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Persistent Müllerian duct syndrome — a rare but important cause of male factor infertility

Nature Reviews Urology (2025)Cite this article

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Abstract

Persistent Müllerian duct syndrome (PMDS) is a rare difference of sex development, characterized by the presence of Müllerian duct derivatives in 46,XY individuals with male-typical development. PMDS typically presents during childhood with features of cryptorchidism, inguinal hernia or transverse testicular ectopia. Untreated PMDS is associated with risks of infertility and malignancy. Infertility is common, arising from cryptorchidism, anatomical malformations (such as epididymal aplasia) or extrinsic compression of the ejaculatory duct by Müllerian structures. At the time of diagnosis, just one in five men with PMDS are reported to have conceived naturally. Preservation of fertility potential requires prompt diagnosis and management via a holistic patient-centred approach that addresses the underlying cause. With cryptorchidism, which is a common manifestation of PMDS, early orchidopexy is the key initial intervention. The input of fertility specialists and assisted reproductive techniques can further support successful conception. Beyond its effects on fertility, PMDS carries a risk of malignant transformation in the testes and Müllerian structures, warranting complex management with inclusion of a multi-disciplinary team and consideration of orchidopexy, orchidectomy, excision of Müllerian remnants and onward surveillance. Thus, although rare, PMDS is an important cause of male factor infertility that might be encountered by urologists. Preservation of fertility potential requires a high index of clinical suspicion and timely intervention. Raising awareness of PMDS among clinicians is crucial to improve its detection, advance its clinical management and provide a basis for future research.

Key points

  • Persistent Müllerian duct syndrome (PMDS) most commonly presents in childhood, with non-specific features of cryptorchidism, inguinal hernia or transverse testicular ectopia.

  • PMDS is a rare but important cause of male factor infertility that requires a high index of suspicion for early detection and timely management.

  • In addition to its effects on male fertility, PMDS also risks malignant transformation of the testes and/or Müllerian duct derivatives.

  • Consensus is lacking regarding the optimal approach to the investigation and management of PMDS.

  • The current evidence base is limited by the low numbers of cases reported in the literature and lack of follow-up studies; in the future, global clinical databases could promote and support research.

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Fig. 1: Physiological and PMDS sexual differentiation.
Fig. 2: Anatomical classifications of persistent Müllerian duct syndrome.

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Authors and Affiliations

  1. Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, UK

    Michael George, Alexander Lewis, Ian Pearce, Theodora Stasinou & Vaibhav Modgil

  2. Manchester Andrology Research Collaborative, Manchester, UK

    Michael George, Susan Wong, Ian Pearce, Theodora Stasinou & Vaibhav Modgil

  3. Solihull Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

    Susan Wong

  4. Developmental Biology and Medicine, School of Medical Sciences, University of Manchester, Manchester, UK

    Raj Mathur, Nikolaos Tsampras, Alexander Lewis, Ian Pearce, Theodora Stasinou & Vaibhav Modgil

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M.G. and S.W. researched data for the article. All authors contributed substantially to discussion of the content and contributed to the writing, review and editing the manuscript before submission.

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George, M., Wong, S., Mathur, R. et al. Persistent Müllerian duct syndrome — a rare but important cause of male factor infertility. Nat Rev Urol (2025). https://doi.org/10.1038/s41585-025-01108-5

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