uterus and fallopian tubes in a patient with a 46, XY karyotype and normal male external genitalia.

   • On MRI, a midline uterine structure may be seen posterior to the bladder and anterior to the rectum, often associated with undescended testes.

   • This is a key to avoid misinterpretation as a pelvic mass.

2. Association with undescended testes

   • Radiology often identifies cryptorchidism (commonly intra-abdominal testes) tethered by Müllerian remnants.

   • Recognition is important because these testes have an increased risk of malignancy, and surgical management is complicated by adherence to Müllerian structures.

MCQs

1. PMDS most commonly presents with:

   1. Ambiguous genitalia

   2. Bilateral inguinal hernia or cryptorchidism

   3. Primary amenorrhea

   4. Gynecomastia

   Answer Key: b

2. The underlying genetic cause of PMDS is usually due to:

   1. Mutation in the SRY gene

   2. Mutation in the AMH or AMH receptor gene

   3. Mutation in the androgen receptor gene

   4. Extra X chromosome (Klinefelter’s syndrome)

   Answer Key: b.

3. Which of the following is a significant clinical implication of PMDS?

   1. Increased risk of ovarian carcinoma

   2. Infertility and risk of testicular malignancy

   3. Early puberty

   4. Absence of secondary sexual characteristics

   Answer Key: b