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.

Non-invasive biomarkers for sperm retrieval in non-obstructive patients: a comprehensive review.

Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval.

New Insights beyond Established Norms: A Scoping Review of Genetic Testing for Infertile Men.

PURPOSE: From a diagnostic standpoint, certain approaches to genetic screening in clinical practice remain ambiguous in the era of assisted reproduction. Even the most current guidelines do not provide definite guidance on testing protocols, leaving clinicians to carefully determine which tests best serve patients struggling with infertility. The lack of uniformity in the current practice of male fertility evaluation can prove to be quite costly, thus necessitating healthcare practitioners to carefully appraise the necessity and weigh the advantages against potential economic and psychological detriments. The objective of this review is to map the existing literature on the general topic of the clinical indications of routine karyotyping and/or AZF screening in infertile men, identify key concepts, determine where the gaps are, and lastly, provide an overview of the conclusions drawn from a body of knowledge that varies widely in terms of methodologies or disciplines. MATERIALS AND METHODS: A thorough search was conducted for the published findings up until July 2023, utilizing PubMed (MEDLINE). This comprehensive search involved the use of specific search keywords, either individually or in combination. The search terms employed were as follows: "Karyotype", "Klinefelter" or "KS" or "47,XXY", "AZF" or "Azoospermi*" and/or "microdeletion*" in the title or abstract. Once the titles and abstracts of selected articles were obtained, the complete texts of linked papers were meticulously scrutinized. RESULTS: A total of 191 records were identified from PubMed. During screening, 161 records (84.3%) were eliminated. Finally, 30 papers were included in this scoping review, which was conducted in 18 countries. The number of sequence tag sites (STSs) used in the studies varied from 5 to 59. The rate of AZF deletions among patients with NOA ranged from 1.3% to 53%. The mean frequency was estimated to be 5.6%. The rate of YCM among patients with XXY karyotype was nil in 19 out of 30 studies (63%), whilst, in the remaining studies, the rate varied from 0.8% to 67%. CONCLUSION: This review provides insights into managing male infertility. The presence of spermatozoa in ejaculation and successful surgical retrieval cannot be excluded for individuals with AZFb/AZFbc microdeletions. Screening for Y chromosome microdeletions is not needed for mosaic or classic KS. Only 1% of individuals with sperm concentration exceeding 1×106 sperm/mL and less than 5×106 sperm/mL exhibit AZF microdeletions; therefore, testing referral for such populations may need reassessment. Individuals with mosaic monosomy X karyotype and certain chromosomal anomalies should be referred for AZF deletion screening. These findings have implications for male infertility management and future research.

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.

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.

Partial Epididymal Obstruction as a Cause of Idiopathic Oligozoospermia: A Reproductive Urologist's Perspective following 35 Years of Surgical and Clinical Experience.

The role of partial epididymal obstruction as contributing to the development of oligozoospermia has been neglected for decades. In the early 1970s, however, Robert Schoysman, a gynecological surgeon devoted to the surgical and medical management of male factor infertility, dedicated many efforts to study such a pathology and its possible effects on male fertility. Following the studies of this pioneer in the field, we concentrated our attention to the patterns of partial and complete epididymal obstruction during surgical scrotal exploration, once made possible even in oligozoospermic men by diagnostic and therapeutic interventions, such as vasovesciculography or seminal tract washout test, at present considered obsolete and no longer feasible in light of the current guidelines. Interestingly, we found signs of partial epididymal obstruction in about 30% of oligozoospermic men with normal testicular volume and serum FSH level as well as normal spermatogenesis at testis biopsy. We, then, compared the findings of scrotal ultrasound with those of scrotal exploration and found that the ultrasound abnormalities of the epididymis were highly predictive of anatomic alteration of the gland. In the present study, we report our experience, together with a historical review of the literature, on this topic.

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.

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.

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.

Successful Bilateral Sperm Retrieval in a Hypogonadal Patient with Non-Obstructive Azoospermia Showing Normal Serum 17-Hydroxyprogesterone Levels Suggestive of Normal Intratesticular Testosterone Production: A Case Report.

The impact of hypogonadism on the probability of retrieving testicular sperm from patients with non-obstructive azoospermia (NOA) is still a matter of debate. Conflicting evidence in this field may be justified by the striking differences between serum and intratesticular testosterone (ITT) levels found in men with severe spermatogenic dysfunction, so that normal ITT levels may coexist with low serum testosterone levels. Here we report the case of a patient with NOA with a steadily reduced serum testosterone level irresponsive to hormonal stimulation with human chorionic gonadotropin. Supported by his normal serum 17-hydroxyprogesterone (17 OHP) levels, previously suggested to be marker of ITT levels, microdissection testicular sperm extraction was performed for both testes on two separate occasions, resulting in the retrieval of enough sperm for ICSI. Three ICSI cycles were then performed, one blastocyst was transferred, and five were cryopreserved. This case report suggests that normal serum 17 OHP levels, being suggestive of normal ITT levels, may support the decision to proceed with surgical sperm retrieval in hypogonadal patients with NOA, even for those irresponsive to hormonal treatment.

ICSI for non-male factor infertility: time to reappraise IVF?

Intracytoplasmic sperm injection (ICSI) was initially introduced to overcome problems due of severe male factor infertility not being solved with conventional in-vitro fertilization (cIVF). However, recent years have witnessed an increasing use of ICSI by most assisted reproductive technique laboratories for non-male factor indications. Examples of the latter include previous fertilization failure after cIVF, few or poor-quality oocytes, immature oocytes, advanced maternal age, preimplantation genetics test (PGT), cryopreserved oocytes, and unexplained infertility. The replacement of cIVF with ICSI in several non-male factor infertility cases is probably because some reproductive specialists consider that ICSI is associated with better reproductive outcomes. Unfortunately, data on reproductive outcomes in favor of ICSI over cIVF are limited or absent. Therefore, the factors that can help define the use of one technique over the other should be identified. These should include the likelihood of fertilization failure, potential risks of the procedure, and its costs. In this review, we aim to highlight the current guidelines, advantages, and limitations of the use of cIVF/ICSI for infertility treatment. Additionally, we provide a comprehensive review of the use of ICSI in indications other than severe male factor infertility.

How to select healthy sperm for intracytoplasmic sperm injection in samples with high sperm DNA fragmentation?

The body of evidence supports the negative impact of increased sperm DNA fragmentation (SDF) on natural fertility as well as assisted reproduction conditions. High SDF has been correlated with low pregnancy and delivery rates following intrauterine insemination. Also, high SDF is accused of reducing the rates of fertilization, implantation, pregnancy, and live birth following in-vitro fertilization (IVF). Despite no impact of high SDF on fertilization or pregnancy rates following intracytoplasmic sperm injection (ICSI), it has been correlated with poor embryo quality and a higher risk of miscarriage. Several methods have been introduced to help select sperm with the best DNA quality to be used in assisted reproductive technology procedures. These include magnetic-activated cell sorting, intracytoplasmic morphologically selected sperm injection, physiologic ICSI, and microfluidic sperm sorters, among others. This article aimed to discuss the impact of high SDF in infertile men on the reproductive outcome of couples undergoing IVF/ICSI. Additionally, this review highlights the principles, advantages, and limitations of different techniques that are currently used for the selection of sperm with intact DNA to be utilized for ICSI.

Sperm DNA fragmentation test: usefulness in assessing male fertility and assisted reproductive technology outcomes.

Male infertility is attributed to multiple factors including high levels of sperm DNA fragmentation (SDF). Conventional semen analysis continues to be the gold standard for diagnosis of male factor infertility around the world. However, the limitations of basic semen analysis have prompted the search for complementary assessments of sperm function and integrity. Sperm DNA fragmentation assays (direct or indirect) are emerging as important diagnostic tools in male infertility workups, and have been advocated for use in infertile couples for a variety of reasons. While a controlled degree of DNA nicking is required for appropriate DNA compaction, excessive fragmentation of sperm DNA is linked to impaired male fertility potential, decreased fertilization, poor embryo quality, recurrent pregnancy loss, and failure of assisted reproductive technology procedures. However, there is an ongoing debate regarding whether or not to employ SDF as a routine test for male infertility. This review compiles up-to-date information regarding the pathophysiology of SDF, the currently available SDF tests, and the role of SDF tests in natural and assisted conception conditions.

Time-lapse embryo monitoring: does it add to standard in-vitro fertilization/intra cytoplasmic sperm injection?

Since the first pioneering studies on time-lapse systems (TLSs) for embryo incubation, many things have changed. Two main factors influence the development of modern time-lapse incubators for human in-vitro fertilization (IVF): 1) the switch from traditional cell culture incubators to benchtops incubators, more suitable for human IVF; and 2) the improvement of imaging technology. Another major factor for the increase in the utilization of TLSs in IVF labs over the last decade was the advances in computer/wireless and smartphone/tablet technology, which allowed patients to see the footage of their growing embryos. Hence, more user-friendly features have allowed their introduction and routine use in IVF labs while image-capturing software has enabled storage and providing additional information to the patients concerning the development of their embryos. This review aims to describe the history and the different TLSs available in the market, to summarize the research and clinical results obtained by using this technology, and to reflect on how this technology is changing the modern IVF laboratory. The current limitations of TLSs will be also reviewed.

Oocytes evaluation and in-vitro fertilization/intra cytoplasmic sperm injection outcomes.

The identification of markers capable of evaluating oocyte quality, its maturation, function, and embryo progression and implantation potential has frequently initiated research interest. However, to date, univocal criteria of oocyte competence do not exist. A major cause of low oocyte quality is evidently advanced maternal age. However, other factors may influence oocyte competence. Among these are obesity, lifestyle factors, genetic and systematic pathologies, ovarian stimulation protocols, laboratory procedures, culture, and environmental conditions. The morphological and maturational evaluation of oocytes is probably the most widely used. Several morphological features, both cytoplasmic (cytoplasmic pattern and hue, presence of vacuoles, refractile bodies, granulation, and smooth endoplasmic reticulum clusters) and extra-cytoplasmic (perivitelline space, zona pellucida thickness, oocyte shape, and polar bodies), have been proposed to distinguish oocytes with the best reproductive potential among a cohort. No single abnormality seems to be sufficiently predictive of the developmental capacity of the oocyte. Some abnormalities such as cumulus cells dysmorphisms, central granulation, vacuoles, and smooth endoplasmic reticulum clusters, however, seem to be associated with poor developmental potential of the embryo, although oocyte dysmorphisms are very common and the data in the literature is limited and provide conflicting views. Other criteria involving gene expression of cumulus cells as well as the metabolomic analysis of spent culture media have been explored. Also, sophisticated technologies such as polar bodies biopsy, meiotic spindle visualization, mitochondrial activity, oxygen consumption, and measurement of glucose-6-phosphate dehydrogenase activity have been proposed. Many of these approaches, however, remain largely research-based and have not found widespread application in clinical service. Due to the lack of consistent data for the assessment of oocyte quality and competence, probably oocyte morphology and oocyte maturity remain important indicators to determine oocyte quality. The aim of this review was to provide spherical attributes and evidence on recent and present research on the topic by analyzing the current methods for evaluation of the oocyte quality, and the impact of oocyte quality on reproductive outcomes. Additionally, current limitations of oocyte quality evaluation are highlighted and insights on future research are provided to optimize the selection techniques of oocytes to improve ART outcomes.

Controversy and Consensus on Indications for Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

Controversy and Consensus on the Management of Elevated Sperm DNA Fragmentation in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. MATERIALS AND METHODS: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method. RESULTS: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. CONCLUSIONS: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

Male Infertility: A Review of Key Papers Appearing in the Reproductive Medicine and Andrology Section of the Journal of Clinical Medicine.

Male infertility accounts for 30% of infertility cases and its prevalence in the general population approximately ranges between 9 and 15%, according to the available surveys [...].

Bridging the Gap between AZF Microdeletions and Karyotype: Twelve Years' Experience of an Infertility Center.

PURPOSE: Despite all past efforts, the current guidelines are not explicit enough regarding the indications for performing azoospermia factor (AZF) screening and karyotype, burdening clinicians with the decision to assess whether such tests are meaningful for the infertile male patient. These assessments can be costly and it is up to the healthcare practitioner to decide which are necessary and to weigh the benefits against economic/psychological harm. The aim of this study is to address such gaps and provide update on current management options for this group of patients. MATERIALS AND METHODS: To address such gaps in male infertility management and to elucidate whether AZF screening is indicated in individuals who concomitantly harbor chromosomal abnormalities we conducted a retrospective cohort analysis of 10,388 consecutive patients with non-obstructive azoospermia (NOA) and severe oligozoospermia. RESULTS: Previously, it has been suggested that all NOA cases with chromosomal defects, except males with 46,XY/45,X karyotype, have no indication for AZF screening. Our findings revealed that cases carrying the following chromosomal abnormalities inv(Y)(p11.2q12); idic(Y)(q11.2); 46,XY,r(Y); idic(Y)(p11.2) and der(Y;Autosome) (76/169; 44.9%; 95% CI, 37.7-52.5) should also be referred for AZF deletion screening. Here, we also report the correlation between sperm count and AZF deletions as a secondary outcome. In accordance with previously reported data from North America and Europe, our data revealed that only 1% of cases with >1×106 sperm/mL had Y chromosome microdeletions (YCMs). CONCLUSIONS: In the era of assisted reproduction, finding cost-minimization strategies in infertility clinics without affecting the quality of diagnosis is becoming one of the top prioritized topics for future research. From a diagnostic viewpoint, the results reflect a need to reconsider the different karyotype presentations and the sperm count thresholds in male infertility guidelines as indicators for YCM screening during an infertility evaluation.