Persistent Mullerian Duct Syndrome Type II A Case Report and Fertility Challenge H Palawan, S Al Thakafi, S Coskun, N Al Hathal King Faisal Specialist Hospital and Research Centre Riyadh, Saudi Arabia Abstract Persistent Mullerian Duct Syndrome Type II (PMDS Type-II) is a rare, autosomal recessive disorder of sex development, of male pseudohermaphroditism, characterized by the persistence of mullerian duct derivatives: uterus, fallopian tubes and upper vagina. Anti-mullerian hormone (AMH) is a glycoprotein produced by Sertoli cells plays a key role in male sexual differentiation. In male fetuses, AMH is responsible for regression of the mullerian duct derivatives. Mutations of the gene or the receptor of AMH are responsible for clinical symptoms of PMDS, with subjects having a 46XY karyotype and a male phenotype. PMDS is normally encountered unexpectedly during surgery for cryptorchidism or inguinal hernia. Imaging techniques such as MRI and tomodensidometry can detect such cases before the patient is scheduled for surgery. Untreated or late treatment results in infertility and germ cell malignancy. Fertility is still uncertain and a challenge for these patients. Case Presentation Hormonal Profile 23 years old male patient, presented with history of bilateral undescended testes(UDT). No other urological complaint. On Examination Phenotypically male patient, with male pattern of external genitalia and secondary sexual characteristics Scrotum underdeveloped MRI report from his local hospital showed only bilateral UDT finding and a repeat MRI at our institution revealed the mullerian structures: upper vagina, uterus, fallopian tubes and ovotestes . Patient’s brother died due to testicular malignancy, had same clinical presentation. No history of medication during pregnancy Laboratory Findings Karyotypically 46 XY male patient Semen analysis (IVF-Lab) : Azoospermia High FSH, LH and normal Testosterone Table 1. Hormones level pre and post surgery Hormones Pre Surgery Post Surgery Normal Level Estrogen (E2) pmol/L 101 <18.4 28-156 Follicle Stimulating Hormone IU/L 19.2 98.9 1.5-12.4 Luteining Hormone IU/L 16 49.9 1.7-8.6 Testesterone nmol/L 18.38 0.909 9.9-27.8 Prolactin µg/L 22.88 17.3 4.1-18.4 Discussion Y chromosome (Yp) undifferentiated testis Surgical Management SRY Determinant Left testis/ovotestis was fixed near the anterior pelvic ring due to short spermatic cord. Orchiectomy of right testicle. Hysterectomy along with complete removal of other mullerian structures. Left testicular biopsy, right testicle, uterus and other structures submitted for histopathology evaluation. Tissue samples of right and left ovotestes sent to IVF lab for processing and assessment. embryonic testis Testosterone (leydig cells) AMH (Sertoli’s Cell) Wolffian duct stabilization. Persistence of Seminal vesicles, vas deferens epididymis. Regression of Mullerian Structures: uterus. Fallopian tubes and vagina Genital virilization, penis Labiosacral fusion Fig.3 Gonadal differentiation Fig.2 Action of SRY and AMH. Conclusion Bilateral undescended testes with male genitalia is a criteria that suggest Disorders of Sex Development (DSD). Mismanagement and care of this patient at birth can be multifactorial. Infertility as a life event is closely associated with PMDS. Patient had unrealistically hoped for a fertile life after the surgery. Patient’s autonomy and personhood was respected by the medical team. Health care professionals faced with a patient with genital ambiguity must be conscious of the importance of their role in a situation that is still surrounded by prejudice and stigma, and which has serious medical, psychological and social implications. Early diagnosis is crucial for early management(during childhood) in terms of prevention of malignancies and fertility preservation. Fig.1 Surgical Management of PMDS OT: Ovotestes; U: Uterus V: Vagina FT: Fallopian tube Post- Surgical Laboratory Findings IVF-Lab: No sperm or immature sperm cells identified after biopsy processing. Left testicular biopsy: Hyalinized seminiferous tubules with intratubular germ cell neoplasia(IGCN). No evidence of spermatogenesis. Right testis, orchidectomy:Mixed germ cell-sex-cord stromal tumor with focal invasion and IGCN present. Uterus: Benign endometrium and myometrium. Negative for malignancy.