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Objective: To explore factors influencing microdissection testicular sperm extraction (micro-TESE) success in hypogonadal men with nonobstructive azoospermia (NOA)., Design: A cohort study., Setting: University-affiliated male reproductive health center., Patient(s): A total of 616 consecutive patients with NOA and hypogonadism (total testosterone [T] levels <350 ng/dL) underwent micro-TESE between 2014 and 2021. All patients had no prior sperm retrieval (SR) history., Intervention(s): Patients aged 23-55 years underwent comprehensive clinical, laboratory, and histopathological diagnostic evaluation for NOA and were further categorized into two cohorts on the basis of pre-SR hormonal stimulation., Main Outcome Measure(s): A multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success, defined as the presence of viable spermatozoa in extracted specimens. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed to assess the relationship between SR success and relevant predictors. Sperm retrieval rates were compared between patients receiving or not hormonal stimulation, and logistic regression analysis evaluated the effect of baseline follicle-stimulating hormone levels (i.e., normogonadotropic vs. hypergonadotropic classes) on SR success., Result(s): The overall micro-TESE success rate was 56.6%. Baseline follicle-stimulating hormone levels (aOR, 0.97; 95% CI, 0.94-0.99), pre-SR hormonal stimulation (aOR, 2.54; 95% CI, 1.64-3.93), presence of clinical varicocele (aOR, 0.05; 95% CI, 0.01-0.51), history of previous varicocelectomy (aOR, 2.55; 95% CI, 1.26-5.16), and testicular histopathology were independent predictors of SR success. Among hormone-pretreated patients, pre-micro-TESE T levels and delta T (an absolute increase in T levels from baseline) were associated with SR success. A pre-micro-TESE T level of 418.5 ng/dL (area under the curve value: 0.78) and a delta T of 258 ng/dL (area under the value: 0.76) distinguished patients with positive and negative SR outcomes. Subgroup analysis showed that pre-SR hormonal stimulation yielded a greater benefit for normogonadotropic patients than for those who were hypergonadotropic., Conclusion(s): This study underscores the association between clinical factors and micro-TESE success in hypogonadal men with NOA. Although causality is not established, our findings suggest that these patients may benefit from pre-SR interventions, particularly hormonal stimulation and varicocele repair., Clinical Trial Registration Number: NCT05110391., Competing Interests: Declaration of Interests S.C.E reports receipt of lecture fees from Med.E.A. (Italy), Sanitanova (Italy), and Merck KGaA (Germany); unrestricted research grants from Merck KGaA, Germany; WHO (Switzerland) - Chair, Male Infertility Group, WHO Infertility Guidelines (in preparation) – unpaid; Brazilian Society of Urology (Brazil) - Member, Department of Education and Research – unpaid; Med.E.A. - Member, Andrology and Reproductive Medicine Committees - unpaid. A.P.P.A. reports funding from ANDROFERT (Brazil) - Institutional support: provision of study materials, funding for statistical analysis as part of a Thesis Project for the submitted work. R.M. has nothing to disclose. S.V. has nothing to disclose. A.F. has nothing to disclose. C.L.Z.R. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Gonadotropin therapy to treat specific male infertility disorders associated with hypogonadotropic hypogonadism is evidence-based and effective in restoring spermatogenesis and fertility. In contrast, its use to improve fertility in men with idiopathic oligozoospermia or nonobstructive azoospermia remains controversial, despite being widely practiced. The existence of two major inter-related pathways for spermatogenesis, including FSH and intratesticular testosterone, provides a rationale for empiric hormone stimulation therapy in both eugonadal and hypogonadal males with idiopathic oligozoospermia or nonobstructive azoospermia. Real-world data (RWD) on gonadotropin stimulating for these patient subsets, mainly using human chorionic gonadotropin and follicle-stimulating hormone, accumulated gradually, showing a positive therapeutic effect in some patients, translated by increased sperm production, sperm quality, and sperm retrieval rates. Although more evidence is needed, current insights from RWD research indicate that selected male infertility patients might be managed more effectively using gonadotropin therapy, with potential gains for all parties involved., Competing Interests: Declaration of competing interest SCE and LC declare receipt of unrestricted research grants from Merck and lecture fees from Merck and Med. E.A and Event Planet. Other authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Nonobstructive azoospermia (NOA) associated with primary spermatogenic failure is a common cause of male infertility usually considered untreatable; however, some reports have suggested that hormonal stimulation to boost the intra-testicular testosterone level and spermatogenesis might increase the chance of achieving pregnancy using homologous sperm., Materials and Methods: We report a series of eight NOA males who received long-term treatment with recombinant human chorionic gonadotropin twice a week for spermatogenesis stimulation. Six males received additional recombinant follicle-stimulating hormone (FSH) supplementation 150-225 IU twice weekly., Results: After recombinant gonadotropin therapy, viable spermatozoa were retrieved from the ejaculate in two patients and by testicular sperm aspiration (TESA) in another two subjects. Singleton spermatozoon retrieved from testes were frozen by vitrification on Cell-Sleeper devices. Two live births were obtained after intracytoplasmic sperm injection with ejaculated spermatozoa and one live birth and an ongoing pregnancy using thawed spermatozoa from TESA., Conclusion: Our proof-of-concept study indicates that hormonal therapy with recombinant gonadotropins could be considered in infertile men with NOA as an alternative to sperm donation. Large-scale studies are needed to substantiate hormone stimulation therapy with recombinant gonadotropins in routine clinical practice for this severe form of male infertility., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Purpose: Microdeletion on Y-chromosome is a well-known genetic cause of infertility in azoospermic and oligozoospermic men. RNA transcripts possess microRNA (miRNA) response elements (MRE) that may interact with competing endogenous RNAs (ceRNA), thus repressing their activity. MiRNAs originally targeting transcripts of genes deleted in the Y-chromosome azoospermia factor (AZF) region are expected to be oriented to binding sites of new targets. We investigated miRNAs targeting genes of each AZF locus (AZFa, AZFb, AZFb-c, and AZFc) to determine their corresponding ceRNA using in silico analysis., Methods: The miRNAs targeting most of the genes deleted in each AZF locus were identified using the miRWalk database. Twelve miRNAs exhibiting potential ceRNA activity were identified and analyzed using the ComiR database. Detected ceRNAs for each AZF locus were processed in the GeneMANIA database for interaction prediction, and the most probably interacted genes were identified., Results: RPPA2, TMED3, STX7 and ATRX, GOGLB1, KMT2C genes were found potential ceRNAs for the AZFa and AZFb regions, respectively. Furthermore, CNB5, KCNC4, NDUFS1 and TROBP, HEMK1, and ORAI2 genes were the potential ceRNAs for the partially AZFb-c-overlapped region and AZFc regions, respectively., Conclusion: Our findings suggest that AZF loci deletion may change post-transcriptional regulation of gene expression through miRNA competition., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Nonobstructive azoospermia (NOA) is associated with intrinsic testicular defects that severely impair sperm production. Although NOA invariably leads to infertility, focal sperm production may exist in the testicles of affected patients, which can be retrieved and used for intracytoplasmic sperm injection (ICSI) to generate healthy offspring. However, geographic locations of testicular sperm producing-areas are uncertain, making microsurgical-guided sperm retrieval (microdissection testicular sperm extraction; micro-TESE) an attractive method to identify and retrieve sperm in patients with NOA due to spermatogenic failure. Given the widespread use of micro-TESE, its effectiveness in harvesting sperm and related potential complications need to be clarified., Methods: We queried PubMed/MEDLINE for studies published in English, from inception to May 2021, concerning the effect of micro-TESE on sperm retrieval rate (SRR), complication rate and ICSI pregnancy rate-using retrieved testicular sperm in subfertile couples where the male had NOA., Results: We found 116 articles, including 70 original papers, 32 review articles, and 14 systematic reviews. The evidence accounted for 4895 patients. Micro-TESE retrieved sperm in 46.6% of men with NOA, but SRRs varied considerably (18.4-70.8%) and were mainly related to the treated population characteristics. Concerning the general population of NOA patients who have not undergone previous sperm retrieval (naïve population), the SRR by micro-TESE was 46.8% (1833 of 3914 patients; range 20-70.8%; 28 studies). In studies reporting SR by micro-TESE for men who had failed percutaneous testicular sperm aspiration or non-microsurgical testicular sperm extraction, the SRR was 39.1% (127 of 325 patients; range 18.4-57.1%; 4 studies). Data on adverse events indicated that micro-TESE was associated with low (~ 3%) short-term postoperative complication rates. The fertilizing ability of testicular sperm retrieved by micro-TESE and used for ICSI was adequate (~ 57%), whereas clinical pregnancy and live birth were obtained in 39% and 24% of couples who had an embryo transfer, respectively. The health of the resulting children seems reassuring, but the evidence is limited. The procedure increases sperm retrieval success compared to non-microsurgical retrieval methods, particularly in men with Sertoli cell-only testicular histopathology., Conclusion: We concluded that micro-TESE is an effective and safe method to retrieve sperm from men with NOA-related infertility, with potential advantages over non-microsurgical methods. Nevertheless, high-quality, head-to-head comparative randomized controlled trials by sperm retrieval method, focusing on SRR, live birth rate and assessing long-term adverse events and health of children conceived using testicular sperm from NOA patients are lacking. Therefore, further research is required to determine the full clinical implications of micro-TESE in male infertility treatment., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Male infertility is a complex condition with a strong genetic and epigenetic background. This review discusses the importance of genetic and epigenetic factors in the pathophysiology of male infertility. The interplay between thousands of genes, the epigenetic control of gene expression, and environmental and lifestyle factors, which influence genetic and epigenetic variants, determines the resulting male infertility phenotype. Currently, karyotyping, Y-chromosome microdeletion screening and CFTR gene mutation tests are routinely performed to investigate a possible genetic aetiology in patients with azoospermia and severe oligozoospermia. However, current testing is limited in its ability to identify a variety of genetic and epigenetic conditions that might be implicated in both idiopathic and unexplained infertility. Several epimutations of imprinting genes and developmental genes have been postulated to be candidate markers for male infertility. As such, development of novel diagnostic panels is essential to change the current landscape with regard to prevention, diagnosis and management. Understanding the underlying genetic mechanisms related to the pathophysiology of male infertility, and the impact of environmental exposures and lifestyle factors on gene expression might aid clinicians in developing individualised treatment strategies., (© 2020 Blackwell Verlag GmbH.)

Objective: To explore predictors of successful sperm retrieval (SR) and to identify potentially suitable candidates for testicular sperm aspiration (TESA), a more straightforward, less traumatic, and less costly procedure than open surgical SR methods., Design: Retrospective chart review., Setting: Academic tertiary medical center., Patients: A total of 297 patients with nonobstructive azoospermia., Interventions: All patients underwent full clinical evaluation before undergoing a staged SR procedure, starting with TESA and proceeding to microsurgical testicular sperm extraction (microTESE). Predictors of positive SR with TESA were selected using the least absolute shrinkage and selection operator (LASSO) regression analysis using k-fold cross-validation. The obtained regression coefficients were used to create a predictive model, and a receiver operating characteristic (ROC) curve was obtained to express its predictive ability. Cut-off values for each significant predictor were also identified using ROC analysis., Main Outcome Measure(s): Development of a prediction model for positive SR with TESA., Results: Overall, a positive SR was observed in 23.6% of patients undergoing TESA. Average testis size (P = .017) and serum follicle-stimulating hormone (FSH) level (P < .001) were the significant predictors of positive SR identified by LASSO regression analysis. The predictive model had an AUC of 0.742 with a sensitivity of 73.9% and specificity of 69.9%. Patients presenting with an average testis size >7.75 mL and serum FSH level <8.5 IU/L had a TESA-positive SR of 43%., Conclusions: TESA may be a suitable alternative to microTESE in selected nonobstructive azoospermia patients presenting with an average testis size >7.75 mL and serum FSH level <8.5 IU/L., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Intracytoplasmic sperm injection (ICSI), combined with surgical sperm retrieval (SR) techniques, is the sole option for patients with non-obstructive azoospermia to achieve fertility; however, with suboptimal results. Given the variability in clinical presentation, the potential role of factors that can predict the likelihood of successful testicular SR needs to be clarified. This article summarizes the current evidence concerning the variables predicting SR success in non-obstructive azoospermic patients with spermatogenic failure. For this, we used 60 articles, including 46 original papers and six meta-analyses. Clinical and laboratory factors, as well as adjuvant therapies and surgical retrieval methods, were the factors most commonly investigated. We found that Klinefelter syndrome, Y chromosome microdeletions in regions AZFa/b, and Sertoli cell-only histopathology were associated with reduced SR success. By contrast, testis volume > 12.5 ml, history of cryptorchidism, use of micro-TESE as the sperm retrieval method, and adjuvant therapy were associated with improved SR success. None of the predictors, alone or combined, provide definitive information about the chances of harvesting sperm in men with non-obstructive azoospermia, except for Y chromosome microdeletions in regions AZFa/b. In the latter, SR success is virtually nil. We conclude that SR outcomes in men with non-obstructive azoospermia are difficult to predict based on the existing variables. Although several predictors can be used for patient counseling, their clinical value is limited to either ensure SR success or discourage reproductive urologists from recommending SR to men with non-obstructive azoospermia seeking fertility. A notable exception includes the deletions involving the regions AZFa and/or AZFb of the Y chromosome; the affected patients should be counseled against undergoing SR.

Sperm retrieval combined with intracytoplasmic sperm injection (ICSI) is the treatment of choice for couples with untreatable azoospermia-related infertility. However, an increasing body of evidence has been mounting, suggesting that ICSI with testicular sperm instead of ejaculated sperm (when both are available) increases pregnancy outcomes in some specific scenarios. This has led to the exploration of extended indications for sperm retrieval. This review summarizes the current literature concerning sperm retrieval and ICSI for non-azoospermic men with elevated sperm DNA fragmentation, oligozoospermia, and cryptozoospermia., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2019 Esteves SC and Roque M.)

In recent years, the management of male factor infertility has undergone important changes with the introduction of novel concepts, advanced testing, and therapeutic interventions. This review highlights some of these changes and discusses their impact to routine clinical practice. First, we discuss the recent changes in the World Health Organization (WHO) laboratory methods and reference values for the examination of human semen. Second, we examine the role of sperm chromatin integrity tests in light of increasing evidence of the detrimental effect of sperm DNA fragmentation on reproductive outcomes. Third, we summarize the main findings of varicocele-related infertility and the outcomes of microsurgical varicocele repair to different case scenarios. Lastly, we critically discuss the current management of men with nonobstructive azoospermia seeking fertility and the new opportunities that emerged to help these men achieve biological fatherhood., Competing Interests: The author declares that he has no conflicts of interest.

The objective of this systemic review was to evaluate the benefit of repairing clinical varicocele in infertile men with nonobstructive azoospermia (NOA). The surgically obtained sperm retrieval rate (SRR) and pregnancy rates following assisted reproductive technology (ART) with the use of retrieved testicular sperm were the primary outcomes. The secondary outcomes included the presence of viable sperm in postoperative ejaculate to avoid the testicular sperm retrieval and pregnancy rates (both assisted and unassisted) using postoperative ejaculated sperm. An electronic search to collect the data was performed using the MEDLINE and EMBASE databases until April 2015. Eighteen studies were included in this systematic review and accounted for 468 patients who were diagnosed with NOA and varicocele. These patients were subjected to either surgical varicocele repair or percutaneous embolization. Three controlled studies evaluating sperm retrieval outcomes indicated that in patients who underwent varicocelectomy, SRR increased compared to those without varicocele repair (OR: 2.65; 95% CI: 1.69-4.14; P< 0.001). Although pregnancy rates with the use of testicular sperm favored the varicocelectomy group, results were not statistically significant (clinical pregnancy rate OR: 2.07; 95% CI: 0.92-4.65; P= 0.08; live birth rate OR: 2.19; 95% CI: 0.99-4.83; P= 0.05). The remaining fifteen studies reported postoperative semen analysis results. In 43.9% of the patients (range: 20.8%-55.0%), sperm were found in postoperative ejaculates. Pregnancy rates for unassisted and assisted (after IVF/ICSI) were 13.6% and 18.9% in the group of men with sperm in postoperative ejaculates, respectively. Our findings indicate that varicocelectomy in patients with NOA and clinical varicocele is associated with improved SRR. In addition, approximately 44% of the treated men will have enough sperm in the ejaculate to avoid sperm retrieval. Limited data on pregnancy outcomes with both postoperative ejaculated sperm and harvested testicular sperm preclude any firm conclusion with regard to the possible increased fertility potential in treated individuals. In conclusion, the results of our study indicate that infertile men with NOA and clinical varicocele benefit from varicocelectomy.  Given the low/moderate quality of evidence available, it is advisable that doctors discuss with their patients with NOA the risks and benefits of varicocele repair.

Main Findings: An intriguing yet perplexing case report of a successful pregnancy and live birth with intracytoplasmic sperm injection using normal testicular sperm, after the finding of azoospermia in the semen analysis and discovering only tail stump abnormal sperm in the epididymis. Case hypothesis: A tail stump sperm defect of genetic origin was suspected. However, after obtaining normal testicular sperm we concluded that obstructive azoospermia, either idiopathic or secondary to multiple minor genital trauma was the plausible scenario. This has rendered the search of previous reports on a similar condition, but none was found. However, it has raised scientific thoughts for future research. Promising future implications: The importance of reporting this case is to alert urologists performing sperm retrieval that healthy and morphologically normal sperm may be found in the testis of azoospermic men with 100% tail stump epididymal sperm. Retrieval of normal testicular sperm obviates the need of a more complex investigation, including sperm electron microscopy. It also offers the possibility of utilizing such gametes for sperm injections rather than abnormal tail stump sperm that may be associated with a poor reproductive outcome.

The clinical management of men with nonobstructive azoospermia (NOA) seeking fertility has been a challenge for andrologists, urologists, and reproductive medicine specialists alike. This review presents a personal perspective on the clinical management of NOA, including the lessons learned over 15 years dealing with this male infertility condition. A five-consecutive-step algorithm is proposed to manage such patients. First, a differential diagnosis of azoospermia is made to confirm/establish that NOA is due to spermatogenic failure. Second, genetic testing is carried out not only to detect the males in whom NOA is caused by microdeletions of the long arm of the Y chromosome, but also to counsel the affected patients about their chances of having success in sperm retrieval. Third, it is determined whether any intervention prior to a surgical retrieval attempt may be used to increase sperm production. Fourth, the most effective and efficient retrieval method is selected to search for testicular sperm. Lastly, state-of-art laboratory techniques are applied in the handling of retrieved gametes and cultivating the embryos resulting from sperm injections. A coordinated multidisciplinary effort is key to offer the best possible chance of achieving a biological offspring to males with NOA.

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

Introduction: Rare foci of sperm production may be found in up to 60% of men with nonobstructive azoospermia (NOA). Sperm production, if present, is minimal for sperm appearance in the ejaculate. Given that there are no treatment options to restore fertility, sperm retrieval is the only alternative to find testicular sperm than then can be used for in vitro fertilization (IVF). Among sperm acquisition methods, micro-TESE has higher success rates at obtaining sperm compared with testicular sperm extraction and testicular sperm aspiration., Materials and Methods: This video describes the operative aspects of micro-TESE, performed on an outpatient basis, in a man with NOA and history of cryptorchidism in whom orchidopexy was performed at age 6. The concept of micro-TESE is to identify areas of sperm production within the testes with the aid of optical magnification (15-25X) and based on the size and appearance of the seminiferous tubules (ST)., Results: Intraoperative findings revealed homogeneous pattern of collapsed STs in which an area containing dilated STs was clearly identified and extracted. Testicular tissue was then processed in the IVF laboratory to allow sperm search. In this case, micro-TESE was successful at obtaining testicular sperm for intracytoplasmic sperm injection (ICSI). Surplus retrieved testicular spermatozoa not used for ICSI was cryopreserved. The operative time was 120 minutes, and intraoperative blood loss was negligible. Postoperatively, the patient recovered to his normal activities within 5 days and no complications were recorded except for minor testicular pain and scrotal swelling., Conclusion: Micro-TESE allowed the identification and extraction of sperm-containing STs with minimum tissue excision and marked reduction in time processing of testicular specimens for sperm injection.

Azoospermia due to obstructive and non-obstructive mechanisms is a common manifestation of male infertility accounting for 10-15% of such cases. Known genetic factors are responsible for approximately 1/3 of cases of azoospermia. Nonetheless, at least 40% of cases are currently categorized as idiopathic and may be linked to unknown genetic abnormalities. It is recommended that various genetic screening tests are performed in azoospermic men, given that their results may play vital role in not only identifying the etiology but also in preventing the iatrogenic transmission of genetic defects to offspring via advanced assisted conception techniques. In the present review, we examine the current genetic information associated with azoospermia based on results from search engines, such as PUBMED, OVID, SCIENCE DIRECT and SCOPUS. We also present a critical appraisal of use of genetic testing in this subset of infertile patients.

The use of non-ejaculated sperm coupled with intracytoplasmic sperm injection has become a globally established procedure for couples with azoospermic male partners who wish to have biological offspring. Surgical methods have been developed to retrieve spermatozoa from the epididymides and the testes of such patients. This article reviews the methods currently available for sperm acquisition in azoospermia, with a particular focus on the perioperative, anesthetic and technical aspects of these procedures. A critical analysis of the advantages and disadvantages of these sperm retrieval methods is provided, including the authors' methods of choice and anesthesia preferences.

This special issue is fully dedicated to the topic of azoospermia and contains the seminal work of renowned scientists and clinicians from seven countries on three continents. In seventeen chapters, a comprehensive review of the epidemiology, genetics, physiopathology, diagnosis, and management of azoospermia addresses our current knowledge on the topic. The clinical results of assisted reproductive techniques applied to this category of male infertility and the health of offspring originating from such fathers are critically analyzed. In addition, the challenges and the future biotechnological perspectives for the treatment of azoospermic males seeking fertility are discussed.

Obstructive azoospermia is a relatively common male infertility condition. The main etiologies of obstructive azoospermia include congenital, surgical-derived, traumatic and post-infectious cases. Although seminal tract reconstruction is a cost-effective treatment in most cases, this approach may not be feasible or desired in some cases. In such cases, assisted reproduction techniques offer a method for achieving pregnancy, notably via sperm retrieval and intracytoplasmic sperm injection. This process requires several considerations and decisions to be made, including the cause and duration of obstruction, which sperm retrieval technique to use, and whether to use fresh or frozen-thawed sperm. We present a review of obstructive azoospermia and assisted reproduction techniques, highlighting the most relevant aspects of the decision-making process for use in clinical practice.

We compared pregnancy outcomes following intracytoplasmic sperm injection for the treatment of male infertility according to the type of azoospermia. First, we analyzed our data from 370 couples who underwent intracytoplasmic sperm injection using sperm from men with obstructive azoospermia and nonobstructive azoospermia, and the outcomes were compared to a group of 465 non-azoospermic infertile males. Then, we performed a systematic review of the published data on pregnancy and neonatal outcomes of children born after sperm injection using sperm from men with obstructive and nonobstructive azoospermia. Live birth rates were significantly lower in the nonobstructive azoospermia group (21.4%) compared with the obstructive azoospermia (37.5%) and ejaculated sperm (32.3%) groups. A total of 326 live births resulted in 427 babies born. Differences were not observed between the groups in gestational age, preterm birth, birth weight and low birth weight, although we noted a tendency towards poorer neonatal outcomes in the azoospermia categories. The overall perinatal death and malformation rates were 2.8% and 1.6%, respectively, and the results did not differ between the groups. We identified 20 published studies that directly compared pregnancy outcomes between obstructive azoospermia and nonobstructive azoospermia. Most of these studies were not designed to detect differences in live birth rates and had lower power to detect differences in less frequent outcomes, and the reporting of neonatal outcomes was unusual. The included studies reported either a decrease or no difference in pregnancy outcomes with intracytoplasmic sperm injection in cases of nonobstructive azoospermia and obstructive azoospermia. In general, no major differences were noted in short-term neonatal outcomes and congenital malformation rates between children from fathers with nonobstructive azoospermia and obstructive azoospermia.

Different surgical methods such as PESA, MESA, TESA, TESE and micro-TESE have been developed to retrieve spermatozoa from either the epididymis or the testis according to the type of azoospermia, i.e., obstructive or non-obstructive. Laboratory techniques are used to remove contaminants, cellular debris, and red blood cells following collection of the epididymal fluid or testicular tissue. Surgically-retrieved spermatozoa may be used for intracytoplasmic sperm injection (ICSI) and/or cryopreservation. In this article, we review the surgical procedures for retrieving spermatozoa from both the epididymis and the testicle and provide technical details of the commonly used methods. A critical analysis of the advantages and limitations of the current surgical methods to retrieve sperm from males with obstructive and non-obstructive azoospermia is presented along with an overview of the laboratory techniques routinely used to process surgically-retrieved sperm. Lastly, we summarize the results from the current literature of sperm retrieval, as well as the clinical outcome of ICSI in the clinical scenario of obstructive and nonobstructive azoospermia.