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Background: The management of Non-Obstructive (NOA) Azoospermia or Obstructive Azoospermia (OA) patients relies on testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI). In NOA patients the sperm recovery is successful in only 50% of cases and therefore the ability to predict those patients with a high probability of achieving a successful sperm retrieval would be a great value in counselling the patient and his partner. Several studies tried to suggest predictors of a positive TESE (e.g. FSH concentration), but most concluded that diagnostic testicular biopsy (histology) is best. Methods: This is a retrospective analysis of 526 TESE patients. After the extraction of the testis, the resulting sample was immediately given to the embryologist, who examined the tubules for sperm cryopreservation. During the same procedure, a different specimen was destined to the histological analysis. The comparison between the two methodological approaches was carried out through a score. Results: Concordance between TESE and testicular histology outcomes was found in 70,7% of patients; discordance was found in 29,3% of patients. Among the discordance outcomes, in approximately 95% we found at least 1 sperm in the TESE retrieval, while the histology report did not find any spermatozoa or found not enough compared to our evaluation; in only 5% of cases we did not find any spermatozoa or found not enough compared to what was detected in the testicular histology. Conclusion: Based on our experience, to increase diagnostic accuracy, a larger biopsy should be sent to the histopathology laboratory; another option may be to use TESE cell suspension (the same embryologists employ for cryopreservation) for cytological evaluation of spermatogenesis. [ABSTRACT FROM AUTHOR]

Background Objectives Materials and methods Results Conclusion Pediatric inguinal hernia repair (IHR) is a common cause of obstructive azoospermia (OA). Yet, the surgical treatment for this kind of OA remains difficult with poor fertility outcome.To evaluate the safety and effectiveness of totally extraperitoneal laparoscopy‐assisted microsurgical vasovasostomy (VV) in the treatment of OA caused by pediatric bilateral IHR.Totally, 37 patients with OA caused by pediatric bilateral IHR were enrolled in this study from March 2015 to December 2020 in Shanghai General Hospital. The clinical data and fertility outcomes were collected and analyzed.All patients enrolled had a history of bilateral IHR at the age of 1–10 years old. The mean age of patients was 27 ± 4.31 (range: 18–35) years. Totally extraperitoneal laparoscopy (TEP) was applied in 31 patients for the exploration and retrieval of pelvic vas deferens end, and 30 of them underwent microsurgical VV successfully. Among the six cases where TEP was not applied, five cases underwent microsurgical anastomosis. Intraoperative exploration revealed that the location of vas deferens injuries included scrotum (2.70%, 1/37), inguinal canal (5.41%, 2/37), pelvic cavity (78.37%, 29/37), and multiple sites (13.51%, 5/37). The mean operation time was 339 ± 96.73 min (range: 130–510 min). There were no surgical complications. Thirty‐three cases were followed up for 5–48 months with four cases lost to follow‐up. The overall patency rate, pregnancy rate, and natural pregnancy rate were 75.86% (22/29), 46.67% (14/30), and 36.84% (7/19, 3 patients without family planning), respectively. And seven couples conceived through the assisted reproductive technique, two of which using fresh sperm in the ejaculate.TEP laparoscopy‐assisted microscopic VV is an effective treatment for patients with OA caused by pediatric bilateral IHR. [ABSTRACT FROM AUTHOR]

Background: The presence of granulocyte–macrophage colony-stimulating factor (GM-CSF) and its receptor in various testicular cells and spermatozoa suggests a potential role in enhancing spermatogonial and postmeiotic cell development. Moreover, GM-CSF activates the pivotal pathways implicated in sperm motility regulation and glucose metabolism. However, the impact of GM-CSF on testicular biopsies from patients with obstructive azoospermia (OA) remains unexplored. Therefore, this study aimed to investigate the in vitro effects of GM-CSF on the expression of genes related to glucose transporters and signaling pathways, sperm motility, and viability in testicular biopsies. Methods and results: Following testicular sperm extraction from 20 patients diagnosed with OA, each sample was divided into two parts: the experimental samples were incubated with medium containing 2 ng/ml GM-CSF at 37 °C for 60 min, and the control samples were incubated with medium without GM-CSF. Subsequently, the oocytes retrieved from the partner were injected with sperm from the treatment and control groups. The sperm parameters (motility and viability), the expression levels of sperm motility-related genes (PIK3R1, PIK3CA, and AKT1), and the expression levels of sperm energy metabolism-related genes (GLUT1, GLUT3, and GLUT14) were assessed. Furthermore, the fertilization and day 3 embryo development rate and embryo quality were evaluated. Compared with those in the nontreated group, the motility parameters and the mRNA expression levels of PIK3R1, AKT1, and GLUT3 in testicular sperm supplemented with GM-CSF were significantly greater (p < 0.05). However, no significant differences in the mRNA expression of PIK3CA, GLUT1, or GLUT14 were detected. According to the ICSI results, compared with the control group, the GM-CSF treatment group exhibited significantly greater fertilization rates (p = 0.027), Day 3 embryo development rate (p = 0.001), and proportions of good-quality embryos (p = 0.002). Conclusions: GM-CSF increased the expression of genes related to motility and the energy metabolism pathway and effectively promoted the motility of testis-extracted spermatozoa, consequently yielding positive clinical outcomes. [ABSTRACT FROM AUTHOR]

BackgroundThe management of Non-Obstructive (NOA) Azoospermia or Obstructive Azoospermia (OA) patients relies on testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI). In NOA patients the sperm recovery is successful in only 50% of cases and therefore the ability to predict those patients with a high probability of achieving a successful sperm retrieval would be a great value in counselling the patient and his partner. Several studies tried to suggest predictors of a positive TESE (e.g. FSH concentration), but most concluded that diagnostic testicular biopsy (histology) is best.MethodsThis is a retrospective analysis of 526 TESE patients. After the extraction of the testis, the resulting sample was immediately given to the embryologist, who examined the tubules for sperm cryopreservation. During the same procedure, a different specimen was destined to the histological analysis. The comparison between the two methodological approaches was carried out through a score.ResultsConcordance between TESE and testicular histology outcomes was found in 70,7% of patients; discordance was found in 29,3% of patients. Among the discordance outcomes, in approximately 95% we found at least 1 sperm in the TESE retrieval, while the histology report did not find any spermatozoa or found not enough compared to our evaluation; in only 5% of cases we did not find any spermatozoa or found not enough compared to what was detected in the testicular histology.ConclusionBased on our experience, to increase diagnostic accuracy, a larger biopsy should be sent to the histopathology laboratory; another option may be to use TESE cell suspension (the same embryologists employ for cryopreservation) for cytological evaluation of spermatogenesis.

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety. [ABSTRACT FROM AUTHOR]

Purpose Design Results Conclusions Comparison of intracytoplasmic sperm injection cycles with testicular sperm extraction in obstructive azoospermia and non‐obstructive azoospermia are limited, and few studies have addressed obstetric and neonatal outcomes.This study analyzed couples who underwent testicular sperm extraction–intracytoplasmic sperm injection cycles for obstructive azoospermia and non‐obstructive azoospermia to determine whether impaired spermatogenesis in non‐obstructive azoospermia patients would lead to worse reproductive outcomes and higher rates of pregnancy complications and fetal anomalies. This study is a retrospective, single‐center analysis of all testicular sperm cycles performed between January 1, 2001 and December 31, 2020.A total of 392 couples were considered in the study, leading to 1066 induction cycles, 620 (58.2%) from patients with obstructive azoospermia and 446 (41.8%) from non‐obstructive azoospermia. The cumulative delivery rate did not significantly differ between the two groups (34% vs. 31%; p = 0.326). The miscarriage rate was similar between obstructive azoospermia and non‐obstructive azoospermia patients. Fertilization rate instead showed a statistically significant difference (obstructive azoospermia: 66.1 ± 25.7 vs. non‐obstructive azoospermia: 56.1 ± 27.0; p < 0.001). The overall maternal complication rate in the non‐obstructive azoospermia group was higher (10.7% vs. 18.4%; p = 0.035), but there was no statistical significance for each pathology. There was no statistical difference in gestational age between the two groups for both single and twin pregnancies. Seven cases of congenital defects occurred in the obstructive azoospermia group, while two cases occurred in the non‐obstructive azoospermia group.Despite impaired spermatogenesis in non‐obstructive azoospermia patients, there were no substantial differences in reproductive outcomes compared to patients with obstructive azoospermia, even in terms of obstetric safety and neonatal well‐being. [ABSTRACT FROM AUTHOR]

Objective: To explore the application value of ultrasound in the etiological diagnosis of azoospermia.Methods: Three hundred and fourteen consecutive cases of azoospermia diagnosed in our hospital from January 1, 2015 to December 31, 2021 were retrospectively analyzed, and their clinical data and ultrasonic examination results were summarized and analyzed. Results: Among 314 patients, 118 (37.6%) had obstructive azoospermia (OA) and 196 (62.4%) had non obstructive azoospermia (NOA). Among OA patients, 89% (105 cases) showed positive ultrasound findings, including congenital bilateral vas deferens absence (40 cases), ejaculatory duct obstruction(33 cases), inflammatory lesions(17 cases), and calcified lesions (15 cases); Among 196 patients with NOA, 40.3% (79 cases) had positive ultrasound findings, including small testis (45 cases), cryptorchidism (13 cases), testicular microlithiasis (16 cases), and varicocele (5 cases). Conclusions: Among the 314 patients with azoospermia in this study, the ratio of NOA to OA is 1.66:1. Ultrasound examination is able to identify the etiology of 58.6% of the patients, including 89% of the causes of OA and 40.3% of the causes of NOA.

Objective To investigate the efficacy, safety and the influence on pregnancy outcome of L-carnitine before intracytoplasmic sperm injection (ICSI) from different sources of sperm in patients with obstructive azoospermia (OA). Methods A total of 141 patients with OA were treated with L-carnitine for three months, and sperms were obtained by testicular sperm aspiration (TESA) and percutaneous epididymal sperm aspiration (PESA) respectively. According to the source of sperm, they were divided into the two groups: the TESA group (n=78) and the PESA group (n=63). The general clinical data, sperm quality, embryonic development and clinical outcome of the two groups were compared. Results In the TESA/PESA group, sperm DFI and sperm spontaneous acrosome reaction rate were significantly lower than those before treatment, and sperm acrosome integrity rate was significantly higher than that before treatment (P＜0.05). There were no significant differences in sperm DFI, sperm acrosome integrity rate and sperm spontaneous acrosome reaction rate between the two groups(P＞0.05). There were no significant differences in the fertilization rate, 2PN fertilization rate, cleavage rate, excellent embryo rate, implantation rate, clinical pregnancy rate, live birth rate, premature birth rate, abortion rate and neonatal malformation rate between the two groups (P＞0.05). A total of 103 fresh transplant cycles, 989 MII oocytes, 773 zygotes, 49 clinical pregnancies and 39 live births were obtained (including 17 in the TESA group and 22 in the PESA group). During a 3-month follow-up after birth, it was found that one newborn had cardiac abnormalities in the TESA group, while the other newborns had no abnormalities. Conclusion In OA patients, L-carnitine before TESA-ICSI and PESAICSI can improve the sperm quality, optimize clinical outcome, and the medication is safe. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we aimed to identify sterility-related variants in a Chinese pedigree with male infertility and to reveal the different phenotypes and intracytoplasmic sperm injection (ICSI) outcomes of the affected members. Methods: Physical examinations were performed on male patients. G-band karyotype analysis, copy number variation sequencing, and quantitative fluorescent PCR were conducted to detect common chromosomal disorders in the probands. Whole-exome sequencing and Sanger sequencing were applied to identify the pathogenic genes and the protein expression changes caused by the very mutation were identified by Western Blot in vitro. Results: A novel nonsense mutation (c.908C > G: p.S303*) in the ADGRG2 was identified in all infertile male patients of the pedigree, which was inherited from their mothers. This variant was absent from the human genome databases. This mutation was also unexpectedly found in a male member with normal reproductive capability. Members with the mutation had different genitalia phenotypes, ranging from normal to dilated phenotypes of the vas deferens, spermatic veins and epididymis. There was a truncated ADGRG2 protein in vitro after mutation. Of the three patients' wives treated with ICSI, only one successfully gave birth. Conclusions: Our study is the first to report the c.908C > G: p.S303* mutation in the ADGRG2 in an X-linked azoospermia pedigree and is the first to report normal fertility in a member with this mutation, expanding the mutation spectrum and phenotype spectrum of this gene. In our study, ISCI had a success rate of only one-third in couples including men with azoospermia with this mutation. [ABSTRACT FROM AUTHOR]

What is the risk of hypogonadism in men with obstructive azoospermia, non-obstructive azoospermia (NOA) or Klinefelter syndrome after testicular sperm extraction (TESE)? This prospective longitudinal cohort study was carried out between 2007 and 2015. Around 36% of men with Klinefelter syndrome, 4% of men with obstructive azoospermia and 3% of men with NOA needed testosterone replacement therapy (TRT). Klinefelter syndrome was strongly associated with TRT while no association was found between obstructive azoospermia or NOA and TRT. Irrespective of the pre-operative diagnosis, a higher testosterone concentration before TESE was associated with a lower chance of needing TRT. Men with obstructive azoospermia or NOA have a similar moderate risk of clinical hypogonadism after TESE, while this risk is much larger for men with Klinefelter syndrome. The risk of clinical hypogonadism is lower when testosterone concentrations are high before TESE. [ABSTRACT FROM AUTHOR]

Vasectomy damage is a common complication of open nonmesh hernia repair. This study was a retrospective analysis of the characteristics and possible causes of vas deferens injuries in patients exhibiting unilateral or bilateral vasal obstruction caused by open nonmesh inguinal herniorrhaphy. The site of the obstructed vas deferens was intraoperatively confirmed. Data, surgical methods, and patient outcomes were examined. The Anderson–Darling test was applied to test for Gaussian distribution of data. Fisher's exact test or Mann–Whitney U test and unpaired t-test were used for statistical analyses. The mean age at operation was 7.23 (standard deviation [s.d.]: 2.09) years and the mean obstructive interval was 17.72 (s.d.: 2.73) years. Crossed (n = 1) and inguinal (n = 42) vasovasostomies were performed. The overall patency rate was 85.3% (29/34). Among the 43 enrolled patients (mean age: 24.95 [s.d.: 2.20] years), 73 sides of their inguinal regions were explored. The disconnected end of the vas deferens was found in the internal ring on 54 sides (74.0%), was found in the inguinal canal on 16 sides (21.9%), and was found in the pelvic cavity on 3 sides (4.1%). Location of the vas deferens injury did not significantly differ according to age at the time of hernia surgery (≥12 years or

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.

Background: Following microsurgical vaso-epididymal anastomosis (VEA), anastomotic patency with sperm returning to the ejaculate is not always present and may even be delayed. The presence of motile spermatozoa is highly suggestive of future patency following surgery. Aims: We prospectively analyse the factors that could predict motile spermatozoa at the epididymis intraoperatively and predictors of patency in patients with obstructive azoospermia (OA) undergoing microsurgical VEA. Settings and Design: Department of Urology of a tertiary care centre in Northern India. It is a prospective observational study. Materials and Methods: Over a 2-year period (July 2019 to June 2021), 26 patients with idiopathic OA were enrolled in the study. Twenty patients underwent microsurgical VEA. Patients were divided into two groups based on the presence/absence of intraoperative motile spermatozoa. Statistical Analysis Used: Analysis of preoperative and intraoperative factors was done using the Mann–Whitney U-test, Chi-squared test and Fischer exact test. Results: Out of 20 patients, 5 (group 2) had intraoperative motile spermatozoa in the epididymal fluid and 15 (group 1) had nonmotile spermatozoa. Low luteinising hormone (LH) levels (P = 0.01) and high testosterone levels (P = 0.05) were the predictive of presence of motile spermatozoa in epididymal fluid. Mean follow-up was 9 months (6–18 months). Predictors of higher patency were grade 2 epididymis (firm, turgid and tense) (P = 0.003), low LH levels (P = 0.03), low sertoli cell index (P = 0.006), high sperm-Sertoli index (P = 0.002) and better surgeon satisfaction (P = 0.01). Conclusion: Low LH levels and high testosterone levels may be predictive of the presence of motile spermatozoa in epididymal fluid. Firm, turgid and tense epididymis, low Sertoli cell index, high sperm-Sertoli index and surgeon satisfaction suggest a greater chance of success after VEA for idiopathic azoospermia.

To design a treatment plan for patients with epididymal obstruction, we explored the potential impact of factors such as body mass index (BMI) and age on the surgical outcomes of vasoepididymostomy (VE). In this retrospective study, 181 patients diagnosed with obstructive azoospermia (OA) due to epididymal obstruction between September 2014 and September 2017 were reviewed. All patients underwent single-armed microsurgical intussusception VEs with longitudinal two-suture placement performed by a single surgeon (KH) in a single hospital (Peking University Third Hospital, Beijing, China). Six factors that could possibly influence the patency rates were analyzed, including BMI, age, mode of anastomosis, site of anastomosis, and sperm motility and quantity in the intraoperative epididymal fluid. Single-factor outcome analysis was performed via Chi-square test and multivariable analysis was performed using logistic regression. A total of 159 (87.8%, 159/181) patients were followed up. The follow-up time (mean ± standard deviation [s.d.]) was 27.7 ± 9.3 months, ranging from 12 months to 48 months. The overall patency rate was 73.0% (116/159). The multivariable analysis revealed that BMI and age significantly influenced the patency rate (P = 0.008 and 0.028, respectively). Younger age (≤28 years; odds ratio [OR] = 3.531, 95% confidence interval [95% CI]: 1.397–8.924) and lower BMI score (

Male infertility may occur due to obstructive and non-obstructive reasons, and some pathologies may be corrected with surgical and medical treatment. Such treatment may increase the possibility of spontaneous pregnancy, the success of assisted reproductive technology, and also testicular sperm retrieval rate. This review will focus on surgical treatment alternatives in infertile males. Although treatment options for varicocele in infertile men include open surgical, radiologic, and laparoscopic approaches; microsurgical varicocele repair has the highest improvement in postoperative sperm parameters with lower complication rates. Recent advances in microsurgical anastomosis techniques have increased the patency rate for proximal epididymal obstruction. Although treatment options for distal ejaculatory duct obstruction include endoscopic resection, balloon dilatation, and laser incision/excision, transurethral resection of the ejaculatory duct (TURED), is still the primary gold standard treatment of distal ejaculatory duct obstruction. The testicular sperm retrieval rate has increased with the management of correctable pathologies in men with non-obstructive azoospermia. In case of treatment failure of correctable or uncorrectable pathologies of male factor infertility, surgical sperm obtained from the urogenital tract may necessary for assisted reproductive technology. Surgical success rates for male infertility and the success of surgical sperm obtained procedures have increased dramatically over the last decades attributable to the development of microsurgical techniques and endoscopic equipment, instrumentation, and techniques.

Expanding established tests, exome sequencing in crypto-/azoospermic men yielded 8.5% additional diagnoses. These predict the success rate of testicular sperm extraction. Thus, an analysis of validated genes in infertile men with crypto- or azoospermia will significantly improve the standard of care. Crypto- and azoospermia (very few/no sperm in the semen) are main contributors to male factor infertility. Genetic causes for spermatogenic failure (SPGF) include Klinefelter syndrome and Y-chromosomal azoospermia factor microdeletions, and CFTR mutations for obstructive azoospermia (OA). However, the majority of cases remain unexplained because monogenic causes are not analysed. To elucidate the monogenic contribution to azoospermia by prospective exome sequencing and strict application of recent clinical guidelines. Since January 2017, we studied crypto- and azoospermic men without chromosomal aberrations and Y-chromosomal microdeletions attending the Centre of Reproductive Medicine and Andrology, Münster. We performed exome sequencing in 647 men, analysed 60 genes having at least previous limited clinical validity, and strictly assessed variants according to clinical guidelines. Overall, 55 patients (8.5%) with diagnostic genetic variants were identified. Of these patients, 20 (3.1%) carried mutations in CFTR or ADGRG2 , and were diagnosed with OA. In 35 patients (5.4%) with SPGF, mutations in 20 different genes were identified. According to ClinGen criteria, 19 of the SPGF genes now reach at least moderate clinical validity. As limitations, only one transcript per gene was considered, and the list of genes is increasing rapidly so cannot be exhaustive. The number of diagnostic genes in crypto-/azoospermia was almost doubled to 21 using exome-based analyses and clinical guidelines. Application of this procedure in routine diagnostics will significantly improve the diagnostic yield and clinical workup as the results indicate the success rate of testicular sperm extraction. When no sperm are found in the semen, a man cannot conceive naturally. The causes are often unknown, but genetics play a major role. We searched for genetic variants in a large group of patients and found causal mutations for one in 12 men; these predict the chances for fatherhood. [ABSTRACT FROM AUTHOR]

Introduction: We have developed a modified vasoepididymostomy procedure, namely "fenestrated" transversal two-suture microsurgical intussusception vasoepididymostomy. This study aimed to investigate the therapeutic efficacy and outcome of this fenestrated vasoepididymostomy for epididymal obstructive azoospermia (OA). Methods: Microsurgical two-suture transversal intussusception vasoepididymostomy was performed using our modified fenestration technique in 64 OA patients due to epididymal obstruction at our hospital. Fenestration means making an opening on the epididymal tubule wall. The edges of the epididymal tubule "window" were stitched transversally (two stitches) using the two double-armed 9–0 atraumatic sutures. The epididymal tubule was anastomosed to the lumen of the vas deferens. The patency rate and pregnancy rate were assessed. Results: Of the 64 OA patients, 45 received bilateral microsurgical two-suture transversal intussusception vasoepididymostomy, while 19 underwent unilateral microsurgical two-suture transversal intussusception vasoepididymostomy. All of the patients were followed up after the operation. The follow-up period ranged from 4 to 54 months. Among 45 cases of bilateral surgery, the patency rate was 88.89% (40/45), and the natural pregnancy rate was 28.89% (13/45). After the patency was confirmed postoperatively, 3 cases had recurrent OA, of which 2 cases had return of sperm to the ejaculate by oral antibiotics and scrotal self-massage. As for the 19 cases of unilateral microsurgery, the patency rate was 68.42% (13/19), and the natural pregnancy rate was 21.05% (4/19). Conclusion: The fenestrated transversal two-suture microsurgical intussusception vasoepididymostomy can achieve a good patency rate in OA patients and did not increase the difficulty and duration of the procedure. [ABSTRACT FROM AUTHOR]

Abstract Background There is a lack of biomarkers for distinguishing non-obstructive azoospermia (NOA) patients with successful sperm retrieval (Sp+) from those with failed sperm retrieval (Sp-). This study aimed to determine the potential of extracellular vesicles tRNA-derived small RNA (tsRNA) as a novel non-invasive biomarker for successful sperm retrieval by microdissection testicular sperm extraction (mTESE). Methods The study included 18 patients with NOA with successful sperm retrieval (Sp+) and 23 patients with NOA with failed sperm retrieval (Sp-), 15 obstructive azoospermia (OA) patients, 5 idiopathic oligospermia (IO) patients, and 12 healthy people. Seminal plasma extracellular vesicles tsRNA levels were used in a two-stage case-control study (screened by tsRNA sequencing on Illumina NextSeq instrument and validated by qRT-PCR). The bioinformatic analysis was performed to determine the role of tsRNA in the pathogenesis of non-obstructive azoospermia. Results Two tsRNAs (tRF-Val-AAC-010: AUC = 0.96, specificity = 80%, sensitivity = 95%; tRF-Pro-AGG-003: AUC = 0.96, specificity = 87%, sensitivity = 95%) were found to have high predictive accuracy for distinguishing the origin of azoospermia. In addition, the extracellular vesicles tRF-Val-AAC-010 resulted in high predictive ability (AUC = 0.89, sensitivity = 72%, specificity = 91%, P

Background: Accurate etiology of azoospermia is required for optimal management of patients. The aim of thisstudy was the determination of serum hormonal levels and testicular long axis cut off points to distinguish obstructiveazoospermia (OA) from non-OA (NOA) in Iranian patients as well as the evaluation of the necessity of diagnostictestis biopsy in azoospermic patients.Materials and Methods: In this retrospective study, data of 471 azoospermic patients such as history and physicalexamination, serum hormonal level, semen fluid parameter, and testicular long axis based on ultrasound wereevaluated from 2016 to 2020. All patients were examined by a single urologist and underwent a diagnostic testisbiopsy for a definite diagnosis. The diagnostic parameters were analyzed using Statistical Package for the SocialSciences (SPSS) version 16 with t test and chi-square test and receiver operating characteristic (ROC) curves todistinguish NOA from OA.Results: A total of 127 patients with OA and 284 with NOA were included in this study. The mean serum testosteronelevel was significantly higher in OA than NOA (4.2 vs. 3.4 ng/ml), whereas the mean serum follicular stimulating hormone(FSH, 5.3 vs. 19.1 mIU/ml) and luteinizing hormone (LH, 5.3 vs. 11 mIU/ml) were lower in OA. ROC curve analysisshowed that FSH and testicular long axis were the best diagnostic predictors. Using a combination of serum FSH (8.9mIU/ml) and testicular long axis (39 mm), the positive predictive value for NOA was 97.02% and for OA was 78.8%.Conclusion: Combination of serum FSH higher than 8.9 mIU/ml and testicular long axis lower than 39 mm werestrong predictors to distinguish NOA from OA in Iranian participants in this study. In addition, diagnostic testicularbiopsy seems to be necessary for patients with OA and NOA characteristics.

Introduction. The difference between obstructive and non-obstructive azoospermia (OA and NOA) is important for the choice of treatment tactics and adequate counseling of a married couple.Objective. To describe, analyze, and classify possible challenges in differentiating between two types of azoospermiaMaterials and methods. The retrospective review of database on surgical sperm retrieval attempts performed our hospital (n = 754). A subpopulation of 216 patients who were preliminary diagnosed with OA, was selected for further analysis. All patients had testicular pathology data following sperm retrieval attempt. Rate of reclassification was assessed as a primary outcome. Reclassified cases were further analyzed to find a possible reason for incorrect differential diagnosis.Results. Among 216 patients with initially suspected OA, 131 (60.6%) had evidence of spermatogenic dysfunction on pathological examination of seminiferous tubules. Multivariate regression analysis showed that only regular exposure to high temperatures was an independent predictor of NOA detection in patients with normal endocrine and clinical parameters (OR = 1.989; 95% CI = 1.101 – 3.595). Analysis of the decision tree showed that patients with inhibin B levels below 93 pg/ml had the highest risk of an incorrect initial diagnosis (82.6%).Conclusions. Differential diagnosis of OA and NOA is not such a simple task. Any case of azoospermia against the background of normal semen volume by default should be considered as a case of NOA if there is no anamnestic or clinical data clearly indicating obstruction. Regular exposure to high temperature is likely to cause azoospermia in men with initially severe disorders of spermatogenesis. Finally, the reference values of inhibin B offered by most laboratories are not intended to assess reproductive function.

Background: Following microsurgical vaso-epididymal anastomosis (VEA), anastomotic patency with sperm returning to the ejaculate is not always present t and may even be delayed. The presence of motile spermatozoa is highly suggestive of future patency following surgery. Aims: We prospectively analyse the factors that could predict motile spermatozoa at the epididymis intraoperatively and predictors of patency in patients with obstructive azoospermia (OA) undergoing microsurgical VEA. Settings and Design: Department of Urology of a tertiary care centre in Northern India. It is a prospective observational study. Materials and Methods: Over a 2-year period (July 2019 to June 2021), 26 patients with idiopathic OA were enrolled in the study. Twenty patients underwent microsurgical VEA. Patients were divided into two groups based on the presence/ absence of intraoperative motile spermatozoa. Statistical Analysis Used: Analysis of preoperative and intraoperative factors was done using the Mann-Whitney U-test, Chi-squared test and Fischer exact test. Results: Out of 20 patients, 5 (group 2) had intraoperative motile spermatozoa in the epididymal fluid and 15 (group 1) had nonmotile spermatozoa. Low luteinising hormone (LH) levels (P = 0.01) and high testosterone levels (P = 0.05) were the predictive of presence of motile spermatozoa in epididymal fluid. Mean follow-up was 9 months (6-18 months). Predictors of higher patency were grade 2 epididymis (firm, turgid and tense) (P = 0.003), low LH levels (P = 0.03), low sertoli cell index (P = 0.006), high sperm-Sertoli index (P = 0.002) and better surgeon satisfaction (P = 0.01). Conclusion: Low LH levels and high testosterone levels may be predictive of the presence of motile spermatozoa in epididymal fluid. Firm, turgid and tense epididymis, low Sertoli cell index, high sperm-Sertoli index and surgeon satisfaction suggest a greater chance of success after VEA for idiopathic azoospermia. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether ICSI outcomes are affected by sperm source or genital tract inflammatory status. Methods: A retrospective cohort study was conducted in all consecutive obstructive azoospermia patients who underwent testicular sperm aspiration (TESA) or percutaneous epididymal sperm aspiration (PESA) and ICSI between February 1, 2017, and December 31, 2020. Couples were excluded if they were diagnosed with monogenic disease, abnormal karyotype, or had female uterine malformation. The primary objective was to determine whether ICSI outcomes are affected by the use of testicular or epididymal spermatozoa, and the secondary objective was to explore the effect of granulocyte elastase on ICSI outcomes using epididymal spermatozoa. Results: Compared with TESA, inflammatory and non-inflammatory PESA patients exhibited a better high-quality embryo rate, with significant differences among the three groups (49.43 vs. 55.39% and 56.03%; odds ratio, 6.345 and 6.631; 95% confidence interval, 0.340–12.350, and 1.712–11.550; P = 0.038 and P = 0.008, respectively). The fertilization rate, clinical pregnancy rate, live birth delivery rate, and congenital anomaly birth rate were similar in patients who underwent TESA or PESA (with or without inflammation). Conclusions: The high-quality embryo rate in PESA patients was higher than that in TESA patients. After successful pregnancy, ICSI outcomes did not differ between patients with obstructive azoospermia who experienced TESA or PESA and those with or without genital tract inflammation. [ABSTRACT FROM AUTHOR]

Differential diagnosis between obstructive and non-obstructive azoospermia is an important task in clinical management of infertile patients. Chances of extracting sperm in obstructive azoospermia are high enough to inform the couple about favorable outcome of assisted reproductive technologies without resorting to donor sperm. Some forms of seminal tract obstruction can be corrected by microsurgical interventions or endoscopic resection of the ejaculatory ducts. Therefore, one of the objectives standing before imaging methods in reproductive andrology is the detection of these cases. In this literature review we present a detailed analysis of how to suspect and diagnose this form of azoospermia using imaging.

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.

Objective To analyze the proteomics of testicular tissue in the patients of obstructive azoospermia with different Johnsen scores and explore the differentially-expressed proteins and their functions and biological processes using bioinformatics to provide basis for the treatment of patients. Methods A total of 22 patients with obstructive azoospermia who admitted to reproductive Medicine Center of our hospital from June 2020 to April 2021 were enrolled in the study. According to the Johnsen score of testicular puncture pathology, they were divided into two groups: normal spermatogenesis group (control group, Johnsen score 9-10, total 12 cases) and low spermatogenesis group (experimental group, Johnsen score 8, total 10 cases). LC-MS/MS platform was used to screen differentially expressed proteins between two groups, and IPA software package was used for functional analysis of differentially expressed proteins. Results A total of 2883 and 2372 proteins were identified in the control group and the experimental group, respectively, and 544 differentially expressed proteins were obtained by comparing the testicular proteomics of obstructive azoospermia with different Johnsen scores. Compared with the control group, 204 proteins in the experimental group were up-regulated and 340 proteins were downregulated. IPA analysis of differential proteins showed that endothelial cell connection, glycolysis and other pathways were markedly inhibited, while 14-3-3 pathway and Rho pathway were significantly activated in testicular tissue of the experimental group. Functional analysis showed that asthenospennia and cell death were noticeably activated in the testes of the experimental group, while protein metabolism, endocytosis and gametogenesis were significantly inhibited. These results suggested that testicular proteomics can reflect the pathological changes of abnormal spermatogenesis. Conclusion The bioinformatics method is used for data mining of proteins of testicular tissue with different Johnsen scores in the patients of inobstructive azoospennia, which provides a reference for further research on low spermatogenesis mechanism and new biomarkers. [ABSTRACT FROM AUTHOR]

Objectives: To report on the live birth rates (LBRs) following percutaneous epididymal sperm aspiration (PESA) in men with obstructive azoospermia (OA) and factors affecting treatment outcome which is under reported in the literature. Methods: This is a multicenter study that was conducted in Egypt including all couples undergoing intra cytoplasmic sperm injection (ICSI) for OA using PESA-derived sperms. Men were subdivided according to aetiology into congenital, iatrogenic and idiopathic groups. Fertilization, pregnancy and LBRs were determined and compared in each group. The longitudinal LBR, crude and expected cumulative delivery rates (CCDR, ECDR) were calculated. Multiple logistic regression analysis was used to determine significant associations between maternal, paternal and ICSI factors with successful live births. Results: Ninety couples were included in the study. Viable sperm for ICSI was retrieved in 89 men (98.9%). A total of 155 ICSI cycles with 17 frozen embryo transfers resulted in 81 pregnan-cies and 55 live births. After 5 cycles, the longitudinal LBR, CCDR and ECDR were 30%, 57.3% and 88.6% respectively. Maternal age and number of fertilized eggs were the only fac-tors significantly affecting LBRs. Conclusions: PESA is a minimally invasive procedure for secur-ing viable sperm for ICSI in OA men, with high cumulative delivery rates. Maternal age and number of fertilized eggs are the only factors that significantly affecting LBR. The contempo-rary longitudinal and cumulative LBRs provide objective out-come data to counsel OA patients undergoing fertility treat-ments.

Background: There is a lack of biomarkers for distinguishing non-obstructive azoospermia (NOA) patients with successful sperm retrieval (Sp+) from those with failed sperm retrieval (Sp-). This study aimed to determine the potential of extracellular vesicles tRNA-derived small RNA (tsRNA) as a novel non-invasive biomarker for successful sperm retrieval by microdissection testicular sperm extraction (mTESE). Methods: The study included 18 patients with NOA with successful sperm retrieval (Sp+) and 23 patients with NOA with failed sperm retrieval (Sp-), 15 obstructive azoospermia (OA) patients, 5 idiopathic oligospermia (IO) patients, and 12 healthy people. Seminal plasma extracellular vesicles tsRNA levels were used in a two-stage case-control study (screened by tsRNA sequencing on Illumina NextSeq instrument and validated by qRT-PCR). The bioinformatic analysis was performed to determine the role of tsRNA in the pathogenesis of non-obstructive azoospermia. Results: Two tsRNAs (tRF-Val-AAC-010: AUC = 0.96, specificity = 80%, sensitivity = 95%; tRF-Pro-AGG-003: AUC = 0.96, specificity = 87%, sensitivity = 95%) were found to have high predictive accuracy for distinguishing the origin of azoospermia. In addition, the extracellular vesicles tRF-Val-AAC-010 resulted in high predictive ability (AUC = 0.89, sensitivity = 72%, specificity = 91%, P < 0.0001) in predicting the presence of sperm in non-obstructive azoospermia undergoing mTESE. Finally, bioinformatic analysis revealed that tRF-Val-AAC-010 were involved in spermatogenesis. Conclusions: This study identified that the extracellular vesicles tRF-Val-AAC-010 and tRF-Pro-AGG-003 are biomarkers for the diagnosis of non-obstructive azoospermia, and that tRF-Val-AAC-010 as a potential non-invasive biomarker for predicting the presence of sperm in non-obstructive azoospermia testicular tissue. [ABSTRACT FROM AUTHOR]

Objectives: To report on the live birth rates (LBRs) following percutaneous epididymal sperm aspiration (PESA) in men with obstructive azoospermia (OA) and factors affecting treatment outcome which is under reported in the literature. Methods: This is a multicenter study that was conducted in Egypt including all couples undergoing intra cytoplasmic sperm injection (ICSI) for OA using PESA-derived sperms. Men were subdivided according to aetiology into congenital, iatrogenic and idiopathic groups. Fertilization, pregnancy and LBRs were determined and compared in each group. The longitudinal LBR, crude and expected cumulative delivery rates (CCDR, ECDR) were calculated. Multiple logistic regression analysis was used to determine significant associations between maternal, paternal and ICSI factors with successful live births. Results: Ninety couples were included in the study. Viable sperm for ICSI was retrieved in 89 men (98.9%). A total of 155 ICSI cycles with 17 frozen embryo transfers resulted in 81 pregnancies and 55 live births. After 5 cycles, the longitudinal LBR, CCDR and ECDR were 30%, 57.3% and 88.6% respectively. Maternal age and number of fertilized eggs were the only factors significantly affecting LBRs. Conclusions: PESA is a minimally invasive procedure for securing viable sperm for ICSI in OA men, with high cumulative delivery rates. Maternal age and number of fertilized eggs are the only factors that significantly affecting LBR. The contemporary longitudinal and cumulative LBRs provide objective outcome data to counsel OA patients undergoing fertility treatments. [ABSTRACT FROM AUTHOR]

Background: Nowadays, pathogenesis of preeclampsia (PE) is still unknown. Among the different etiological hypotheses, some authors proposed that it might be because of an abnormal immunologic response to a foreign fetal antigen derived from the father's spermatozoa. Indeed, the fetus is considered a semi‐allograft, being one half paternally derived in its antigenicity, and the first pathogenic insult of PE may be an abnormal maternal immune response toward this semi‐allogenic implant. In the context of artificial reproductive techniques, it has been shown that the use of donor and surgically retrieved spermatozoa (e.g., testicular sperm extraction [TESE]) increases the risk of PE, confirming the protective effect of sperm exposure on maternal complications. Objective: Determining whether the lack of exposure to sperm antigens is associated with worse maternal and neonatal outcomes in pregnancies obtained through intracytoplasmic sperm injection after TESE (ICSI–TESE) for obstructive azoospermia (OA). Materials and methods: This is a single‐center case–control retrospective study, focusing on all first pregnancies obtained through ICSI–TESE for OA at Humanitas Fertility Center between January 1, 2010 and December 31, 2019. Controls included patients that achieved their first pregnancy with ICSI and ejaculated spermatozoa, for a diagnosis other than azoospermia, in the same time period. Cases were matched with controls in a 1:2 ratio, considering female age, female BMI, and year of controlled ovarian stimulation. The primary outcome measure was the delivery rate, defined as the number of deliveries divided by the total number of clinical pregnancies. Secondary outcome measures focused on maternal and neonatal complications, such as miscarriage rate, rate of main obstetric complications, prematurity rate, and rate of congenital malformations. Results: By analyzing overall 113 pregnancies among cases and 214 pregnancies among controls, this study showed that the delivery rate was higher in controls with respect to cases (92.06% vs. 84.07%, p = 0.026); among deliveries, live births were 98.95% and 100%, respectively, whereas only one stillbirth occurred in cases. The first trimester miscarriage rate was higher in the cases than controls (13.27% vs. 6.07%, p = 0.027), whereas no difference was found among the rate of second trimester miscarriages, therapeutic abortions, and ectopic pregnancies. There was no difference regarding the rate of maternal complications, including gestational hypertension, PE, HELLP syndrome, gestational diabetes, placenta previa, placental abruption, and premature rupture of the membranes. Considering neonatal complications, it was shown that twins belonging to controls had a higher prematurity rate with respect to cases (65.79% vs. 50.00%) but without a statistical relevance. Lastly, the rate of congenital malformations did not differ among the two groups. Discussion: This study showed that, once couples diagnosed with OA achieve a pregnancy, they have a much higher risk of miscarriage in the first trimester in respect to non‐azoospermic patients. Moreover, controls had a higher delivery rate in respect to cases; however, when the fetal status at birth was compared, no difference was found between live births and stillbirths. Conclusions: Differently from the findings in the literature, no association with PE was found. This might be related to a collider bias/left truncation bias: As azoospermic patients are at higher risk of early termination of pregnancy, it results that they do not have the possibility to develop PE and other adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: Accurate etiology of azoospermia is required for optimal management of patients. The aim of this study was the determination of serum hormonal levels and testicular long axis cut off points to distinguish obstructive azoospermia (OA) from non-OA (NOA) in Iranian patients as well as the evaluation of the necessity of diagnostic testis biopsy in azoospermic patients. Materials and Methods: In this retrospective study, data of 471 azoospermic patients such as history and physical examination, serum hormonal level, semen fluid parameter, and testicular long axis based on ultrasound were evaluated from 2016 to 2020. All patients were examined by a single urologist and underwent a diagnostic testis biopsy for a definite diagnosis. The diagnostic parameters were analyzed using Statistical Package for the Social Sciences (SPSS) version 16 with t test and chi-square test and receiver operating characteristic (ROC) curves to distinguish NOA from OA. Results: A total of 127 patients with OA and 284 with NOA were included in this study. The mean serum testosterone level was significantly higher in OA than NOA (4.2 vs. 3.4 ng/ml), whereas the mean serum follicular stimulating hormone (FSH, 5.3 vs. 19.1 mIU/ml) and luteinizing hormone (LH, 5.3 vs. 11 mIU/ml) were lower in OA. ROC curve analysis showed that FSH and testicular long axis were the best diagnostic predictors. Using a combination of serum FSH (8.9 mIU/ml) and testicular long axis (39 mm), the positive predictive value for NOA was 97.02% and for OA was 78.8%. Conclusion: Combination of serum FSH higher than 8.9 mIU/ml and testicular long axis lower than 39 mm were strong predictors to distinguish NOA from OA in Iranian participants in this study. In addition, diagnostic testicular biopsy seems to be necessary for patients with OA and NOA characteristics. [ABSTRACT FROM AUTHOR]

A variety of surgical options exists for sperm retrieval in the setting of obstructive azoospermia (OA). With appropriate preparation, the majority of these techniques can safely be performed in the office with local anesthesia and with or without monitored anesthesia care (MAC). The available techniques include percutaneous options such as percutaneous epididymal sperm aspiration (PESA) and testicular sperm aspiration (TESA), as well as open techniques that include testicular sperm extraction (TESE) and microsurgical epididymal sperm aspiration (MESA). In addition to providing a step-by-step description of each available approach, we introduce and describe a new technique for sperm retrieval for OA called minimally invasive epididymal sperm aspiration (MIESA). The MIESA utilizes a tiny keyhole incision, and the epididymis is exposed without testicular delivery. Epididymal aspiration is performed in the style of MESA, except using loupe magnification rather than an operating microscope. MIESA is a safe, office-based procedure in which millions of motile sperm can be retrieved for cryopreservation. While we prefer the MIESA technique for OA, there remain distinct advantages of each open and percutaneous approach. In the current era of assisted reproductive technology, sperm retrieval rates for OA should approach 100% regardless of the technique. This reference provides a roadmap for both advanced and novice male reproductive surgeons to guide them through every stage of sperm retrieval for OA, including preoperative evaluation, patient selection, procedural techniques, and complications. With the incredible advances in in vitro fertilization (IVF), combined with innovative surgical treatment for male factor infertility in recent years, OA is no longer a barrier for men to become biologic fathers.

ObjectiveTo compare and contrast the effects of percutaneous epididymal sperm aspiration (PESA) and testicular sperm aspiration (TESA) on the outcome of intracytoplasmic sperm injection (ICSI)-assisted fertility treatment in patients with obstructive azoospermia.MethodsPatients with obstructive azoospermia with an age distribution of 20–36 years admitted to the male department of the Reproductive Center of the Second Affiliated Hospital of South China University (Hengyang Nanhua Xing Hui Reproductive Health Hospital) from December 2018 to December 2020 were used in this study. One group was set up as the PESA group to perform PESA, and the other group was set up as the TESA group to perform percutaneous testicular biopsy for sperm extraction. Patients who were unsuccessful in PESA continued to undergo TESA, and if sperm were retrieved, they were classified as the TESA group. General information on male patients and their partners was collected and compared in patients from different sperm source groups. Embryo development (normal fertilization rate, high-quality embryo rate, and high-quality blastocyst rate) and pregnancy outcome (clinical pregnancy rate, miscarriage rate, and ectopic pregnancy rate) were compared between the two groups.ResultsFinally, there were 26 patients in the PESA group and 31 patients in the TESA group. There were no significant differences in terms of age, years of infertility, testosterone level, (FSH) follicle-stimulating hormone level, and testicular volume between the male patients in the PESA and TESA groups of two different sperm sources, and no significant differences were found in the general conditions of the female patients in terms of age, number of eggs obtained, number of sinus follicles, basal FSH value, and basal E2 value (p > 0.05). The rate of high-quality blastocysts in the TESA group was significantly higher than that in the PESA group (p 0.05).ConclusionICSI with different sources of sperm in patients with male factor infertility alone, which had no significant effect on embryo development, embryo implantation rate, clinical pregnancy rate, and miscarriage rate, resulting in better clinical outcomes.

Objective: Evaluate the influence of fellowship training, resident participation, reconstruction type, and patient factors on outcomes after vasectomy reversals in a high volume, open access system. Methods: Retrospective review of all vasectomy reversals performed at a single institution from January 1, 2002 to December 31, 2016 was conducted. Patient and spouse demographics, patient tobacco use and comorbidities, surgeon training and case volume, resident participation, reconstruction type, and postoperative patency were collected and analyzed. Results: Five hundred and twenty-six vasectomy reversals were performed during the study period. Follow-up was available in 80.6% of the cohort and overall patency, regardless of reconstruction type was 88.7%. The mean time to reversal was 7.87 years (range of 0–34 years). The majority of cases included resident participation. Case volume was high with faculty and residents logging a mean of 37.0 and 38.7 (median 18 and 37) cases respectively. Bilateral vasovasostomy was the most common reconstruction type (83%) and demonstrated a significantly better patency rate (89%) than all other reconstructions (p=0.0008). Overall patency and patency by reconstruction type were not statistically different among faculty surgeons and were not impacted by fertility fellowship training, resident participation or post-graduate year. Multivariate analysis demonstrated that increased time to reversal and repeat reconstructions had a negative impact on patency (p=0.0023 and p=0.043, respectively). Conclusions: Surgeons with a high volume of vasectomy reversals have outcomes consistent with contemporary series regardless of fellowship training in fertility. Patency was better for bilateral vasovasostomies. Patency was not negatively impacted by tobacco use, comorbidities, resident participation, or post-graduate year.

Purpose: To compare the neonatal birthweight of singletons derived from ICSI cycles with fresh or frozen–thawed epididymal sperm in patients with obstructive azoospermia. Methods: A total of 436 singletons derived from ICSI cycles with fresh (n = 220) or frozen–thawed (n = 216) epididymal sperm in obstructive azoospermia evaluated from 2012 to 2018 in the retrospective study. Multivariate generalized linear model was used to analyze the association between epididymal sperm cryopreservation and neonatal birthweight. Results: The crude birthweight and z-score in neonates derived from frozen–thawed epididymal sperm were significantly lower than those from fresh epididymal sperm (3186.57 g vs 3303.61 g and − 0.18 vs 0.08, respectively), with a mean difference of 117.04 (95% CI 32.36–201.72) g and 0.25 (95% CI 0.06–0.45). Adjusted for confounders including parental age and BMI, maternal ovarian reserve, paternal FSH and T levels, peak E2 during OPU cycles, frozen–thawed embryo transfer, embryo development stage, gestational age, maternal parity and child gender, the multivariate model suggested that singletons conceived from ICSI with fresh epididymal sperm was on average 91.21 g heavier than those conceived from ICSI with frozen–thawed epdidiymal sperm (95% CI 12.72 to 166.7, P = 0.016). Conclusion: Cryopreservation of epididymal sperm may negatively affect birthweight. [ABSTRACT FROM AUTHOR]

Male infertility may occur due to obstructive and non-obstructive reasons, and some pathologies may be corrected with surgical and medical treatment. Such treatment may increase the possibility of spontaneous pregnancy, the success of assisted reproductive technology, and also testicular sperm retrieval rate. This review will focus on surgical treatment alternatives in infertile males. Although treatment options for varicocele in infertile men include open surgical, radiologic, and laparoscopic approaches; microsurgical varicocele repair has the highest improvement in postoperative sperm parameters with lower complication rates. Recent advances in microsurgical anastomosis techniques have increased the patency rate for proximal epididymal obstruction. Although treatment options for distal ejaculatory duct obstruction include endoscopic resection, balloon dilatation, and laser incision/excision, transurethral resection of the ejaculatory duct (TURED), is still the primary gold standard treatment of distal ejaculatory duct obstruction. The testicular sperm retrieval rate has increased with the management of correctable pathologies in men with non-obstructive azoospermia. In case of treatment failure of correctable or uncorrectable pathologies of male factor infertility, surgical sperm obtained from the urogenital tract may necessary for assisted reproductive technology. Surgical success rates for male infertility and the success of surgical sperm obtained procedures have increased dramatically over the last decades attributable to the development of microsurgical techniques and endoscopic equipment, instrumentation, and techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: Nowadays, there is no doubt that estrogens play an important role in male reproduction, affecting testicular cell differentiation, proliferation, apoptosis and metabolism. It is also widely believed that intratesticular balance of androgens and estrogens is crucial for the testicular development and function and that the increased testicular estrogen production may be associated with spermatogenic failure. There is also growing epidemiological evidence that the exposure of men to endocrine disruptors demonstrating estrogenic activity (xenoestrogens) may lead to impairment of male fertility via interference with estrogen signaling pathways. Besides the two classical nuclear estrogen receptors, the membrane-bound G protein-coupled estrogen receptor (GPER) was described in human testicular tissue. However, there are little data on its expression in testes with disturbed spermatogenesis. In this study, we investigated the GPER expression pattern in biopsies of azoospermic men with complete and aberrant spermatogenesis. Our results showed an increased expression of the GPER in testes with impaired spermatogenesis. Moreover, they indicate a possible involvement of estrogen signaling through GPER in disturbed function of Sertoli cells—the cells that support spermatogenic process. In this study, we retrospectively investigated GPER expression in biopsies of azoospermic men with complete (obstructive azoospermia—OA) and aberrant spermatogenesis (nonobstructive azoospermia—NOA). Each biopsy was histologically evaluated with morphometry. The testicular GPER expression was analyzed by the immunohistochemistry and RT-PCR technique in the whole testicular tissue and in seminiferous tubules and Leydig cells after laser-capture microdissection. In laser-microdissected compartments, we also analyzed transcriptional expression of selected Leydig (CYP17A1, HSD17B3, StAR) and Sertoli cell (AMH, SCF, BMP4) function markers. Immunohistochemical staining revealed expression of GPER in the cytoplasm of Leydig and Sertoli cells. Its stronger intensity was observed in Sertoli cells of NOA biopsies. The RT-PCR analysis of the GPER mRNA level unequivocally showed its increased expression in seminiferous tubules (i.e., Sertoli cells), not Leydig cells in NOA biopsies. This increased expression correlated positively with the transcriptional level of AMH—a marker of Sertoli cell immaturity, as well as FSH serum level in NOA but not in the OA group. Our results clearly demonstrate altered GPER expression in testes with primary spermatogenic impairment that might be related to Sertoli cell maturity/function. [ABSTRACT FROM AUTHOR]

Recent data suggest that cystic fibrosis transmembrane conductance regulator (CFTR) gene alterations negatively impact male fertility beyond obstruction. We sought to compare gene alterations, sperm retrieval rates, and intracytoplasmic sperm injection (ICSI) outcomes among men with cystic fibrosis (CF) disease and congenital bilateral absence of the vas deferens (CBAVD) only. We retrospectively evaluated all men who underwent surgical sperm retrieval at two academic, high-volume andrology centers from 2010 to 2018. Only men with documented CFTR alterations and obstructive azoospermia from either CBAVD or CF were included. Differences between groups for CFTR abnormality, sperm retrieval, and ICSI outcomes were statistically analyzed. Overall, 39 patients were included with 10 in the CF and 29 in the CBAVD groups. Surgical sperm retrieval rates were significantly lower in the CF group for sperm concentration (14.8 × 10[6] ml-1 vs 61.4 × 10[6] ml−1, P = 0.02) and total motile sperm count (2.9 million vs 11.4 million, P = 0.01). This difference was only predicted by homozygous delta F508 CFTR mutations (P < 0.05). The CF group also demonstrated a significantly higher rate of rescue testicular sperm extraction (70.0% vs 27.6%, P < 0.03) and lower fertilization rate with ICSI (32.5% vs 68.9%, P < 0.01). In conclusion, those with CF demonstrated lower sperm quality, greater difficulty with sperm retrieval, and worse ICSI outcomes compared with CBAVD-only patients. Homozygous delta F508 CFTR mutations appear to significantly impair spermatogenesis and sperm function.

Objective: To demonstrate that serum follicle-stimulating hormone (FSH) in men rises with age, and to explore FSH reference intervals of age-related partitioning. Methods: Men aged 20-50 years (n=1 190) underwent semen analysis according to World Health Organization (2010) methods. Serum was frozen prior to measurement of FSH by using the Siemens ADVIA Centaur® XP immunoassay system. FSH central 95% intervals after logarithmic transformation based on age were derived from 1 037 normozoospermic men. These were then applied to oligozoospermic and azoospermic men. Men producing azoospermic semen samples were further classified as having non-obstructive azoospermia by clinical diagnostic criteria, including genetic analysis and surgical exploration. Results: Serum FSH in normozoospermic men increased with age (P

Infertility affects 8%–12% of couples worldwide with a male factor contributing to nearly 50% of couples either as a primary or contributing cause. Several genetic factors that include single-gene and multiple-gene defects associated with male infertility were reported in the past two decades. However, the etiology remains ambiguous in a majority of infertile men (~40%). The objective of this narrative review is to provide an update on the genetic factors associated with idiopathic male infertility and male reproductive system abnormalities identified in the last two decades. We performed a thorough literature search in online databases from January 2000 to July 2021. We observed a total of 13 genes associated with nonobstructive azoospermia due to maturation/meiotic arrest. Several studies that reported novel genes associated with multiple morphological abnormalities of the sperm flagella are also discussed in this review. ADGRG2, PANK2, SCNN1B, and CA12 genes are observed in non-CFTR-related vas aplasia. The genomic analysis should be quickly implemented in clinical practice as the detection of gene abnormalities in different male infertility phenotypes will facilitate genetic counseling.

Background: Failed oocyte activation following intracytoplasmic sperm injection (ICSI) as a result of calcium deficiency is a major challenge. Objective: We compared the effect of cult-active medium (CAM) on ICSI outcomes in obstructive azoospermia cases. Materials and Methods: The present study was conducted with 152 ICSI cases, classified into CAM and control groups. The injected oocytes in the control group were cultured in the cleavage medium, while in the artificial oocyte activation group, oocytes were chemically activated through exposure to 200 μL of CAM for 15 min. Fertilization and cleavage rates, quality of embryos, and biochemical pregnancy and live birth rates were assessed in both groups. Results: There were significant differences between the groups in terms of fertilization and cleavage rates after using the CAM in the percutaneous epididymal sperm aspiration (PESA) subgroup (p = 0.05, p ≤ 0.001) and in the testicular sperm extraction subgroup (p = 0.02, p = 0.04), compared to their control groups. Also, the pregnancy rate was significantly higher in the PESA-CAM subgroup (p = 0.03). The PESA-CAM subgroup demonstrated a significant difference in embryo quality after ICSI (p = 0.04). Unsuccessful embryo transfer and abortion were lower in both subgroups compared to the control groups, but this difference was not significant. Surprisingly, live birth rate was higher in the PESA-CAM subgroup (p = 0.03). Conclusion: CAM treatment could improve fertilization and cleavage rates in obstructive azoospermia participants. It had a significant effect on embryo quality, and pregnancy and live birth rates in PESA cases. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate the clinical outcomes and the duration required for the sperm to return to the ejaculate after a modified single-armed 2-suture longitudinal intussusception vasoepididymostomy (SA-LIVE). Methods From March 2015 to December 2018, 134 patients with epididymal obstruction azoospermia underwent the modified single-armed vasoepididymostomy at Shanghai General Hospital. The outcomes and clinical findings were documented and evaluated. The mean follow-up period was 17 (range: 3–36) months. Results Patency was assessed by the return of sperm in the ejaculate. The overall patency rate was 55.2%, and the patency rates were 58.9, 40.7, 36.4, and 58.9% for bilateral surgery, unilateral surgery, proximal anastomosis, and distal anastomosis, respectively. The average time to achieve patency was 4.11 ± 2.74 months. In the first 6 months, 87.8% (65/74) patency patients reported sperm in the ejaculate. The overall pregnancy rate was 40.9% (29/66) at the follow-up of 3–36 months, and the natural pregnancy rate was 30.3% (20/66). The natural pregnancy rate was 32.1% post-bilateral surgery and 33.3% for the site of distal anastomosis; surprisingly, it was 0% for the site of proximal anastomosis. Conclusion Modified SA-LIVE is safe and may achieve favorable patency and pregnancy rates. When double-armed sutures are not accessible, single-armed may be preferable. The expected patency time was within 1 year. Moreover, because of the low natural pregnancy rate for proximal anastomosis, sperm banking is preferred to SA-LIVE.

Emad Babakhanzadeh,1,2,* Ali Khodadadian,1,* Majid Nazari,1 Masoud Dehghan Tezerjani,1 Seyed Mohsen Aghaei,1 Sina Ghasemifar,1 Mehdi Hosseinnia,3 Mahta Mazaheri1,4 1Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 2Medical Genetics Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; 3Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran; 4Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran*These authors contributed equally to this workCorrespondence: Mahta Mazaheri Email mahta.mazaheri2019@gmail.comIntroduction: DiGeorge syndrome critical region gene 8 (DGCR8) contributes to miRNA biogenesis, and defects in its expression could lead to defects in spermatogenesis.Methods: Here, we assess gene and protein expression levels of DGCR8 in the testicular biopsy specimens obtained from men with obstructive azoospermia (OA, n = 19) and various types of non-obstructive azoospermia (NOA) including maturation arrest (MA, n = 17), Sertoli cell-only syndrome (SCOS, n = 20) and hypospermatogenesis (HYPO, 18). Also, samples of men with NOA were divided into two groups based on successful and unsuccessful sperm recovery, NOA+ in 21 patients and NOA− in 34 patients.Results: Examinations disclosed a severe decrease in DGCR8 in samples with MA and SCOS in comparison to OA samples (P < 0.001). Also, the results showed DGCR8 has significantly lower expression in testis tissues of NOA− group in comparison to NOA+ group (p< 0.05). Western blot analysis confirmed that the DGCR8 protein was not expressed in SCOS samples and had a very low expression in MA and HYPO samples.Discussion: The results of this survey showed that DGCR8 is an important gene for the entire spermatogenesis pathway. Moreover, DGCR8 gene plays an important role in the diagnosis of NOA subgroups, and also the expression changes in it might contribute to SCOS or MA phenotypes. This gene with considering other related genes can also be a predictor of sperm retrieval.Keywords: DGCR8, obstructive azoospermia, non-obstructive azoospermia, spermatogenesis

To understand the infertility development it is important to study how individual components of the connective complexes of Sertoli’s cells are formed and developed in order to allow not only individual cells, but also entire syncytia of germ cells to migrate from the basal to the adluminal compartment of the spermatic epithelium, without causing loss of permeability. Testicular tissue changes in azoospermia with an increase in the duration of the disease and the prognosis of the possibility of conception are of particular interest. The aim. To reveal changes in the testicular tissue on azoospermia with an increase in the duration of the disease. Materials and methods: to achieve the aim, a pathomorphological study was carried out. The material for the study was testicular biopsies of patients aged 26-45 years with a diagnosis of obstructive azoospermia (OA). The material was divided into three groups: group 1, control: healthy fertile men; group 2 (study group): men of mature age (26–45 y. o.) with a clinical diagnosis of OA up to 5 years of duration. Group 3 (study group): men of mature age (30–45 y. o.) with a clinical diagnosis of OA up to 10 years of duration. The preparations were studied macroscopically, microscopically, morphometrically and immunohistochemically. Results and discussion. Healthy spermatogenesis was typical for all control group samples. In group 2 (disease up to 5 years from the previous conception) there were three spermatogenesis samples out of eight. There were focal processes of fibrosis and hyalinosis, with focal proliferation of interstitial tissue. In the the group of men with OA lasting up to ten years from the previous conception, the absence of healthy spermatogenesis in all cases was noted. Conclusions.1. In the group of men with OA lasting up to five years from the previous conception there were violations of spermatogenesis, a decrease in the transport of biologically active substances through the blood-testicular barrier. The latter leads to degenerative processes in the germ cells.2. In the group of men with OA lasting up to ten years from the previous conception, there was a pronounced deterioration in spermatogenesis, the transition of OA to NOA with increased duration of the pathological process. The latter significantly worsens the prognosis of the disease course and significantly reduces the possibility of conception.

Abstract Background The purpose of this study is to compare the outcome of intracytoplasmic sperm injection (ICSI) using fresh sperm versus frozen-thawed sperm in both obstructed and non-obstructed azoospermias. This retrospective study included 159 ICSI cycles from 126 couples. In 91 obstructed azoospermia cases, 66 cycles were treated with fresh testicular sperm and 25 cycles were treated with frozen-thawed testicular samples. In 68 non-obstructed azoospermia cases, 32 cycles were treated with fresh testicular sperm and 36 cycles were treated with frozen-thawed testicular sperm, and the main measure and outcomes calculated are fertilization rate, clinical pregnancy, and live birth rate. Results In case of obstructed azoospermia, there were no statistically significant differences between fresh sperm and frozen-thawed testicular sperm used for ICSI regarding fertilization rate, clinical pregnancy rate, and live birth rate as shown (57%, 47%, 0.093 p value; 23.7%, 17.4%, 0.54 p value; and 11.9%, 8.7%, 0.68 p value, respectively). Non-obstructed azoospermia cases also show no significant differences in fertilization rate (37%, 36%, 0.91 p value), clinical pregnancy rate (20%, 14.3%, 0.58 p value), and live birth rate (4%, 3.6%, 0.93 p value). Conclusion Cryopreservation of testicular sperm is reliable if carried out before ovulation induction especially in cases with non-obstructive azoospermia

Iatrogenic causes of male infertility can include medications, chemotherapy, radiation, and surgery. In this review, we discuss commonly performed urologic cancer surgeries and nonurologic surgeries that harbor a high risk of iatrogenic infertility. These include radical prostatectomy, radical cystectomy, retroperitoneal lymph node dissection, pelvic colon surgery, and anterior spine surgery. In addition, we review the anatomy and surgical strategies that help to reduce the risks of infertility. With an increase in life expectancy and improvements in fertility preservation, it is important to properly counsel patients about the risks of infertility and provide options for fertility preservation before surgery. [ABSTRACT FROM AUTHOR]