Deletion or underexpression of the Y-chromosome genes CDY2 and HSFY is associated with maturation arrest in American men with nonobstructive azoospermia

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 MA.

Testicular volume is a noninvasive predictor of sperm retrieval failure in idiopathic nonobstructive azoospermia

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.

Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing

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.

Efficacy of stepwise mini-incision microdissection testicular sperm extraction for nonobstructive azoospermia with varied etiologies

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.

Clinical management of infertile men with nonobstructive azoospermia

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.

Predictive value of FSH, testicular volume, and histopathological findings for the sperm retrieval rate of microdissection TESE in nonobstructive azoospermia： a meta-analysis

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.

Y-chromosome microdeletions in nonobstructive azoospermia and severe oligozoospermia

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.

Follicle-stimulating hormone as a predictor for sperm retrieval rate in patients with nonobstructive azoospermia, a systematic review and meta-analysis

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.

Seminal plasma miR-192a： a biomarker predicting successful resolution of nonobstructive azoospermia following varicocele repair

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.

Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia

Prior studies have investigated sperm retrieval rates in men with non obstructive azoospermia(NOA)secondary to specific etiologies,yet most cases of NOA are idiopathic.We compared sperm retrieval rates and testicular histopathology in idiopathic NOA(iNOA)and nonidiopathic NOA(niNOA).We performed a retrospective review of men with NOA who underwent microdissection testicular sperm extraction(microTESE)between 2000 and 2016.Men with no history of malignancy or cryptorchidism and negative genetic evaluation were considered idiopathic.Multivariable regression determined the association between idiopathic etiology and primary outcomes of sperm retrieval and active spermatogenesis on histopathology.Among 224 men,86(38.4%)were idiopathic,75(33.5%)were nonidiopathic,and 63(28.1%)did not undergo genetic testing.Median age and serum testosterone were higher among iNOA or no testing versus niNOA.Median follicle-stimulating hormone(FSH)was lower among iNOA or no testing versus niNOA.A higher proportion of iNOA or no testing versus niNOA had a clinical varicocele.Sperm retrieval rates were similar between iNOA,niNOA,and no testing(41.8%vs 48.0%vs 55.6%,respectively;P=0.255).Active spermatogenesis was seen in a higher proportion of iNOA or no testing versus niNOA(31.4%and 27.0%vs 16.0%,P=0.073).On multivariable analysis,iNOA was not associated with sperm retrieval or spermatogenesis(P=0.430 and P=0.078,respectively).Rates of sperm retrieval and spermatogenesis on testis pathology were similar in men with iNOA and niNOA.These data will be useful to clinicians in preoperative counseling for men with NOA and negative genetic evaluation.

Endocrine aberrations of human nonobstructive azoospermia

Nonobstructive azoospermia(NOA)refers to the failure of spermatogenesis,which affects approximately 1%of the male population and contributes to 10%of male infertility.NOA has an underlying basis of endocrine imbalances since proper human spermatogenesis relies on complex regulation and cooperation of multiple hormones.A better understanding of subtle hormonal disturbances in NOA would help design and improve hormone therapies with reduced risk in human fertility clinics.The purpose of this review is to summarize the research on the endocrinological aspects of NOA,especially the hormones involved in hypothalamic–pituitary–testis axis(HPTA),including gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone,prolactin,testosterone,estradiol,sex hormone binding globulin,inhibin B,anti-Müllerian hormone,and leptin.For the NOA men associated with primary testicular failure,the quality of currently available evidence has not been sufficient enough to recommend any general hormone optimization therapy.Some other NOA patients,especially those with hypogonadotropic hypogonadism,could be treated with hormonal replacement.Although these approaches have succeeded in resuming the fertility in many NOA patients,the prudent strategies should be applied in individuals according to specific NOA etiology by balancing fertility benefits and potential risks.This review also discusses how NOA can be induced by immunization against hormones.

MBOAT1 homozygous missense variant causes nonobstructive azoospermia

Nonobstructive azoospermia(NOA)is a common cause of infertility and is defined as the complete absence of sperm in ejaculation due to defective spermatogenesis.The aim of this study was to identify the genetic etiology of NOA in an infertile male from a Chinese consanguineous family.A homozygous missense variant of the membrane-bound O-acyltransferase domain-containing 1(MBOAT1)gene(c.770C>T,p.Thr257Met)was found by whole-exome sequencing(WES).Bioinformatic analysis also showed that this variant was a pathogenic variant and that the amino acid residue in MBOAT1 was highly conserved in mammals.Quantitative polymerase chain reaction(Q-PCR)analysis showed that the mRNA level of MBOAT1 in the patient was 22.0%lower than that in his father.Furthermore,we screened variants of MBOAT1 in a broader population and found an additional homozygous variant of the MBOAT1 gene in 123 infertile men.Our data identified homozygous variants of the MBOAT1 gene associated with male infertility.This study will provide new insights for researchers to understand the molecular mechanisms of male infertility and will help clinicians make accurate diagnoses.

Mutational analysis of the GATA4 gene in Chinese men with nonobstructive azoospermia

As a crucial transcription factor for spermatogenesis,GATA-binding protein 4(GATA4)plays important roles in the functioning of Sertoli and Leydig cells.Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility.However,whether GATA4 is associated with human azoospermia has not been reported.Herein,we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia(NOA).We identified a missense mutation(c.191G>A,p.G64E),nine single-nucleotide polymorphisms(SNPs),and one rare variant(c.^(*)84C>T)in the 3′untranslated region(UTR).Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes(claudin-11 and steroidogenic acute regulatory protein,Star),and the 3′UTR rare variant c.^(*)84C>T did not generate microRNA-binding sites to repress GATA4 expression.To our knowledge,this is the first report to investigate the association between GATA4 and azoospermia;our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.

A new TEX11 mutation causes azoospermia and testicular meiotic arrest

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.

Low XIST expression in Sertoli cells of Klinefelter syndrome patients causes high susceptibility of these cells to an extra X chromosome

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.

An examination of predictive markers for successful sperm extraction procedures:a linear model and systematic review

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.

Comparison of intracytoplasmic sperm injection(ICSI)outcomes in infertile men with spermatogenic impairment of differing severity

The extent of spermatogenic impairment on intracytoplasmic sperm injection(ICSI)outcomes and the risk of major birth defects have been little assessed.In this study,we evaluated the relationship between various spermatogenic conditions,sperm origin on ICSI outcomes,and major birth defects.A total of 934 infertile men attending the Center for Reproductive Medicine of Ren Ji Hospital(Shanghai,China)were classified into six groups:nonobstructive azoospermia(NOA;n=84),extremely severe oligozoospermia(esOZ;n=163),severe oligozoospermia(sOZ,n=174),mild oligozoospermia(mOZ;n=148),obstructive azoospermia(OAZ;n=155),and normozoospermia(NZ;n=210).Rates of fertilization,embryo cleavage,high-quality embryos,implantation,biochemical and clinical pregnancies,abortion,delivery,newborns,as well as major birth malformations,and other newborn outcomes were analyzed and compared among groups.The NOA group showed a statistically lower fertilization rate(68.2%vs esOZ 77.3%,sOZ 78.0%,mOZ 73.8%,OAZ 76.6%,and NZ 79.3%,all P<0.05),but a significantly higher implantation rate(37.8%)than the groups esOZ(30.1%),sOZ(30.4%),mOZ(32.6%),and OAZ(31.0%)(all P<0.05),which was similar to that of Group NZ(38.4%).However,there were no statistically significant differences in rates of embryo cleavage,high-quality embryos,biochemical and clinical pregnancies,abortions,deliveries,major birth malformations,and other newborn outcomes in the six groups.The results showed that NOA only negatively affects some embryological outcomes such as fertilization rate.There was no evidence of differences in other embryological and clinical outcomes with respect to sperm source or spermatogenic status.Spermatogenic failure and sperm origins do not impinge on the clinical outcomes in ICSI treatment.

The association between the two more common genetic causes of spermatogenic failure:a 7-year retrospective study

Chromosomal abnormalities and Y chromosome microdeletions are considered to be the two more common genetic causes of spermatogenic failure.However,the relati on ship between chromosomal aberrations and Y chromosome microdeletio ns is still un clear.This study was to investigate the incidenee and characteristics of chromosomal aberrations and Y chromosome microdeletions in infertile men,and to explore whether there was a correlation between the two genetic defects of spermatogenic failure.A 7-year retrospective study was conducted on 5465 infertile men with nonobstructive azoospermia or oligozoospermia.Karyotype analysis of peripheral blood lymphocytes was performed by standard G-banding techniques.Y chromosome microdeletions were screened by multiplex PCR amplification with six specific sequence-tagged site(STS)markers.Among the 5465 infertile men analyzed,371(6.8%)had Y chromosome microdeletions and the prevalence of microdeletions in azoospermia was 10.5%(259/2474)and in severe oligozoospermia was 6.3%(107/1705).A total of 4003(73.2%)infertile men underwent karyotyping;370(9.2%)had chromosomal abnormalities and 222(5.5%)had chromosomal polymorphisms.Karyotype analysis was performed on 272(73.3%)patients with Y chromosome microdeletions and 77(28.3%)had chromosomal aberrations,all of which involved sex chromosomes but not autosomes.There was a sign ifica nt d iff ere nee in the frequency of chromosomal abno rmalities betwee n men with and without Y chromosome microdeletions(P<0.05).

Differences and similarities between extremely severe oligozoospermia and cryptozoospermia in intracytoplasmic sperm injection

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.