Identification of risk genes in Chinese nonobstructive azoospermia patients based on whole-exome sequencing / 亚洲男科学杂志(英文版)

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.

An examination of predictive markers for successful sperm extraction procedures: a linear model and systematic review / 亚洲男科学杂志(英文版)

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.

Research progress on the genetic etiology and treatment of nonobstructive azoospermia / 现代泌尿外科杂志

Nonobstructive azoospermia (NOA) is a disease with complex etiology, genetic heterogeneity and phenotypic heterogeneity caused by multiple factors, including chromosome abnormalities, Y chromosome microdeletions, gene mutations and epigenetic modifications. At present, there is no unified and effective treatment strategy to restore spermatogenesis. The current treatment options include preoperative hormone optimization therapy, changing the testicular spermatogenesis microenvironment, and stem cell therapy. This article reviews the existing genetic etiology of NOA and related treatment methods, in order to provide reference for the clinical treatment.

Endocrine aberrations of human nonobstructive azoospermia / 亚洲男科学杂志(英文版)

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.

Comparison of intracytoplasmic sperm injection (ICSI) outcomes in infertile men with spermatogenic impairment of differing severity / 亚洲男科学杂志(英文版)

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.

MBOAT1 homozygous missense variant causes nonobstructive azoospermia / 亚洲男科学杂志(英文版)

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.

The timing of micro-TESE: what is the ideal age for male and female partner to bring a child to home?

SUMMARY OBJECTIVE: The aim of this study was to analyze the results of microsurgical testicular sperm extraction (micro-TESE) and investigate the potential factors that may affect the successful sperm retrieval and timing of micro-TESE. METHODS: A total of 56 patients with nonobstructive azoospermia (NOA) who underwent micro-TESE procedure between January 2017 and December 2019 were retrospectively analyzed. The patient age, marriage duration, infertility duration, smoking, chronic illness, varicocele status, previous scrotal surgeries, and the presence of genetic disease were noted by an urologist for all patients. RESULTS: The mean age of patients was 33.28±4.4 (22-44) years. Our total sperm-retrieval rate was 55.4% (n:31). Sixteen (28.6%) pregnancies were achieved and 15 (26.8%) healthy live births could be managed. Only the marriage duration (p=0.016) and infertility duration (p=0.015) were detected to be the significant factors to manage successful sperm retrieval. Men with NOA younger than 35.2 years and having a female partner younger than 36.9 years seemed to have the best chance to have a living healthy baby. CONCLUSIONS: The fertility decreased by both male and female age and for men with NOA. The early visit to doctor seemed to have positive effect.

A new / 亚洲男科学杂志(英文版)

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.

Mutational analysis of the / 亚洲男科学杂志(英文版)

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.

The association between the two more common genetic causes of spermatogenic failure: a 7-year retrospective study / 亚洲男科学杂志(英文版)

Chromosomal abnormalities and Y chromosome microdeletions are considered to be the two more common genetic causes of spermatogenic failure. However, the relationship between chromosomal aberrations and Y chromosome microdeletions is still unclear. This study was to investigate the incidence 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 significant difference in the frequency of chromosomal abnormalities between men with and without Y chromosome microdeletions (P< 0.05).

Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia / 亚洲男科学杂志(英文版)

Prior studies have investigated sperm retrieval rates in men with nonobstructive 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 multivariaile 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.

Altered microRNA profiles of testicular biopsies from patients with nonobstructive azoospermia / 亚洲男科学杂志(英文版)

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.

Bilateral versus unilateral cryptorchidism in nonobstructive azoospermia: Testicular sperm extraction outcomes / 亚洲男科学杂志(英文版)

Cryptorchidism is one of the most frequent causes of nonobstructive azoospermia (NOA) in adulthood. Although it is well known that spermatogenesis is more impaired in bilateral than in unilateral cryptorchidism, previous studies have only described small cohorts or inhomogeneous population. Consequently, we analyzed a cohort of 225 men with only a history of cryptorchidism as sole etiopathogenetic factor for NOA, and compared testicular sperm extraction (TESE) outcomes between men with bilateral versus unilateral cryptorchidism. Our results show no difference in follicle-stimulating hormone (FSH) levels and testicular volumes between men with a history of bilateral cryptorchidism compared to unilateral cryptorchidism (median: 21.3 IU l-1 vs 19.3 IU l-1, P = 0.306; and 7.2 ml vs 7.9 ml, P = 0.543, respectively). In addition, sperm retrieval rates were similar (66.2% vs 60.0%, P = 0.353). Using multivariate analysis, we have found that only a low inhibin B level (above the assay's detection limit) was positively associated with successful sperm retrieval (P 0.05). Regarding intracytoplasmic sperm injection outcomes, we found that cumulative pregnancy rate and live birth rate per cycle were not statistically different between the two groups (17.4% vs 27.8%, P = 0.070; and 16.1% vs 26.4%, P = 0.067, respectively). Unexpectedly, there was no significant difference in hormonal profiles (FSH, luteinizing hormone [LH], testosterone, and inhibin B levels) and TESE outcomes between unilateral versus bilateral cryptorchidism. This suggests that a history of unilateral cryptorchidism could reflect a bilateral testicular impairment. Interestingly, inhibin B level might be a predictor of successful TESE.

Predictive value of FSH, testicular volume, and histopathological findings for the sperm retrieval rate of microdissection TESE in nonobstructive azoospermia: A meta-analysis / 亚洲男科学杂志(英文版)

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.

Seminal plasma miR-192a: A biomarker predicting successful resolution of nonobstructive azoospermia following varicocele repair / 亚洲男科学杂志(英文版)

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 0.05). 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.

Application of contrast enhanced ultrasound in assessing the testicular spermatogenesis of nonobstructive azoospermia patients / 上海交通大学学报（医学版）

Objective · To assess the usefulness of contrast enhanced ultrasound (CEUS) in locating the testicular area to guide microdissection testicular sperm extraction (M-TESE) for patients with nonobstructive azoospermia (NOA). Methods · CEUS was performed in 95 NOA patients. M-TESE was performed in the best and poorest perfusion areas on CEUS and in the conventional area. Sperm retrieval rates (SRR) of the three areas were compared. Results · M-TESE was performed in 147 testicles (95 patients). SRRs in best perfusion area, poorest perfusion area and conventional area were 66.3%, 32.6% and 47.3% respectively, and the differences between groups were statistically significant (all P<0.05). The arriving time (AT), time to peak intensity (TTP), peak intensity (PI) and area under the curve (AUC) showed statistical significance (all P<0.05)between the successful retrieval group (94 points) and unsuccessful retrieval group (200 points). And the SRR showed statistical difference among the three pathological groups. In maturation arrest group and Sertoli cell only group, the SRR in the best perfusion area was higher than that in the conventional area (both P<0.05). Conclusion · SRR was different in different pathological groups. The locating of the best perfusion area could guide M-TESE so as to improve the SRRs of maturation arrest group and Sertoli cell only group.

Application of contrast enhanced ultrasound in assessing the testicular spermatogenesis of nonobstructive azoospermia patients / 上海交通大学学报（医学版）

Objective · To assess the usefulness of contrast enhanced ultrasound (CEUS) in locating the testicular area to guide microdissection testicular sperm extraction (M-TESE) for patients with nonobstructive azoospermia (NOA). Methods · CEUS was performed in 95 NOA patients. M-TESE was performed in the best and poorest perfusion areas on CEUS and in the conventional area. Sperm retrieval rates (SRR) of the three areas were compared. Results · M-TESE was performed in 147 testicles (95 patients). SRRs in best perfusion area, poorest perfusion area and conventional area were 66.3%, 32.6% and 47.3% respectively, and the differences between groups were statistically significant (all P<0.05). The arriving time (AT), time to peak intensity (TTP), peak intensity (PI) and area under the curve (AUC) showed statistical significance (all P<0.05)between the successful retrieval group (94 points) and unsuccessful retrieval group (200 points). And the SRR showed statistical difference among the three pathological groups. In maturation arrest group and Sertoli cell only group, the SRR in the best perfusion area was higher than that in the conventional area (both P<0.05). Conclusion · SRR was different in different pathological groups. The locating of the best perfusion area could guide M-TESE so as to improve the SRRs of maturation arrest group and Sertoli cell only group.

Y-chromosome microdeletions in nonobstructive azoospermia and severe oligozoospermia / 亚洲男科学杂志(英文版)

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.

XRCC1 rs25487 locus genetic polymorphisms and susceptibility to nonobstructive azoospermia in Hui minority ethnic population of Shaanxi province / 西安交通大学学报(医学版)

Objective To explore the association between X-ray repair cross complementing group 1 (XRCC1)gene rs25487 locus polymorphisms and nonobstructive azoospermia in Hui minority ethic population of Shaanxi Province.Methods We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)method for genotyping at XRCC1 gene rs25487 locus in 79 patients with nonobstructive azoospermia and 82 healthy male controls in Hui minority ethic population of Shaanxi Province.Then we analyzed the association be-tween XRCC1 gene rs25487 locus and nonobstructive azoospermia.Results Compared with GG genotype,GA, AA and GA + AA genotypes demonstrated a significantly increased risk for nonobstructive azoospermia (OR =2.286,95% CI 1.1 5 1-4.539;OR =2.202,95% CI 0.753-6.439;OR =2.271,95% CI 1.1 71-4.403),respec-tively.Meanwhile,the A allele frequency was significantly higher in azoospermic patients than in controls (OR =1.582,95% CI 1.005-2.492,P =0.047).Conclusion G→A in XRCC1 gene rs25487 locus is correlated with nonobstructive azoospermia in Hui minority ethic population of Shaanxi province.