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.
Humans ; Male ; Azoospermia/pathology* ; East Asian People ; Exome Sequencing ; Mutation ; Proteins/genetics*

Adult ; Azoospermia/pathology* ; Carbonic Anhydrases/genetics* ; Congenital Abnormalities/genetics* ; Epithelial Sodium Channels/genetics* ; Gene Expression Regulation/genetics* ; Genome, Human ; Humans ; Infertility, Male/genetics* ; Male ; Male Urogenital Diseases/genetics* ; Mutation ; Vas Deferens/abnormalities*

Seminal duct obstruction may result in obstructive azoospermia (OA) and severe oligoasthenoteratozoospermia (OAT) (<0.5 million/mL) (Nordhoff et al., 2015). Cases of partial OA and OAT can be treated effectively by microsurgical anastomosis (Goldstein and Kim, 2013) to obtain successful surgical reversal. However, microsurgical vasovasostomy (VV) (Dickey et al., 2015) and vasoepididymostomy (VE) (Peng et al., 2017) are not suitable for patients with atypical OA and poor epididymis conditions or unpredictable obstruction of the distal vas deferens. For those patients, cross anastomosis may be applied instead of routine VE or VV. A single-center, retrospective, comparison study was conducted, which assessed the usefulness of the cross VV (CVV) in the scrotum for indication and efficacy. A total of 77 cases with OA or OAT were included, and 20 cases implemented cross anastomosis, including unilateral CVV (UCVV) in 4 cases, unilateral VE plus CVV (UVE+CVV) in 11 cases, and unilateral VV-based CVV (UVV+CVV) in 5 cases. The other 57 cases received no cross-matching anastomosis. The patency and natural pregnancy rates in one year were 75.0% and 50.0%, respectively, in the UCVV group; 54.5% and 27.3%, respectively, in the UVE+CVV group; and 60.0% and 40.0%, respectively, in the UVV+CVV group. The CVV in the scrotum in the selected patients with OA and severe OAT could yield good results. We regard the CVV in the scrotum as an efficacious operation with a lower risk of injury in cases of atypical OA.
Adult ; Anastomosis, Surgical ; Azoospermia/surgery* ; Epididymis/pathology* ; Female ; Humans ; Infertility/surgery* ; Male ; Oligospermia/surgery* ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Scrotum/surgery* ; Treatment Outcome ; Vas Deferens ; Vasovasostomy/methods* ; Young Adult

Adult ; Azoospermia/genetics* ; Follicle Stimulating Hormone/metabolism* ; Gonadal Dysgenesis, Mixed/pathology* ; Growth Disorders/genetics* ; Humans ; In Situ Hybridization, Fluorescence ; Infertility, Male/genetics* ; Karyotype ; Luteinizing Hormone/metabolism* ; Male ; Mosaicism ; Testis/pathology* ; Testosterone/metabolism* ; Turner Syndrome

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.
Adult ; Azoospermia/therapy* ; Follicle Stimulating Hormone/blood* ; Humans ; Male ; Microdissection ; Oligospermia/pathology* ; Predictive Value of Tests ; Sensitivity and Specificity ; Sertoli Cell-Only Syndrome/pathology* ; Sperm Maturation ; Sperm Retrieval ; Spermatozoa ; Testis/pathology* ; Threshold Limit Values

Adult ; Azoospermia/pathology* ; DNA Breaks, Double-Stranded ; DNA Repair ; Humans ; Infertility, Male/pathology* ; Male ; Prophase ; Prostate/pathology* ; Recombination, Genetic ; Synapses/pathology* ; Testis/pathology*

OBJECTIVE: Azoospermia owing to testicular disorders is the most severe manifestation of male infertility. The main concern for patients with nonobstructive azoospermia (NOA) is the probability of successful sperm retrieval following testicular sperm extraction (TESE). Therefore, the goal of this study was to determine predictive factors correlated with sperm retrieval. METHODS: We assessed the testicular histopathological patterns, the choice of TESE surgical procedure, hormone levels, and chromosomal abnormalities in patients with NOA (n=170). The histopathology specimens were analyzed based on the histopathological patterns of hypospermatogenesis, maturation arrest, and Sertoli cell-only syndrome. RESULTS: The mean rate of sperm retrieval was 48.8%. The rate of sperm retrieval was significantly higher in the hypospermatogenesis group than in the other groups (p<0.001). There was a positive correlation between micro-TESE (vs. conventional TESE) and the sperm retrieval rate (odds ratio, 8.077; p<0.01). A logistic regression model demonstrated that high levels of follicle-stimulating hormone (FSH) and small testicular volume were significantly associated with lower chances of successful sperm retrieval. CONCLUSION: Some parameters, including testicular histopathology patterns, FSH levels, testicular volume, and method of TESE surgery, may be able to predict the chances of obtaining spermatozoa in patients with NOA. However, despite the efficiency of some predictive models, the hope of retrieving any functioning spermatozoa may be sufficient to disregard predictive factors of the success of intracytoplasmic sperm injection in these patients.
Azoospermia* ; Chromosome Aberrations ; Follicle Stimulating Hormone ; Hope ; Humans ; Infertility, Male ; Logistic Models ; Male ; Methods ; Oligospermia ; Pathology ; Sertoli Cell-Only Syndrome ; Sperm Injections, Intracytoplasmic ; Sperm Retrieval* ; Spermatozoa*

Objective: To investigate whether testicular histology influences the clinical outcomes of intracytoplasmic sperm injection (ICSI) in men with non-obstructive azoospermia (NOA). METHODS: We retrospectively analyzed the clinical data about 73 cases of NOA undergoing ICSI, including 105 ICSI cycles and 79 embryo transfer cycles. The infertility of the patients was attributed to male factors only or both male and female tube factors and the females' age was ≤38 years. Based on testicular histology, we divided the ICSI cycles into three groups: hypospermatogenesis (HS, n = 72), maturation arrest (MA, n = 21) and Sertoli cells only (SCO, n = 12). We recorded and analyzed the age of both the males and females, infertility duration, base follicle-stimulating hormone (FSH) level, dose and days of gonadotropin (Gn) administration, estradiol (E2) and progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration, endometrial thickness, number of metaphase II (MII) oocytes, and rates of fertilization, transferrable embryos, high-quality embryos, clinical pregnancy, and abortion. RESULTS: The rates of fertilization, failed fertilization, transferrable embryos, and high-quality embryos, and the average number of transferred embryos were 67.03% (553/825), 9.52% (10/105), 85.66% (472/551), 35.03% (193/551), and 2.10, respectively, resulting in 44 pregnancies (55.70%) and 42 live births (53.16%), with no birth defects. No statistically significant differences were observed among the HS, MA and SCO groups in the mean age of the men and women, infertility duration, base FSH level, Gn dose, Gn days, E2 and P levels on the hCG day, endometrial thickness, or number of MII oocytes, nor in the rates of fertilization (68.51% vs 64.39% vs 61.45%), transferrable embryos (85.05% vs 90.48% vs 83.05%), or high-quality embryos (33.09% vs 41.67% vs 38.98%). The rates of clinical pregnancy and embryo implantation were higher in the HS (60.00% and 37.61%) and SCO (62.50% and 50.00%) than in the MA group (37.50% and 21.21%), but with no statistically significant differences (P >0.05). CONCLUSIONS Once testicular sperm is retrieved, desirable clinical outcomes can be achieved in ICSI for NOA patients, which is not affected by testicular histopathology.
Abortion, Spontaneous ; etiology ; Azoospermia ; Chorionic Gonadotropin ; administration & dosage ; Embryo Implantation ; Embryo Transfer ; statistics & numerical data ; Female ; Humans ; Infertility, Male ; etiology ; Male ; Oocytes ; Pregnancy ; Retrospective Studies ; Sperm Injections, Intracytoplasmic ; statistics & numerical data ; Spermatozoa ; Testis ; pathology

OBJECTIVE: To evaluate the fertility of infertile males of large samples by the routine semen examination, and to provide a scientific basis for clinical treatment of male infertility and improve efficacy. METHODS: We collected 16 835 semen specimens of infertile man in our hospital (the infertility group), and 1 567 semen specimens of sperm donating candidates from the sperm bank of our hospital (the control group). Semen routine examination was performed by computer-assisted semen analysis (CASA) technology, and the data of semen routine examination were analyzed statistically. RESULTS: The infertile patients with semen abnormalities in our hospital mainly suffered asthenospermia. The proportion of azoospermia, asthenospermia and oligoasthenospermia in the infertility group was higher than that in the control group, while the proportion of oligozoospermia was lower than that in the control group (P<0.001). CONCLUSION Azoospermia, asthenospermia and oligoasthenospermia are related to infertility, but simply oligozoospermia is not necessarily related to infertility.
Asthenozoospermia ; Azoospermia ; China ; Humans ; Infertility, Male ; epidemiology ; Male ; Oligospermia ; Semen Analysis ; Sperm Count ; Spermatozoa ; pathology

OBJECTIVETo compare cell suspension examination with histopathology in detecting spermatozoa in the testicular tissue of non-obstructive azoospermia (NOA) patients, and to investigate the reliability of sperm retrieval and appropriate therapeutic options when the results of the two methods are inconsistent.

METHODSA total of 1 112 NOA patients underwent testicular sperm extraction (TESE), their testicular tissues subjected to cell suspension examination and histopathology, respectively.

RESULTSThe consistency rate of the two methods was 92.63%, with the sperm detection rate of 41.82% and non-sperm detection rate of 50.81%. Sperm were retrieved from 96.0% (24/25) of the patients on the day of oval retrieval, in whom sperm were found in cell suspension examination but not in histopathology. After intracytoplasmic sperm injection (ICSI), pregnancy was achieved in 8 cases (33.33%), abortion occurred in 4 (16.67%), and non-pregnancy in 12 (50.0%).

CONCLUSIONCell suspension examination combined with histopathology for detecting sperm in the testicular tissue of NOA patients gives instant, accurate, reliable and consistent results, and therefore insures successful sperm retrieval for NOA patients during the IVF cycle. In case of inconsistency between the results of the two methods, cell suspension examination is more helpful for clinical therapeutic option.

Adult ; Azoospermia ; pathology ; Biopsy ; Humans ; Male ; Middle Aged ; Sperm Count ; Sperm Injections, Intracytoplasmic ; Sperm Retrieval ; Spermatozoa ; pathology ; Suspensions ; Testis ; pathology ; Young Adult