Patients with extremely severe oligozoospermia （ESO） and cryptozoospermia （CO） are suitable using intracytoplasmic sperm injection （ICSI） as an infertility treatment. However, some andrologists are confused to d...Patients with extremely severe oligozoospermia （ESO） and cryptozoospermia （CO） are suitable using intracytoplasmic sperm injection （ICSI） as an infertility treatment. However, some andrologists are confused to distinguish ESO and CO in clinic diagnose. This study was designed for the first time to evaluate and compare patients with ESO and CO to determine whether these are useful clinical distinctions. A total of 270 infertile men in our center were classified into four groups as Group nonobstruction azoospermia （NOA, n = 44）, Group ESO （n = 78）, Group CO （n = 40）, and Group obstruction azoospermia （OA, n = 108）. Comparisons of the volume of bilateral testes, the level of follicle stimulating hormone （FSH） and inhibin B were obtained in four groups. Then comparisons of fertilization rates, cleavage rate, and excellent embryos rate were obtained when couples performed ICSh All indexes （volume of bilateral testis, level of FSH and inhibin B） in Groups ESO and CO were no difference, while Groups OA versus NOA, OA versus ESO, and OA versus CO were significant differences （P 〈 0.05）. The rates of fertilization were no differences in Groups ESO and CO while Groups OA versus ESO, OA versus CO were significant differences （P 〈 0.05）. Therefore, the spermatogenic functions in patients with CO and ESO were similar, better than NOA but worse than OA. However, it would be helpful to evaluate their spermatogenesis using testicular biopsies, especially accompanied azoospermia in clinical practice.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
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
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
There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men.Here,we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and...There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men.Here,we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del(p.D51fs)frame-shift mutation in exon 3 of the testis expressed 11(TEX11)gene in one patient.Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation.Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes.In contrast,testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression.Western blotting of human embryonic kidney(HEK293)cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression.In conclusion,we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient,emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.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
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
Maturation arrest （MA） refers to failure of germ cell development leading to clinical nonobstructive azoospermia. Although the azoospermic factor （AZF） region of the human Y chromosome is clearly implicated in som...Maturation arrest （MA） refers to failure of germ cell development leading to clinical nonobstructive azoospermia. Although the azoospermic factor （AZF） region of the human Y chromosome is clearly implicated in some cases, thus far very little is known about which individual Y-chromosome genes are important for complete male germ cell development. We sought to identify single genes on the Y chromosome that may be implicated in the pathogenesis of nonobstructive azoospermia associated with MA in the American population. Genotype-phenotype analysis of 132 men with Y-chromosome microdeletions was performed. Protein-coding genes associated with MA were identified by visual analysis of a genotype-phenotype map. Genes associated with MA were selected as those genes within a segment of the Y chromosome that, when completely or partially deleted, were always associated with MA and absence of retrievable testicular sperm. Expression of each identified gene transcript was then measured with quantitative RT-PCR in testicular tissue from separate cohorts of patients with idiopathic MA and obstructive azoospermia. Ten candidate genes for association with MA were identified within an 8.4-Mb segment of the Y chromosome overlapping the AZFb region. CDY2and HSFYwere the only identified genes for which differences in expression were observed between the MA and obstructive azoospermia cohorts. Men with obstructive azoospermia had 12-fold higher relative expression of CDY2transcript （1.33__.0.40 vs. 0.11＋_0.04; P=O.O003） and 16-fold higher expression of HSFYtranscript （0.78__.0.32 vs. 0.05_0.02; P=O.O005） compared to men with MA. CDY2 and HSFYwere also underexpressed in patients with Sertoli cell only syndrome. These data indicate that CDY2and HSFYare located within a segment of the Y chromosome that is important for sperm maturation, and are underexpressed in testicular tissue derived from men with MA. These observations suggest that impairments in CDY2 or HSFYexpression could be implicated in the pathogenesis of M展开更多
The authors performed a comprehensive review of current literature to create a model comparing commonly evaluated variables in male factor infertility,for example,follicle-stimulating hormone(FSH),testicular volume(TV...The authors performed a comprehensive review of current literature to create a model comparing commonly evaluated variables in male factor infertility,for example,follicle-stimulating hormone(FSH),testicular volume(TV),and testosterone(T),to better predict sperm retrieval rate(SRR).Twenty-nine studies were included,9 with data on conventional testicular sperm extraction(cTESE)for a total of 1227 patients and 20 studies including data on microdissection testicular sperm extraction(mTESE)for a total of 4760 patients.A weighted-means value of SRR,FSH,T,and TV was created,and a weighted linear regression was then used to describe associations among SRR,type of procedure,FSH,T,and TV.In this study,weighted-means values demonstrated mTESE to be superior to cTESE with an SRR of 51.9%vs 40.1%.Multiple weighted linear regressions were created to describe associations among SRR,procedure type,FSH,T,and TV.The models showed that for every 1.19 mIU ml^(−1)increase in FSH,there would be a significant decrease in SRR by 1.0%.Seeking to create a more clinically relevant model,FSH values were then divided into normal,moderate elevation,and significant elevation categories(FSH<10 mIU ml^(−1),10–19 mIU ml^(−1),and>20 mIU ml^(−1),respectively).For an index patient undergoing cTESE,the retrieval rates would be 57.1%,44.3%,and 31.2%for values normal,moderately elevated,and significantly elevated,respectively.In conclusion,in a large meta-analysis,mTESE was shown to be more successful than cTESE for sperm retrievals.FSH has an inverse relationship to SRR in retrieval techniques and can alone be predictive of cTESE SRR.展开更多
Klinefelter syndrome(KS)is the most common genetic cause of human male infertility.However,the effect of the extra X chromosome on different testicular cell types remains poorly understood.Here,we profiled testicular ...Klinefelter syndrome(KS)is the most common genetic cause of human male infertility.However,the effect of the extra X chromosome on different testicular cell types remains poorly understood.Here,we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals.Among the different somatic cells,Sertoli cells showed the greatest transcriptome changes in KS patients.Further analysis showed that X-inactive-specific transcript(XIST),a key factor that inactivates one X chromosome in female mammals,was widely expressed in each testicular somatic cell type but not in Sertoli cells.The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes,and further disrupts their transcription pattern and cellular function.This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells.These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia.Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.展开更多
Nonobstructive azoospermia(NOA)is a severe condition in infertile men,and increasing numbers of causative genes have been identified during the last few decades.Although certain causative genes can explain the presenc...Nonobstructive azoospermia(NOA)is a severe condition in infertile men,and increasing numbers of causative genes have been identified during the last few decades.Although certain causative genes can explain the presence of NOA in some patients,a proportion of NOA patients remain to be addressed.This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing.Whole-exome sequencing was performed in 46 male patients diagnosed with NOA.First,screening was performed for 119 genes known to be related to male infertility.Next,further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls.Finally,risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed.The frequency of cystic fibrosis transmembrane conductance regulator(CFTR)gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls.Potential risk genes that may be causes of NOA were identified,including seven genes that were highly/specifically expressed in the testes.Four risk genes previously reported to be involved in spermatogenesis(MutS homolog 5[MSH5],cilia-and flagella-associated protein 54[CFAP54],MAP7 domain containing 3[MAP7D3],and coiled-coil domain containing 33[CCDC33])and three novel risk genes(coiled-coil domain containing 168[CCDC168],chromosome 16 open reading frame 96[C16orf96],and serine protease 48[PRSS48])were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls.This study on clinical NOA patients provides further evidence for the four previously reported risk genes.The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of 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
AIM To assess the arrhythmic determinants and prognosis of patients presenting with myocardial infarction and nonobstructive coronary arteries(MINOCA)with normal ejection fraction(EF).METHODS This is an observational ...AIM To assess the arrhythmic determinants and prognosis of patients presenting with myocardial infarction and nonobstructive coronary arteries(MINOCA)with normal ejection fraction(EF).METHODS This is an observational analysis of 131 MINOCA patients with normal EF.Three cardiac magnetic resonance(CMR)diagnosis classes were recognized according to the late gadolinium enhancement(LGE)pattern:Myocardial infarction(MI)(n=34),myocarditis(n=47),and"no LGE"(n=50).Ventricular events occurring during hospitalization were recorded and the entire population was followed-up at 1 year.RESULTS Ventricular arrhythmia was observed in 18(13.8%)patients during hospitalization.The"no LGE"patients experienced fewer ventricular events than the MI and myocarditis patients[4.0%vs 26.5%and 14.9%,respectively(P=0.013)].There was no significant difference between the MI and myocarditis groups.On multivariate analysis,LGE transmural extent[OR=1.52(1.08-2.15),P=0.017]and ST-segment elevation[OR=4.65(1.61-13.40),P=0.004]were independent predictors of ventricular arrhythmic events,irrespective of the diagnosis class.Finally,no patient experienced sudden cardiac death or ventricular arrhythmia recurrence at 1-year.CONCLUSION MINOCA patients with normal EF presented no 1-year cardiovascular events,irrespective of the CMR diagnosis class.LGE transmural extent and ST segment elevation at admission are risk markers of ventricular arrhythmia during hospitalization.展开更多
Stepwise mini-incision microdissection testicular sperm extraction(mTESE)is a procedure that attempts to minimize testicular damage.However,the mini-incision approach may vary in patients with different etiologies.Her...Stepwise mini-incision microdissection testicular sperm extraction(mTESE)is a procedure that attempts to minimize testicular damage.However,the mini-incision approach may vary in patients with different etiologies.Here,we performed a retrospective analysis of 665 men with nonobstructive azoospermia(NOA)who underwent stepwise mini-incision mTESE(Group 1)and 365 men who underwent standard mTESE(Group 2).The results showed that the operation time(mean±standard deviation)for patients with successful sperm retrieval in Group1(64.0±26.6min)was significantly shorter than that in Group2(80.2±31.3min),with P<0.001.The total sperm retrieval rate(SRR)was 23.1%in our study,and there was no significant difference between Group 1 and Group 2(P>0.05),even when the etiologies of NOA were taken into consideration.The results of consecutive multivariate logistic regression analysis(odds ratio[0R]:0.57;95%confidence interval[Cl]:0.38-0.87;P=0.009)and receiver operating characteristic(ROC)analysis(area under the ROC curve[AUC]=O.628)showed that preoperative anti-Mullerian hormone(AMH)level in idiopathic NOA patients was a potential predictor for surgical outcomes after initial three small incisions made in the equatorial region without sperm examined under an operating microscope(Steps 2-4).In conclusion,stepwise mini-incision mTESE is a useful technique for NOA patients,with comparable SRR,less surgical invasiveness,and shorter operation time compared with the standard approach.Low AMH levels may predict successful sperm retrieval in idiopathic patients even after a failed initial mini-incision procedure.展开更多
BACKGROUND Acute myocardial infarction(AMI) is characterized by chest pain as well as cardiac troponin I(cTnI) and electrocardiography(ECG) changes. Recently,clinical researchers have used the term "MINOCA" ...BACKGROUND Acute myocardial infarction(AMI) is characterized by chest pain as well as cardiac troponin I(cTnI) and electrocardiography(ECG) changes. Recently,clinical researchers have used the term "MINOCA" to indicate myocardial infarction with nonobstructive coronary arteries. To the best of our knowledge,no report has documented MINOCA in a young patient after choledocholithiasis by endoscopic retrograde cholangiopancreatography(ERCP).CASE SUMMARY An 18-year-old Chinese man presented to the cardiac intensive care unit with chest pain radiating to the left shoulder for 1 h after choledocholithiasis by ERCP and the following treatment. ECG showed a sinus rhythm with ST-segment elevation in the Ⅱ,Ⅲ, and aVF leads compared with the baseline. Laboratory data revealed cTnI levels of 67.55 ng/mL and 80 ng/mL at the peak(relative index below 0.034 ng/mL) and creatine kinase-MB levels of 56 U/L and 543 U/L at the peak(relative index below 24 U/L). AMI was suspected, and coronary angiography was performed the second day. The results revealed a smooth angiographic appearance of all arteries. The patient had been diagnosed with gallstones and cholecystitis for four years but had not accepted treatment. He had abdominal pain and bloating a week previously and underwent ERCP and subsequent treatments on the second day of admission;1.4 cm × 1.6 cm of stones were removed from his common bile duct during surgery. The results of his laboratory tests at admission revealed abnormal alanine aminotransferase,aspartate aminotransferase, glutamyl transpeptidase, total bile acid, total bilirubin, direct bilirubin, and indirect bilirubin levels. His temperature, heart rate, blood pressure, and body mass index were normal. His echocardiographic examination revealed no obvious abnormalities in the structure and movement of the ventricular wall and an estimated left ventricular ejection fraction of 57% after the heart attack. His cholesterol and triglycerides were within normal ranges, and his low-density lipoprotein cholesterol was 展开更多
文摘Patients with extremely severe oligozoospermia （ESO） and cryptozoospermia （CO） are suitable using intracytoplasmic sperm injection （ICSI） as an infertility treatment. However, some andrologists are confused to distinguish ESO and CO in clinic diagnose. This study was designed for the first time to evaluate and compare patients with ESO and CO to determine whether these are useful clinical distinctions. A total of 270 infertile men in our center were classified into four groups as Group nonobstruction azoospermia （NOA, n = 44）, Group ESO （n = 78）, Group CO （n = 40）, and Group obstruction azoospermia （OA, n = 108）. Comparisons of the volume of bilateral testes, the level of follicle stimulating hormone （FSH） and inhibin B were obtained in four groups. Then comparisons of fertilization rates, cleavage rate, and excellent embryos rate were obtained when couples performed ICSh All indexes （volume of bilateral testis, level of FSH and inhibin B） in Groups ESO and CO were no difference, while Groups OA versus NOA, OA versus ESO, and OA versus CO were significant differences （P 〈 0.05）. The rates of fertilization were no differences in Groups ESO and CO while Groups OA versus ESO, OA versus CO were significant differences （P 〈 0.05）. Therefore, the spermatogenic functions in patients with CO and ESO were similar, better than NOA but worse than OA. However, it would be helpful to evaluate their spermatogenesis using testicular biopsies, especially accompanied azoospermia in clinical practice.
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.
基金the Key Research and Development Program of Shandong Province(2019GSF108237)the Young Scholars Program of Shandong University(2016WLJH50)the Natural Science Foundation of Shandong Province(ZR2017MH049).
文摘There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men.Here,we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del(p.D51fs)frame-shift mutation in exon 3 of the testis expressed 11(TEX11)gene in one patient.Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation.Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes.In contrast,testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression.Western blotting of human embryonic kidney(HEK293)cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression.In conclusion,we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient,emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.
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.
文摘Maturation arrest （MA） refers to failure of germ cell development leading to clinical nonobstructive azoospermia. Although the azoospermic factor （AZF） region of the human Y chromosome is clearly implicated in some cases, thus far very little is known about which individual Y-chromosome genes are important for complete male germ cell development. We sought to identify single genes on the Y chromosome that may be implicated in the pathogenesis of nonobstructive azoospermia associated with MA in the American population. Genotype-phenotype analysis of 132 men with Y-chromosome microdeletions was performed. Protein-coding genes associated with MA were identified by visual analysis of a genotype-phenotype map. Genes associated with MA were selected as those genes within a segment of the Y chromosome that, when completely or partially deleted, were always associated with MA and absence of retrievable testicular sperm. Expression of each identified gene transcript was then measured with quantitative RT-PCR in testicular tissue from separate cohorts of patients with idiopathic MA and obstructive azoospermia. Ten candidate genes for association with MA were identified within an 8.4-Mb segment of the Y chromosome overlapping the AZFb region. CDY2and HSFYwere the only identified genes for which differences in expression were observed between the MA and obstructive azoospermia cohorts. Men with obstructive azoospermia had 12-fold higher relative expression of CDY2transcript （1.33__.0.40 vs. 0.11＋_0.04; P=O.O003） and 16-fold higher expression of HSFYtranscript （0.78__.0.32 vs. 0.05_0.02; P=O.O005） compared to men with MA. CDY2 and HSFYwere also underexpressed in patients with Sertoli cell only syndrome. These data indicate that CDY2and HSFYare located within a segment of the Y chromosome that is important for sperm maturation, and are underexpressed in testicular tissue derived from men with MA. These observations suggest that impairments in CDY2 or HSFYexpression could be implicated in the pathogenesis of M
文摘The authors performed a comprehensive review of current literature to create a model comparing commonly evaluated variables in male factor infertility,for example,follicle-stimulating hormone(FSH),testicular volume(TV),and testosterone(T),to better predict sperm retrieval rate(SRR).Twenty-nine studies were included,9 with data on conventional testicular sperm extraction(cTESE)for a total of 1227 patients and 20 studies including data on microdissection testicular sperm extraction(mTESE)for a total of 4760 patients.A weighted-means value of SRR,FSH,T,and TV was created,and a weighted linear regression was then used to describe associations among SRR,type of procedure,FSH,T,and TV.In this study,weighted-means values demonstrated mTESE to be superior to cTESE with an SRR of 51.9%vs 40.1%.Multiple weighted linear regressions were created to describe associations among SRR,procedure type,FSH,T,and TV.The models showed that for every 1.19 mIU ml^(−1)increase in FSH,there would be a significant decrease in SRR by 1.0%.Seeking to create a more clinically relevant model,FSH values were then divided into normal,moderate elevation,and significant elevation categories(FSH<10 mIU ml^(−1),10–19 mIU ml^(−1),and>20 mIU ml^(−1),respectively).For an index patient undergoing cTESE,the retrieval rates would be 57.1%,44.3%,and 31.2%for values normal,moderately elevated,and significantly elevated,respectively.In conclusion,in a large meta-analysis,mTESE was shown to be more successful than cTESE for sperm retrievals.FSH has an inverse relationship to SRR in retrieval techniques and can alone be predictive of cTESE SRR.
基金This work was supported by grants from the National Key R&D Program of China(2022YFC2702700)National Natural Science Foundation of China(82201756 and 82171597)+1 种基金China Postdoctoral Science Foundation(2021M703747)GuangDong Basic and Applied Basic Research Foundation(2021A1515111109)。
文摘Klinefelter syndrome(KS)is the most common genetic cause of human male infertility.However,the effect of the extra X chromosome on different testicular cell types remains poorly understood.Here,we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals.Among the different somatic cells,Sertoli cells showed the greatest transcriptome changes in KS patients.Further analysis showed that X-inactive-specific transcript(XIST),a key factor that inactivates one X chromosome in female mammals,was widely expressed in each testicular somatic cell type but not in Sertoli cells.The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes,and further disrupts their transcription pattern and cellular function.This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells.These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia.Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.
基金supported by grants from the National Natural Science Foundation of China (No.81971440)the Beijing Natural Science Foundation (No.7212129).
文摘Nonobstructive azoospermia(NOA)is a severe condition in infertile men,and increasing numbers of causative genes have been identified during the last few decades.Although certain causative genes can explain the presence of NOA in some patients,a proportion of NOA patients remain to be addressed.This study aimed to investigate potential high-risk genes associated with spermatogenesis in idiopathic NOA patients by whole-exome sequencing.Whole-exome sequencing was performed in 46 male patients diagnosed with NOA.First,screening was performed for 119 genes known to be related to male infertility.Next,further screening was performed to determine potential high-risk causative genes for NOA by comparisons with 68 healthy male controls.Finally,risk genes with high/specific expression in the testes were selected and their expression fluctuations during spermatogenesis were graphed.The frequency of cystic fibrosis transmembrane conductance regulator(CFTR)gene pathogenic variant carriers was higher in the NOA patients compared with the healthy controls.Potential risk genes that may be causes of NOA were identified,including seven genes that were highly/specifically expressed in the testes.Four risk genes previously reported to be involved in spermatogenesis(MutS homolog 5[MSH5],cilia-and flagella-associated protein 54[CFAP54],MAP7 domain containing 3[MAP7D3],and coiled-coil domain containing 33[CCDC33])and three novel risk genes(coiled-coil domain containing 168[CCDC168],chromosome 16 open reading frame 96[C16orf96],and serine protease 48[PRSS48])were identified to be highly or specifically expressed in the testes and significantly different in the 46 NOA patients compared with 68 healthy controls.This study on clinical NOA patients provides further evidence for the four previously reported risk genes.The present findings pave the way for further functional investigations and provide candidate risk genes for genetic diagnosis of 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.
基金Supported by The French Federation of Cardiology(Fédération francaise de Cardiologie)
文摘AIM To assess the arrhythmic determinants and prognosis of patients presenting with myocardial infarction and nonobstructive coronary arteries(MINOCA)with normal ejection fraction(EF).METHODS This is an observational analysis of 131 MINOCA patients with normal EF.Three cardiac magnetic resonance(CMR)diagnosis classes were recognized according to the late gadolinium enhancement(LGE)pattern:Myocardial infarction(MI)(n=34),myocarditis(n=47),and"no LGE"(n=50).Ventricular events occurring during hospitalization were recorded and the entire population was followed-up at 1 year.RESULTS Ventricular arrhythmia was observed in 18(13.8%)patients during hospitalization.The"no LGE"patients experienced fewer ventricular events than the MI and myocarditis patients[4.0%vs 26.5%and 14.9%,respectively(P=0.013)].There was no significant difference between the MI and myocarditis groups.On multivariate analysis,LGE transmural extent[OR=1.52(1.08-2.15),P=0.017]and ST-segment elevation[OR=4.65(1.61-13.40),P=0.004]were independent predictors of ventricular arrhythmic events,irrespective of the diagnosis class.Finally,no patient experienced sudden cardiac death or ventricular arrhythmia recurrence at 1-year.CONCLUSION MINOCA patients with normal EF presented no 1-year cardiovascular events,irrespective of the CMR diagnosis class.LGE transmural extent and ST segment elevation at admission are risk markers of ventricular arrhythmia during hospitalization.
基金supported by the National Natural Science Foundation of China(No.82171590,82171597,and 82001530)Clinical Research Innovation Plan of Shanghai General Hospital(KD007-ly01,and CTCCR-C04)。
文摘Stepwise mini-incision microdissection testicular sperm extraction(mTESE)is a procedure that attempts to minimize testicular damage.However,the mini-incision approach may vary in patients with different etiologies.Here,we performed a retrospective analysis of 665 men with nonobstructive azoospermia(NOA)who underwent stepwise mini-incision mTESE(Group 1)and 365 men who underwent standard mTESE(Group 2).The results showed that the operation time(mean±standard deviation)for patients with successful sperm retrieval in Group1(64.0±26.6min)was significantly shorter than that in Group2(80.2±31.3min),with P<0.001.The total sperm retrieval rate(SRR)was 23.1%in our study,and there was no significant difference between Group 1 and Group 2(P>0.05),even when the etiologies of NOA were taken into consideration.The results of consecutive multivariate logistic regression analysis(odds ratio[0R]:0.57;95%confidence interval[Cl]:0.38-0.87;P=0.009)and receiver operating characteristic(ROC)analysis(area under the ROC curve[AUC]=O.628)showed that preoperative anti-Mullerian hormone(AMH)level in idiopathic NOA patients was a potential predictor for surgical outcomes after initial three small incisions made in the equatorial region without sperm examined under an operating microscope(Steps 2-4).In conclusion,stepwise mini-incision mTESE is a useful technique for NOA patients,with comparable SRR,less surgical invasiveness,and shorter operation time compared with the standard approach.Low AMH levels may predict successful sperm retrieval in idiopathic patients even after a failed initial mini-incision procedure.
基金Supported by Beijing University of Chinese Medicine 1166 Development Program for Junior Scientists,No.030903010331
文摘BACKGROUND Acute myocardial infarction(AMI) is characterized by chest pain as well as cardiac troponin I(cTnI) and electrocardiography(ECG) changes. Recently,clinical researchers have used the term "MINOCA" to indicate myocardial infarction with nonobstructive coronary arteries. To the best of our knowledge,no report has documented MINOCA in a young patient after choledocholithiasis by endoscopic retrograde cholangiopancreatography(ERCP).CASE SUMMARY An 18-year-old Chinese man presented to the cardiac intensive care unit with chest pain radiating to the left shoulder for 1 h after choledocholithiasis by ERCP and the following treatment. ECG showed a sinus rhythm with ST-segment elevation in the Ⅱ,Ⅲ, and aVF leads compared with the baseline. Laboratory data revealed cTnI levels of 67.55 ng/mL and 80 ng/mL at the peak(relative index below 0.034 ng/mL) and creatine kinase-MB levels of 56 U/L and 543 U/L at the peak(relative index below 24 U/L). AMI was suspected, and coronary angiography was performed the second day. The results revealed a smooth angiographic appearance of all arteries. The patient had been diagnosed with gallstones and cholecystitis for four years but had not accepted treatment. He had abdominal pain and bloating a week previously and underwent ERCP and subsequent treatments on the second day of admission;1.4 cm × 1.6 cm of stones were removed from his common bile duct during surgery. The results of his laboratory tests at admission revealed abnormal alanine aminotransferase,aspartate aminotransferase, glutamyl transpeptidase, total bile acid, total bilirubin, direct bilirubin, and indirect bilirubin levels. His temperature, heart rate, blood pressure, and body mass index were normal. His echocardiographic examination revealed no obvious abnormalities in the structure and movement of the ventricular wall and an estimated left ventricular ejection fraction of 57% after the heart attack. His cholesterol and triglycerides were within normal ranges, and his low-density lipoprotein cholesterol was
