One major challenge in male factor infertility is nonobstructive azoospermia(NOA),which is characterized by spermatozoa-deficient semen without physical duct blockage.This review offers a thorough overview of the hist...One major challenge in male factor infertility is nonobstructive azoospermia(NOA),which is characterized by spermatozoa-deficient semen without physical duct blockage.This review offers a thorough overview of the histopathology of the testes in NOA cases,clarifying its complex etiology and emphasizing the possible value of histopathology inspection for both diagnosis and treatment.Variable histopathological findings have been linked to NOA,such as tubular hyalinization,Sertoli cell-only syndrome,hypospermatogenesis,and germ cell arrest.Understanding the pathophysiology and forecasting the effectiveness of treatment are further enhanced by both morphometric and ultrastructural analyses.The potential significance of testicular biopsy in forecasting reproductive outcomes is assessed,especially concerning assisted reproductive technologies like intracytoplasmic sperm injection(ICSI).Besides,testicular microlithiasis,serum hormone profiles,and testicular size are investigated concerning NOA histopathology.It is concluded that understanding the histopathological patterns in NOA is crucial for its accurate diagnosis and appropriate management.Further research is still warranted to improve understanding of the complex pathophysiology underlying NOA.展开更多
This review focuses on the diagnostic algorithm for nonobstructive azoospermia(NOA),a significant male factor contributing to infertility.NOA,characterized by the absence of sperm in the ejaculate,requires a systemati...This review focuses on the diagnostic algorithm for nonobstructive azoospermia(NOA),a significant male factor contributing to infertility.NOA,characterized by the absence of sperm in the ejaculate,requires a systematic diagnostic approach to identify reversible conditions,genetic factors,and prognosis for achieving pregnancy.The diagnostic pathway involves semen analysis and a comprehensive evaluation for hormonal deficiencies,anatomical abnormalities,and genetic factors.The importance of medical history,physical examination,endocrine evaluation,imaging,and genetic testing is emphasized.This review highlights the significance of differentiating NOA from obstructive azoospermia(OA)and outlines key considerations for effective management,including surgical sperm retrieval and assisted reproductive techniques.Testicular biopsy is discussed as a definitive method to distinguish obstructive cases from nonobstructive cases,providing valuable prognostic information.Overall,a thorough and systematic diagnostic approach is essential for the effective management of men suspected with NOA,offering insights into potential treatment options and reproductive outcomes.展开更多
To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testic...To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.展开更多
Nonobstructive azoospermia(NOA)is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis.Although various factors are well defined in the disruption of spermatogenesis,not ...Nonobstructive azoospermia(NOA)is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis.Although various factors are well defined in the disruption of spermatogenesis,not all aspects due to the heterogeneity of the disorder have been determined yet.In this review,we focus on the recent findings and summarize the current data on epigenetic mechanisms such as DNA methylation and different metabolites produced during methylation and demethylation and various types of small noncoding RNAs involved in the pathogenesis of different groups of NOA.展开更多
The advent of intracytoplasmic sperm injection,along with the realization that many men with azoospermia due to primary testicular failure may have a few spermatozoa in their testes,has resulted in the revolutionary p...The advent of intracytoplasmic sperm injection,along with the realization that many men with azoospermia due to primary testicular failure may have a few spermatozoa in their testes,has resulted in the revolutionary possibility of azoospermic men fathering their own genetic offspring.展开更多
Infertility,defined as the inability to conceive after 1 year of regular unprotected intercourse,impacts 10%–20%of couples globally.Both male and female factors contribute equally to this condition.Azoospermia,partic...Infertility,defined as the inability to conceive after 1 year of regular unprotected intercourse,impacts 10%–20%of couples globally.Both male and female factors contribute equally to this condition.Azoospermia,particularly nonobstructive azoospermia(NOA),which affects 10%–15%of infertile men,represents a significant challenge in male infertility.The advent of assisted reproductive technology(ART),specifically microdissection testicular sperm extraction(micro-TESE)followed by intracytoplasmic sperm injection(ICSI),offers a possibility for men with NOA to father biological children.Recent studies have focused on the predictors of sperm retrieval in NOA patients,such as age,testicular volume,and follicle-stimulating hormone(FSH)level.This review aims to explore the limited data on the anatomical characteristics of NOA patients and provide surgical considerations for micro-TESE,thereby enhancing understanding and improving outcomes for this challenging condition.展开更多
Oncological microdissection testicular sperm extraction(onco-micro-TESE)represents a significant breakthrough for patients with nonobstructive azoospermia(NOA)and a concomitant in situ testicular tumor,to be managed a...Oncological microdissection testicular sperm extraction(onco-micro-TESE)represents a significant breakthrough for patients with nonobstructive azoospermia(NOA)and a concomitant in situ testicular tumor,to be managed at the time of sperm retrieval.Onco-micro-TESE addresses the dual objectives of treating both infertility and the testicular tumor simultaneously.The technique is intricate,necessitating a comprehensive understanding of testicular anatomy,physiology,tumor biology,and advanced microsurgical methods.It aims to carefully extract viable spermatozoa while minimizing the risk of tumor dissemination.This review encapsulates the procedural intricacies,evaluates success determinants,including tumor pathology and spermatogenic tissue health,and discusses the implementation of imaging techniques for enhanced surgical precision.Ethical considerations are paramount,as the procedure implicates complex decision-making that weighs the potential oncological risks against the profound desire for fatherhood using the male gametes.The review aims to provide a holistic overview of onco-micro-TESE,detailing methodological advances,clinical outcomes,and the ethical landscape,thus offering an indispensable resource for clinicians navigating this multifaceted clinical scenario.展开更多
Azoospermia is the complete absence of spermatozoa in the ejaculate in two or more semen analyses after centrifugation.Nonobstructive azoospermia(NOA)represents the most severe form of male factor infertility accounti...Azoospermia is the complete absence of spermatozoa in the ejaculate in two or more semen analyses after centrifugation.Nonobstructive azoospermia(NOA)represents the most severe form of male factor infertility accounting for 10%–15%of cases and stems from an impairment to spermatogenesis.Understanding of the hypothalamic–pituitary–testicular axis has allowed NOA to be subcategorized by anatomic and/or pathophysiologic level.The etiologies of NOA,and therefore,the differential diagnoses when considering NOA as a cause of male factor infertility,can be subcategorized and condensed into several distinct classifications.Etiologies of NOA include primary hypogonadism,secondary hypogonadism,defects in androgen synthesis and/or response,defective spermatogenesis and sperm maturation,or a mixed picture thereof.This review includes up-to-date clinical,diagnostic,cellular,and histologic features pertaining to the multitude of NOA etiologies.This in turn will provide a framework by which physicians practicing infertility can augment their clinical decision-making,patient counseling,thereby improving upon the management of men with NOA.展开更多
Nonobstructive azoospermia(NOA),one of the most severe types of male infertility,etiology often remains unclear in most cases.Therefore,this study aimed to detect four biallelic detrimental variants(0.5%)in the minich...Nonobstructive azoospermia(NOA),one of the most severe types of male infertility,etiology often remains unclear in most cases.Therefore,this study aimed to detect four biallelic detrimental variants(0.5%)in the minichromosome maintenance domain containing 2(MCMDC2)genes in 768 NOA patients by whole-exome sequencing(WES).Hematoxylin and eosin(H&E)demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients(c.1360G>T,c.1956G>T,and c.685C>T)and hypospermatogenesis in one patient(c.94G>T),as further confirmed through immunofluorescence(IF)staining.The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis.The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses.The results revealed four MCMDC2 variants related to NOA,which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.展开更多
Myocardial infarction with nonobstructive coronary arteries is a unique presentation of acute coronary syndrome occurring in patients without significant coronary artery disease.Its pathophysiology involves atheroscle...Myocardial infarction with nonobstructive coronary arteries is a unique presentation of acute coronary syndrome occurring in patients without significant coronary artery disease.Its pathophysiology involves atherosclerotic and nonatherosclerotic mechanisms such as plaque erosion,coronary microvascular dysfunction,vasospasm,spontaneous coronary artery dissection,autoimmune and inflammatory diseases,and myocardial oxygen supply-demand imbalance.A systematic approach to diagnosis is needed due to the diverse range of underlying causes.Cardiac troponins confirm the myocardial injury and coronary angiography rules out significant obstruction.Cardiac magnetic resonance imaging differentiates ischemic from nonischemic causes,and additional investigations,such as intravascular ultrasound,optical coherence tomography,and provocative testing,play a role in identifying the etiology to guide management strategies.Atherosclerotic cases require antiplatelet therapy and statins,vasospastic cases respond to calcium channel blockers,spontaneous coronary artery dissection is typically managed conservatively,and coronary microvascular dysfunction may require vasodilators.Lifestyle modifications and cardiac rehabilitation are essential for improving outcomes.The prognosis of patients experiencing recurrent events despite treatment is uncertain,but long-term outcomes depend on the etiology,highlighting the need for personalized management.Future research should focus on refining diagnostic protocols and identifying optimal therapeutic strategies.Randomized controlled trials are necessary to establish evidence-based treatments for different subtypes of myocardial infarction with nonobstructive coronary arteries.展开更多
Male infertility has seen an increase in prevalence with cases of azoospermia estimated to affect 10%–15%of infertile men.Confirmation of azoospermia subsequently necessitates an early causal differentiation between ...Male infertility has seen an increase in prevalence with cases of azoospermia estimated to affect 10%–15%of infertile men.Confirmation of azoospermia subsequently necessitates an early causal differentiation between obstructive azoospermia(OA)and nonobstructive azoospermia(NOA).Although less common when compared to NOA,OA can represent upward 20%–40%of cases of azoospermia.While there are a multitude of etiologies responsible for causing NOA and OA,correctly distinguishing between the two types of azoospermia has profound implications in managing the infertile male.This review represents an amalgamation of the current guidelines and literature which will supply the reproductive physician with a diagnostic armamentarium to properly distinguish between NOA and OA,therefore providing the best possible care to the infertile couple.展开更多
Nonobstructive azoospermia(NOA)is the most challenging and complex clinical scenario for infertile men.Besides circumstances such as hypogonadotropic hypogonadism,surgical sperm retrieval is typically necessary,and mi...Nonobstructive azoospermia(NOA)is the most challenging and complex clinical scenario for infertile men.Besides circumstances such as hypogonadotropic hypogonadism,surgical sperm retrieval is typically necessary,and microdissection testicular sperm extraction(micro-TESE)is the procedure of choice for men with NOA desiring to father children with their own gametes.Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection(ICSI)in comparison to all other techniques for surgical sperm retrieval in men with NOA.Several factors may affect sperm retrieval rate and ICSI outcomes,including the patient’s age,testicular volume,histopathological and genetic profile,and serum hormone levels.This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.展开更多
We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia(iNOA).We studied 193 patients with nonobstructive azoospermia who underwe...We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia(iNOA).We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction.The Chi-square test and Mann–Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons.A logistic regression analysis was conducted to identify predictors of retrieval failure.Area under the receiver operating characteristic curve for each variable was evaluated,and the net clinical benefit was calculated using a clinical decision curve.Patients with iNOA had a lower sperm retrieval rate than those with known causes.Moreover,testicular volume was an independent factor affecting sperm extraction outcomes(odds ratio=0.79,P<0.05).The testicular volume cut-off value was 6.5 ml(area under the curve:0.694).The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed.The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution.There was also a significant association between a uniform tubule distribution and testicular volume.In conclusion,a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.展开更多
Microdissection testicular sperm extraction(mTESE)is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia(iNOA).However,the suc...Microdissection testicular sperm extraction(mTESE)is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia(iNOA).However,the success rate of sperm retrieval varies among individuals.We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA.We searched PubMed,EMBASE,and Web of Science from database inception to August 2,2023.The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE.Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models.The overall sperm retrieval rate was 36.8%(95%confidence interval[CI]:27.5%-46.0%,I 2=95.0%)in nine studies comprising 1892 patients with iNOA.No significant differences were found in age,testicular volume,serum total testosterone concentrations,or inhibin B concentrations between positive and negative sperm retrieval outcomes.Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE(weighted mean differences:−2.70;95%CI:−3.94-−1.46,I 2=79.0%).In conclusion,this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA,while age,testicular volume,total testosterone,and inhibin B show no significant association.These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.展开更多
The clinical management of men with nonobstructive azoospermia （NOA） seeking fertility has been a challenge for andrologists, urologists, and reproductive medicine specialists alike. This review presents a personal ...The clinical management of men with nonobstructive azoospermia （NOA） seeking fertility has been a challenge for andrologists, urologists, and reproductive medicine specialists alike. This review presents a personal perspective on the clinical management of NOA, including the lessons learned over 15 years dealing with this male infertility condition. A five-consecutive-step algorithm is proposed to manage such patients. First, a differential diagnosis of azoospermia is made to confirm/establish that NOA is due to spermatogenic failure. Second, genetic testing is carried out not only to detect the males in whom NOA is caused by microdeletions of the long arm of the Y chromosome, but also to counsel the affected patients about their chances of having success in sperm retrieval. Third, it is determined whether any intervention prior to a surgical retrieval attempt may be used to increase sperm production. Fourth, the most effective and efficient retrieval method is selected to search for testicular sperm. Lastly, state-of-art laboratory techniques are applied in the handling of retrieved gametes and cultivating the embryos resulting from sperm injections. A coordinated multidisciplinary effort is key to offer the best possible chance of achieving a biological offspring to males with NOA.展开更多
Many studies have shown that microRNAs(miRNAs)play vital roles during the spermatogenesis.However,little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia(NOA).Using microar...Many studies have shown that microRNAs(miRNAs)play vital roles during the spermatogenesis.However,little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia(NOA).Using microarray technology,the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined.Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs.The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),the results of which were then validated with a larger sample size.Correlations between the miRNA expression levels and clinical characteristics were analyzed.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia.Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups.Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis,cell cycle,and mitotic prometaphase.In the subsequent qRT-PCR assays,the selected miRNA expression levels were consistent with the microarray results,and similar validated results were obtained with a larger sample size.Some clinical characteristics were significantly associated with the expression of certain miRNAs.In particular,we identified a combination of two miRNAs(miR-10b-3p and miR-34b-5p)that could serve as a predictive biomarker of azoospermia.This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis.These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.展开更多
The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection （ICSI）, either using fresh （TESE） or frozen-thawed （TESE-C） te...The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection （ICSI）, either using fresh （TESE） or frozen-thawed （TESE-C） testicular sperm and ejaculated sperm （EJAC）. The originality of this work resides in the comparisons between the different types of Y-microdeletions （AZFa, AZFb, and AZFc） and treatments, with detailed demographic, stimulation, embryological, clinical, and newborn （NB） outcomes. Of 125 patients with Y-microdeletions, 33 patients presented severe oligozoospermia （18 performed ICSI with ejaculated sperm） and 92 secretory azoospermia （65 went for TESE with 40 having successful sperm retrieval and performed ICSI）. There were 51 TESE treatment cycles and 43 TESE-C treatment cycles, with a birth of 19 NB （2 in AZFa/TESE-C, 12 in AZFc/TESE, and 5 in AZFc/TESE-C）. Of the 29 EJAC cycles, there was a birth of 8 NB （in AZFc）. In TESE and EJAC cycles, there were no significant differences in embryological and clinical parameters. In TESE-C cycles, there was a significant lower oocyte maturity rate, embryo cleavage rate and mean number of embryos transferred in AZFb, and a higher mean number of oocytes and lower fertilization rate in AZFc. In conclusion, although patients with AZFc microdeletions presented a high testicular sperm recovery rate and acceptable clinical outcomes, cases with AZFa and AZFb microdeletions presented a poor prognosis. Due to the reported heredity of microdeletions, patients should be informed about the infertile consequences on NB and the possibility of using preimplantation genetic diagnosis for female sex selection.展开更多
We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate （SRR） of microdissection testicular sperm extraction （TESE） in patients with nonobstructive azoo...We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate （SRR） of microdissection testicular sperm extraction （TESE） in patients with nonobstructive azoospermia （NOA）. All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis： follicle-stimulating hormone （FSH）, testicular volume, and testicular histopathological findings which included three patterns： hypospermatogenesis （HS）, maturation arrest （MA）, and Sertoli-cell-only syndrome （SCOS）. If there was a threshold effect, only the area under the summary receiver operating characteristic curve （AUSROC） was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio （PLR）, negative likelihood ratio （NLR）, and the diagnostic odds ratio （DOR） were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.展开更多
Noninvasive parameters for predicating sperm retrieval rate （SRR） are desirables. Follicle-stimulating hormone （FSH） has been an important predictor since the first years of testicular sperm extraction. Recent stu...Noninvasive parameters for predicating sperm retrieval rate （SRR） are desirables. Follicle-stimulating hormone （FSH） has been an important predictor since the first years of testicular sperm extraction. Recent studies showed continuous interests in FSH, with both pros and cons. Thus, we conducted a meta-analysis to evaluate the diagnostic value of FSH as a predictor for patients with nonobstructive azoospermia （NOA） taking testicular sperm retrieval. Eligible diagnosis tests were identified from electronic databases （Cochrane Central Register of Controlled Trials, Medline, and EMBASE） without language restrictions. The database search, quality assessment, and data extraction were performed independently by two reviewers. The reference standard was the sperm retrieval result. Diagnostic value of FSH were explored by area under receiver operation characteristics （ROC） curve using Review Manager, version 5.1.0 （Cochrane Collaboration, Oxford, UK） and Meta-DiSc, version 1.4. Meta regression will be done if there is heterogeneity. Then, we find 11 tests including a total of 1350 patients met the inclusion criteria. Our pooled analysis showed that the area under ROC curve of FSH was 0.72 ~ 0.04. Meta regression analyses showed that region and average age have an influence on the diagnostic value. FSH showed more diagnostic value with patients in East Asia and with younger patients. We concluded that FSH had moderate value in independently predicating SRR in men with NOA （area under curve 〉0.7）. More detailed diagnosis tests should be anticipated in the future to confirm the diagnostic value of other noninvasive parameters.展开更多
This study was performed to investigate a potential marker for the presence of spermatozoa in the ejaculate following varicocelectomy in Chinese men with nonobstructive azoospermia and varicoceles. The micro-RNA （miR...This study was performed to investigate a potential marker for the presence of spermatozoa in the ejaculate following varicocelectomy in Chinese men with nonobstructive azoospermia and varicoceles. The micro-RNA （miR）-192a levels in seminal plasma and testicular tissue were evaluated by quantitative real-time polymerase chain reaction from 60 men with nonobstructive azoospermia and varicoceles （Group A： 27 men with spermatozoa found in the ejaculate after surgery; Group B： 33 men without spermatozoa found in the ejaculate after surgery） and 30 controls. The seminal plasma and testicular tissue miR-192a levels were higher in Group B than in Group A and the controls （P〈 0.001）, and there was no significant difference between Group A and the controls （P〉 0.05）. Apoptosis and proliferation assays with miR mimics and inhibitors showed that miR-192a induced GC-2 cell apoptosis through the activation of Caspase-3 protein. Thus, seminal plasma miR-192a appears to be a potential marker for successfully indicating spermatozoa in the ejaculate following microsurgical varicocelectomy in men with nonobstructive azoospermia and varicoceles. Seminal plasma miR-192a may be a useful clinical marker for prescreening to determine which patients with nonobstructive azoospermia and varicoceles would benefit from varicocelectomy.展开更多
文摘One major challenge in male factor infertility is nonobstructive azoospermia(NOA),which is characterized by spermatozoa-deficient semen without physical duct blockage.This review offers a thorough overview of the histopathology of the testes in NOA cases,clarifying its complex etiology and emphasizing the possible value of histopathology inspection for both diagnosis and treatment.Variable histopathological findings have been linked to NOA,such as tubular hyalinization,Sertoli cell-only syndrome,hypospermatogenesis,and germ cell arrest.Understanding the pathophysiology and forecasting the effectiveness of treatment are further enhanced by both morphometric and ultrastructural analyses.The potential significance of testicular biopsy in forecasting reproductive outcomes is assessed,especially concerning assisted reproductive technologies like intracytoplasmic sperm injection(ICSI).Besides,testicular microlithiasis,serum hormone profiles,and testicular size are investigated concerning NOA histopathology.It is concluded that understanding the histopathological patterns in NOA is crucial for its accurate diagnosis and appropriate management.Further research is still warranted to improve understanding of the complex pathophysiology underlying NOA.
文摘This review focuses on the diagnostic algorithm for nonobstructive azoospermia(NOA),a significant male factor contributing to infertility.NOA,characterized by the absence of sperm in the ejaculate,requires a systematic diagnostic approach to identify reversible conditions,genetic factors,and prognosis for achieving pregnancy.The diagnostic pathway involves semen analysis and a comprehensive evaluation for hormonal deficiencies,anatomical abnormalities,and genetic factors.The importance of medical history,physical examination,endocrine evaluation,imaging,and genetic testing is emphasized.This review highlights the significance of differentiating NOA from obstructive azoospermia(OA)and outlines key considerations for effective management,including surgical sperm retrieval and assisted reproductive techniques.Testicular biopsy is discussed as a definitive method to distinguish obstructive cases from nonobstructive cases,providing valuable prognostic information.Overall,a thorough and systematic diagnostic approach is essential for the effective management of men suspected with NOA,offering insights into potential treatment options and reproductive outcomes.
基金supported by the Shenzhen Fundamental Research Program(No.JCYJ20210324121807021).
文摘To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.
文摘Nonobstructive azoospermia(NOA)is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis.Although various factors are well defined in the disruption of spermatogenesis,not all aspects due to the heterogeneity of the disorder have been determined yet.In this review,we focus on the recent findings and summarize the current data on epigenetic mechanisms such as DNA methylation and different metabolites produced during methylation and demethylation and various types of small noncoding RNAs involved in the pathogenesis of different groups of NOA.
文摘The advent of intracytoplasmic sperm injection,along with the realization that many men with azoospermia due to primary testicular failure may have a few spermatozoa in their testes,has resulted in the revolutionary possibility of azoospermic men fathering their own genetic offspring.
文摘Infertility,defined as the inability to conceive after 1 year of regular unprotected intercourse,impacts 10%–20%of couples globally.Both male and female factors contribute equally to this condition.Azoospermia,particularly nonobstructive azoospermia(NOA),which affects 10%–15%of infertile men,represents a significant challenge in male infertility.The advent of assisted reproductive technology(ART),specifically microdissection testicular sperm extraction(micro-TESE)followed by intracytoplasmic sperm injection(ICSI),offers a possibility for men with NOA to father biological children.Recent studies have focused on the predictors of sperm retrieval in NOA patients,such as age,testicular volume,and follicle-stimulating hormone(FSH)level.This review aims to explore the limited data on the anatomical characteristics of NOA patients and provide surgical considerations for micro-TESE,thereby enhancing understanding and improving outcomes for this challenging condition.
基金supported by the National Natural Science Foundation of China(No.82371633)Peking University Clinical Scientist Training Program and the Fundamental Research Funds for the Central University(BMU2023PYJ H012).
文摘Oncological microdissection testicular sperm extraction(onco-micro-TESE)represents a significant breakthrough for patients with nonobstructive azoospermia(NOA)and a concomitant in situ testicular tumor,to be managed at the time of sperm retrieval.Onco-micro-TESE addresses the dual objectives of treating both infertility and the testicular tumor simultaneously.The technique is intricate,necessitating a comprehensive understanding of testicular anatomy,physiology,tumor biology,and advanced microsurgical methods.It aims to carefully extract viable spermatozoa while minimizing the risk of tumor dissemination.This review encapsulates the procedural intricacies,evaluates success determinants,including tumor pathology and spermatogenic tissue health,and discusses the implementation of imaging techniques for enhanced surgical precision.Ethical considerations are paramount,as the procedure implicates complex decision-making that weighs the potential oncological risks against the profound desire for fatherhood using the male gametes.The review aims to provide a holistic overview of onco-micro-TESE,detailing methodological advances,clinical outcomes,and the ethical landscape,thus offering an indispensable resource for clinicians navigating this multifaceted clinical scenario.
文摘Azoospermia is the complete absence of spermatozoa in the ejaculate in two or more semen analyses after centrifugation.Nonobstructive azoospermia(NOA)represents the most severe form of male factor infertility accounting for 10%–15%of cases and stems from an impairment to spermatogenesis.Understanding of the hypothalamic–pituitary–testicular axis has allowed NOA to be subcategorized by anatomic and/or pathophysiologic level.The etiologies of NOA,and therefore,the differential diagnoses when considering NOA as a cause of male factor infertility,can be subcategorized and condensed into several distinct classifications.Etiologies of NOA include primary hypogonadism,secondary hypogonadism,defects in androgen synthesis and/or response,defective spermatogenesis and sperm maturation,or a mixed picture thereof.This review includes up-to-date clinical,diagnostic,cellular,and histologic features pertaining to the multitude of NOA etiologies.This in turn will provide a framework by which physicians practicing infertility can augment their clinical decision-making,patient counseling,thereby improving upon the management of men with NOA.
基金supported by the National Key Research and Development Program of China(2022YFC2702700)the National Natural Science Foundation of China(No.82171586)+1 种基金Inner Mongolia Academy of Medical Sciences Public Hospital Joint Science and Technology Project(2023GLLH0045)Specific Project of Shanghai Jiao Tong University for“Invigorating Inner Mongolia through Science and Technology”(2022XYJG001-01-19).
文摘Nonobstructive azoospermia(NOA),one of the most severe types of male infertility,etiology often remains unclear in most cases.Therefore,this study aimed to detect four biallelic detrimental variants(0.5%)in the minichromosome maintenance domain containing 2(MCMDC2)genes in 768 NOA patients by whole-exome sequencing(WES).Hematoxylin and eosin(H&E)demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients(c.1360G>T,c.1956G>T,and c.685C>T)and hypospermatogenesis in one patient(c.94G>T),as further confirmed through immunofluorescence(IF)staining.The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis.The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses.The results revealed four MCMDC2 variants related to NOA,which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
文摘Myocardial infarction with nonobstructive coronary arteries is a unique presentation of acute coronary syndrome occurring in patients without significant coronary artery disease.Its pathophysiology involves atherosclerotic and nonatherosclerotic mechanisms such as plaque erosion,coronary microvascular dysfunction,vasospasm,spontaneous coronary artery dissection,autoimmune and inflammatory diseases,and myocardial oxygen supply-demand imbalance.A systematic approach to diagnosis is needed due to the diverse range of underlying causes.Cardiac troponins confirm the myocardial injury and coronary angiography rules out significant obstruction.Cardiac magnetic resonance imaging differentiates ischemic from nonischemic causes,and additional investigations,such as intravascular ultrasound,optical coherence tomography,and provocative testing,play a role in identifying the etiology to guide management strategies.Atherosclerotic cases require antiplatelet therapy and statins,vasospastic cases respond to calcium channel blockers,spontaneous coronary artery dissection is typically managed conservatively,and coronary microvascular dysfunction may require vasodilators.Lifestyle modifications and cardiac rehabilitation are essential for improving outcomes.The prognosis of patients experiencing recurrent events despite treatment is uncertain,but long-term outcomes depend on the etiology,highlighting the need for personalized management.Future research should focus on refining diagnostic protocols and identifying optimal therapeutic strategies.Randomized controlled trials are necessary to establish evidence-based treatments for different subtypes of myocardial infarction with nonobstructive coronary arteries.
文摘Male infertility has seen an increase in prevalence with cases of azoospermia estimated to affect 10%–15%of infertile men.Confirmation of azoospermia subsequently necessitates an early causal differentiation between obstructive azoospermia(OA)and nonobstructive azoospermia(NOA).Although less common when compared to NOA,OA can represent upward 20%–40%of cases of azoospermia.While there are a multitude of etiologies responsible for causing NOA and OA,correctly distinguishing between the two types of azoospermia has profound implications in managing the infertile male.This review represents an amalgamation of the current guidelines and literature which will supply the reproductive physician with a diagnostic armamentarium to properly distinguish between NOA and OA,therefore providing the best possible care to the infertile couple.
文摘Nonobstructive azoospermia(NOA)is the most challenging and complex clinical scenario for infertile men.Besides circumstances such as hypogonadotropic hypogonadism,surgical sperm retrieval is typically necessary,and microdissection testicular sperm extraction(micro-TESE)is the procedure of choice for men with NOA desiring to father children with their own gametes.Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection(ICSI)in comparison to all other techniques for surgical sperm retrieval in men with NOA.Several factors may affect sperm retrieval rate and ICSI outcomes,including the patient’s age,testicular volume,histopathological and genetic profile,and serum hormone levels.This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.
文摘We investigated the prognostic importance of noninvasive factors in predicting sperm retrieval failure in idiopathic nonobstructive azoospermia(iNOA).We studied 193 patients with nonobstructive azoospermia who underwent microsurgical testicular sperm extraction.The Chi-square test and Mann–Whitney U tests for clinical parameters and seminiferous tubule distribution were used for between-group comparisons.A logistic regression analysis was conducted to identify predictors of retrieval failure.Area under the receiver operating characteristic curve for each variable was evaluated,and the net clinical benefit was calculated using a clinical decision curve.Patients with iNOA had a lower sperm retrieval rate than those with known causes.Moreover,testicular volume was an independent factor affecting sperm extraction outcomes(odds ratio=0.79,P<0.05).The testicular volume cut-off value was 6.5 ml(area under the curve:0.694).The patients with iNOA were categorized into two groups on the basis of the distribution of seminiferous tubules observed.The sperm retrieval rate and testicular volume were significantly different between the groups with a uniform or heterogeneous tubule distribution.There was also a significant association between a uniform tubule distribution and testicular volume.In conclusion,a testicular volume of more than 6.5 ml effectively predicts microsurgical testicular sperm extraction failure due to a uniform tubule distribution in patients with iNOA.
文摘Microdissection testicular sperm extraction(mTESE)is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia(iNOA).However,the success rate of sperm retrieval varies among individuals.We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA.We searched PubMed,EMBASE,and Web of Science from database inception to August 2,2023.The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE.Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models.The overall sperm retrieval rate was 36.8%(95%confidence interval[CI]:27.5%-46.0%,I 2=95.0%)in nine studies comprising 1892 patients with iNOA.No significant differences were found in age,testicular volume,serum total testosterone concentrations,or inhibin B concentrations between positive and negative sperm retrieval outcomes.Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE(weighted mean differences:−2.70;95%CI:−3.94-−1.46,I 2=79.0%).In conclusion,this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA,while age,testicular volume,total testosterone,and inhibin B show no significant association.These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.
文摘The clinical management of men with nonobstructive azoospermia （NOA） seeking fertility has been a challenge for andrologists, urologists, and reproductive medicine specialists alike. This review presents a personal perspective on the clinical management of NOA, including the lessons learned over 15 years dealing with this male infertility condition. A five-consecutive-step algorithm is proposed to manage such patients. First, a differential diagnosis of azoospermia is made to confirm/establish that NOA is due to spermatogenic failure. Second, genetic testing is carried out not only to detect the males in whom NOA is caused by microdeletions of the long arm of the Y chromosome, but also to counsel the affected patients about their chances of having success in sperm retrieval. Third, it is determined whether any intervention prior to a surgical retrieval attempt may be used to increase sperm production. Fourth, the most effective and efficient retrieval method is selected to search for testicular sperm. Lastly, state-of-art laboratory techniques are applied in the handling of retrieved gametes and cultivating the embryos resulting from sperm injections. A coordinated multidisciplinary effort is key to offer the best possible chance of achieving a biological offspring to males with NOA.
文摘Many studies have shown that microRNAs(miRNAs)play vital roles during the spermatogenesis.However,little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia(NOA).Using microarray technology,the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined.Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs.The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),the results of which were then validated with a larger sample size.Correlations between the miRNA expression levels and clinical characteristics were analyzed.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia.Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups.Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis,cell cycle,and mitotic prometaphase.In the subsequent qRT-PCR assays,the selected miRNA expression levels were consistent with the microarray results,and similar validated results were obtained with a larger sample size.Some clinical characteristics were significantly associated with the expression of certain miRNAs.In particular,we identified a combination of two miRNAs(miR-10b-3p and miR-34b-5p)that could serve as a predictive biomarker of azoospermia.This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis.These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.
文摘The aim of the present work was to present the outcomes of the patients with Y-chromosome microdeletions treated by intracytoplasmic sperm injection （ICSI）, either using fresh （TESE） or frozen-thawed （TESE-C） testicular sperm and ejaculated sperm （EJAC）. The originality of this work resides in the comparisons between the different types of Y-microdeletions （AZFa, AZFb, and AZFc） and treatments, with detailed demographic, stimulation, embryological, clinical, and newborn （NB） outcomes. Of 125 patients with Y-microdeletions, 33 patients presented severe oligozoospermia （18 performed ICSI with ejaculated sperm） and 92 secretory azoospermia （65 went for TESE with 40 having successful sperm retrieval and performed ICSI）. There were 51 TESE treatment cycles and 43 TESE-C treatment cycles, with a birth of 19 NB （2 in AZFa/TESE-C, 12 in AZFc/TESE, and 5 in AZFc/TESE-C）. Of the 29 EJAC cycles, there was a birth of 8 NB （in AZFc）. In TESE and EJAC cycles, there were no significant differences in embryological and clinical parameters. In TESE-C cycles, there was a significant lower oocyte maturity rate, embryo cleavage rate and mean number of embryos transferred in AZFb, and a higher mean number of oocytes and lower fertilization rate in AZFc. In conclusion, although patients with AZFc microdeletions presented a high testicular sperm recovery rate and acceptable clinical outcomes, cases with AZFa and AZFb microdeletions presented a poor prognosis. Due to the reported heredity of microdeletions, patients should be informed about the infertile consequences on NB and the possibility of using preimplantation genetic diagnosis for female sex selection.
文摘We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate （SRR） of microdissection testicular sperm extraction （TESE） in patients with nonobstructive azoospermia （NOA）. All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis： follicle-stimulating hormone （FSH）, testicular volume, and testicular histopathological findings which included three patterns： hypospermatogenesis （HS）, maturation arrest （MA）, and Sertoli-cell-only syndrome （SCOS）. If there was a threshold effect, only the area under the summary receiver operating characteristic curve （AUSROC） was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio （PLR）, negative likelihood ratio （NLR）, and the diagnostic odds ratio （DOR） were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.
文摘Noninvasive parameters for predicating sperm retrieval rate （SRR） are desirables. Follicle-stimulating hormone （FSH） has been an important predictor since the first years of testicular sperm extraction. Recent studies showed continuous interests in FSH, with both pros and cons. Thus, we conducted a meta-analysis to evaluate the diagnostic value of FSH as a predictor for patients with nonobstructive azoospermia （NOA） taking testicular sperm retrieval. Eligible diagnosis tests were identified from electronic databases （Cochrane Central Register of Controlled Trials, Medline, and EMBASE） without language restrictions. The database search, quality assessment, and data extraction were performed independently by two reviewers. The reference standard was the sperm retrieval result. Diagnostic value of FSH were explored by area under receiver operation characteristics （ROC） curve using Review Manager, version 5.1.0 （Cochrane Collaboration, Oxford, UK） and Meta-DiSc, version 1.4. Meta regression will be done if there is heterogeneity. Then, we find 11 tests including a total of 1350 patients met the inclusion criteria. Our pooled analysis showed that the area under ROC curve of FSH was 0.72 ~ 0.04. Meta regression analyses showed that region and average age have an influence on the diagnostic value. FSH showed more diagnostic value with patients in East Asia and with younger patients. We concluded that FSH had moderate value in independently predicating SRR in men with NOA （area under curve 〉0.7）. More detailed diagnosis tests should be anticipated in the future to confirm the diagnostic value of other noninvasive parameters.
文摘This study was performed to investigate a potential marker for the presence of spermatozoa in the ejaculate following varicocelectomy in Chinese men with nonobstructive azoospermia and varicoceles. The micro-RNA （miR）-192a levels in seminal plasma and testicular tissue were evaluated by quantitative real-time polymerase chain reaction from 60 men with nonobstructive azoospermia and varicoceles （Group A： 27 men with spermatozoa found in the ejaculate after surgery; Group B： 33 men without spermatozoa found in the ejaculate after surgery） and 30 controls. The seminal plasma and testicular tissue miR-192a levels were higher in Group B than in Group A and the controls （P〈 0.001）, and there was no significant difference between Group A and the controls （P〉 0.05）. Apoptosis and proliferation assays with miR mimics and inhibitors showed that miR-192a induced GC-2 cell apoptosis through the activation of Caspase-3 protein. Thus, seminal plasma miR-192a appears to be a potential marker for successfully indicating spermatozoa in the ejaculate following microsurgical varicocelectomy in men with nonobstructive azoospermia and varicoceles. Seminal plasma miR-192a may be a useful clinical marker for prescreening to determine which patients with nonobstructive azoospermia and varicoceles would benefit from varicocelectomy.
