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.

Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations.

PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: An overview on male genital tract ultrasound reference ranges.

BACKGROUND: So far, male genital tract color-Doppler ultrasound (MGT-CDUS) was not standardized. Recently, the European Academy of Andrology (EAA) published the results of a multicenter study assessing the CDUS characteristics of healthy-fertile men (HFM) to obtain normative parameters. OBJECTIVES: To report the EAA US study (i) standard operating procedures (SOPs) for assessing MGT-CDUS, (ii) main MGT-CDUS normative parameters, and (iii) compare the EAA and previously published "normal" CDUS values. METHODS: A cohort of 248 HFM (35.3 ± 5.9 years) was studied, evaluating MGT-CDUS before and after ejaculation following SOPs. RESULTS: SOPs for MGT-CDUS assessment are summarized here. All subjects underwent scrotal CDUS and 188 men underwent transrectal ultrasound before and after ejaculation. The main CDUS reference ranges and characteristics of the HFM-MGT are reported here. The mean testicular volume was ∼17 mL. The lower limit for right and left testis was 12 and 11 mL, defining testicular hypotrophy. The upper limit for epididymal head, body, tail, and vas deferens was 11.5, 5, 6, and 4.5 mm, respectively. Testicular and epididymal arterial reference ranges are reported. The EAA varicocoele classification is reported. CDUS-varicocoele was detected in ∼37% of men. Prostate mean volume was ∼25 mL, while lower and upper limits were 15 and 35 mL, defining hypotrophy and enlargement, respectively. Prostate arterial reference ranges are reported. Prostate calcifications and inhomogeneity were frequent; midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. The upper limit for periprostatic venous plexus was 4.5 mm. Lower and upper limits of seminal vesicles (SV) anterior-posterior diameter were 6 and 16 mm, defining hypotrophy or dilation, respectively. Seminal vesicle volume and ejection fraction reference ranges are reported. SV-US abnormalities were rare. Deferential ampullas upper limit was 6 mm. A discussion on the EAA and previously published "normal" CDUS values is reported here. CONCLUSIONS: The EAA findings will help in reproductive and general male health management.

The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: Prostate-vesicular transrectal ultrasound reference ranges and associations with clinical, seminal and biochemical characteristics.

BACKGROUND: Transrectal ultrasound (TRUS) parameters are not standardized, especially in men of reproductive age. Hence, the European Academy of Andrology (EAA) promoted a multicenter study to assess the TRUS characteristics of healthy-fertile men (HFM) to establish normative parameters. OBJECTIVES: To report and discuss the prostate and seminal vesicles (SV) reference ranges and characteristics in HFM and their associations with clinical, seminal, biochemical parameters. METHODS: 188 men (35.6 ± 6.0 years) from a cohort of 248 HFM were studied, evaluating, on the same day, clinical, biochemical, seminal, TRUS parameters following Standard Operating Procedures. RESULTS: TRUS reference ranges and characteristics of the prostate and SV of HFM are reported herein. The mean PV was ∼25 ml. PV lower and upper limits were 15 and 35 ml, defining prostate hypotrophy and enlargement, respectively. PV was positively associated with age, waistline, current smoking (but not with T levels), seminal volume (and negatively with seminal pH), prostate inhomogeneity, macrocalcifications, calcification size and prostate arterial parameters, SV volume before and after ejaculation, deferential and epididymal size. Prostate calcifications and inhomogeneity were frequent, while midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. Periprostatic venous plexus size was positively associated with prostate calcifications, SV volume and arterial peak systolic velocity. Lower and upper limits of SV anterior-posterior diameter after ejaculation were 6 and 16 mm, defining SV hypotrophy or dilation, respectively. SV total volume before ejaculation and delta SV total volume (DSTV) positively correlated with ejaculate volume, and DSTV correlated positively with sperm progressive motility. SV total volume after ejaculation was associated negatively with SV ejection fraction and positively with distal ampullas size. SV US abnormalities were rare. No association between TRUS and time to pregnancy, number of children or history of miscarriage was observed. CONCLUSIONS: The present findings will help in better understanding male infertility pathophysiology and the meaning of specific TRUS findings.

Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices.

PURPOSE: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. MATERIALS AND METHODS: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. RESULTS: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. CONCLUSIONS: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy.

Sperm Vitality and Necrozoospermia: Diagnosis, Management, and Results of a Global Survey of Clinical Practice.

Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) test. In the 6th (2021) edition of the WHO Laboratory Manual, sperm vitality assessment is mainly recommended if the total motility is less than 40%. Hence, a motile spermatozoon is considered alive, however, in certain conditions an immotile spermatozoon can also be alive. Therefore, the differentiation between asthenozoospermia (pathological decrease in sperm motility) and necrozoospermia (pathological decrease in sperm vitality) is important in directing further investigation and management of infertile patients. The causes leading to necrozoospermia are diverse and can either be local or general, testicular or extra-testicular. The andrological management of necrozoospermia depends on its etiology. However, there is no standardized treatment available presently and practice varies among clinicians. In this study, we report the results of a global survey to understand current practices regarding the physician order of sperm vitality tests as well as the management practices for necrozoospermia. Laboratory and clinical scenarios are presented to guide the reader in the management of necrozoospermia with the overall objective of establishing a benchmark ranging from the diagnosis of necrozoospermia by sperm vitality testing to its clinical management.

A Comprehensive Guide to Sperm Recovery in Infertile Men with Retrograde Ejaculation.

Retrograde ejaculation (RE) is a condition defined as the backward flow of the semen during ejaculation, and when present can result in male infertility. RE may be partial or complete, resulting in either low seminal volume or complete absence of the ejaculate (dry ejaculate). RE can result from anatomic, neurological or pharmacological conditions. The treatment approaches outlined are determined by the cause. Alkalinizing urinary pH with oral medications or by adding sperm wash media into the bladder prior to ejaculation may preserve the viability of the sperm. This article provides a step-by-step guide to diagnose RE and the optimal techniques to retrieve sperm.

Relevance of Leukocytospermia and Semen Culture and Its True Place in Diagnosing and Treating Male Infertility.

The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×106/mL of semen. Granular leukocytes when activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with poor sperm quality, increased level of sperm DNA fragmentation and low fertility potential. The presence of leukocytes and pathogens in the semen may be a sign of infection and/or localized inflammatory response in the male genital tract and the accessory glands. Common uro-pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Mycoplasma hominis, and Escherichia coli can cause epididymitis, epididymo-orchitis, or prostatitis. The relationship between leukocytospermia and infection is unclear. Therefore, we describe the pathogens responsible for male genital tract infections and their association with leukocytospermia. The review also examines the diagnostic tests available to identify seminal leukocytes. The role of leukocytospermia in male infertility and its management is also discussed.

A Global Survey of Reproductive Specialists to Determine the Clinical Utility of Oxidative Stress Testing and Antioxidant Use in Male Infertility.

PURPOSE: The use of antioxidants is common practice in the management of infertile patients. However, there are no established guidelines by professional societies on antioxidant use for male infertility. MATERIALS AND METHODS: Using an online survey, this study aimed to evaluate the practice pattern of reproductive specialists to determine the clinical utility of oxidative stress (OS) testing and antioxidant prescriptions to treat male infertility. RESULTS: Responses from 1,327 participants representing 6 continents, showed the largest participant representation being from Asia (46.8%). The majority of participants were attending physicians (59.6%), with 61.3% having more than 10 years of experience in the field of male infertility. Approximately two-thirds of clinicians (65.7%) participated in this survey did not order any diagnostic tests for OS. Sperm DNA fragmentation was the most common infertility test beyond a semen analysis that was prescribed to study oxidative stress-related dysfunctions (53.4%). OS was mainly tested in the presence of lifestyle risk factors (24.6%) or sperm abnormalities (16.3%). Interestingly, antioxidants were prescribed by 85.6% of clinicians, for a duration of 3 (43.7%) or 3-6 months (38.6%). A large variety of antioxidants and dietary supplements were prescribed, and scientific evidence were mostly considered to be modest to support their clinical use. Results were not influenced by the physician's age, geographic origin, experience or training in male infertility. CONCLUSIONS: This study is the largest online survey performed to date on this topic and demonstrates 1) a worldwide understanding of the importance of this therapeutic option, and 2) a widely prevalent use of antioxidants to treat male infertility. Finally, the necessity of evidence-based clinical practice guidelines from professional societies is highlighted.

Penile low intensity shock wave treatment for PDE5I refractory erectile dysfunction: a randomized double-blind sham-controlled clinical trial.

PURPOSE: Over the last decade, penile low-intensity extracorporeal shockwave therapy (LI-ESWT) has emerged as a promising alternative for the treatment of erectile dysfunction (ED). The aim of this trial is to assess the effect of electromagnetic LI-ESWT on the erectile function of vascular phosphodiesterase type 5 inhibitor (PDE5I) refractory ED patients. METHODS: Randomized, double-blind, sham-controlled study. 76 patients with vascular PDE5I-refractory ED completed the study. 40 men were treated with LI-ESWT (1 session/week for 4 weeks, 5000 shocks/session, 0.09 mJ/mm2 energy density) and 36 were treated with a sham probe. Baseline and post-treatment (1, 3 and 6 months) evaluations were performed using validated erectile function questionnaires (IIEF-EF, EHS, SEP2, SEP3 and GAQ1). The groups were compared using Mann-Whitney-Wilcoxon and chi-squared tests, with results considered statistically significant at p < 0.05. RESULTS: At the 3-month follow-up, median change in IIEF-EF score for active and sham groups was 3.5 (IQR 0-10) and - 0.5 (IQR - 11 to 1), respectively (p < 0.05). Six months after treatment, 52.5% of patients (21/40) in the active group and 27.8% of patients (10/36) in the sham group presented an EHS > 2 (p < 0.05). At the same evaluation, 40.0% (16/40) and 13.9% (5/36) of patients had positive answers to GAQ-1, in the treated and sham groups, respectively (p < 0.05). No adverse events were observed during the study. CONCLUSION: This study showed that penile electromagnetic shockwave therapy may improve erectile function, to a modest extent, on certain patients that do not respond to PDE5I; making it an alternative for vascular ED patients that reject more invasive therapies.

Seminal human papillomavirus infection and reproduction: a systematic review and meta-analysis.

BACKGROUND: The impact of human papillomavirus (HPV) on male fertility and associated reproductive outcomes has not been clarified. OBJECTIVES: To elucidate the prevalence of seminal HPV infection and assess the associated effects on seminal parameters, male infertility, and reproductive outcomes. MATERIALS AND METHODS: A systematic review and meta-analysis was performed in accordance with PRISMA guidelines. A search was performed using PubMed, MEDLINE, SCOPUS, and Cochrane databases. Studies published until November 2019 were included. HPV prevalence, risk of infertility, seminal parameters, and reproductive outcomes were evaluated among the general population and infertile men. RESULTS: Fifty studies met the inclusion criteria. The prevalence of seminal HPV infection is significantly higher in infertile compared to the general population (20.9% versus 8.2%). A significant association between seminal HPV infection and male infertility (OR 3.30, 95% CI 1.87-5.84), even when adjusting for female infertility (OR 3.02, 95% CI = 2.11-4.33) was founded. In addition, HPV infection is related to a significant decrease in progressive motility (DM -10.35, IC -13.75, -6.96), a low sperm morphology score (DM -2.46, 95% CI -3.83, -1.08), and a significant increase in the sperm DNA fragmentation index (7.24, 95% CI 4.44.10.03) compared with HPV-negative patients. It was also observed an increased risk of miscarriage (OR 5.13, 95% CI 2.40,10.94), and a reduced chance of ongoing pregnancy (OR 0.33, IC 95% 0.13,0,82) in patients undergoing ART with seminal HPV infection. DISCUSSION: Infertile men have a higher prevalence of seminal HPV infection compared to the general population, regardless of the HPV genotype detected. CONCLUSIONS: HPV in semen may have an impact in sperm quality and reproductive outcomes. Additional well-designed studies are warranted to improve the quality of evidence.

The European Academy of Andrology (EAA) ultrasound study on healthy, fertile men: clinical, seminal and biochemical characteristics.

BACKGROUND: Infertility affects 7%-12% of men, and its etiology is unknown in half of cases. To fill this gap, use of the male genital tract color-Doppler ultrasound (MGT-CDUS) has progressively expanded. However, MGT-CDUS still suffers from lack of standardization. Hence, the European Academy of Andrology (EAA) has promoted a multicenter study ("EAA ultrasound study") to assess MGT-CDUS characteristics of healthy, fertile men to obtain normative parameters. OBJECTIVES: To report (a) the development and methodology of the "EAA ultrasound study," (b) the clinical characteristics of the cohort of healthy, fertile men, and (c) the correlations of both fertility history and seminal features with clinical parameters. METHODS: A cohort of 248 healthy, fertile men (35.3 ± 5.9 years) was studied. All subjects were asked to undergo, within the same day, clinical, biochemical, and seminal evaluation and MGT-CDUS before and after ejaculation. RESULTS: The clinical, seminal, and biochemical characteristics of the cohort have been reported here. The seminal characteristics were consistent with those reported by the WHO (2010) for the 50th and 5th centiles for fertile men. Normozoospermia was observed in 79.6% of men, while normal sperm vitality was present in almost the entire sample. Time to pregnancy (TTP) was 3.0[1.0-6.0] months. TTP was negatively correlated with sperm vitality (Adj.r =-.310, P = .011), but not with other seminal, clinical, or biochemical parameters. Sperm vitality and normal morphology were positively associated with fT3 and fT4 levels, respectively (Adj.r = .244, P < .05 and Adj.r = .232, P = .002). Sperm concentration and total count were negatively associated with FSH levels and positively, along with progressive motility, with mean testis volume (TV). Mean TV was 20.4 ± 4.0 mL, and the lower reference values for right and left testes were 15.0 and 14.0 mL. Mean TV was negatively associated with gonadotropin levels and pulse pressure. Varicocoele was found in 33% of men. CONCLUSIONS: The cohort studied confirms the WHO data for all semen parameters and represents a reference with which to assess MGT-CDUS normative parameters.

From exome analysis in idiopathic azoospermia to the identification of a high-risk subgroup for occult Fanconi anemia.

PURPOSE: In about 10% of patients affected by Fanconi anemia (FA) the diagnosis is delayed until adulthood, and the presenting symptom in these "occult" FA cases is often a solid cancer and cancer treatment-related toxicity. Highly predictive clinical parameter(s) for diagnosing such an adult-onset cases are missing. METHODS: (1) Exome sequencing (ES), (2) Sanger sequencing of FANCA, (3) diepoxybutane (DEB)-induced chromosome breakage test. RESULTS: ES identified a pathogenic homozygous FANCA variant in a patient affected by Sertoli cell-only syndrome (SCOS) and in his azoospermic brother. Although they had no overt anemia, chromosomal breakage test revealed a reverse somatic mosaicism in the former and a typical FA picture in the latter. In 27 selected SCOS cases, 1 additional patient showing compound heterozygous pathogenic FANCA variants was identified with positive chromosomal breakage test. CONCLUSION: We report an extraordinarily high frequency of FA in a specific subgroup of azoospermic patients (7.1%). The screening for FANCA pathogenic variants in such patients has the potential to identify undiagnosed FA before the appearance of other severe clinical manifestations of the disease. The definition of this high-risk group for "occult" FA, based on specific testis phenotype with mild/borderline hematological alterations, is of unforeseen clinical relevance.

Más controversias en el tratamiento con testosterona / More controversy around treatment with testosterone

La testosterona es la principal hormona masculina y el testículo es la glándula principal en donde se produce a lo largo de toda la vida. La producción hormonal desciende de forma progresiva. La relación de la hormona con el comportamiento sexual es clara. El déficit hormonal provoca alteraciones en diferentes órganos y sistemas. Los valores circulantes bajos de testosterona se relacionan con varias patologías y con aumento de morbimortalidad. Durante estos últimos años se ha propiciado el tratamiento con testosterona para evitar o mejorar trastornos sexuales y diferentes patologías. El valor de testosterona plasmática por debajo del cual se ha de diagnosticar y tratar a los hombres sigue siendo motivo de controversia. La comunicación de efectos adversos con el tratamiento ha producido una llamada de atención de las autoridades sanitarias de diferentes países y reacciones diversas en la comunidad científica internacional. El síndrome de hipogonadismo de inicio tardío debe diagnosticarse con cautela y nunca solo con análisis hormonales aislados. Recordar que en muchas ocasiones los valores bajos de testosterona se corrigen sin necesidad de sustitución hormonal, solo tratando las causas que lo ocasionan (AU)

Testosterone is the main male hormone and the testicle is the main gland where it is produced during the whole life. Hormone production falls progressively. There is a clear relation between the hormone and sexual behaviour. Hormone deficit causes alterations in different organs and systems. Low testosterone circulating values are related to many conditions as well as to the increase of mortality and morbidity. During the last years, treatment with testosterone to avoid or improve sexual disorders and other conditions has been promoted. Testosterone plasma level under which men should be diagnosed and treated is still in dispute. The communication of side effects of the treatment has attracted health authorities’ attention in different countries and produced diverse reactions over the international scientific community. Late-onset hypogonadism syndrome must be diagnosed carefully and never under just isolated hormonal analysis. Low testosterone values get very often corrected without needing hormonal substitution, but just by treating the causes which give rise to it (AU)

Clinical relevance of Y-linked CNV screening in male infertility: new insights based on the 8-year experience of a diagnostic genetic laboratory.

AZF microdeletion screening is routinely performed in the diagnostic work-up for male infertility; however, some issues remain debated. In this study, we provide insights into the sperm concentration cutoff value for routine testing, the predictive value of AZFc deletion for testicular sperm retrieval and the Y-background contribution to the interpopulation variability of deletion frequencies. In the Spanish population, partial AZFc rearrangements have been poorly explored and no data exist on partial duplications. In our study, 27/806 (3.3%) patients carried complete AZF deletions. All were azoo/cryptozoospermic, except for one whose sperm concentration was 2 × 10(6)/ml. In AZFc-deleted men, we observed a lower sperm recovery rate upon conventional TESE (9.1%) compared with the literature (60-80% with microTESE). Haplogroup E was the most represented among non-Spanish and hgr P among Spanish AZF deletion carriers. The analysis of AZFc partial rearrangements included 330 idiopathic infertile patients and 385 controls of Spanish origin. Gr/gr deletion, but not AZFc partial duplications, was significantly associated with spermatogenic impairment. Our data integrated with the literature suggest that: (1) routine AZF microdeletion testing could eventually include only men with ≤2 × 10(6)/ml; (2) classical TESE is associated with low sperm recovery rate in azoospermic AZFc-deleted men, and therefore microTESE should be preferred; (3) Y background could partially explain the differences in deletion frequencies among populations. Finally, our data on gr/gr deletion further support the inclusion of this genetic test in the work-up of infertile men, whereas partial AZFc duplications do not represent a risk for spermatogenic failure in the Spanish population.

ESR1 promoter polymorphism is not associated with nonsyndromic cryptorchidism.

The ESR1 promoter microsatellite (TA)n was reported as a potential functional polymorphism. In a case-control study, we were unable to demonstrate any association between (TA)n and nonsyndromic cryptorchidism in Italian and Spanish study populations.

Meiotic chromosome abnormalities in fertile men: are they increasing?

OBJECTIVE: To determine the basal frequencies of meiotic chromosome abnormalities in fertile men. DESIGN: Descriptive design. SETTING: Research university laboratory and clinical andrology service. PATIENT(S): Seventeen fertile donors undergoing vasectomy. INTERVENTION(S): Analysis of testicular biopsies. MAIN OUTCOME MEASURE(S): Meiotic chromosome abnormalities in metaphase I spermatocytes. RESULT(S): A total of 1,407 spermatocytes I was analyzed. The main meiotic abnormality was absence or low chiasma number of individual bivalents (23.4%), followed by structural (3.3%) and numerical (0.7%) abnormalities. Sex chromosomes and G-group chromosomes were the most commonly found as univalents at metaphase I. Statistically significant heterogeneity was found for meiotic abnormalities among fertile men, caused by interindividual variation in the level of dissociated sex chromosomes (ranging from 3.2% to 43.7%). The mean total percentage of meiotic abnormalities in spermatocytes I from fertile men was 27.4%, 1.7 times higher than those described a few decades ago in fertile and even in infertile men. CONCLUSION(S): Fertile men are a heterogeneous group for meiotic errors, with individuals showing percentages of meiotic abnormalities as high as 50%. From these findings, caution is recommended when using meiotic studies to diagnose and provide genetic counselling to patients consulting for infertility.

Baseline expression profile of meiotic-specific genes in healthy fertile males.

OBJECTIVE: To establish the quantitative gene-expression profile of nine meiotic genes involved in synapsis and chromosome cohesion (SYCP1, SPO11, MSH4, MSH5, MLH1, MLH3, PMS2, STAG3, and REC8) in healthy fertile males. DESIGN: Prospective study. SETTING: Research university laboratory and clinical andrology service. PATIENT(S): Twenty healthy males of proven fertility underwent a vasectomy procedure and four infertile patients with Sertoli cell-only syndrome (SCOS). INTERVENTION(S): Analysis of testicular biopsies from 20 fertile males and four SCOS patients. MAIN OUTCOME MEASURE(S): Quantitative gene expression by real-time polymerase chain reaction in testicular biopsies. RESULT(S): Four of the nine genes under study (PMS2, MLH3, MLH1, and REC8) are expressed in both fertile males and SCOS patients. The remaining five genes are only (SYCP1, SPO11, MSH4, and MSH5) or mainly (STAG3) expressed in fertile males, and thus they could be considered meiotic-specific genes. All genes analyzed are expressed at similar levels among fertile individuals CONCLUSION(S): Gene expression levels reported in this study could be considered the gene expression profile of fertile population, and could be used to compare with the expression pattern of infertile patients. Expression of meiotic-specific genes could be used as a clinical diagnosis tool to ascertain the origin of some cases of idiopathic male infertility and sterility.

Premature separation of sister chromatids in human male meiosis.

BACKGROUND: Meiotic disorders result in meiotic arrest and aneuploid spermatozoa, leading to male infertility, spontaneous abortions or affected offspring. We carried out meiotic studies in an infertile male to detect meiotic nondisjunction mechanisms leading to aneuploidy in spermatogenesis. METHODS AND RESULTS: Meiotic studies were performed in testicular and semen samples from a 38-year-old teratozoospermic male with normal somatic karyotype and a history of spontaneous abortions. We analysed 262 spermatocytes (69 pachytene cells, 106 metaphases I (MI), 87 metaphases II (MII)) by multiplex-fluorescence in situ hybridization and 20,193 spermatozoa by multicolour-FISH with probes for chromosomes 9, 10, 15, 21, X and Y. The results indicate high increase of 21 and XY disomies, as well as diploidy in both spermatocytes at MII and spermatozoa (P < 0.0001). Achiasmate segregation of sex chromosomes was found in 3.4% of spermatocytes II, preceded by early-dissociated XY bivalent at MI (41.5% of cells). We also detected premature separation of sister chromatids (PSSC) in 4.6% of MII. CONCLUSIONS: This individual presents high levels of numerical abnormalities in germ cells, caused by two different nondisjunction mechanisms during meiosis I. To our knowledge, this work represents the first time that PSSC has been demonstrated in human male germ cells.

[Azoospermia should not be given as the result of vasectomy]. / La azoospermia no debería ofrecerse como resultado de la vasectomia.

OBJECTIVES: Vasectomy is a surgical method of male contraception. Azoospermia is offered as result of the technique and this is not always attained, resulting in legal matters. The purpose of this study is to know the number of semen samples needed to discharge a patient after intervention. To identify sperm count on semen analysis at time of discharge. METHODS: Retrospective study of men who underwent vasectomy in a 15-month period with a 2 year follow up. Consecutive semen analyses up to 5 samples were measured at 2 to 3 months interval in all men who had persistence of spermatozoa. RESULTS: 618 men were intervened, 106 did not bring semen to the laboratory (17%), 2 (0.39%) presented motile sperm and were considered a failure of the technique and excluded. 510 men completed controls. 316 (61.9%) were azoospermic in the first sperm analysis, 74 (14.5%) in the second, 27 (5.2%) in the third, 6 (1.2%) in the fourth and one (0,.%) in the fifth analysis. The remaining 86 men (16.8%) had persistence of immotile sperm in the ejaculate and were less than 100,000/ml. No pregnancy was reported during 2 years follow up or after. CONCLUSIONS: Five or more semen analysis can be made after the surgery. Persistence of immotile sperm in the ejaculate is frequent and may exist for a long period afterwards. Immotile sperm count of 100,000/ml or less should be accepted as result of the procedure. The patient should be informed about the fact that persistent immotile sperm can be found in his semen. In the informed consent azoospermia should not be a concern as it is frequent to find immotile sperm in the ejaculate and this is an acceptable issue. As with other contraceptive methods, vasectomy should be offered as a safe method although clearly stating that the possibilities of failure do exist.