Predictive value of seminal oxidation-reduction potential analysis for reproductive outcomes of ICSI.

RESEARCH QUESTION: Is seminal oxidation-reduction potential (ORP) clinically relevant to reproductive outcome? DESIGN: Prospective observational study including a total of 144 couples who had an intracytoplasmic sperm injection (ICSI) cycle between June 2018 and December 2020. The study included patients undergoing fresh ICSI cycles with autologous gametes. Cycles that had day 3 embryo transfers and cryopreservation cycles were excluded. There was no restriction on patients with severe male infertility; couples with unexplained infertility and unexplained male infertility were included, those with azoospermia were excluded. Semen analysis, seminal ORP as determined by means of the MiOXSYS system, sperm DNA fragmentation (SDF) and reproductive outcomes (fertilization, blastocyst development, clinical pregnancy and live birth) were determined. RESULTS: Seminal ORP was significantly negatively correlated with fertilization rate (r = -0.267; P = 0.0012), blastocyst development rate (r = -0.432; P < 0.0001), implantation/clinical pregnancy (r = -0.305; P = 0.0003) and live birth (r = -0.366; P < 0.0001). Receiver operating characteristic curve analysis showed significant predictive power for ORP for fertilization (≥80%; area under the curve [AUC] 0.652; P = 0.0012), blastocyst development rate (≥60%; AUC 0.794; P < 0.0001), implantation/clinical pregnancy (AUC 0.680; P = 0.0002) and live birth (AUC 0.728; P < 0.0001). Comparable results were obtained for SDF (fertilization: AUC 0.678; blastocyst development: AUC 0.777; implantation/clinical pregnancy: AUC 0.665; live birth: AUC 0.723). Normal sperm morphology showed the lowest predictive power for all reproductive outcome parameters. With male age as confounding factor, ORP (cut-off value of 0.51 mV/106 sperm/ml) has significant (P < 0.04667) effects on odds ratios for all reproductive outcome parameters. Multivariate logistic regression to investigate potential seminal and female confounding factors revealed that seminal ORP significantly (P < 0.0039; P < 0.0130) affects reproductive outcome. CONCLUSION: Seminal ORP is relevant for good fertilization, blastocyst development, implantation, clinical pregnancy and live birth.

In vitro antifungal susceptibility testing of fungi in patients with onychomycosis.

Onychomycosis is the most common nail disorder. To examine in vitro antifungal susceptibility of fungi among onychomycosis patients. The study included 68 patients with onychomycosis. Nail specimens were cultured on Sabouraud dextrose agar and Dermasel agar base-media. Isolated fungi were subjected to antifungal susceptibility tests against terbinafine, itraconazole, fluconazole, and griseofulvin. Candida species (Candida spp.) were detected in 32.4% of the cases of candidal onychomycosis (n = 37), 23.5% of the cases of distal and lateral subungual onychomycosis (n = 17), and 21.4% of the cases of total dystrophic onychomycosis (n = 14). Candida spp. were sensitive to fluconazole in 73.5%, itraconazole in 58.8%, and terbinafine in 5.9% of the cases. Aspergillus spp. were sensitive to itraconazole in all cases, and terbinafine in 87.5% of cases. Penicillium spp. were sensitive to itraconazole and terbinafine in 88.9% and 77.8% of cases, respectively. Trichophyton spp. were sensitive to terbinafine and resistant to itraconazole. Microsporum spp. were sensitive to itraconazole and resistance to terbinafine. All isolated fungi were resistant to griseofulvin. An increasing proportion of Candida spp. was observed among patients with different clinical varieties of onychomycosis. Candida spp. were highly sensitive to fluconazole and a lesser extent to itraconazole.

High levels of oxidation-reduction potential in frozen-thawed human semen are significantly correlated with poor post-thaw sperm quality.

This study examined the relationship between oxidation-reduction potential (ORP) in frozen-thawed semen and the post-thaw sperm parameters. Levels of ORP were measured in 25 samples from men presenting for routine infertility work-up and were expressed as millivolt (mV)/106 sperm/ml. Frozen-thawed samples were examined for post-thaw total motility (TM%), progressive motility (PM%), total sperm count (TSC) and ORP. The cryo-survival rate (CSR) was calculated as post-thaw TM/pre-freeze TM × 100. Data are provided as median and interquartile range (25th and 75th percentiles). The post-thaw TM% (10.0% [4.00%, 15.1%]), PM% (5.88% [2.97%, 9.33%]) and TSC (12.5 [10.0, 17.5] × 106 sperm) were significantly lower than the pre-freeze TM% (45.9% [32.9%, 59.1%], PM% (31.5% [24.4%, 40.0%] and TSC (120 [90, 250] ×106 sperm) (p < .001). Post-thaw ORP (2.62 [2.52, 3.13] mV/106 sperm/ml) was significantly higher than pre-freeze ORP (0.73 [0.54, 1.21] mV/106 sperm/ml; p < .001). The CSR was 21.7% (11.3%, 31.9%). The post-thaw seminal ORP was negatively correlated with post-thaw TM% (r = -.5; p = .02), PM% (r = -.41; p = .03), TSC (r = -.60; p = .03) and CSR (r = -.52; p = .01). Increased levels of ORP are significantly correlated with poor post-thaw sperm quality and CSR.

Evaluation of pubertal onset and characteristics in Egyptian boys: A cross-sectional study.

The objective of this study was to evaluate pubertal onset and characteristics in Egyptian boys. Examination of schoolboys (9-18 years) included height (cm), penile length (cm) and testicular volume (ml). Pubertal onset was considered at gonadal (G) stage 2 (G2 indicated testicular volume from 4-8 ml). Out of 1,078 boys, 270 (25%) were residents in urban areas, 414 (38.4%) in suburban areas and 394 (36.5%) in rural areas. The mean (±SD) age of G2 was 11.1 ± 1.2 years (5th and 95th percentiles were 10 and 13 years respectively). The age of 10.5 years was predictive of G2 with 89.9% sensitivity and 86.2% specificity (95% confidence interval; p < 0.001). The changes in testicular volumes and penile lengths, at the age interval from 16 to 18 years, were not significant. Pubertal onset was earlier among Egyptian boys in urban areas, with smaller family size, less crowding conditions, adequate illumination and good ventilation, although the difference was not statistically significant (p > 0.05). In conclusion, the mean age of pubertal onset among Egyptian boys was 11.1 years. A tendency towards earlier pubertal onset was observed in Egyptian boys who lived in urban areas and had better socio-demographic conditions.

Clinical predictors of successful outcomes for couples with nonobstructive azoospermic male partners undergoing micro-TESE.

ABSTRACT: Nonobstructive azoospermia (NOA) is the most challenging and complex clinical scenario for infertile men. Besides circumstances such as hypogonadotropic hypogonadism, surgical sperm retrieval is typically necessary, and microdissection testicular sperm extraction (micro-TESE) is the procedure of choice for men with NOA desiring to father children with their own gametes. Micro-TESE results in the highest numbers of sperm cells retrieved for use with in vitro fertilization/intracytoplasmic sperm injection (ICSI) in comparison to all other techniques for surgical sperm retrieval in men with NOA. Several factors may affect sperm retrieval rate and ICSI outcomes, including the patient's age, testicular volume, histopathological and genetic profile, and serum hormone levels. This article aims to review the medical literature describing predictors of successful micro-TESE and the outcomes of ICSI in men with NOA.

Varicocele and male infertility conundrum: Making sense of a never-ending story for the busy clinician.

Background: Varicocele is a common occurrence, particularly among men with primary and secondary infertility. There has been extensive research into the management of varicocele in the context of male infertility. Methods: This article aims to explore the variations in clinical practice in diagnosing and managing varicoceles in infertile men. A summary of the current recommendations on varicocele management from professional societies is included. Results: Substantial gaps in knowledge persist regarding varicoceles and male infertility, with significant variation in clinical approaches, despite the wealth of existing data in the medical literature. Conclusion: The existing literature leaves many questions surrounding varicocele management in infertile men unanswered. This lack of clarity contributes to the ongoing controversy among clinicians in the field. New research is essential to address these contentious points and areas of debate.

Sixth edition of the World Health Organization laboratory manual of semen analysis: Updates and essential take away for busy clinicians.

Background: Semen analysis is the cornerstone for male fertility evaluation. In 2021, the World Health Organization (WHO) released its 6th edition of semen analysis manual. Methods: We highlight the main changes in the latest 6th edition of the WHO manual of semen analysis and their possible interpretations. Results: The manual is highly comprehensive, offering detailed information, and is widely regarded as an excellent technical reference for laboratory staff. Nevertheless, several aspects of the manual require further elucidation for infertility practitioners. Conclusion: The recently published 6th edition of the WHO manual provides a strong framework for the assessment and processing of human semen. Grasping the modifications introduced in this updated edition and their clinical significance can enhance the quality of patient care.

Artificial intelligence in andrology - fact or fiction: essential takeaway for busy clinicians.

ABSTRACT: Artificial intelligence (AI) is revolutionizing the current approach to medicine. AI uses machine learning algorithms to predict the success of therapeutic procedures or assist the clinician in the decision-making process. To date, machine learning studies in the andrological field have mainly focused on prostate cancer imaging and management. However, an increasing number of studies are documenting the use of AI to assist clinicians in decision-making and patient management in andrological diseases such as varicocele or sexual dysfunction. Additionally, machine learning applications are being employed to enhance success rates in assisted reproductive techniques (ARTs). This article offers the clinicians as well as the researchers with a brief overview of the current use of AI in andrology, highlighting the current state-of-the-art scientific evidence, the direction in which the research is going, and the strengths and limitations of this approach.

Male Infertility: New Developments, Current Challenges, and Future Directions.

There have been many significant scientific advances in the diagnostics and treatment modalities in the field of male infertility in recent decades. Examples of these include assisted reproductive technologies, sperm selection techniques for intracytoplasmic sperm injection, surgical procedures for sperm retrieval, and novel tests of sperm function. However, there is certainly a need for new developments in this field. In this review, we discuss advances in the management of male infertility, such as seminal oxidative stress testing, sperm DNA fragmentation testing, genetic and epigenetic tests, genetic manipulations, artificial intelligence, personalized medicine, and telemedicine. The role of the reproductive urologist will continue to expand in future years to address different topzics related to diverse questions and controversies of pathophysiology, diagnosis, and therapy of male infertility, training researchers and physicians in medical and scientific research in reproductive urology/andrology, and further development of andrology as an independent specialty.

Anti-sperm Antibody Positivity in Men with Varicocele: A Systematic Review and Meta-Analysis.

PURPOSE: Despite the significant role of varicocele in the pathogenesis of male infertility, its association with anti-sperm antibodies (ASA) remains controversial. This systematic review and meta-analysis (SRMA) aims to investigate the frequency of ASA positivity in men with varicocele. MATERIALS AND METHODS: This SRMA is conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. We investigated the frequency of ASA positivity in ejaculates or serum of men with varicocele as compared to men without varicocele (controls). A literature search was performed using the Scopus and PubMed databases following the Population Exposure Comparison Outcome, Study Design model. Data extracted from eligible studies were meta-analyzed and expressed as odds ratios (ORs) and confidence intervals (CIs). RESULTS: Out of 151 abstracts identified during the initial screening, 6 articles met the inclusion criteria and were included in the meta-analysis. Using mixed antiglobulin reaction (MAR) assay, 61 out of the 153 (39.8%) patients with varicocele tested positive for ASA in their ejaculates as compared to 22 out of the 129 control subjects (17%, OR=4.34 [95% CI: 1.09-17.28]; p=0.04). Using direct or indirect immunobead test, 30 out of 60 cases diagnosed with varicocele (50%) had shown ASA positivity in their ejaculates as compared to 16 out of 104 controls (15.4%, OR=3.57 [95% CI: 0.81-15.68]; p=0.09). Using enzyme-linked immunosorbent assay (ELISA), out of 89 varicocele patients, 33 (37.1%) tested positive for serum ASA as compared to 9 out of 57 participants in the control group (15.8%, OR=7.87 [95% CI: 2.39-25.89]; p<0.01). CONCLUSIONS: This SRMA indicates that ASA positivity is significantly higher among men with varicocele when tested by direct method (MAR) or indirect method (ELISA). This data suggests an immunological pathology in infertile men with varicocele and may have implications for the management of these patients.

Impact of Varicocele on Testicular Oxidative Stress and Sperm Parameters in Experimental Animals: A Systematic Review and Meta-Analysis.

PURPOSE: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele. MATERIALS AND METHODS: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×106), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist. RESULTS: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high. CONCLUSIONS: This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.

Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele: A Systematic Review and Meta-Analysis.

PURPOSE: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). MATERIALS AND METHODS: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). RESULTS: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%). CONCLUSIONS: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Does Varicocele Repair Improve Conventional Semen Parameters? A Meta-Analytic Study of Before-After Data.

PURPOSE: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. MATERIALS AND METHODS: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). RESULTS: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864. CONCLUSIONS: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele.

Regenerative Therapy in Erectile Dysfunction: A Survey on Current Global Practice Trends and GAF Expert Recommendations.

PURPOSE: This study aimed to examine current global practices in regenerative therapy (RT) for erectile dysfunction (ED) and to establish expert recommendations for its use, addressing the current lack of solid evidence and standardized guidelines. MATERIALS AND METHODS: A 39-question survey was developed by senior Global Andrology Forum (GAF) experts to comprehensively cover clinical aspects of RT. This was distributed globally via a secure online Google Form to ED specialists through the GAF website, international professional societies, and social media, the responses were analyzed and presented for frequencies as percentages. Consensus on expert recommendations for RT use was achieved using the Delphi method. RESULTS: Out of 479 respondents from 62 countries, a third reported using RT for ED. The most popular treatment was low-intensity shock wave therapy (54.6%), followed by platelet-rich plasma (24.5%) and their combination (14.7%), with stem cell therapy being the least used (3.7%). The primary indication for RT was the refractory or adverse effects of PDE5 inhibitors, with the best effectiveness reported in middle-aged and mild-to-moderate ED patients. Respondents were confident about its overall safety, with a significant number expressing interest in RT's future use, despite pending guidelines support. CONCLUSIONS: This inaugural global survey reveals a growing use of RT in ED treatment, showcasing its diverse clinical applications and potential for future widespread adoption. However, the lack of comprehensive evidence and clear guidelines requires further research to standardize RT practices in ED treatment.

Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Sperm DNA fragmentation in male infertility: From bench to bedside.

Objectives: Sperm DNA fragmentation (SDF) is a molecular marker of sperm chromatin health. Elevated SDF is associated with male infertility, recurrent pregnancy loss, and failure of assisted reproductive technologies (ART). In 2021, the sixth edition of the World Health Organization (WHO) Manual for the Laboratory Examination and Processing of Human Semen has listed SDF as an extended test of semen that can be ordered under certain circumstances. However, the manual neither explained the indications for testing nor provided clear guidance on diagnostic thresholds. Methods: This article summarizes the current body of knowledge regarding clinical applications of SDF, including the appropriate population to test, methods of testing, and management strategies. Results: Several etiologic factors and pathophysiologic mechanisms for SDF have been described including poor lifestyle habits, noxious exposures, and varicocele. Four SDF assays are included in the WHO manual and may be utilized based on resources and expertise. Strategies to lower SDF levels in infertile men include addressing underlying causes, supplementation with antioxidants, shorter abstinence periods, and use of testicular sperm for intracytoplasmic sperm injection. Conclusion: SDF testing can be implemented in the evaluation of infertile men and couples experiencing ART failure and appropriate management strategies can be offered to improve reproductive outcomes. There is vast potential for future research regarding the clinical utility of SDF in the evaluation and treatment of infertile couples.

Sperm epigenetics landscape: correlation with embryo quality, reproductive outcomes and offspring's health.

Epigenetics refers to how gene expression and function are modulated without modifying the DNA sequence but through subtle molecular changes or interactions with it. As spermatogenesis progresses, male germ cells suffer plenty of epigenetic modifications, resulting in the definitive epigenome of spermatozoa conditioning its functionality, and this process can be altered by several internal and external factors. The paternal epigenome is crucial for sperm function, fertilization, embryo development, and offspring's health, and altered epigenetic states are associated with male infertility with or without altered semen parameters, embryo quality impairment, and worse ART outcomes together with the future offspring's health risks mainly through intergenerational transmission of epigenetic marks. Identifying epigenetic biomarkers may improve male factor diagnosis and the development of targeted therapies, not only to improve fertility but also to allow an early detection of risk and disease prevention in the progeny. While still there is much research to be done, hopefully in the near future, improvements in high-throughput technologies applied to epigenomes will permit our understanding of the underlying epigenetic mechanisms and the development of diagnostics and therapies leading to improved reproductive outcomes. In this review, we discuss the mechanisms of epigenetics in sperm and how epigenetics behave during spermatogenesis. Additionally, we elaborate on the relationship of sperm epigenetics with sperm parameters and male infertility, and highlight the impact of sperm epigenetic alterations on sperm parameters, embryo quality, ART outcomes, miscarriage rates and offspring's health. Furthermore, we provide insights into the future research of epigenetic alterations in male infertility.