Truncating PICK1 Variant Identified in Azoospermia Affected Mitochondrial Dysfunction in Knockout Mice

Objective The protein interacting with C kinase 1(PICK1)plays a critical role in vesicle trafficking,and its deficiency in sperm cells results in abnormal vesicle trafficking from Golgi to acrosome,which eventually disrupts acrosome formation and leads to male infertility.Methods An azoospermia sample was filtered,and the laboratory detection and clinical phenotype indicated typical azoospermia in the patient.We sequenced all of the exons in the PICK1 gene and found that there was a novel homozygous variant in the PICK1 gene,c.364delA(p.Lys122SerfsX8),and this protein structure truncating variant seriously affected the biological function.Then we constructed a PICK1 knockout mouse model using clustered regularly interspaced short palindromic repeat cutting technology(CRISPRc).Results The sperm from PICK1 knockout mice showed acrosome and nucleus abnormalities,as well as dysfunctional mitochondrial sheath formation.Both the total sperm and motility sperm counts were decreased in the PICK1 knockout mice compared to wild-type mice.Moreover,the mitochondrial dysfunction was verified in the mice.These defects in the male PICK1 knockout mice may have eventually led to complete infertility.Conclusion The c.364delA novel variant in the PICK1 gene associated with clinical infertility,and pathogenic variants in the PICK1 may cause azoospermia or asthenospermia by impairing mitochondrial function in both mice and humans.

Frequency of Y chromosome microdeletions and chromosomal abnormalities in infertile Thai men with oligozoospermia and azoospermia

Aim： To investigate the possible causes of oligozoospermia and azoospermia in infertile Thai men, and to find the frequencies of Y chromosome microdeletions and cytogenetic abnormalities in this group. Methods： From June 2003 to November 2005, 50 azoospermic and 80 oligozoospermic men were enrolled in the study. A detailed history was taken for each man, followed by general and genital examinations. Y chromosome microdeletions were detected by multiplex polymerase chain reaction （PCR） using 11 gene-specific primers that covered all three regions of the azoospermic factor （AZFa, AZFb and AZFc）. Fifty men with normal semen analysis were also studied. Karyotyping was done with the standard G- and Q-banding. Serum concentrations of follicle stimulating hormone （FSH）, luteinizing hormone （LH）, prolactin （PRL） and testosterone were measured by electrochemiluminescence immunoassays （ECLIA）. Results： Azoospermia and oligozoospermia could be explained by previous orchitis in 22.3%, former bilateral cryptorchidism in 19.2%, abnormal karyotypes in 4.6% and Y chromosome microdeletions in 3.8% of the subjects. The most frequent deletions were in the AZFc region （50%）, followed by AZFb （33%） and AZFbc （17%）. No significant difference was detected in hormonal profiles of infertile men, with or without microdeletions. Conclusion： The frequencies of Y chromosome microdeletions and cytogenetic abnormalities in oligozoospermic and azoospermic Thai men are comparable with similarly infertile men from other Asian and Western countries.

Clinical and pathological correlation of the microdeletion of Y chromosome for the 30 patients with azoospermia and severe oligoasthenospermia

Aim: To review the accumulated 30 patients with different area of Y chromosome microdeletions, focusing on their correlation with the clinical and pathological findings. Methods: A total of 334 consecutive infertile men with azoospermia (218 patients) and severe oligoasthenospermia (116 patients) were screened. Complete physical and endocrinological examinations, general chromosome study and multiplex polymerase chain reaction assay to evaluate the Y chromosome microdeletion were performed. Ten patients received testicular biopsy. Then the clinical and pathological findings were analyzed with reference to the areas of Y chromosome microdeletion. Results: There is a decline of the percentage of sperm appearing in semen in the group that the gene deletion region from AZFc to AZFb. The clinical evidence of the impairment (decreased testicular size and elevated serum FSH) is also relevantly aggravated in this group. However, the pathology of testicular biopsy specimen was poorly correlated with the different deletion areas of the Y chromosome, which may be due to the limited number of specimens. Conclusion: The clinical correlation of spermatogenic impairment to the different AZF deletion regions may provide the information for the infertile couples in pre-treatment counseling.

Outcome of repeated micro-surgical testicular sperm extraction in patients with non-obstructive azoospermia

Aim： To evaluate the outcome of repetitive micro-surgical testicular sperm extraction （mTESE） attempts in non-obstructive azoospermia （NOA） cases, in relation to patients＇ initial testicular histology results. Methods： A total of 68 patients with NOA in whom mTESE had been performed in previous intracytoplasmic sperm injection （ICSI） attempts were reviewed. Results： Among the 68 patients with NOA, the first mTESE yielded mature sperm for ICSI in 44 （64%） （Sp^＋）, and failed in the remaining 24 （36%） （Sp^-）. Following their first trial, 24 patients decided to undergo a second mTESE. Of these 24 patients, no spermatozoa were obtained in 5 patients, and Sp^＋ but no fertilization/pregnancy were achieved in 19. In these 24 cases, mTESE was successively repeated for two （n = 24）, three （n = 4） and four （n = 1） times. The second attempt yielded mature sperm in 3/5 patients from the Sp group and 16/19 patients from the Sp^＋ group. At the third and fourth trials, 4/4 and 1/1 of the original Sp^＋ patients were Sp^＋ again, respectively. Distribution of main testicular histology included Sertoli cell-only syndrome （16%）, maturation arrest （22%）, hypospermatogenesis （21%） and focal spermatogenesis （41%）. Overall, in repetitive mTESE, 24/29 （82%） of the attempts were finally Sp^＋. Conclusion： Repeated mTESE in patients with NOA is a feasible option, yielding considerably high sperm recovery rate. In patients with NOA, mTESE may safely be repeated one or more times to increase sperm retrieval rate, as well as to increase the chance of retrieving fresh spermatozoa to enable ICSI.

A susceptibility locus rs7099208 is associated with non-obstructive azoospermia via reduction in the expression of FAM160B1

Non-obstructive azoospermia （NOA） is a severe defect in male reproductive health that occurs in 1% of adult men. In a previous study, we identified that rs7099208 is located within the last intron of FAM160B1 at 10q25.3. In this study, we analysed expression Quantitative Trait Loci （eQTL） of FAM16OB1, ABLIM1 and TRUB1, the three genes surrounding rs7099208. Only the expression level of FAM16OB1 was reduced for the homozygous alternate genotype （GG） of rs7099208, but not for the homozygous reference or heterozygous geno- types. FAM160B1 is predominantly expressed in human testes, where it is found in spermatocytes and round sper- matids. From 17 patients with NOA and five with obstructive azoospermia （OA）, immunohistochemistry revealed that expression of FAM160B1 is reduced, or undetectable in NOA patients, but not in OA cases or normal men. We conclude that rs7099208 is associated with NOA via a reduction in the expression of FAM160B1.

The prevalence of azoospermia factor microdeletion on the Y chromosome of Chinese infertile men detected by multi-analyte suspension array technology

Aim： To develop a high-throughput multiplex, fast and simple assay to scan azoospermia factor （AZF） region microdeletions on the Y chromosome and establish the prevalence of Y chromosomal microdeletions in Chinese infertile males with azoospermia or oligozoospermia. Methods： In total, 178 infertile patients with azoospermia （nonobstructed）, 134 infertile patients with oligozoospermia as well as 40 fertile man controls were included in the present study. The samples were screened for AZF microdeletion using optimized multi-analyte suspension array （MASA） technology. Results： Of the 312 patients, 36 （11.5%） were found to have deletions in the AZF region. The rnicrodeletion frequency was 14% （25/178） in the azoospermia group and 8.2% （11/134） in the oligospermia group. Among 36 patients with microdeletions, 19 had deletions in the AZFc region, seven had deletions in AZFa and six had deletions in AZFb. In addition, four patients had both AZFb and AZFc deletions. No deletion in the AZF region was found in the 40 fertile controls. Conclusion： There is a high prevalence of Y chromosomal microdeletions in Chinese infertile males with azoospermia or oligozoospermia. The MASA technology, which has been established in the present study, provides a sensitive and high-throughput method for detecting the deletion of the Y chromosome. And the results suggest that genetic screening should be advised to infertile men before starting assisted reproductive treatments.

The value of testicular ＇mapping＇ in men with non-obstructive azoospermia

As the field of assisted reproduction has advanced, many previously untreatable men are now biological fathers. Although finding sperm in men with obstructive azoospermia is not difficult, locating and retrieving spermatozoa in men with non-obstructive azoospermia remains a clinical challenge, largely because sperm production in these men can be patchy or focal in nature. In response to this challenge, strategies such as fine-needle aspiration （FNA） mapping have been developed to find spermatozoa. This review discusses the history, evolution and current clinical utility and findings with FNA mapping for male infertility）. Review of the current literature in the English language on FNA （diagnostic or therapeutic） with a keyword focuses on sperm detection, retrieval, safety and complications. FNA was described in human medicine over 100 years ago. Testis FNA was described 45 years ago and FNA ＇mapping＇ of spermatozoa was described in 1997. This comparative review of the literature on sperm detection and complication rates with FNA and open testis biopsy or microdissection procedures suggests that FNA is highly informative, minimally invasive and is associated with fewer complications than other commonly used approaches to sperm detection in non-obstructive azoospermic patients. FNA mapping has gained considerable traction as an informative, ＇testis sparing＇ technique for sperm detection in non-obstructive azoospermia. With knowledge of sperm presence and location prior to sperm retrieval, FNA maps can help clinicians tailor sperm retrieval to optimize time, effort and extent of procedures needed to procure spermatozoa in these difficult cases.

Can inhibin-B predict the outcome of microsurgical epididymal sperm aspiration in patients with suspected primary obstructive azoospermia？

Aim： To evaluate whether inhibin-B can predict the outcome of a microsurgical epidymal sperm aspiration （MESA） procedure in patients with suspected primary obstructive azoospermia （OA） and if inhibin-B can replace testicular biopsy in the diagnostic work-up of these patients. Methods： Inhibin-B levels and testicular biopsy scores were related to the outcome of MESA in 43 patients with suspected primary OA. MESA was considered to be successful when epididymal sperm could be identified during the procedure. Results： Spermatozoa were present in the epididymal aspirate in 28 out of the 43 patients （65%）. lnhibin-B values were not significantly different in patients with successful or unsuccessful MESA. The modified Johnsen score, however, was significantly lower in patients with unsuccessful MESA （P = 0.003）. A rete testis obstruction or epididymal malfunctioning was found in 15% of patients with suspected primary OA, reflected by unsuccessful MESA despite normal inhibin-B levels and normal testicular histology. Conclusion： Inhibin-B cannot replace testicular biopsy as a diagnostic tool in the work-up of patients with suspected primary OA. Testicular biopsy is useful in identifying patients with spermatogenic arrest, who might have normal inhibin-B values.

Y-chromosomal microdeletions and partial deletions of the Azoospermia Factor c(AZFc)region in normozoospermic,severe oligozoospermic and azoospermic men in Sri Lanka

Aim： To assess for the first time the occurrence of Y chromosomal microdeletions and partial deletions of the Azoospermia Factor c （AZFc） region in Sri Lankan men and to correlate them with clinical parameters. Methods： In a retrospective study, we analyzed 96 infertile men （78 with non-obstructive azoospermia） and 87 controls with normal spermatogenesis. AZFa, AZFb, AZFc and partial deletions within the AZFc region were analyzed by multiplex polymerase chain reaction （PCR） according to established protocols. Results： No AZFa, AZFb or AZFc deletions were found in the control group. Seven patients in the group of infertile men were found to have deletions as following： one AZFa, two AZFc, two AZFbc and two AZFabc. The relative distribution of these patterns was significantly different compared with that found in the German population. Extension analysis confirmed that the deletions occurred according to the current pathogenic model, gr/gr deletions were found to be equally present both in the patients （n = 4） and in the control group （n = 4）. One b2/b3 deletion was found in the patient group. Conclusion： These results suggest that the frequency and pattern of microdeletions of the Y chromosome in Sri Lankan men are similar to those found in other populations and confirm that gr/gr deletions are not sufficient to cause spermatogenetic failure. （Asian J Androl 2006 Jan; 8： 39-44）

Comparison of sperm retrieval and reproductive outcome in azoospermic men with testicular failure and obstructive azoospermia treated for infertility

We assessed the rates of sperm retrieval and intracytoplasmic sperm injection outcomes, including the neonatal profile of infants conceived, in men with testicular failure. Three-hundred and sixty-five men with testicular failure who underwent micro-dissection testicular sperm extraction were included in this study. We compared their outcomes with 40 men with testicular failure who used donor sperm for injections due to failed retrieval, and 146 men with obstructive azoospermia who underwent percutaneous sperm retrieval. The retrieval rate in testicular failure was 41.4%, and the results were lower than the obstructed azoospermia （100%; adjusted odds ratio： 0.033; 95% Ch 0.007-0.164; P 〈 0.001）. Live birth rates after sperm injections were lower in men with testicular failure （19.9%） compared with donor sperm （37.5%; adjusted OR： 0.377 （95% Ch 0.233-0.609, P 〈 0.001）） and obstructive azoospermia （34.2%; adjusted OR： 0.403 （95% CI： 0.241-0.676, P= 0.001）. Newborn parameters of infants conceived were not significantly different among the groups. We concluded that the chances of obtaining sperm on retrieval and achieving a live birth after intracytoplasmic sperm injection （ICSI） are reduced in men with testicular failure. The profile of infants conceived after sperm injection does not seem to be negatively affected by testicular failure.

Routine screening for classical azoospermia factor deletions of the Y chromosome in azoospermic patients with Klinefelter syndrome

Aim： To evaluate the occurrence of classical azoospermia factor （AZF） deletions of the Y chromosome as a routine examination in azoospermic subjects with Klinefelter syndrome （KS）. Methods： Blood samples were collected from 95 azoospermic subjects with KS （91 subjects had a 47,XXY karyotype and four subjects had a mosaic 47,XXY/46, XY karyotype） and a control group of 93 fertile men. The values of testosterone, follicle stimulating hormone （FSH） and luteinizing hormone （LH） were measured. To determine the presence of Y chromosome microdeletions, polymerase chain reaction （PCR） of five sequence-tagged site primers （sY84, sY 129, sY 134, sY254, sY255） spanning the AZF region, was performed on isolated genomic DNA. Results： Y chromosome microdeletions were not found in any of the 95 azoosperrnic subjects with KS. In addition, using similar conditions of PCR, no microdeletions were observed in the 93 fertile men evaluated. The level of FSH in KS subjects was higher than that in fertile men （38.2 ± 10.3 mIU/mL vs. 5.4 ±2.9 mIU/mL, P 〈 0.001） and the testosterone level was lower than that in the control group （1.7 ±0.3 ng/mL vs. 4.3 ± 1.3 ng/mL, P 〈 0.001）. Conclusion： Our data and review of the published literature suggest that classical AZF deletions might not play a role in predisposing genetic background for the phenotype of azoospermic KS subjects with a 47,XXY karyotype. In addition, routine screening for the classical AZF deletions might not be required for these subjects. Further studies including partial AZFc deletions （e.g. gr/gr or b2/b3） are necessary to establish other mechanism underlying severe spermatogenesis impairment in KS.

Preliminary study of letrozole use for improving spermatogenesis in non-obstructive azoospermia patients with normal serum FSH

We investigated whether letrozole （2.5 mg day-1） improves sperm count in non-obstructive azoospermia （NOA） patients. Four men were included in this study, and they had folliculo-stimulating hormone and other hormone levels within the normal range and no varicoceles or chromosomal aberrations. These four patients were administered letrozole for 3 months. Sperm count, testicular volume, gonadotropin, testosterone （T） and estradiol （E2） blood levels were assessed before, during and 1 week after the suspension of treatment. All patients showed spermatozoa in their ejaculate, increased gonadotropin and T levels and lower E2 levels （P〈0.05 in all cases）, when letrozole was administered. This suggests that letrozole treatment might improve sperm count in an NOA sub-population; however, more studies, including the proper controls, are needed to confirm its efficacy.

Association of XRCC1 gene polymorphisms with idiopathic azoospermia in a Chinese population

Aim： To assess the possible role of genetic polymorphisms in DNA repair gene XRCC 1 （X-ray repair cross-comple- menting group l） during spermatogenesis by investigating the associations of one promoter polymorphism （T-77C） and two exonic polymorphisms （Argl94Trp and Arg399Gln） in XRCC1 gene with risk of idiopathic azoospermia in a Chinese population. Methods： The genotype and allele frequencies of three observed polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism based on a Chinese population consisting of 171 idiopathic azoospermia subjects and 247 normal-spermatogenesis controls. Results： In our study, all the observed genotype frequencies were in agreement with Hardy-Weinberg equilibrium. The 399A （GA＋AA） allele frequency for idiopathic azoospermia subjects and controls was 0.216 and 0.269, respectively. Compared with GG genotype, the AA genotype of Arg399Gln showed a significant association with a decreased risk of idiopathic azoospermia （odds ratio = 0.315; 95% confidence interval = 0.12-0.86）. However, no significant differences were found between the cases and controls for T-77C and Arg194Trp polymorphisms. The major haplotypes of XRCC1 gene were TCG, TrG and TCA, whereas no haplotypes appeared to be significantly associated with idiopathic azoospermia based on the cutoff of P 〈 0.05. Conclusion： In a selected Chinese population, AA genotype of Arg399Gln appears to contribute to a decreased risk of idiopathic azoospermia, while we have not any evidence of involvement of XRCC1 T-77C and Arg194Trp polymorphisms in idiopathic azoospermia. （Asian J Androl 2007 Nov; 9： 843-848）

Genetic polymorphism of glutathione S-transferase T1 gene and susceptibility to idiopathic azoospermia or oligospermia in northwestern China

Aim： To investigate the association of glutathione S-transferase T1 （GSTT1） gene polymorphism in patients with idiopathic azoospermia or oligospermia in the northwestern China population. Methods： In the case-control study, GSTT1 genotypes were identified by multiplex polymerase chain reaction （PCR） with peripheral blood DNA samples from 78 patients with idiopathic azoospermia, 103 patients with idiopathic oligospermia and 156 age-matched controls with normal sperm concentration and motility, according to the criteria adapted from World Health Organization guidelines. All of the patients and controls were from northwestern China. Results： There is a significant association between GSTT1 null genotype with idiopathic azoospermia risk （odds ratio [OR]： 2.36, 95% confidence interval [CI]： 1.33-4.20, P = 0.003） or idiopathic oligospermia risk （OR： 2.00, 95% CI： 1.17-3.27, P = 0.010）. Conclusion： GSTT1 null genotype is a predisposing risk factor for sporadic idiopathic azoospermia or oligospermia in northwestern China. （Asian J Androl 2008 Mar; 10： 266-270）

Single-nucleotide polymorphisms in HORMAD1 may be a risk factor for azoospermia caused by meiotic arrest in Japanese patients

Genetic mechanisms are implicated as a cause of some male infertility, yet are poorly understood. Meiosis is unique to germ cells and essential for reproduction. The synaptonemal complex is a critical component for chromosome pairing, segregation and recombination. Hormadl is essential for mammalian gametogenesis as knockout male mice are infertile. Hormadl-deficient testes exhibit meiotic arrest in the early pachytene stage and synaptonema! complexes cannot be visualized. To analyze the hypothesis that the human HORMAD1 gene defects are associated with human azoospermia caused by meiotic arrest, mutational analysis was performed in all coding regions by direct sequence analysis of 30 Japanese men diagnosed with azoospermia resulting from meiotic arrest. By the sequence analysis, three polymorphism sites, Single Nucleotide Polymorphism 1 （c. 163A〉G）, SNP2 （c. 501T〉G） and SNP3 （c. 918C〉T）, were found in exons 3, 8 and 10. The 30 patients with azoospermia and 80 normal pregnancy-proven, fertile men were analyzed for HORMAD1 polymorphisms. Both SNP1 and SNP2 were associated with human azoospermia caused by complete early meiotic arrest （P〈0.0S）. We suggest that the HORMAD1 has an essential meiotic function in human spermatogenesis.

Quick recovery and characterization of cell-free DNA in seminal plasma of normozoospermia and azoospermia： implications for non-invasive genetic utilities

We established a quick and reliable method for recovering cell-free seminal DNA （cfsDNA）, by using the binding-washing-elution procedure on the DNA purification column. Low variations （below 15%） among the triplicate values of cfsDNA quantity verified the reproducibility of our cfsDNA recovery method. Similar cfsDNA yield and size distribution between seminal plasma acquired by filtration and centrifugation confirmed the presence of cfsDNA. To investigate the general characterization of cfsDNA, the quantitation and size distribution of cfsDNA from normozoospermic and azoospermic semen were analyzed by real-time PCR and electrophoresis, respectively. CfsDNA concentration in semen with normozoospermia （n = 11） was 1.34 ± 0.65 μg ·mL^-1, whereas a higher cfsDNA concentration was observed in azoospermia （2.56 ± 1.43 μg ·mL^-1, n = 9）. The continuous distribution of DNA fragments ranging from -1 kb to 15 kb and a spectrum of multiples of 180-bp fragments were observed in each normozoospermic and azoospermic sample. Distinct characteristic DNA ladder fragmentations in some azoospermic samples implicated that cfsDNA originate partly from apoptotic cells. CfsDNAs of 36 selected azoospermic patients with known information of Y chromosome microdeletion were subjected to the same microdeletion analysis by multiplex PCR and PCR amplification of sY114 （1 450 bp）. All multiplex PCR reactions with cfsDNA amplified successfully and provided the same result as leukocyte DNA. PCR amplification of sY114 gave a 1 450-bp amplicon as expected. Our data suggested the potential use of cfsDNA in search of biomarker or diagnostic procedures.

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.

Clinical observation of loupe-assisted intussusception vasoepididymostomy in the treatment of obstructive azoospermia(analysis of 49 case reports)

To evaluate the clinical outcomes of loupe-assisted intussusception vasoepididymostomy(VE)in the treatment of epididymal obstructive azoospermia(EOA),we retrospectively analyzed data from 49 patients with EOA who underwent two-suture longitudinal intussusception vasoepididymostomy(LIVE)between 2000 and 2007.The data included the surgical method,postoperative motile sperm count per ejaculation,percentage of progressive motile sperm and patency and pregnancy outcomes.There were a total of 49 men undergoing scrotal exploration,and epididymal obstruction was found in all cases.Bilateral or unilateral anastomoses were performed in 40 and 6 men,respectively.The postoperative courses of 42 patients were followed up for more than 6 months,and the courses of 38 patients were followed up for more than 1 year.The overall patency and pregnancy rates were 71.4%and 26.3%,respectively.Moreover,progressive motile sperm was more frequently present in those patients who had undergone anastomosis at cauda than at corpus or caput.Pregnancy was achieved only in those patients who had undergone anastomosis at least on one side of the cauda epididymis.We think that the loupe-assisted method,with a lower overall cost and a simplified surgical procedure,can achieve satisfactory patency outcomes and pregnancy results.Data from this paper also suggest that paternity outcomes occur more frequently after anastomoses at cauda than at corpus or caput.

Induction of spermatogenesis in men with azoospermia or severe oligoteratoasthenospermia after antegrade internal spermatic vein sclerotherapy for the treatment of varicocele

Aim： To evaluate the treatment outcome of antegrade internal spermatic vein sclerotherapy in men with non-obstructive azoospermia or severe oligoteratoasthenospermia （OTA） as a result of varicocele. Methods： Between September 1995 and January 2004, 47 patients （mean age 33.8 ± 6.3 years） underwent antegrade internal spermatic vein sclerotherapy for the treatment of varicocele with azoospermia （14 patients） or severe OTA （33 patients）. Testicular core biopsy was also performed in complete azoospermic patients who provided informed consent. The outcome was assessed in terms of improvement in semen parameters and conception rate. Results： Forty-two （89.4%） of 47 patients had bilateral varicocele. Serum follicle stimulating hormone （FSH） did not differ between patients with azoospermia and severe OTA. After the follow-up of 24.8 ± 9.2 months, significant improvement was noted in mean sperm concentration, motility and morphology in 35 patients （74.5%）. Comparison between groups during the follow-up revealed significantly higher values of sperm concentration, motility and normal morphology in the severe OTA group. Pregnancy was achieved in 14 cases （29.8%）. Testicular histopathology of the azoospermic patients with postoperative induction of spermatogenesis revealed maturation arrest at spermatid stage, Sertoli-cell-only （SCO） with focal spermatogenesis or hypospermatogenesis. None of the patients with pure SCO pattern or maturation arrest at spermatocyte stage achieved spermatogenesis after the treatment. Preoperative serum FSH levels didn＇t relate to treatment outcome. Conclusion： Antegrade internal spermatic vein sclerotherapy is an easy and effective treatment for symptomatic varicocele. It can significantly reverse testicular dysfunction and improve spermatogenesis in men with severe OTA, as well as induce sperm production in men with azoospermia, improving pregnancy rates in subfertile couples.

Surgical management of nonobstructive azoospermia

Nonobstructive azoospermia(NOA)is characterized by the complete absence of sperm in the ejaculate due to testicular failure.The evaluation and management of patients with NOA offer a challenge to the reproductive urologist.In the era of in vitro fertilization with intracytoplasmic sperm injection,surgical sperm extraction techniques can afford men with NOA biologic paternity.To provide a comprehensive review of surgical sperm retrieval approaches in the patient with NOA emphasizing complications,success rates and outcome optimization,a Medline search was conducted querying surgical approaches used to manage NOA.Four sperm extraction techniques are described including:testicular sperm aspiration,testicular sperm extraction,fine needle aspiration mapping and microdissection testicular sperm extraction.In addition,the roles for pre-extraction varicocelectomy and sperm cryopreservation are discussed.The management of NOA continues to evolve as newer tools become available.Several modalities of sperm acquisition exist.An understanding of their complications and success rates is fundamental to the treatment of NOA.