Do sperm factors influence embryonic aneuploidy? Long live the oocyte.

STUDY QUESTION: What is the impact of male age- and sperm-related factors on embryonic aneuploidy? SUMMARY ANSWER: Using a 3-fold analysis framework encompassing patient-level, embryo-level, and matching analysis, we found no clinically significant interactions between male age and sperm quality with embryo ploidy. WHAT IS KNOWN ALREADY: While the effect of maternal age on embryo chromosomal aneuploidy is well-established, the impact of male age and sperm quality on ploidy is less well-defined. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analyzed autologous preimplantation genetic testing for aneuploidy (PGT-A) and frozen embryo transfer cycles from December 2014 to June 2021. The study involved 11 087 cycles from 8484 patients, with a total of 35 797 embryos. PARTICIPANTS/MATERIALS, SETTING, METHODS: The aneuploidy rate, calculated as the ratio of aneuploid blastocysts to the total number of blastocysts biopsied in a single treatment cycle, was evaluated. In the embryo-level analysis, the main outcome measure was the ploidy state of the embryos. The study employed a multifaceted analytical approach that included a patient-level analysis using generalized linear mixed models, an embryo-level analysis focusing on chromosomal ploidy, and a propensity score matching analysis contrasting groups with distinct ploidy rates (0% and 100%). There were no interventions as this was an observational study of PGT-A cycles. MAIN RESULTS AND THE ROLE OF CHANCE: No clinically relevant factors influencing ploidy rate related to male and sperm quality were revealed. In contrast, female age (coefficient = -0.053), BMI (coefficient = 0.003), prior ART cycle (coefficient = -0.066), and number of oocytes retrieved (coefficient = -0.018) were identified at the patient level. Embryo analysis identified age (coefficient = -0.1244) and ICSI usage (coefficient = -0.0129) as significant factors. Despite these, no significant interactions between male and female assessed factors on the ploidy rate emerged. Propensity score matching between maximal (100% vs 0%) euploid rates did not reveal significant differences of influence by male age and sperm quality. LIMITATIONS, REASONS FOR CAUTION: The focus on patients having blastocyst biopsy for PGT-A may not reflect the broader IVF population. Other semen quality parameters like DNA fragmentation were not included. Exclusion of embryo mosaicism from the analysis could affect aneuploidy rate interpretations. There may also be unmeasured influences like lifestyle or environmental factors. WIDER IMPLICATIONS OF THE FINDINGS: Male age and sperm quality parameters were consistent across both maximal and minimal ploidy rate comparisons. No significant clinical characteristics related to the factors assessed for the male-influenced blastocyst ploidy status, confirming the dominancy of the oocyte and female age. STUDY FUNDING/COMPETING INTEREST(S): The study was not funded. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

A modified U-Net to detect real sperms in videos of human sperm cell.

Background: This study delves into the crucial domain of sperm segmentation, a pivotal component of male infertility diagnosis. It explores the efficacy of diverse architectural configurations coupled with various encoders, leveraging frames from the VISEM dataset for evaluation. Methods: The pursuit of automated sperm segmentation led to the examination of multiple deep learning architectures, each paired with distinct encoders. Extensive experimentation was conducted on the VISEM dataset to assess their performance. Results: Our study evaluated various deep learning architectures with different encoders for sperm segmentation using the VISEM dataset. While each model configuration exhibited distinct strengths and weaknesses, UNet++ with ResNet34 emerged as a top-performing model, demonstrating exceptional accuracy in distinguishing sperm cells from non-sperm cells. However, challenges persist in accurately identifying closely adjacent sperm cells. These findings provide valuable insights for improving automated sperm segmentation in male infertility diagnosis. Discussion: The study underscores the significance of selecting appropriate model combinations based on specific diagnostic requirements. It also highlights the challenges related to distinguishing closely adjacent sperm cells. Conclusion: This research advances the field of automated sperm segmentation for male infertility diagnosis, showcasing the potential of deep learning techniques. Future work should aim to enhance accuracy in scenarios involving close proximity between sperm cells, ultimately improving clinical sperm analysis.

Sperm Migration and Hyaluronic Acid Binding: Implications for Male Fertility Evaluation.

Mature, vital, and motile spermatozoa are essential for reaching the oocyte and binding to hyaluronic acid (HA) in the cumulus oophorus matrix. This study aims to determine the relationship between sperm-migration ability and HA-binding potential, as well as the relationship between sperm concentration and motility. Semen samples were collected from 702 men aged 20-56 years (median 34.8). We evaluated the sperm concentration and motility from basic semen analysis, the swim-up test (expressed as millions per mL and the migration efficiency percentage), and the hyaluronan-binding assay (HBA). A moderate positive correlation was found between the migration test results and HBA (R = 0.48). The highest correlation was observed between the concentration of motile spermatozoa and the migration test results (R = 0.85) and HBA (R = 0.4). The sperm migration efficiency strongly correlated with progressive motility (R = 0.6). Although significantly higher sperm migration was observed in patients with normal HBA results, the results of the functional tests were found to differ in some cases. For infertility treatment, the current diagnostic algorithm should be enhanced with more comprehensive seminological methods that assess the sperm-migration ability and HA-binding potential. We also recommend incorporating the swim-up method into the diagnostic protocol before planning assisted reproductive technology (ART) treatment.

Reliable Detection of Excessive Sperm Ros Production in Subfertile Patients: How Many Men with Oxidative Stress?

Sperm oxidative stress has been extensively associated to male infertility. However, tests to detect this parameter have not been yet introduced in clinical practice and no definitive data are present on the extent of oxidative stress in male infertility. In this study, we used a novel and reliable flow cytometric method to reveal sperm ROS production in subfertile patients (n = 131) and in healthy donors (n = 31). Oxidative stress was higher in subfertile patients (14.22 [10.21-22.08]%) than in healthy donors (9.75 [8.00-14.90]% (p < 0.01)), but no correlation was found with age, semen quality or sDF. We also failed to detect an increase in sperm ROS production with semen viscosity or leukocytospermia, but a sharp impact of semen bacteria was evident (with bacteria: 31.61 [14.08-46.78]% vs. without bacteria: 14.20 [10.12-22.00]%, p < 0.01). Finally, after establishing a threshold as the 95th percentile in healthy donors, we found that 29% of subfertile patients exceeded this threshold. The percentage decreased to 25.56% when we excluded subjects with bacteriospermia and increased to 60.87% when only these patients were considered. In conclusion, 29% of subfertile patients showed an excessive sperm ROS production. Surprisingly, this parameter appears to be independent from routine semen analysis and even sDF determination, promising to provide additional information on male infertility.

Spermiogram, Kinetics, Flow Cytometric Characteristics and DNA Damage Degree in Boar Ejaculates: Summarization and Clustering.

Boar semen analysis includes sperm motility, concentration, morphology and other more complex analyses such as membrane integrity, DNA damage and seminal plasma components. This study aims to summarize these numerous data by linear combinations of them, to classify ejaculates in several categories (clusters) and to investigate the potential differences among clusters on fertility and prolificacy. Young Pietrain boars (23 ± 3.6 months) were investigated: ten boars from the Nucléus genetic line (group 1: 90 ejaculates weekly) and five boars from the Batallé genetic line (group 2: 30 ejaculates weekly). Computer-assisted semen analysis (CASA) examined motility. Sperm viability, acrosome reaction, early apoptosis, mitochondrial activity and DNA damage were studied by flow cytometry analysis. SPSS v.26 software was used to perform principal component analysis (PCA) and clustering. Three principal components (PC1: speed; PC2: linear path; PC3: DNA damage) were detected and four clusters identified in both groups. Clusters also differed significantly in several variables not included in these PCs (group 1: beat cross frequency and poly (ADP-ribose) polymerase; group 2: cathepsin B, abnormal forms, mitochondrial activity and high DNA stainability). PCA and clustering achieved adequate description of these ejaculates, but no differences among clusters were found for fertility or prolificacy, probably because the minimum sperm requirements had been met.

The Andrological Landscape in the Twenty-First Century: Making Sense of the Advances in Male Infertility Management for the Busy Clinicians.

Male infertility represents a significant global problem due to its essential health, social, and economic implications. It is unsurprising that scientific research is very active in this area and that advances in the diagnostic and therapeutic fields are notable. This review presents the main diagnostic advances in male infertility, starting from the changes made in the latest WHO Manual of semen analysis and discussing the more molecular aspects inherent to "omics". Furthermore, the usefulness of artificial intelligence in male infertility diagnostics and the latest advances in varicocele diagnosis will be discussed. In particular, the diagnostic path of male infertility is increasingly moving towards a personalized approach to the search for the specific biomarkers of infertility and the prediction of treatment response. The treatment of male infertility remains empirical in many regards, but despite that, advances have been made to help formulate evidence-based recommendations. Varicocele, the most common correctable cause of male infertility, has been explored for expanded indications for repair. The following expanded indications were discussed: elevated sperm DNA fragmentation, hypogonadism, orchalgia, and the role of varicocele repair in non-obstructive azoospermia. Moving forward with the available data, we discussed the stepwise approach to surgical sperm retrieval techniques and the current measures that have been investigated for optimizing such patients before testicular sperm extraction. Finally, the key points and expert recommendations regarding the best practice for diagnosing and treating men with infertility were summarized to conclude this review.

Correlation of mediterranean diet pattern and lifestyle factors with semen quality of men attending fertility clinics: A cross-sectional study.

BACKGROUND: While numerous studies have examined the impact of individual or combined nutrients on semen quality, research on the correlation between overall dietary patterns and semen quality remains limited. This cross-sectional study investigates the relationship between adherence to the alternative Mediterranean diet (aMED) and semen quality. METHODS: A total of 274 men, presenting with both normal and abnormal semen parameters, participated in this study. Dietary data were collected using a 147-item semi-quantitative food frequency questionnaire (FFQ). Participants were divided into three groups based on their adherence to the Mediterranean diet (T1, T2, and T3). Statistical analyses, including ANOVA for numerical data and Chi-square tests for categorical data, were conducted. Multivariable logistic regression models were employed to estimate the association between aMED scores and abnormal semen parameters. RESULTS: Participants in the highest adherence group (T3) were younger and had lower BMI compared to those in the other tertiles. Significant differences in sperm parameters were observed across the tertiles. T3 recorded the highest levels of sperm concentration, total sperm count, motility, progressive motility, and normal morphology (57.53 ± 36.16, 213.8 ± 158.9, 73.4 ± 25.9, 61.2 ± 24.6, and 6.42 ± 1.51, respectively), whereas T1 had the lowest values (11.92 ± 22.29, 43.3 ± 73.8, 36.7 ± 33.8, 4.6 ± 5.7, respectively). No significant differences were found in semen volume and viscosity. The regression analysis revealed a significant positive correlation between aMED scores and sperm concentration (B = 1.32, P = 0.001), total sperm count (B = 1.12, P = 0.001), and total motility (B = 0.71, P = 0.001). CONCLUSION: Adherence to a high-quality Mediterranean diet is positively associated with improved semen quality and increased male fertility potential. Promoting healthy dietary patterns may be an effective strategy to enhance sperm motility and overall male reproductive health.

Weight Loss as Therapeutic Option to Restore Fertility in Obese Men: A Meta-Analytic Study.

PURPOSE: Weight loss has been shown to significantly elevate testosterone serum levels, though the impact on semen analysis parameters and fertility remains incompletely understood. The objective of this study was to examine the influence of body weight loss on semen parameters in obese men. MATERIALS AND METHODS: A meta-analysis was performed that included clinical trials in which a semen analysis before and after weight loss was evaluated. All strategies potentially available for weight loss were considered eligible. The primary outcome was the comparison of conventional semen analysis parameters before and after weight loss. RESULTS: Twelve studies were considered including 345 subjects (mean age 37.6±7.9 years; mean baseline body mass index 45.4±6.0 kg/m²). Weight loss resulted in a significant increase of sperm concentration (effect size 0.495, standard error 0.251 [0.003, 0.986], p=0.049) and progressive motility (effect size 0.567, standard error 0.372 [0.370, 0.764], p<0.001). Moreover, a significant decrease of sperm DNA fragmentation index after weight loss (effect size -0.689, standard error 0.278 [-1.123, -0.255], p=0.002) was observed. CONCLUSIONS: This meta-analytic analysis confirmed that body weight loss may improve qualitative and quantitative sperm characteristics providing evidence for suggesting weight loss to male partners with obesity and semen analysis alteration in couples attempting conception.

Relationship between hemoglobinopathies and male infertility: a scoping review.

Infertility is a common issue that threatens couples worldwide. Infertility can result from the male or female partner alone, or both partners. It can be due to multiple factors related to the patient's overall health or lifestyle. Causes related to patient health can be systemic or related to gonadal dysfunction. One of the systematic causes can be hematological. The two most common hemoglobinopathies that are thought to cause infertility, especially male infertility, are sickle cell disease (SCD) and thalassemia major (TM). These two hemoglobinopathies cause male infertility through pathophysiological alterations. Specifically, they alter the oxygen carrying ability of red blood cells (RBCs), causing tissue hypoxia that affects the normal physiological process of spermatogenesis, eventually inducing infertility. Semen analyses and other systemic blood testing can be used to investigate male infertility. Both hemoglobinopathies can be helped by blood transfusions, which can then alleviate male infertility. This paper aims to explore the relationship between hemoglobinopathies (SCD and TM) and their role in contributing to male infertility, in addition to the role of blood transfusions in addressing male infertility by correcting the root cause.

Correlation of sibling couple infertility history with semen parameters of infertile men, a cohort study.

INTRODUCTION: Infertility is a growing issue globally, particularly in industrialized cultures, affecting 13%-18% of couples of reproductive ages. In recent years, numerous studies have aimed to identify prognostic factors for infertility and abnormal semen analysis. To date, no study has examined the relationship between the number of infertile siblings and abnormal sperm parameters. This study aims to investigate whether the number of infertile siblings can be considered a prognostic factor for abnormal sperm parameters. METHOD: Semen samples were collected from the male partners of couples experiencing infertility issues. Study participants completed a questionnaire detailing demographic information including age and family history of infertility. Each participant provided two semen samples, with a minimum 15-day interval between collections. Sperm concentration, motility, and morphology were assessed for each sample. Clinical investigators conducted physical examinations, using an orchidometer to measure testicular size. RESULTS: The number of infertile brothers and testis volume were prognostic factors for abnormal sperm count (OR = 1.374, p-value = 0.03; OR = 0.786, p-value < 0.001; respectively) and abnormal motility (OR = 1.514, p-value = 0.018; OR = 26.74, p-value < 0.001, respectively). There was no significant association between the percentage of abnormal morphology of sperm cells and the mentioned prognostic factors. The optimal cut-off point of the number of infertile brothers for both abnormal sperm count and abnormal sperm motility was one. CONCLUSION: It is recommended that males with at least one infertile brother, undergo sperm analysis to identify individuals at risk of infertility.

Beyond the Incision: A Comparative Study of Suprainguinal and Inguinal Varicocele Surgeries.

Background Varicocele, characterised by the abnormal dilation of the pampiniform plexus of scrotal veins, is a prevalent and treatable cause contributing to male infertility, affecting 40% of men experiencing primary infertility and 80% of those with secondary infertility. Often asymptomatic, it can lead to chronic scrotal pain or a feeling of heaviness. Surgical interventions such as open, laparoscopic, or microsurgical varicocelectomy aim to eliminate venous reflux into the scrotum. This study sought to assess and evaluate the surgical outcomes and postoperative complications of the suprainguinal and inguinal approaches to varicocelectomy, offering evidence-based insights to improve varicocele management. Methodology A total of 60 males diagnosed with grade II or III unilateral or bilateral varicocele were included in the study. Patients with subclinical or grade I varicocele, recurrent varicocele, or concomitant inguinoscrotal pathology (hydrocele, epididymal cyst, and inguinal hernia) were excluded. Participants were randomly assigned to one of two groups based on the surgical technique: Group A (suprainguinal approach) and Group B (inguinal approach). Surgical outcomes were assessed by evaluating operating time, postoperative pain, wound hematoma, wound infection, hydrocele development, testicular atrophy, and semen analysis, both pre- and postoperatively. Results The study included 60 patients with a mean age of 29.05±5.96 years and an age range of 18-40 years. The suprainguinal approach offers a significantly shorter operating time than the inguinal approach (33.1 vs. 40.8 minutes). Both surgical techniques resulted in similar postoperative pain levels. The incidence of complications, such as wound hematoma, wound infection, and hydrocele development, showed no significant differences between the two approaches. In Group A (suprainguinal approach), the rates were 3.3%, 6.6%, and 3.3%, respectively, while in Group B (inguinal approach), they were 6.6%, 13.3%, and 6.6%. Additionally, 75% of patients in the infertility group showed improvements in semen parameters, with 80% in Group A and 71.4% in Group B, with no significant difference between the surgical approaches. Conclusion The suprainguinal and inguinal approaches to varicocelectomy effectively manage varicoceles, with the suprainguinal approach offering a shorter operating time. Postoperative complications and improvements in semen parameters were comparable between the two methods.

Differential impacts of ambient PM2.5 exposure on sperm quality in northern Thailand.

OBJECTIVE: This study aimed to explore the correlation between ambient particulate matter 2.5 (PM2.5) concentration and sperm quality among northern Thai men exposed to the seasonal air pollution from the agricultural burning process. METHODS: The demographic data and semen analysis of Thai men living in Chiang Mai, Thailand, who visited the infertile clinic were collected. The correlation test between the monthly amount of PM2.5 and sperm quality was carried out. RESULTS: From 2017 to 2021, 1,109 Thai men visited the Infertile Clinic. The correlation test between PM2.5 and sperm quality in years with a better climate revealed a weak positive correlation between the mean PM2.5 and percentage of progressive motile sperm and normal morphology (r=0.08, p=0.05 and r=0.1, p=0.02). However, there was a negative correlation between the mean PM2.5 and sperm concentration, progressive motility and normal sperm morphology during the years with a higher amount of ambient PM2.5, and especially PM2.5 exposure 3 months before semen collection (r=-0.12, p=0.01, r=-0.11, p=0.003, r=-0.15, p=0.004). CONCLUSIONS: Exposure to a high amount of PM2.5 air pollution negatively affects sperm quality.

Intensity and type of physical activity and semen quality in healthy young men.

OBJECTIVE: To study the relationship between intensity of physical activity (PA) and semen quality in healthy young men. DESIGN: A prospective cohort study with repeated measures for each subject. SETTING: Not applicable. PATIENT(S): Healthy high school and university students who did not regularly smoke tobacco, drink alcohol, or take drugs or medicine, with normal body mass index and abdominal circumference. INTERVENTION(S): The participants underwent urologic visit, fasting blood and semen sampling, and anthropometric measurements, and filled in the International Physical Activity Questionnaire, at enrollment and after 4 and 8 months. Duration and frequency of walking, moderate-intensity, and vigorous-intensity activities in the last week were assessed, and a score was computed for total PA. MAIN OUTCOME MEASURE(S): Semen specimens were taken at each visit through masturbation, after 3-5 days of abstinence, and analyzed by an expert urologist. Sperm concentration, total and progressive motility, and proportion of spermatozoa with normal morphology were measured. Linear and generalized linear mixed models with the Poisson family were fitted to assess the relationships between PA variables and sperm parameters, after adjusting for season, time, and study arm. The shape of the relationship was modeled through restricted cubic spline regression. RESULT(S): A total of 143 male subjects, aged 18-23 years (median, 20 years), were enrolled. They had a median PA of 1,960 (95% confidence interval, 1,055-3,182) Metabolic Equivalent of Tasks in min/wk. Statistically significant differences were found for total, progressive motility, and percent of cell with normal morphology across categories of total PA; the highest medians of total (47%) and progressive motility (34%) and of the percentage of normal morphology cells (7%) were found for medium PA. Positive associations of sperm total motility and normal morphology with medium levels of PA, and negative associations with walking and vigorous-intensity activity emerged. Spline regression analysis confirmed these findings, showing an inverse U-shape relationship, with the highest value of total motility and normal morphology for medium PA, and the lowest values for lower and higher activity. CONCLUSION(S): These findings support the present recommendations to practice moderate PA for health improvement, including semen quality.

UK Data Collection of Semen Quality in Transgender Adolescent Females Seeking Fertility Preservation.

OBJECTIVE: Increasing numbers of adolescents with gender dysphoria start gonadotropin-releasing hormone agonists to halt puberty, minimising psychological distress. The uncertainty of long-term effects of this medication, and the subsequent likelihood of accessing gender affirming hormone treatment, highlights the importance of fertility preservation prior to starting hormone treatment. We investigated the take up, hormonal profile and sperm quality in adolescents undergoing fertility preservation via cryopreservation by masturbation or surgical sperm retrieval, prior to starting hormonal therapy. DESIGN: Data was prospectively maintained from a tertiary UK-based hospital. 122 people under 19 years, mean age 15.2 +/- 1.7 years, referred by gender clinics and GPs, were included in this cohort study. SUBJECTS: Participants were counselled for fertility preservation, and serum testosterone, follicle stimulating hormone, and luteinizing hormone levels were recorded prior to providing semen samples. INTERVENTION: Masturbation semen samples were classified as normal (>15mil/ml), oligozoospermia (1mil-15mil/ml), cryptozoospermia (<1mil/ml) or azoospermia. If the sample was insufficient or the person was unwilling to masturbate, surgical sperm retrieval was offered in a stepwise manner using electroejaculation, TESE +/- mTESE. MAIN OUTCOME MEASUREMENTS: Quality of semen produced by participants, via masturbation or surgical sperm retrieval, was analysed to determine if it was good enough to cryopreserve for future fertility use. RESULTS: 23/122 (19%) participants declined sample storage. In the masturbation group (average age 16.3), 78 people produced 106 samples. 86/106 were stored - 43.7% were normospermic, 35.9% oligozoospermic, 8.7% cryptozoospermic, 11.7% azoospermic. Overall, semen parameters varied but were generally abnormal, illustrated by only 43.7% of the masturbation samples produced being normospermic. For surgical sperm retrieval subjects (average age 15.2), electroejaculation was successful in 4/21 people, while the rest proceeded with TESE/mTESE. Encouragingly, 16/21 subjects had an average of 5 vials stored, and all participants had a testosterone level >8nmol/l. Semen parameters in this sub-cohort were poor but possibly adequate for intracytoplasmic sperm injection. CONCLUSIONS: In this large database of transgender girls referred for fertility preservation in the UK, fertility preservation is possible, even with those unwilling to masturbate. Long-term data is required to check the health of these gametes, observing live birth rates using these preserved gametes.

Postvasectomy Semen Analysis Compliance With Utilization of a Mail-In Semen Analysis Kit.

PURPOSE: The AUA recommends postvasectomy semen analysis (PVSA) to verify successful vasectomy. However there remains poor patient compliance. We sought to assess whether mail-in PVSA improves patient compliance across a wide range of practice types. MATERIALS AND METHODS: Prospective data were collected on all men who received a Fellow PVSA kit between April 2021 and August 2023 in a nationwide cohort. Date of kit activation, practice type, clinic zip code, and date of kit accession/processing at the lab was collected. Compliance rates for each practice area were reported. χ2 tests of independence, logistic regression models, and multivariable logistic analysis were performed to assess the impact of relevant variables. RESULTS: Overall compliance across all practice areas was 69% following an 18-week period of observation (n = 16,105) and 82% (n = 6687) following a 40-week period. Compliance rates were highest and similar for small urology practices (<5 providers), including Veterans Affairs practices, ranging from 76% to 82% at 18 weeks to 85% to 87% at 40 weeks. Large urology practices had slightly lower compliance rates with 66% at 18 weeks to 80% at 40 weeks. The univariable logistic regression model demonstrated that patients in small urology practices have a 63% greater odds of 26-week compliance, on average, compared to those who receive care in large urology practices (odds ratio 1.63, 95% CI 1.48-1.79). CONCLUSIONS: Fellow's mail-in PVSA offers improved PVSA compliance over previously published data. Improved compliance is seen across all practice types. Despite these successes, there is significant room for improvement to achieve 100% compliance.

Screening of cytokine expression in human seminal plasma in associations with sperm disorders and markers of oxidative-antioxidant balance.

Among the many factors with a proven relation to semen quality and male fertility, the determination of seminal plasma cytokines provides a promising direction for research into the identification of factors connected with male infertility. The interleukins: IL-1α, -1ß, -2, -4, -6, -8, -10, -12p40, -12p70, -18, IFNγ, and GM-CSF, total oxidant (TOS) and antioxidant (TAS) status, were simultaneously examined in seminal plasmas and blood sera in terato- (n = 32), asthenoterato- (n = 33), and oligoasthenoteratozoospermic (n = 29) infertile men and in normozoospermic fertile men (n = 20). Our research shows different cytokine composition of the sera and seminal plasmas in all studied groups, along with much higher concentrations of seminal plasma GM-CSF, IFNγ, IL-1α, IL-4, IL-6, and IL-8 and lower IL-18 and TOS in the comparison to their sera levels. The seminal plasma concentrations of GM-CSF, IFNγ, IL-1α, -4, and -6 differ significantly between fertile and infertile as well as between teratozoospermic, asthenoteratozoospermic, and oligoasthenoteratozoospermic groups. The indication of the cause of different concentrations of cytokines in seminal plasmas of infertile men, and their associations with semen parameters and oxidative status, may be a promising direction for the search for new therapeutic targets that would directly affect the cells and tissues of male reproductive organs.

Retrospective study investigating the performance of the SQA-vision analyser compared with manual semen analysis.

The objective of this study was to compare the results of semen analysis using the manual method and the SQA-Vision sperm analyser after four years of practice and with a large cohort of patients. This was a comparative study of 1130 cases collected for semen analysis between October 2019 and October 2023, which were analysed simultaneously and independently by different operators using the manual microscopic method and an SQA-V automated analyser. For each sample, sperm concentration, progressive motility, motility, normal morphology, and round cells count were performed. There was no significant difference between the SQA-V method and manual assessment for all sperm parameters (Mann-Whitney test p > 0.05). According to the parameter studied, there was a strong correlation (rho = 0.81) and a very high correlation (rho = 0.98) between manual assessment and the SQA-V method. In the analysis of sperm concentration, the sensitivity and specificity were 0.90 and 0.99, respectively. The sensitivity and specificity for the analysis of sperm progressive motility were 0.98 and 0.99, respectively, while the sensitivity and specificity for the analysis of sperm motility were 0.87 and 0.99, respectively. The sensitivity and specificity for the analysis of normal morphology were 0.88 and 0.99, respectively. Regarding the analysis of round cells, the sensitivity and specificity were 0.98 and 0.99, respectively. The results of this retrospective study indicate that the SQA-V system offers satisfactory performance for routine sperm analysis.

Regulatory challenges of new male contraceptive methods.

INTRODUCTION: Progress in male contraception development faces the challenge of a lack of regulatory precedent and guidelines on the evidence (trial design and primary endpoint) required for marketing approval. Moreover, the development of a male contraceptive is complicated by the fact that the clinical treatment effect; prevention of pregnancy, is not measured in the patient receiving the intervention. DISCUSSION: Regulatory precedent and guidelines exist for female hormonal contraceptives but their applicability to male contraceptive products likely varies based on the mode of action and the anticipated pharmacodynamic effects of the product. The unique attributes of male contraceptives, including the frequent delay between the intervention (e.g., vasectomy and hormonal methods) and ultimate contraceptive effect, sperm suppression near azoospermia, and pregnancy prevention need to be addressed. CONCLUSION: This article describes the regulatory challenges faced by developers of male contraceptive products and offers proposals, paving the way for the development of both hormonal methods and non-hormonal approaches. Our article intends to suggest the directions but cannot substitute for the advice of regulatory agencies.

FSH Therapy in Male Factor Infertility: Evidence and Factors Which Might Predict the Response.

Follicle-stimulating hormone (FSH) administration is applied in the management of subjects affected by hypogonadotropic hypogonadism. Whilst this application is widely recognized and established alone or in combination with human chorionic gonadotropin (hCG), a similar strategy is empirically advocated in idiopathic male factor infertility (MFI). In this setting, FSH therapy has been used to increase sperm quantity, quality, and pregnancy rate when FSH plasma concentrations are below 8 IU/L and when the seminal tract is not obstructed. In the literature, several studies suggested that giving FSH to patients with idiopathic MFI increases sperm count and motility, raising the overall pregnancy rate. However, this efficacy seems to be limited, and about 10-18 men should be treated to achieve one pregnancy. Thus, several papers suggest the need to move from a replacement approach to an overstimulating approach in the management of FSH therapy in idiopathic MFI. To this aim, it is imperative to determine some pharmacologic markers of FSH efficacy. Furthermore, it should be useful in clinical practice to distinguish, before starting the treatment, among patients who might respond or not to FSH treatment. Indeed, previous studies suggest that infertile men who have normal levels of gonadotropins in plasma might not respond to FSH treatment and about 50% of patients might be defined as "non-responders". For these reasons, identifying predictive markers of FSH action in spermatogenesis and clinical markers of response to FSH treatment is a fascinating area of study that might lead to new developments with the aim of achieving personalization of the treatment of male infertility. From this perspective, seminal parameters (i.e., spermatid count), testicular cytology, genetic assessment, and miRNA or protein markers in the future might be used to create a tailored FSH therapy plan. The personalization of FSH treatment is mandatory to minimize side effects, to avoid lost time with ineffective treatments, and to improve the efficacy, predicting the most efficient dose and the duration of the treatment. This narrative review's objective is to discuss the role of the different putative factors which have been proposed to predict the response to FSH treatment in idiopathic infertile men.

Investigation of the Effect of Hafnium Chloride on Sperm Viability and Motility in Normospermic Cases: An In Vitro Study.

INTRODUCTION: Hafnium alloys are employed in medical applications due to their biocompatibility and high corrosion resistance. These alloys have demonstrated osteogenic and antimicrobial activities in surgical implants and have been utilized in the treatment of sarcoma. Additionally, a sensor based on hafnium nanoparticles has been reported for the detection of coronavirus disease 2019. Despite the increasing usage of hafnium, a literature review reveals no studies examining its effects on sperm in both human and animal species. METHODS: Semen samples were analyzed according to the 2010 World Health Organization (WHO) criteria, and 20 normospermic specimens were included in the study. Three groups were formed: control, hafnium chloride 2 mg/mL, and 4 mg/mL. Motility and viability were assessed in all groups at the 20th and 40th minutes. RESULTS: The decrease in viable sperm count was found to be significant in the 2 mg/ml HfCl4 group (difference: 12.73 ± 0.8, p<0.001) and the 4 mg/ml HfCl4 group (difference: 41.72 ± 1.34, p<0.001) compared to the control group. A time-dependent decrease in sperm viability was significant across all groups (difference: 8.93 ± 0.59, p<0.001). The decrease in viable sperm count in the 4 mg/ml HfCl4 group was significant when compared to the 2 mg/ml HfCl4 group (difference: 29 ± 1.27, p<0.001). The decrease in total motile sperm count was observed in both the 2 mg/ml HfCl4 group (difference: 12.80 ± 1.30, p<0.001) and the 4 mg/ml HfCl4 group (difference: 35.63 ± 1.12, p<0.001) compared to the control group. Additionally, the decrease in total motile sperm count in the 4 mg/ml HfCl4 group was significant compared to the 2 mg/ml HfCl4 group (difference: 22.80 ± 1.60, p<0.001). A time-dependent decrease in total motile sperm count was also significant (difference: 6.03 ± 0.49, p<0.001). CONCLUSION: The study determined that hafnium chloride negatively affects sperm motility and viability in vitro. These effects may be due to the presence of an acidic environment. It has been demonstrated that instruments containing this element may pose a potential risk.