Lower Sperm Concentration Research Articles

Male fertility is preserved following ixekizumab treatment-a real life pilot study.

Preserving fertility is crucial when managing male patients with spondyloarthritis (SpA) and/or psoriasis (PsO), especially in young men. Chronic inflammation, hormonal dysregulation, and immunosuppressive therapies can negatively impact male fertility. Over the past decades, positive data have emerged regarding the reproductive safety of various therapies in men. Ixekizumab (IXE), a high-affinity monoclonal antibody targeting IL-17A, has shown a safe profile for male fertility in small studies. This pilot study assesses the impact of IXE treatment on sperm parameters in SpA and/or PsO patients in a real-world setting. Consecutive adult male SpA and/or PsO patients eligible for or undergoing IXE treatment were prospectively enrolled. Demographic data, disease characteristics, laboratory assessments, comorbidities, and previous treatments were recorded. Sperm analysis was conducted after a minimum of 6 months of IXE treatment, and also before treatment inititation in a subgroup of patients. Parallel sperm evaluations were performed in a control group of healthy donors. Ten patients were enrolled: 8 with SpA and 2 with PsO. After 6 months of IXE treatment, all patients had normal sperm parameters. One SpA and PsO patient with baseline oligozoospermia showed normal parameters at follow-up and achieved a successful pregnancy post-treatment. Compared with controls, IXE-treated patients had lower sperm concentrations but higher vitality. In our limited size pilot study on SpA and PsO patients, Ixekizumab exposure did not impair male fertility. Sperm parameters remained within normal ranges after a minimum of 6 months of treatment. Early Ixekizumab treatment may preserve or potentially reverse fertility impairment.

Mediterranean Diet, ultra-processed food consumption and semen quality in healthy young men

Abstract Background Diet quality can have beneficial effects on male reproductive health, although studies are still limited, and little is known on the potential impact of ultra-processed foods (UPFs) on semen quality parameters. Methods A cross-sectional analysis was run on 126 participants (mean age 20.0 ± 1.2 y) from the FAST randomized controlled trial in 2018-2019. Food intake was assessed through a FFQ. UPF was defined following the Nova classification and calculated as the ratio (weight ratio) between UPF (g/d) and total food (g/d). Adherence to the Mediterranean Diet (MD) was ascertained by the Mediterranean Diet Score (MDS). The semen analyses were performed using a microscope for optical evaluation with a Makler counting chamber and two automated semen analysers. The primary outcomes were sperm volume, concentration, motility and morphology. A hierarchical mixed model approach was utilized to accommodate the within-subject correlation arising from the triple temporal repetition of measurements. Results Highest UPF consumption (Q4), compared to lowest (Q1), was associated with lower sperm concentration (β=-54.1×106 spz./ml; 95%CI: -92.9 to -15.4; p-trend=0.002 across quarters), and progressive motility (β=-14.2%; 95%CI: -28.2 to -0.09; p-trend=0.036). The percentage of cells with normal morphology tended to be reduced in young men consuming more UPF compared to lowest intake (β=-2.93%; 95%CI: -6.22 to 0.37; p-trend=0.071). The MDS was not associated with any of the parameters under study. Conclusions A larger dietary share of UPF was inversely associated with sperm concentration and progressive motility in young men of reproductive age. MD adherence was not associated with semen quality parameters, and this is possibly due to the low variability of MD adherence in this sample. Dietary recommendations for improving sperm health should prioritize limiting UPF in the diet. Key messages • Ultra-processed food (UPF) intake was unfavourably associated with semen quality parameters amongst young men. • Dietary recommendations for improving sperm health should recommend limiting UPF.

One out of two idiopathic infertile men has pathologic sperm DNA fragmentation values: Potential implications for clinical practice.

To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men. Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort. Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF≥30%. Men with pathologic SDF were older (p = .02), had higher Follicle-stimulating hormone(FSH) (p = .04) but lower total testosterone (p = .03) values than those with SDF<30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF≥30% (p = .01). Idiopathic infertile men with SDF≥30% presented with lower sperm concentration (p < .001) and lower progressive sperm motility (p < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, p = .02) and higher HOMA-IR score (OR: 1.8, p = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values. Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonaland semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men.

Testicular ultrasonographic features predict future risk for bilateral testicular germ cell tumour: A long-term single centre follow-up study.

Bilateral testicular germ cell tumours (B-GCT) are rare, with an incidence of 2-5%, and can be classified as synchronous (sB-GCT) or metachronous (mB-GCT). Our study aimed to identify clinical, biochemical, and radiological risk factors for mB-GCT in a cohort of patients with GCT at a single tertiary referral centre. This retrospective case-control study included patients with GCT referred to Policlinico Umberto I-Sapienza University of Rome, from 2005 to 2023. We evaluated clinical history, testicular ultrasound features, hormone levels, semen analysis, histological characteristics, staging, and treatments. mB-GCTs were compared with unilateral GCT patients with a follow-up longer than the median time-to-onset of the second tumour. Of 319 patients, 52 experienced B-GCT, with a median time-to-onset of the second tumour of 62 months (range: 8-229). The mB-GCT group showed higher gonadotropin levels (FSH 13.6mUI/mL vs. 7.4mUI/mL, p<0.001; LH 6.6mUI/mL vs. 3.9mUI/mL, p=0.004), lower sperm concentration (27×106/ejaculate vs. 78×106/ejaculate, p=0.009), smaller residual testis volume (10.4mL vs. 16.3mL, p<0.001), more inhomogeneous echotexture [57.5% vs. 14%, p<0.001], and presence of microlithiasis (75% vs. 19.5%, p<0.001). Kaplan-Meier curves confirmed that ultrasound features of the residual testis increased the cumulative risk of developing a second tumour. Microlithiasis was a strong independent predictor (OR 30.712, 95% CI 3.357-280.942, p=0.002). Histological features of the first tumour or its treatment do not influence the onset of a second tumour. However, low residual testis volume, inhomogeneous echotexture, and microlithiasis significantly increase this risk. A comprehensive evaluation of the residual testis at baseline is essential for developing a personalised surveillance programme in GCT survivors, with regular ultrasound follow-up recommended beyond the conventional 5-year limit.

The use of time-dynamic patterns of temperature and flexible generalized models to clarify the relations between temperature and semen quality

BackgroundSperm quality has decreased over the last decades worldwide. It is affected, among others, by season and heat. This study aimed to address the association between ambient temperature and sperm quality by assessing its shape using flexible multivariate models and identifying distinct time-dynamic patterns of temperature change based on unsupervised analysis. Material and methodsA retrospective population-based study has been conducted, including all samples of males attending the Fertility and In-Vitro-Fertilization unit at a single medical center during 2016–2022. Flexible generalized models were fitted to characterize the relations between sperm quality and temperature while accounting for patients characteristics, and to identify temperature levels that correspond with the optimal sperm quality. This information was then used to estimate adjusted slope coefficients at specified time-windows. ResultsIn total, 4555 sperm samples were provided by 3229 individuals. Sperm concentration, motility and progressive motility were higher by 8 %, 11 % and 16 %, respectively, during the spring versus the fall season. Furthermore, their quality during early spermatogenesis improved with temperature, until a certain optimum around 23 °C–24 °C. Increasing temperature at later developmental stages was associated with lower sperm concentration and higher motility. Sperm concentration and motility were highest following a period of moderate gradual warming. Motility was higher and sperm concentration was lower, following a period with heatwaves or summer. ConclusionsThis study assessed temperature role in sperm production quality by considering both average and time-dynamic temperatures. It identified several temperature change patterns over time and stratified the analysis by them. The differences in the relations across stages of spermatogenesis were addressed. Several mechanisms may explain the associations found, including heat-induced apoptosis of the sperm cells, and destruction of sperm cells DNA integrity by over-production of reactive oxygen species. The gradual global warming necessitates exploration of individual response to outdoor temperature in relations to genetic predisposition, lifestyle, and other health characteristics.

P-082 Use of TetraSOD® in male infertility: double-blind randomized placebo-controlled study

Abstract Study question Can the use of TetraSOD® (microalgae with high content of the antioxidant enzyme superoxide dismutase) improve semen quality and reduce oxidative stress in sperm? Summary answer The use of TetraSOD® reduces the oxidative stress of sperm, increasing the total sperm count in oligozoospermia and reducing the double-stranded DNA sperm fragmentation. What is known already Male factor is present in approximately 50% of the infertile couples, a large number of them of unknown or idiopathic origin. It has been demonstrated that semen quality is deteriorating over time, perhaps as a result of exposure to several environmental factors related with lifestyle that could impact both directly and indirectly on the complex process of spermatogenesis. Some of these bad habits of lifestyle increase the levels of oxidative stress in semen, which is associated with lower sperm concentration and motility. In this scenario, the use of antioxidants can be useful to increase sperm quality. Study design, size, duration Double-blind randomized placebo-controlled clinical study to assess the effect of 250 mg of TetraSOD® (microalgae with high content of the primary antioxidant enzyme superoxide dismutase). Eighty patients with idiopathic infertility showing asthenozoospermia, oligozoospermia or oligoasthenozoospermia were recruited and randomized to receive 250 mg of TetraSOD® (TSOD group) or placebo (Placebo group) for 3 months. Participants/materials, setting, methods Men with asthenozoospermia, oligozoospemia or aligoastenozoospermia and idiopatic infertility were recruited after informed consent signature. Patients were randomized into two groups. TetraSOD® group received 250 mg of TetraSOD®during 3 months, and Placebo group received capsules without TetraSOD® during the same period of time. Seminogram, double-strand sperm DNA fragmentation (COMET assay) and sORP (static oxidation- reduction potential) were studied at baseline (V0) and after 3 months (V3). Main results and the role of chance TetraSOD® consumption for three months elicited a statistically significant increase (Wilcoxon matched-pairs signed rank test; p=0.02) in the average number of sperms per ejaculate (from 17.06 x 106 to 41.94 x 106) in participants displaying oligozoospermia (&amp;lt;39 x 106 sperms) at V0. In contrast, the lower variation in the measured values in the Placebo group was not statistically significant. Regarding sORP, a statistically significant decrease (Wilcoxon matched-pairs signed rank test; p=0.0233) was observed in participants who displayed a value at V0 between 1.34-10. After TetraSOD® consumption, the average changed from 2.96 to 1.91 mv/106 sperm/ml from V0 to V3. However, not statistically significant changes were detected in the Placebo group between sORP values at V0 and V3. Moreover, in relation to double-stranded DNA breaks, a statistically significant decrease (Wilcoxon matched-pairs signed rank test; p=0.01) in the average percentages (from 31.81% to 25.93%) was measured after consumption of TetraSOD® at V3 in participants displaying a compromised redox status (sORP&amp;gt;1.34-10) at V0. No significant changes were found in the Placebo group. Limitations, reasons for caution The study was performed only in one ethnic group, so in future studies other ethnicities should be included. Wider implications of the findings TetraSOD® may improve male fertility because increases the number of sperms per ejaculate in oligozoospermia and reduces double-stranded DNA fragmentation in sperm when individuals display an altered redox status in semen. Such results might be related to the indirect antioxidant effect of TetraSOD®, reducing oxidative stress in seminal fluid. Trial registration number Not applicable

P-050 Microfluidic chip-sorted spermatozoa selection yields embryo euploidy rate and reproductive outcomes similar to density-gradient centrifugation

Abstract Study question Does microfluidic chip-sorted spermatozoa selection (MSS) improve good quality blastocyst (GQB) and embryo euploidy rates compared to density gradient centrifugation (DGC)? Summary answer The use of MSS before intracytoplasmatic sperm injection (ICSI) does not improve good quality blastocist and euploidy rates comparing to DGC. What is known already The integrity of sperm DNA plays a crucial role in embryonic development. Conventional sperm selection methods, such as DGC, may potentially damage sperm DNA due to oxidative stress generated during centrifugation. One of the recent advances in sperm selection techniques is the microfluidic chamber, which, requiring less processing time and eliminating the need for centrifugation, allows for the selection of sperm with better mobility, morphology, and reduced DNA damage. Consequently, improved GQB and euploid embryo rates, as well as enhanced reproductive outcomes, are expected. Study design, size, duration Retrospective study of 1739 blastocysts from 404 couples undergoing 544 autologous cycles of ICSI/PGT-A (preimplantation genetic testing for aneuploidies) from January 2020 to December 2022. Those patients with sperm concentration &amp;lt;5 × 106/mL or motility &amp;lt;10%, altered karyotype, women aged &amp;gt; 43 years, uterine anomalies and thrombophilia were excluded. Besides comparing euploidy rates and blastocyst formation, reproductive outcomes were analyzed and compared. Participants/materials, setting, methods According to the sperm selection technique, two groups were established. One group underwent MSS (ZyMōt ICSI® or ZyMōt Multi®), resulting in 295 blastocysts from 96 cycles. It was compared with a control group (DGC) including 1444 blastocysts from 448 ICSI/PGT-A cycles. PGT-A was performed in day 5/6 using Next Generation Sequencing (NGS) technology. For a 95% confidence interval, statistical significance was considered at p &amp;lt; 0.05. Chi-square analysis was used for the statistical evaluation. Main results and the role of chance Both groups were comparable in terms of demographic data, including age, sperm analysis parameters, and cycle characteristics. There were no significant differences between the DGC and MSS groups in the women’s age (mean ± SD) (37.9 ± 3.9 vs. 38 ± 3.9 years, p = 0.99) or men’s age (38.4 ± 7.1 vs. 39.8 ± 5.9 years, p = 0.11). No significant differences were found between the DGC and MSS groups in terms of GQB rate (49.3% vs. 50.7%, p = 0.55), euploidy rate (35.8% vs. 32.2%, p = 0.23), fertilization rate (69.5% vs. 69.5%, p = 0.99), clinical pregnancy rate per transfer (63% vs. 76%, p = 0.13), clinical miscarriage (9% vs. 21%, p = 0.33), and live birth rate per transfer (44% vs. 37%, p = 0.42). The results also showed a higher number of euploid embryos per initiated cycle in the DGC group (1.154) compared to the MSS group (0.989). Despite this difference, the results were not statistically significant (p &amp;gt; 0.05). Limitations, reasons for caution The limitations of this study include the potential impact of selection bias, as it is a retrospective study in which groups were not randomly assigned. Additionally, the low number of blastocysts in the MSS group and the potential bias of DNA fragmentation, which was not evaluated in the study. Wider implications of the findings Both methods demonstrated similar effectiveness. While MSS could potentially be more effective in samples with high DNA fragmentation and they feature a user-friendly application, its major limitation lies in its challenging application with samples having a low concentration of motile sperm. Specific semen samples may need different sperm selection methods. Trial registration number Not Applicable

P-018 Study of sperm DNA fragmentation in the infertile population before, during and after the SARS-CoV-2 pandemic: a nationwide retrospective cohort study

Abstract Study question Did the values of single- and double-strand sperm DNA breaks (SSB and DSB) increase during the SARS-CoV-2 pandemic? Summary answer During the SARS-CoV-2 pandemic (2020), the mean values of SSB and DSB in infertile patients were statistically higher compared to the periods 2018-2019 and 2021-2022. What is known already Some studies have found lower sperm concentration and motility in patients during and after SARS-CoV-2 infection (COVID-19). These effects appear to be reversible, with significant improvements being observed after three months post-infection (complete spermatogenesis cycle). On the contrary, vaccination against this virus does not seem to affect semen parameters. The objective of the study was to compare the values of SSB and DSB sperm DNA fragmentation in the periods before the pandemic (2018-2019), during (2020, highest number of infections and social confinement), and after (2021-2022, lower infection rate, end of social confinement and vaccination period). Study design, size, duration The average SSB and DSB sperm DNA fragmentation values of 11,215 patients referred from 74 fertility centres throughout Spain from January 2018 to December 2022 were retrospectively compared. Participants/materials, setting, methods Semen samples from infertile patients were analysed using the Comet assay in alkaline or neutral pH conditions to evaluate SSB or DSB, respectively. Three periods were compared (two years before, during 2020, and two years after). Mean SSB and DSB values were statistically compared among these periods using the Kruskal-Wallis and Mann-Whitney tests. Differences were established at the 99% confidence interval. Main results and the role of chance The average SSB values obtained were: 41.67%±15.33 in 2018-2019; 43.92%±17.84 in 2020, and 41.68%±18.58 in 2021-2022. The average DSB values obtained were: 65.64%±14.27 in 2018-2019; 67.77%±13.90 in 2020, and 65.23%±15.18 in 2021-2022. The SSB and DSB values were statistically higher in 2020 compared to the periods 2018-2019 and 2021-2022 (p &amp;lt; 0.001 in both cases). No differences were detected between the previous period (2018-2019) and the following period (2021-2022) (p = 0.101 and p = 0.235, respectively). Limitations, reasons for caution The observed increase in SSB and DSB values during 2020 cannot be directly attributed to the SARS-CoV-2 infection (COVID-19). It is possible that it is associated with other concurrent factors. The studied samples were only from infertile patients, not from the general male population. Wider implications of the findings Given that the SARS-CoV-2 virus still exists in 2021-2022 but the social situation has normalized, the increase in fragmentation observed during 2020 could be more related to other aspects of the pandemic, such as social confinement, stress, among others. Trial registration number Not applicable

Clinical outcomes of fresh and frozen embryos transfer after in vitro fertilization in spouses of patients with severely low sperm concentration and motility.

To compare the pregnancy and neonatal outcomes of in vitro fertilization-embryo transfer (IVF-ET) with fresh or frozen embryos in spouses of patients with severely low sperm concentration and motility. A total of 2300 patients whose spouses have severely low sperm concentration and motility underwent IVT-ET in the Reproduction Medicine Center, Sir Run Run Shaw Hospital from April 2018 to April 2022. After applying the propensity score matching (PSM), 473 fresh embryo transferred cycles and 473 frozen embryo transferred cycles were selected for the study, and the pregnancy and neonatal outcomes were compared between the two groups. There were no significant differences in pregnancy outcomes and neonatal outcomes between fresh and frozen embryo groups (all P>0.05). In the stratification analysis, the number of retrieved oocytes in the fresh good-quality embryo transfer group was significantly increased compared with the fresh poor-quality embryo group (P<0.05), but the very early pregnancy loss rates were similar between the two groups (P>0.05), while the rate in fresh good-quality embryo transfer group was significantly higher than that in the frozen good-quality embryo transfer group (P<0.05). Among different age groups of women, the number of retrieved oocytes and the level of estrogen in the fresh embryo transfer group was significantly higher in the 20 to <30 years old group than that in the 30 to <35 years old group (both P<0.05), but the clinical pregnancy rate was lower in the 20 to <30 years old group than that in the 30 to <35 years old group (P>0.05). Additionally, the very early pregnancy loss was significantly increased in the fresh embryo group compared with the frozen embryo group in the 20 to <30 years age group (P<0.05). There were no significant differences in pregnancy and neonatal outcomes between fresh and frozen embryo transfer in spouses of patients with severely low sperm concentration and motility undergoing IVF-ET. Due to the shorter transfer times, less embryo freezing damage and reduced costs, fresh embryo transfer can be considered as the first choice. However, it is not necessary to pursue fresh embryo transfer if maternal oestrogen levels are too high and there is a tendency of overstimulation.

Ameliorative potentials of diosmin and hesperidin fractions on chlorpyriphos-induced changes in reproductive hormones, sperm characteristics, and testicular glycogen in male Wistar rats.

Reproductive deficiency is a major outcome of pesticide exposure sequel to cellular oxidative damage to sex organs. Flavonoid possess potent antioxidant capacities to mitigate pesticide related cellular injury. The present investigation examined the mitigative effect of micronized purified fractions of diosmin and hesperidin on reproductive hormones, sperm parameters, and testicular glycogen in male Wistar rats after sub-chronic Chlorpyriphos (CPF) exposure. Twenty-five male Wistar rats (120-145g) were randomly allocated five rats per group. Group I (DW) received distilled water (2ml/kg), Group II (S/oil) received soya oil (2ml/kg), Group III (DAF) received Daflon at 1000mg/kg, Group IV (CPF) received Chlorpyriphos (7.74mg/kg), and Group V (DAF + CPF) received Daflon (1000mg/kg) followed by CPF (7.74mg/kg) after 30min of Daflon. This regimen was administered daily for 60days. After cervical venesection under light chloroform anesthesia, blood samples were examined for levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Each rat's testicular tissue was quickly cut, collected, and glycogen evaluated. Sperm concentration, motility, morphology, and viability were measured in the right caudal epididymis. Results revealed that the untreated CPF group had significantly lower FSH, LH, testosterone, testicular glycogen, and sperm concentration. Additionally, CPF group sperm characteristics were abnormal compared to other groups. These reproductive hormones, testicular glycogen, and sperm parameters improved in the Daflon-treated groups. Hence, pre-treatment with flavonoid fractions of diosmin and hesperidin mitigated CPF-induced reproductive toxicity.

Investigating the potential of X chromosome shredding for mouse genetic biocontrol

CRISPR-Cas9 technology has facilitated development of strategies that can potentially provide more humane and effective methods to control invasive vertebrate species, such as mice. One promising strategy is X chromosome shredding which aims to bias offspring towards males, resulting in a gradual and unsustainable decline of females. This method has been explored in insects with encouraging results. Here, we investigated this strategy in Mus musculus by targeting repeat DNA sequences on the X chromosome with the aim of inducing sufficient DNA damage to specifically eliminate X chromosome-bearing sperm during gametogenesis. We tested three different guide RNAs (gRNAs) targeting different repeats on the X chromosome, together with three male germline-specific promoters for inducing Cas9 expression at different stages of spermatogenesis. A modest bias towards mature Y-bearing sperm was detected in some transgenic males, although this did not translate into significant male-biasing of offspring. Instead, cleavage of the X chromosome during meiosis typically resulted in a spermatogenic block, manifest as small testes volume, empty tubules, low sperm concentration, and sub/infertility. Our study highlights the importance of controlling the timing of CRISPR-Cas9 activity during mammalian spermatogenesis and the sensitivity of spermatocytes to X chromosome disruption.

Impact of varicocelectomy on sperm parameters and hormone levels in infertile patients with sickle cell disease

Purpose: This study analyzes the semen parameters and gonadal hormone levels in infertile patients with sickle cell disease (SCD) and palpable varicoceles who underwent varicocelectomy for impaired semen parameters. Patients and methods: Improvements in the semen parameters—serum levels of total testosterone, follicle-stimulating hormone (FSH), and inhibin B—and testicular volume (TV) in 18 infertile patients with SCD were evaluated before and at 6 months after varicocelectomy. Results: Before varicocelectomy, all sperm parameters were affected, with high rates of low sperm concentration (83.3%), poor motility (88.9%), and abnormal morphology (77.8%). All sperm parameters were altered in 61.1%. On follow-up at 55.5 months after varicocelectomy, improvement in all the semen parameters was successful and complete in 22.2% but was not significant in 77.8%. The median follow-up period for sperm recovery was relatively long at 60.3 months. Total testosterone, FSH, and inhibin B were not significantly different before and after treatment (P &gt; 0.05). However, testosterone, FSH, and TV significantly correlated with the semen parameters (P &lt; 0.05). Moreover, a significant positive correlation was found between TV and inhibin B (P &lt; 0.05), and the improvement in the semen parameters was significantly correlated with primary hypogonadism (P &lt; 0.05). Conclusion: In adult men with SCD, varicocelectomy had a positive impact on the impaired seminal parameters and may be an option before sperm cryopreservation to improve future male fertility. Furthermore, primary testicular failure may be a feature of reversible spermatogenesis recovery in these patients.

Elucidating the impact of Y chromosome microdeletions and altered gene expression on male fertility in assisted reproduction.

Genetic abnormalities like Y chromosome microdeletions are implicated in male infertility. This study investigated the association of azoospermia factor (AZF) region microdeletions with unsuccessful assisted reproductive techniques (ART), including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). This cross-sectional analysis study examined 80 Iranian oligospermic men (mean age 34years) with prior failed ICSI and IVF cycles (IR.IAU.TNB.REC.1401.041). Semen analysis evaluated quantity/quality parameters based on World Health Organization guidelines. Participants were stratified by sperm DNA fragmentation (SDF) levels into: control (SDF < 15%, n = 20), mild elevation (15% ≤ SDF ≤ 30%, n = 60), and high (SDF > 30%, n = 20). Multiplex PCR mapped AZF microdeletions in the high SDF group. The AZF-associated genes were selected by RNA Seq analysis, and the candidate genes were checked for expression level by real-time PCR. High SDF individuals exhibited poorer semen metrics, including 69% lower sperm concentration (P = 0.04) than those without SDF. Of this subset, 45% (9/20 men) harboured predominately AZF microdeletions. Men with AZF microdeletions showed higher SDF (32% vs 21%, P = 0.02) and altered AZF-associated genes expression. As USP9Y 3-fold, UTY 1.3-fold, and BPY2 1-fold revealed up-regulation, while IQCF1 8-fold, CDY 6.5-fold, DAZ 6-fold, and DDX3Y 1-fold underwent down-regulation. The PAWP gene was also down-regulated (5.7-fold, P = 0.029) in the IVF/ICSI failure group. AZF microdeletions significantly impact male infertility and ART outcomes. High SDF individuals exhibited poorer semen metrics, with 45% AZF microdeletions. These microdeletions altered AZF-associated genes expression, affecting fertility mediator PAWP independently. Dual AZF and SDF screening enables personalized management in severe male infertility, potentially explaining IVF/ICSI failures.

Phase angle at bioelectric impedance analysis is associated with detrimental sperm quality in idiopathic male infertility: a preliminary clinical study.

In 2020, 38% of adults were affected by obesity, while infertility globally affected 1 in 6 people at some stage of their lives.Body mass index (BMI) provides an easy but occasionally inaccurate estimation of body composition. To achieve a more precise assessment, bioelectric impedance analysis serves as a validated tool that administers electrical energy through surface electrodes. Phase angle as a function of the relationship between tissues resistance and reactance, is a trustworthy predictor of body composition and cell membrane integrity. We aim to assess whether there is an association between phase angle and seminal parameters, as well as sperm DNA fragmentation percentage. Semen samples of 520 idiopathic infertile patients were analyzed according to 2021 World Health Organization guidelines and evaluated for sperm DNA fragmentation rate. Each participants underwent bioelectric impedance analysis. Median age was 40 years old, median BMI was 26.3 kg/m2, median phase angle was 6.2°. In the logistic regression analysis adjusted for age and total intracorporeal water, phase angle (continuous) was significantly associated with oligozoospermia (odds ratio [OR]:0.4; p<0.01) and sperm morphology (OR: 0.65; p=0.05) and slightly with sperm DNA fragmentation (OR: 0.98; p=0.07). In subgroup analysis, the logistic regression analysis adjusted for the mentioned parameters showed that a phase angle between 6.2 and 7 (°) (OR: 0.63; p=0.02) and >7 (°) (OR: 0.12; p<0.01) were associated with a reduced risk of oligozoospermia compared to values <6.2 (°). Similarly, a phase angle between 6.2 and 7 (°) (OR: 0.57; p< 0.01 and OR: 0.58; p= 0.01) and PA > 7 (°) (OR: 0.12; p= 0.03 and OR: 0.21; p< 0.01) were associated with a reduced risk of lower sperm concentration and lower total sperm count, respectively, compared to a phase angle < 6.2 (°). Our study suggests a negative association between phase angle and detrimental sperm parameters in male idiopathic infertility.

Orchiopexy: one procedure, two diagnoses - different male infertility outcomes.

Infertility, affecting one in six couples, is often related to the male partner's congenital and/or environmental conditions or complications postsurgery. This retrospective study examines the link between orchiopexy for undescended testicles (UDT) and testicular torsion (TT) in childhood and adult fertility as assessed through sperm analysis. The study involved the analysis of semen samples from 7743 patients collected at Soroka University Medical Center (Beer Sheva, Israel) between January 2009 and December 2017. Patients were classified into two groups based on sperm concentration: those with concentrations below 5 × 10 6 sperm per ml (AS group) and those above (MN group). Medical records and surgical histories were reviewed, categorizing orchiopexies by surgical approach. Among 140 individuals who had undergone pediatric surgery, 83 (59.3%) were placed in the MN group and 57 (40.7%) in the AS group. A higher likelihood of being in the MN group was observed in Jewish compared to Arab patients (75.9% vs 24.1%, P = 0.006). In cases of childhood UDT, 45 (78.9%) patients exhibited sperm concentrations below 5 × 10 6 sperm per ml ( P < 0.001), and 66 (76.7%) had undergone unilateral and 18 (20.9%) bilateral orchiopexy. Bilateral orchiopexy was significantly associated with lower sperm concentration, total motility, and progressive motility than unilateral cases ( P = 0.014, P = 0.001, and P = 0.031, respectively). Multivariate analysis identified UDT as a weak risk factor for low sperm concentration (odds ratio [OR]: 2.712, P = 0.078), with bilateral UDT further increasing this risk (OR: 6.314, P = 0.012). Jewish ethnicity and TT diagnosis were associated with a reduced risk of sperm concentrations below 5 × 10 6 sperm per ml. The findings indicate that initial diagnosis, surgical approach, and ethnicity markedly influence male fertility outcomes following pediatric orchiopexy.

Evaluation of the Congjiang Xiang Pig’s Sperm Quality by Flow Cytometry

Background: Sperm quality plays an important role in the animal industry. The study of the sperm quality of Congjiang Xiang pigs is limited and the Rh123/PI double staining has not been used to detect the sperm quality of boars. Thus, the study aimed to evaluate the sperm quality of the Congjiang Xiang pigs and the feasibility of the flow cytometry (FCM) method in assessing sperm quality in pigs. Methods: Semen samples were evaluated for routine indicators of semen quality and using FCM with single staining and double staining to analyze the integrity of membrane and acrosome, the mitochondrial function. The sperm quality of the Congjiang Xiang pigs was compared with the Large White pigs. Result: The semen of the Congjiang Xiang pigs had a lower sperm concentration than that of the Large White pigs (P less than 0.01). There were no significant differences in sperm vitality, sperm motility and abnormality between the two breeds (P greater than 0.05). Single sperm staining revealed a lower sperm acrosomal integrity in the semen of the Congjiang Xiang pigs than that of the Large White pigs (P less than 0.01). No significant difference between the two breeds in membrane integrity and mitochondrial function was observed (P greater than 0.05). Rh123/PI double staining demonstrated that the rate of live sperm with a normal mitochondrial function of the Congjiang Xiang pigs was significantly higher than that of the Large White pigs (P less than 0.05). The rate of necrotic sperms in the semen of the Congjiang Xiang pigs was significantly lower than that in the semen of the Large White pigs (P less than 0.05). Correlation analysis revealed a positive association between the rates of live sperm in the semen of the congjiang xiang pigs and their sperm motility (P=0.051). Our results suggest that Rh123/PI double staining with flow cytometry can provide more reliable information to assess the boar sperm quality.

A preconception cohort study of sugar-sweetened beverage consumption and semen quality.

Dietary factors, including high sugar intake, may have adverse effects on male reproduction. Studies of the association between sugar-sweetened beverage (SSB) intake and semen quality have reported inconsistent results. We estimated the effects of SSB consumption on semen quality in a North American preconception cohort study. We analyzed baseline data from 690 males (n=1,247 samples) participating in Pregnancy Study Online (PRESTO) during 2015-2022. Participants aged ≥21 years completed a baseline questionnaire on which they reported information about intake of SSBs, including sodas, energy drinks, sports drinks, and fruit juices. After enrollment, we invited U.S. participants to a semen testing substudy, in which they collected and analyzed two samples using an at-home semen testing kit. We used linear regression models to estimate adjusted percent differences (%D) and 95% confidence intervals (CI) for associations of SSB intake with semen volume, sperm concentration, total sperm count (TSC), motility, and total motile sperm count (TMSC). We used modified Poisson regression models to estimate adjusted risk ratios (RRs) and 95% CIs for the association of SSB intake with World Health Organization semen parameter cut points. Relative to non-consumers of SSBs, those who consumed ≥7 SSBs/week had lower semen volume (%D=-6, 95% CI: -13, 0), sperm concentration (%D=-22, 95% CI: -38, 0), TSC (%D=-22, 95% CI: -38, -2), motility (%D=-4, 95% CI: -10, 2), and TMSC (%D=-25, 95% CI: -43, -2). High SSB consumers also had greater risks of low sperm concentration (≤16 million/mL; RR=1.89, 95% CI: 1.11, 3.21), low TSC (≤39 million; RR=1.75, 95% CI: 0.92, 3.33), low motility (≤42%; RR=1.23, 95% CI: 0.87, 1.75) and low TMSC (≤21 million; RR=1.95, 95% CI: 1.12, 3.38). Associations were stronger among participants with body mass index ≥ 25kg/m2 . Greater SSB consumption was associated with reduced semen quality in a North American preconception cohort.

Low-serum antimüllerian hormone is linked with poor semen quality in infertile men screened for participation in a randomized controlled trial

ObjectiveStudies investigating associations between serum anti-Müllerian Hormone (AMH) and semen quality in infertile men have shown conflicting results. Here, we investigated possible associations between serum AMH and semen quality in infertile men. DesignInfertile men were included during screening for participation in FITMI, a double-blinded, placebo-controlled 1:1, single-center randomized clinical trial. SubjectsAt the screening visit, 400 participants produced a semen sample and had their serum analyzed for AMH. Main Outcome MeasuresSerum AMH and semen quality ResultsAll men were stratified according to serum AMH in quartiles (Q1-Q4). Men in the lowest quartile had a lower sperm concentration (million/mL) (Q1: 8.0 vs. Q2: 10.4 vs. Q3: 11.0 vs. Q4: 13.0; p=0.006), total sperm count (million) (Q1: 29.1 vs. Q2: 38.2 vs. Q3: 44.4 vs. Q4: 55.7; p=0.022), sperm motility (%) (Q1: 41 vs. Q2: 57 vs. Q3: 50 vs. Q4: 53; p=0.042), and progressive sperm motility (%) (Q1: 31 vs. Q2: 44 vs. Q3: 35 vs. Q4: 40; p=0.031) compared with the other quartiles. Moreover, men with a sperm concentration < 2 million/mL had a lower serum AMH compared with men having 2-16 million/mL and > 16 million/mL (31 pmol/L vs. 38 pmol/L vs. 43 pmol/L, respectively; p=0.015). In accordance, men with sperm motility < 20% had a lower serum AMH compared with men with sperm motility 20-42%, and > 42% (31 pmol/L vs. 43 pmol/L. vs. 39 pmol/L, respectively; p=0.008). ConclusionThis study shows that low serum AMH is associated with poor semen quality in infertile men, which implies that serum AMH may have clinical value during the evaluation of male infertility.

Prenatal exposure to Di(2-ethylhexyl) phthalate and high-fat diet synergistically disrupts gonadal function in male mice†.

Prenatal exposure to Di (2-ethylhexyl) phthalate (DEHP) impairs the reproductive system and causes fertility defects in male offspring. Additionally, high-fat (HF) diet is a risk factor for reproductive disorders in males. In this study, we tested the hypothesis that prenatal exposure to a physiologically relevant dose of DEHP in conjunction with HF diet synergistically impacts reproductive function and fertility in male offspring. Female mice were fed a control or HF diet 7days prior to mating and until their litters were weaned on postnatal day 21. Pregnant dams were exposed to DEHP or vehicle from gestational day 10.5 until birth. The male offspring's gross phenotype, sperm quality, serum hormonal levels, testicular histopathology, and testicular gene expression pattern were analyzed. Male mice born to dams exposed to DEHP + HF had smaller testes, epididymides, and shorter anogenital distance compared with those exposed to HF or DEHP alone. DEHP + HF mice had lower sperm concentration and motility compared with DEHP mice. Moreover, DEHP + HF mice had more apoptotic germ cells, fewer Leydig cells, and lower serum testosterone levels than DEHP mice. Furthermore, testicular mRNA expression of Dnmt1 and Dnmt3a was two to eight-fold higher than in DEHP mice by qPCR, suggesting that maternal HF diet and prenatal DEHP exposure additively impact gonadal function by altering the degree of DNA methylation in the testis. These results suggest that the combined exposure to DEHP and high-fat synergistically impairs reproductive function in male offspring, greater than exposure to DEHP or HF dietalone.

Effect of chemical activators after intracytoplasmic sperm injection (ICSI) on embryo development in alpacas

Low motility and low sperm concentration are characteristics of alpaca semen. Thus, the intracytoplasmic sperm injection (ICSI) technique represents an alternative to improve the reproductive capacity of the male. However, the effect of post-ICSI activation in alpaca is not yet known. The aim of the present study was to compare the effect of chemical activators on alpaca embryo development after ICSI. Alpaca ovaries were collected from a local slaughterhouse and transported to the laboratory. Category I, II and III oocytes were matured for 30 h at 38.5 °C. After ICSI, injected oocytes were randomly divided and activated as follows: i) 5 μM ionomycin for 5 min, ii) 7% ethanol for 4 min, iii) 5 μM ionomycin for 5 min, window period 3 h plus 7% ethanol for 4 min, iv) 5 μM ionomycin for 5 min, window period 3 h, a second ionomycin treatment for 5 min, followed by 1.9 mM 6-DMAP for 3 h, v) 10 mM SrCl2 for 3 h. Culture was carried out for 5 days in SOFaa at 38.5 °C. The cleavage rate was the lowest in the SrCl2 group, morula development was the lowest in the SrCl2 and without activation groups, and blastocyst stage was not different between groups (P<0.05). The rates with SrCl2 were lower in total embryos produced, whereas in transferable embryos they were lower with 2Io/6-DMAP and with SrCl2 (P<0.05). In conclusion, alpaca oocyte activation is more efficient with ionomycin and ethanol to produce transferable embryos.