Histological evaluation of the human testis--approaches to optimizing the clinical value of the assessment: mini review.

Testicular biopsy is a crucial assessment in reproductive practice with diagnostic and prognostic importance for assisted reproductive technologies (ARTs) and risk of testicular neoplasia. Endocrine and genetic tests cannot reliably distinguish obstructive azoospermia (OA) from non-obstructive azoospermia (NOA) or predict recovery of mature spermatids by testicular sperm extraction (TESE). Currently, divergent histological reporting systems and the use of imprecise terminology seriously degrade the value of the literature on TESE recovery rates and hamper evaluation of treatments and research on genotype-phenotype relationships. The rising incidence of testis cancer and carcinoma in situ (CIS), especially in infertile populations, requires that every effort be made for its early detection. We provide a systematic approach to the histological classification of spermatogenic disorders and detection of CIS in adult patients. We evaluate a large consecutive series of bilateral biopsies from infertile men and report (i) the frequency of bilateral or discordant patterns that supports the use of bilateral biopsy for comprehensive evaluation and (ii) a high prevalence of mixed patterns, particularly within the hypospermatogenesis classification, that helps account for reported success of TESE. We propose a new diagnosis code for testicular biopsies that addresses the needs of ART clinicians and allows data storage and retrieval of value in clinical practice and research.

[1]  N. Callewaert,et al.  Azoospermia: virtual reality or possible to quantify? , 2006, Journal of andrology.

[2]  M. Goldstein,et al.  Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. , 2005, The Journal of urology.

[3]  Z. Rosenwaks,et al.  Success of testicular sperm injection and intracytoplasmic sperm injection in men with klinefelter syndrome , 2005 .

[4]  David Handelsman,et al.  Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays. , 2005, The Journal of clinical endocrinology and metabolism.

[5]  M. Cooperberg,et al.  Variability in testis biopsy interpretation: implications for male infertility care in the era of intracytoplasmic sperm injection. , 2005, Fertility and sterility.

[6]  N. Skakkebaek,et al.  Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[7]  R. Mieusset,et al.  Hypospadias: psychosocial, sexual, and reproductive consequences in adult life. , 2005, Journal of andrology.

[8]  H. Adami,et al.  Testicular cancer incidence in eight northern European countries: secular and recent trends. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[9]  H. Tournaye,et al.  Should diagnostic testicular sperm retrieval followed by cryopreservation for later ICSI be the procedure of choice for all patients with non-obstructive azoospermia? , 2004, Human reproduction.

[10]  Christian Schwager,et al.  Embryonic Stem Cell-Like Features of Testicular Carcinoma in Situ Revealed by Genome-Wide Gene Expression Profiling , 2004, Cancer Research.

[11]  C. Bokemeyer,et al.  Pathobiological implications of the expression of markers of testicular carcinoma in situ by fetal germ cells , 2004, The Journal of pathology.

[12]  C. Cheng,et al.  Ectoplasmic specialization, a testis-specific cell-cell actin-based adherens junction type: is this a potential target for male contraceptive development? , 2004, Human reproduction update.

[13]  N. Skakkebaek,et al.  Impaired Leydig cell function in infertile men: a study of 357 idiopathic infertile men and 318 proven fertile controls. , 2004, The Journal of clinical endocrinology and metabolism.

[14]  R. Mclachlan,et al.  Stereological analysis of the human testis after vasectomy indicates impairment of spermatogenic efficiency with increasing obstructive interval. , 2004, Fertility and sterility.

[15]  N. Jørgensen,et al.  Biology and epidemiology of testicular dysgenesis syndrome , 2004, BJU international.

[16]  P. Beachy,et al.  597: Requirement for Autonomous Hedgehog Signal Response in Prostate Cancer Metastases , 2004 .

[17]  U. Pichlmeier,et al.  Clinical epidemiology of testicular germ cell tumors , 2004, World Journal of Urology.

[18]  Christina Wang,et al.  Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. , 2004, The Journal of clinical endocrinology and metabolism.

[19]  P. Schlegel,et al.  Testicular sperm extraction with intracytoplasmic sperm injection is successful for the treatment of nonobstructive azoospermia associated with cryptorchidism. , 2003, The Journal of urology.

[20]  N. Skakkebaek,et al.  Increased risk of carcinoma in situ in patients with testicular germ cell cancer with ultrasonic microlithiasis in the contralateral testicle. , 2003, The Journal of urology.

[21]  H. Tournaye,et al.  Cumulative delivery rates after ICSI treatment cycles with freshly retrieved testicular sperm: a 7-year follow-up study. , 2003, Human reproduction.

[22]  N. Skakkebaek,et al.  Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer , 2003, The Journal of pathology.

[23]  M. Meseguer,et al.  Gaps in the evidence for fertility treatment—an analysis of the Cochrane Menstrual Disorders and Subfertility Group database , 2003 .

[24]  J. Bartek,et al.  Deregulation of the G1/S‐phase control in human testicular germ cell tumours , 2003, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[25]  N. Skakkebæk,et al.  Association between testicular dysgenesis syndrome (TDS) and testicular neoplasia: Evidence from 20 adult patients with signs of maldevelopment of the testis , 2003, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[26]  M. Bergmann,et al.  Update on the diagnostic safety for detection of testicular intraepithelial neoplasia (TIN) , 2003, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[27]  K. Dieckmann,et al.  Diagnosis and management of testicular intraepithelial neoplasia (carcinoma in situ) – surgical aspects , 2003, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[28]  A. Tsujimura,et al.  Conventional multiple or microdissection testicular sperm extraction: a comparative study. , 2002, Human reproduction.

[29]  S. Friedler,et al.  Outcome of first and repeated testicular sperm extraction and ICSI in patients with non-obstructive azoospermia. , 2002, Human reproduction.

[30]  D. Mortimer,et al.  ESHRE basic semen analysis courses 1995-1999: immediate beneficial effects of standardized training. , 2002, Human reproduction.

[31]  J. Seo,et al.  Predictive factors of successful testicular sperm recovery in non-obstructive azoospermia patients. , 2001, International journal of andrology.

[32]  Z. Rosenwaks,et al.  Testicular sperm extraction combined with intracytoplasmic sperm injection in the treatment of men with persistent azoospermia postchemotherapy , 2001, Cancer.

[33]  C. Foresta,et al.  Prognostic value of Y deletion analysis. The role of current methods. , 2001, Human reproduction.

[34]  N. Skakkebaek,et al.  Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects , 2001, Human reproduction.

[35]  N. Skakkebæk,et al.  Microcalcifications and carcinoma in situ of the testis , 2001, BJU international.

[36]  L. Rienzi,et al.  Criteria predicting the absence of spermatozoa in the Sertoli cell-only syndrome can be used to improve success rates of sperm retrieval. , 2000, Human reproduction.

[37]  S. Silber Microsurgical TESE and the distribution of spermatogenesis in non-obstructive azoospermia. , 2000, Human reproduction.

[38]  J. Olsen,et al.  Risk of testicular cancer in men with abnormal semen characteristics: cohort study , 2000, BMJ : British Medical Journal.

[39]  L. Quintana-Murci,et al.  Prognostic value of Y deletion analysis: what is the clinical prognostic value of Y chromosome microdeletion analysis? , 2000, Human reproduction.

[40]  A. Nuhoğlu,et al.  Outcome of testicular sperm retrieval procedures in non-obstructive azoospermia: percutaneous aspiration versus open biopsy. , 2000, Human reproduction.

[41]  M. Amer,et al.  Testicular sperm extraction: impact of testicular histology on outcome, number of biopsies to be performed and optimal time for repetition. , 1999, Human reproduction.

[42]  W. Schulze,et al.  Testicular sperm extraction: comprehensive analysis with simultaneously performed histology in 1418 biopsies from 766 subfertile men. , 1999, Human reproduction.

[43]  L. Yogev,et al.  Testicular sperm retrieval and cryopreservation prior to initiating ovarian stimulation as the first line approach in patients with non-obstructive azoospermia. , 1999, Human reproduction.

[44]  O. Hovatta,et al.  Testicular biopty gun needle biopsy in collecting spermatozoa for intracytoplasmic injection, cryopreservation and histology. , 1999, Human reproduction.

[45]  Henrik Møller,et al.  Risk of testicular cancer in subfertile men: case-control study , 1999, BMJ.

[46]  W. Schulze,et al.  Successful testicular sperm extraction (TESE) in spite of high serum follicle stimulating hormone and azoospermia: correlation between testicular morphology, TESE results, semen analysis and serum hormone values in 103 infertile men. , 1998, Human reproduction.

[47]  N. Zaninovic,et al.  Births after intracytoplasmic injection of sperm obtained by testicular extraction from men with nonmosaic Klinefelter's syndrome. , 1998, The New England journal of medicine.

[48]  Z. Nagy,et al.  Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure. , 1997, Human reproduction.

[49]  I. Craft,et al.  Testicular needle aspiration as an alternative to biopsy for the assessment of spermatogenesis. , 1997, Human reproduction.

[50]  S. Friedler,et al.  Testicular sperm retrieval by percutaneous fine needle sperm aspiration compared with testicular sperm extraction by open biopsy in men with non-obstructive azoospermia. , 1997, Human reproduction.

[51]  J. Mulhall,et al.  Fertilization and pregnancy using intentionally cryopreserved testicular tissue as the sperm source for intracytoplasmic sperm injection in 10 men with non-obstructive azoospermia. , 1997, Human reproduction.

[52]  K. Dieckmann,et al.  Prevalence of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell neoplasms. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  R. Zucali,et al.  Primary chemoradiation therapy with fluorouracil and cisplatin for cancer of the anus: results in 35 consecutive patients. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[54]  Z. Nagy,et al.  Normal pregnancies resulting from testicular sperm extraction and intracytoplasmic sperm injection for azoospermia due to maturation arrest. , 1996, Fertility and sterility.

[55]  H. Tournaye,et al.  Seminoma discovered in two males undergoing successful testicular sperm extraction for intracytoplasmic sperm injection. , 1996, Fertility and sterility.

[56]  H. Møller,et al.  Testicular cancer, cryptorchidism, inguinal hernia, testicular atrophy, and genital malformations: case-control studies in Denmark , 1996, Cancer Causes & Control.

[57]  Z. Nagy,et al.  Pregnancies after testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia. , 1995, Human reproduction.

[58]  N. Skakkebaek,et al.  Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells. , 1995, Laboratory investigation; a journal of technical methods and pathology.

[59]  H. Baker,et al.  Fine needle tissue aspiration biopsy of the testis. , 1994, Fertility and sterility.

[60]  K. Dieckmann,et al.  Carcinoma in situ of the testis , 1991 .

[61]  K. Dieckmann,et al.  Incidence and distribution of carcinoma in situ in testes removed for germ cell tumour: possible inadequacy of random testicular biopsy in detecting the condition , 1990, Histopathology.

[62]  N. Skakkebaek,et al.  Prevalence of carcinoma in situ and other histopathological abnormalities in testes of men with a history of cryptorchidism. , 1989, The Journal of urology.

[63]  N. Skakkebaek,et al.  Testicular biopsy as an outpatient procedure in screening for carcinoma-in-situ: complications and the patient's acceptance. , 1987, International journal of andrology.

[64]  D. Mortimer,et al.  Standardization and quality control of sperm concentration and sperm motility counts in semen analysis. , 1986, Human reproduction.

[65]  N. Skakkebæk,et al.  Testicular cancer: abnormal structure and function of the contralateral testis , 1983 .

[66]  H. Levin Testicular biopsy in the study of male infertility: its current usefulness, histologic techniques, and prospects for the future. , 1979, Human pathology.

[67]  H. Burger,et al.  Hormonal, histological and chromosomal studies in adult males with testicular disorders. , 1972, The Journal of clinical endocrinology and metabolism.

[68]  N. Skakkebaek,et al.  Dimorphism in sex chromatin pattern of Sertoli cells in adults with Klinefelter's syndrome: correlation with 2 types of "Sertoli-cell-only" tubules. , 1971, The Journal of clinical endocrinology and metabolism.

[69]  N. Skakkebæk Two Types of Tubules containing only Sertoli Cells in Adults with Klinefelter's Syndrome , 1969, Nature.

[70]  E. Roosen-Runge,et al.  Quantitative investigations on human testicular biopsies. II. Infertility and other conditions. , 1957, Fertility and sterility.

[71]  E. Roosen-Runge Quantitative investigations on human testicular biopsies. I. Normal testis. , 1956, Fertility and sterility.

[72]  W. Nelson Testicular morphology in eunuchoidal and infertile men. , 1950, Fertility and sterility.

[73]  R. C. Sniffen THE TESTES. I THE NORMAL TESTIS , 1950 .

[74]  R. Hotchkiss FERTILITY IN MEN , 1944 .

[75]  D. Leys Toxic Reactions to Sodium Dehydrocholate , 1944 .

[76]  C. W. Charny TESTICULAR BIOPSY: ITS VALUE IN MALE STERILITY , 1940 .

[77]  L. Looijenga,et al.  Bilateral testicular microlithiasis predicts the presence of the precursor of testicular germ cell tumors in subfertile men. , 2004, The Journal of urology.

[78]  J. Bartek,et al.  The emerging phenotype of the testicular carcinoma in situ germ cell. , 2003 .

[79]  C. Niederberger,et al.  The role of testicular biopsy in the modern management of male infertility. , 2002, The Journal of urology.

[80]  P. Schlegel Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. , 1999, Human reproduction.

[81]  F. Ubaldi,et al.  Are there any predictive factors for successful testicular sperm recovery in azoospermic patients? , 1997, Human reproduction.

[82]  J. Mulhall,et al.  Presence of mature sperm in testicular parenchyma of men with nonobstructive azoospermia: prevalence and predictive factors. , 1997, Urology.

[83]  S. Johnsen Testicular biopsy score count--a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. , 1970, Hormones.

[84]  Y. Clermont,et al.  KINETICS OF THE GERMINAL EPITHELIUM IN MAN. , 1964, Recent progress in hormone research.

[85]  Y. Clermont The cycle of the seminiferous epithelium in man. , 1963, The American journal of anatomy.

[86]  M. Huhner Aspiration of the Testicle in the Diagnosis and Prognosis of Sterility1 , 1928 .