A novel stepwise micro-TESE approach in non obstructive azoospermia

Background: The purpose of the study was to investigate whether micro-TESE can improve sperm retrieval rate (SRR) compared to conventional single TESE biopsy on the same testicle or to contralateral multiple TESE, by employing a novel stepwise micro-TESE approach in a population of poor prognosis patients with non-obstructive azoospermia (NOA). Methods: Sixty-four poor prognosis NOA men undergoing surgical testicular sperm retrieval for ICSI, from March 2007 to April 2013, were included in this study. Patients inclusion criteria were a) previous unsuccessful TESE, b) unfavorable histology (SCOS, MA, sclerahyalinosis), c) Klinefelter syndrome. We employed a stepwise micro-TESE consisting three-steps: 1) single conventional TESE biopsy; 2) micro-TESE on the same testis; 3) contralateral multiple TESE. Results: SRR was 28.1 % (18/64). Sperm was obtained in both the initial single conventional TESE and in the following micro-TESE. The positive or negative sperm retrieval was further confirmed by a contralateral multiple TESE, when performed. No significant pre-operative predictors of sperm retrieval, including patients’ age, previous negative TESE or serological markers (LH, FSH, inhibin B), were observed at univariate or multivariate analysis. Micro-TESE (step 2) did not improve sperm retrieval as compared to single TESE biopsy on the same testicle (step 1) or multiple contralateral TESE (step 3). Conclusions: Stepwise micro-TESE could represent an optimal approach for sperm retrieval in NOA men. In our view, it should be offered to NOA patients in order to gradually increase surgical invasiveness, when necessary. Stepwise micro-TESE might also reduce the costs, time and efforts involved in surgery

Testicular expression of TDRD1, TDRD5, TDRD9 and TDRD12 in azoospermia.

BACKGROUND: Tudor domain-containing proteins (TDRDs) play a critical role in piRNA biogenesis and germ cell development. piRNAs, small regulatory RNAs, act by silencing of transposons during germline development and it has recently been shown in animal model studies that defects in TDRD genes can lead to sterility in males. METHODS: Here we evaluate gene and protein expression levels of four key TDRDs (TDRD1, TDRD5, TDRD9 and TDRD12) in testicular biopsy samples obtained from men with obstructive azoospermia (OA, n = 29), as controls, and various types of non-obstructive azoospermia containing hypospermatogenesis (HP, 28), maturation arrest (MA, n = 30), and Sertoli cell-only syndrome (SCOS, n = 32) as cases. One-way ANOVA test followed by Dunnett's multiple comparison post-test was used to determine inter-group differences in TDRD gene expression among cases and controls. RESULTS: The results showed very low expression of TDRD genes in SCOS specimens. Also, the expression of TDRD1 and TDRD9 genes were lower in MA samples compared to OA samples. The expression of TDRD5 significantly reduced in SCOS, MA and HP specimens than the OA specimens. Indeed, TDRD12 exhibited a very low expression in HP specimens in comparison to OA specimens. All these results were confirmed by Western blot technique. CONCLUSION: TDRDs could be very important in male infertility, which should be express in certain stages of spermatogenesis

Testicular histopathology, semen analysis and FSH, predictive value of sperm retrieval: supportive counseling in case of reoperation after testicular sperm extraction (TESE)

Background: To provide indicators for the likelihood of sperm retrieval in patients undergoing testicular sperm extraction is a major issue in the management of male infertility by TESE. The aim of our study was to determine the impact of different parameters, including testicular histopathology, on sperm retrieval in case of reoperation in patients undergoing testicular sperm extraction. Methods: We retrospectively analyzed 486 patients who underwent sperm extraction for intracytoplasmic sperm injection and testicular biopsy. Histology was classified into: normal spermatogenesis; hypospermatogenesis (reduction in the number of normal spermatogenetic cells); maturation arrest (absence of the later stages of spermatogenesis); and Sertoli cell only (absence of germ cells). Semen analysis and serum FSH, LH and testosterone were measured. Results: Four hundred thirty patients had non obstructive azoospermia, 53 severe oligozoospermia and 3 necrozoospermia. There were 307 (63%) successful sperm retrieval. Higher testicular volume, lower levels of FSH, and better histological features were predictive for sperm retrieval. The same parameters and younger age were predictive factors for shorter time for sperm recovery. After multivariable analysis, younger age, better semen parameters, better histological features and lower values of FSH remained predictive for shorter time for sperm retrieval while better semen and histology remained predictive factors for successful sperm retrieval. The predictive capacity of a score obtained by summing the points assigned for selected predictors (1 point for Sertoli cell only, 0.33 points for azoospermia, 0.004 points for each FSH mIU/ml) gave an area under the ROC curve of 0.843. Conclusions: This model can help the practitioner with counseling infertile men by reliably predicting the chance of obtaining spermatozoa with testicular sperm extraction when a repeat attempt is planne

Azoospermia: a Genomic Review

Azoospermia or the absence of sperm in semen is one of the sperm disorders that results in male infertility. There are two types of azoospermia, the first one isazoospermia caused by obstruction of the vas deferens (obstructive azoospermia) and the second one is azoospermia due to the damage of testes (nonobstructive azoospermia). The etiology of azoospermia could be genetic or non-genetic. Genetic factors may occur in genomics starting from chromosome until gene level or single nucleotide polymorphism (SNPs). At the chromosome level, there is Klinefelter’s syndrome (47, XXY) to the Y chromosome microdeletion, whereas at the gene level there is mutation of jsd, Bmp8b and other genes. At the level of SNPs, Genome Wide SNP Association Study (GWAS) had uncovered 20 SNPs which were related significantly to azoospermia. Extensive knowledge of genomics review on male infertility, is expected to promote the development of investigation and management of azoospermia

Nonobstruktif azospermi olgularında yeni yaklaşımlar

Azospermi semende hiç sperm bulunamaması durumudur. Obstrüktif ve nonobstrüktif olmak üzere iki kategoriye ayrılır. Azospermi tanısı alan hastalardan elde edilen spermatozoayla, ilk gebelik ICSI (intrasitoplazmik sperm enjeksiyonu) işlemiyle 1993 yılında oluşmuştur. Obstrüktif azospermi olgularında sperm bulma şansı daha yüksek olmasına karşın, erkek infertilitesinin en şiddetli formu olan nonobstrüktif azospermide ise bu oran yaklaşık olarak %40-50 aralığındadır. Yapılan mikroTESE (testiküler sperm ekstraksiyonu) işlemiyle testiste immatür germ hücreleri bulunursa ROSI (round spermatid enjeksiyonu) işlemi yapılır ya da in vitro kültürlerle bu hücreler farklılaştırılmaya çalışılır. Matür germ hücresi bulunamayan bir mikroTESE sonrasında, hormon replasmanı veya ilaç tedavileriyle spermatozoaların elde edilmesi hedeflenir. Son yıllara kadar testislerde varlıkları bilinen spermatogoniumlara (sperm kök hücresi) ek olarak, yeni keşfedilen VSEL (very small embriyonic-like stem cell) kök hücrelerinin gösterilmesi tedavi yönündeki umutları daha da artırmıştır. Bunlardan başka deneysel olarak, hücre kültürleri, seminifer tübül kültürleri, organ kültürleri, testiküler organoidler, gen tedavileriİnsan üzerinde başlayan gen terapilerinde ve mezenkimal kök hücre çalışmalarında, önemli ilerlemeler olması nedeniyle yakın bir zamanda azospermi tedavisinde de önemli gelişmeler olacağı düşünülmektedir. ve kök hücre bazlı tedavilerin etkinliği gösterilmiştir

Sperm retrieval rate and pregnancy rate in infertile couples undergoing in-vitro fertilisation and testicular sperm extraction for non-obstructive azoospermia in Hong Kong

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Update on male reproductive endocrinology.

Practitioners of male reproductive and sexual medicine must have an intimate understanding of the physiology of male reproductive endocrinology, as such a knowledge is the cornerstone on which hormonal treatments are based. In this review, we highlight what is known about male reproductive endocrine physiology and the various control mechanisms for the system. We also discuss the limitations of our current understanding of the reproductive physiology. We hope that this review is helpful for male reproductive medicine practitioners in understanding the principles on which hormonal treatments are based

Microdissection testicular sperm extraction causes spermatogenic alterations in the contralateral testis

Testicular sperm extraction (TESE) associated with intracytoplasmic sperm injection has allowed many men presenting non-obstructive azoospermia to achieve fatherhood. Microdissection TESE (microTESE) was proposed as a method to improve sperm retrieval rates in these patients; however, there have been failures. Little is known about whether microTESE leads to spermatogenic alterations in the contralateral testis. We assessed histological outcomes of experimental microTESE in the contralateral testis of adult male rabbits. Nine adult male rabbits were divided into three groups: control (testicular biopsy to observe normal histological and morphometric values), sham (incision of the tunica vaginalis, and a contralateral testicular biopsy to observe histological and morphometric patterns, 45 days later), and study (left testicular microTESE, and a right testicular biopsy to observe histological and morphometric patterns, 45 days later). Sections were assessed by calculating Johnsen-like scores, and measuring total tubule diameter, lumen diameter and epithelial height. the results were compared using ANOVA and Bonferroni's statistical analysis. Morphometric evaluation of the seminiferous tubules did not demonstrate differences between the three groups. However, microTESE caused spermatogenic alterations, leading to maturation arrest in the contralateral testis.Universidade Federal de São Paulo, Dept Cirurgia, Div Urol, Secao Reprod Humana, São Paulo, BrazilUniv Estadual Paulista, Dept Biol, Inst Biociencias Letras & Ciencias Exatas Sao Jos, Sao Jose Do Rio Preto, SP, BrazilUniversidade Federal de São Paulo, Dept Cirurgia, Div Urol, Secao Reprod Humana, São Paulo, BrazilWeb of Scienc

Systematic analysis of protein interaction network associated with azoospermia

Non-obstructive azoospermia is a severe infertility factor. Currently, the etiology of this condition remains elusive with several possible molecular pathway disruptions identified in the post-meiotic spermatozoa. In the presented study, in order to identify all possible candidate genes associated with azoospermia and to map their relationship, we present the first protein-protein interaction network related to azoospermia and analyze the complex effects of the related genes systematically. Using Online Mendelian Inheritance in Man, the Human Protein Reference Database and Cytoscape, we created a novel network consisting of 209 protein nodes and 737 interactions. Mathematical analysis identified three proteins, ar, dazap2, and esr1, as hub nodes and a bottleneck protein within the network. We also identified new candidate genes, CREBBP and BCAR1, which may play a role in azoospermia. The gene ontology analysis suggests a genetic link between azoospermia and liver disease. The KEGG analysis also showed 45 statistically important pathways with 31 proteins associated with colorectal, pancreatic, chronic myeloid leukemia and prostate cancer. Two new genes and associated diseases are promising for further experimental validation