Clinical Manifestations And Mechanisms Of Reproductive Tract Obstruction And Malformation Combined With Adenomyosi

BackgroundCongenital obstructive reproductive tract anomaly is a rare anatomic malformation occurring at different levels from the uterus to the lower vagina,resulting in outflow obstruction.Common types of the disease include Herlyn-Werner-Wunderlich syndrome(HWWS)and unicornuate uterus with a rudimentary horn.Though the pathogenesis remains unclear,it is now generally considered that the anomaly is correlated with deficiency of Mullerian duct development during embryogenesis.Adenomyosis is a common complication of obstructive reproductive tract anomaly.Researches have suggested that the lesions originate from differentiation of pluripotent Mullerian remnants or adult uterine stem cells,meanwhile abnormal local regulation of prolactin and relevant receptors may also be involved.However,due to limited cases and the sporadic characteristic of the disease,systematic reports summarizing clinical features and intensive researches on pathogenesis are quite few.Materials and MethodsIn this retrospective study,17 cases of two types of representative obstructive reproductive tract anomaly(HWWS and unicornuate uterus with a functional rudimentary horn)complicated with adenomyosis,diagnosed by Department of Pathology,Peking Union Medical College Hospital,were included.Clinical data including manifestations,treatment and fertility outcomes were collected.Samples of uterine tissue of patients were obtained.Immunohistochemistry was used to localize a series of markers indicating Mullerian-derived tissue,uterine stem cells and prolactin pathway expression.Comparing with different control groups,expression patterns of these markers were determined,in order to find similarities and differences between patients and normal control.ResultsAll 17 patients include 10 cases of unicornuate uterus with a functional rudimentary horn and 7 cases of HWWS.All patients with obstructive reproductive tract anomaly complicated with adenomyosis were most presented with progressive dysmenorrhea,followed by abnormal uterine bleeding,and some cases may report reduced menstrual flow,which is different from the clinical features of adenomyosis in patients with normal reproductive tract.Endometriosis is the most common complication,and ovarian endometrial cysts all occurred at the same side of obstruction.Adenomyotic lesion most occurred at the obstructive side(94.1%),and the incidence of diffuse adenomyosis is significantly higher than that of focal adenomyosis.Satisfactory fertility outcomes could be achieved after correction of obstruction and excision of adenomyotic lesions by surgery.Immunohistochemistry showed no significant difference between adenomyosis with obstructive reproductive tract and with normal reproductive tract in local expression of Mullerian-derived tissue markers(PAX8,PAX2,GATA3),uterine stem cell markers(β-catenin,SSEA-1,CD146)and prolactin pathway markers(PRL,PRLR,DRD2).However,all adenomyotic uterine expressed abnormal localization of PRLR and DRD2 compared with normal uterine tissue.ConclusionsPatients with obstructive reproductive tract anomaly complicated with adenomyosis have unique clinical symptoms,characterized by adenomyotic lesion and ovarian endometrial cyst commonly occurring at the obstructive side.Surgery correcting the obstruction could improve patients’ fertility outcome.No significant differences were found between adenomyosis with obstructive reproductive tract and with normal reproductive tract in expression of markers representing Mullerian-derived tissues,uterine stem cells and prolactin pathway,suggesting that outflow obstruction might not play a decisive role in pathogenesis of adenomyosis.However,abnormal local regulation of prolactin receptors is likely to participate in the mechanism of adenomyosis.