Establishment Of Qualitative And Quantitative Evaluation System Of Testicular Biopsy In Azoospermic Men

BACKGROUND&OBJECTIVEHistopathologic evaluation of testicular biopsy can reveal the status of spermatogenesis,and provide guidance for medical management of azoospermic men.However,the ambiguous terminology and no consensus on quantitative and qualitative diagnostic criteria result in decreased value of testicular biopsy.In an effort to increase the diagnostic and prognostic accuracy of testicular biopsy,we have established a uniform and comprehensive reporting system to qualitatively and quantitatively evaluate testicular biopsy specimen.In this study,we re-evaluate testicular biopsy specimens of a large cohort of azoospermic men,as to investigate the applicability and validity of the system in clinical practice.MATERIALS&METHODSWe re-evaluated histopathologic characteristics of 828 azoospermic patients with testis biopsies in Nanfang hospital from 2008 to 2015.Testicular sperm extraction(TESE)was performed in 226 cases in our hospital.During histopathologic analysis,features of seminiferous tubules and interstitial tissue should be analyzed,including total number of tubules sections in the slides,tubular diameter,mature spermatozoa count,thickened basement membrane,the change of Leydig cells.According to our methodology of testicular biopsy,we classified the histopathology into 10 patterns:Normal testicular appearance,normal spermatogenesis,hypospermatogenesis,spermatidic dysgenesis,Sertoli cell-only syndrome,spermatogenic arrest,mixed pattern,prepubertal testis,seminiferous tubule hyalinization and other patterns.All included men underwent karyotype analysis,semen analysis and hormone analysis(luteinizing hormone(LH),follicle stimulating hormone(FSH),testosterone(T))by standardize procedure.Men with abnormal karyotype or older than 50 years-old were excluded in this study.RESULTSIn 828 azoospermic men,mature spermatozoa can be detected in 546 cases(65.9%).The frequency of histological patterns in these patients was 234 patients with normal spermatogenesis(28.3%),305 patients with hypospermatognesis(36.8%),95 patients with spermatidic dysgenesis(11.5%),142 patients with Sertoli cell-only syndrome(17.1%),27 with mixed pattern(3.3%),8 patients with spermatogenic arrest(1.0%),10 patients with seminiferous tubule hyalinization(1.2%)and 7 patients with other patterns(0.8%).According to the mean mature spermatozoa count of tubule circular cross section,we further subdivided hypospermatogenesis into three subtypes.The frequency of them was 170 patients with mild(55.7%),89 patients with moderate(29.2%),46 patients with severe(15.1%).Testicular biopsy findings revealed that the degree of testicular impairment was associated with spermatogenic cells as well as tubular diameter,tubular basement membrane and Leydig cells hyperplasia in azoospermic patients.Depending on changes of tubular basement membrane,we described tubular basement membranes as normal,incomplete sclerohyalinosis and complete sclerohyalinosis.We classified Leydig cell hyperplasia into five grades based on the Leydig cell number of the largest cluster.There was significant difference in the grading of Leydig cell hyperplasia,the proportion of complete tubular sclerohyalinosis,tubular diameter.the concentrations of FSH,LH among histopathologic patterns(p<0.05).In addition,there was statistically significant difference in FSH level(p<0.001)and LH level(p<0.001)among grades of Leydig cell hyperplasia.The three subtypes of hypospermatogenesis was significant difference in tubular diameter,while there was no difference in the concentrations of FSH,LH,T.212 out of 226 patients who underwent testicular sperm extraction had successful sperm retrieval.Spermatozoa can be always recovered in patients with normal spermatogenesis(100%)and hypospermatogenesis(100%),while only 56.5%of patients with spermatidic dysgenesis were successful.CONCLUSION1.The histopathologic changes of testes in azoospermic men are heterogenous.Testicular impairment is associated with spermatogenic epithelium as well as tubular diameter,tubular sclerohyalinosis and Leydig cells hyperplasia.2.The concentrations of FSH,LH can reflect the damage of testis to some extent,including the changes of seminiferious epithelium and Leydig cells.But it just can be regarded as a reference index.3.Quantitative and qualitative methodology for testicular biopsy is of a clear definitions,accurate and comprehensive histopathologic criteria for pathologists.4.A standardized reporting system proposed by us may be more accurately predict prognosis and guide clinical decision-making of azoospermic men.