Normal Semen Parameters Research Articles

(249) Seminal Parameters after Tamsulosin Oral Intake in Young Fertile Men

Abstract Introduction Fertility and birth control is a worldwide health concerning since it is an important issue regarding economic, religious, or social impacts for couples. Women have plenty options since oral hormonal anticonception were introduced in daily practice. However, men remain restricted to condoms or vasectomy surgery and until now 50% of natural conceptions are considered not desired. Many options have been proposed for oral contraception (hormonal or non-hormonal strategies) but still none of them seems to be safe about efficacy, side effects, or reversibility. Alpha-blockers have shown effects in ejaculation and is a matter of debate if those are from retrograde ejaculation or impaired sperm emission. Actual data suggest specific alfa-1A blockage effect may achieve azoospermia, however it is not clear when it occurs and the exact mechanism concerning ejaculation disorder. Objective The main objective of this study is to determine how semen analysis on sperm concentration is affected by oral tamsulosin 0,8mg in a 24-hour range after intake. Methods 34 health men between 18-45 years-old recruited after consent for semen analysis with inclusion criteria OMS normal parameters and ability to masturbation for collect samples. Exclusion criteria were hepatic disorders, neurological disorders, renal disorders, inability to collect sperm from masturbation, previous or concomitant use of testosterone or other anabolic steroids and previous or concomitant use of possible medications regarding interaction. 31 individuals met including criteria and were designated to oral intake for tamsulosin 0,8mg and collect sperm sample after 4, 8, 12, 16,20 and 24 hours in different moments to determine 6 semen analysis in different medication serum concentrations. Minimum interval with each intake and semen analysis were 1 week. In case of any participant achieve azoospermia, urine analysis was performed to determine if it was retrograde ejaculation. Samples were determined about volume and sperm concentration. Side effects were considered after each week. Protocol was approved at local ethical committee (CAAE: 26124719.2.0000.0082). Results Low volume and sperm concentration compared to basal was achieved in 29/31 (93,6%) while azoospermia was diagnosed in 25/31 (80,7%). Only 1 subject was identified as retrograde ejaculation with 24 men with absolute azoospermia. Intervals of azoospermia achievement varied from 8 to 16 hours after oral tamsulosin 0,8mg intake. Most of subjects returned normal semen parameters with 24 hours after intake medication. Side effects were most regarding ejaculation disorder and discomfort, minor subjects with headache or dizziness but not considered bothering or incapacitant. Conclusions Ejaculation disorder in men after oral tamsulosin intake correspond to impaired emission in most subjects in this study. This could be an option for further studies regarding male birth control without risks of impaired spermatogenesis as hormonal approach with safe reversibility and well tolerated side effects. Disclosure No

Novel mutations in PLCZ1 lead to early embryonic arrest as a male factor.

Early embryonic arrest is one of the causes of assist reproduction technology (ART) failure. We have previously reported that the first sperm-derived genetic factor, ACTL7a mutations, could lead to early embryonic arrest. However, whether there are other male genetic factors associated with early embryonic arrest remains elusive. Here, we reported bi-allelic mutations in PLCZ1, a well-known causal gene of total fertilization failure, in four infertile males. Among these mutations, p.403_404del, p.I489S, and p.W536X were newly reported in this study. Histological and Western blotting analysis of the patients' sperm indicated these variants as loss-of-function mutations. These patients manifested normal conventional semen parameters and ultra-structures in sperm heads. However, among four in vitro fertilization (IVF) cycles, 81.8% (18/22) of the oocytes were polyspermic fertilized, which was rarely reported in PLCZ1-related male patients. In the following six ICSI cycles, artificial oocyte activation (AOA) was applied and successfully rescued the fertilization failure and polyspermy phenotypes, with 31.3% (15/48) of the MII oocytes normally fertilized. However, 60.0% (9/15) of these normally fertilized zygotes were arrested at 2-5-cell stage, with one failing to cleave, indicating that PLCZ1 was not only necessary for fertilization, but also crucial for early embryonic development. However, these rescued zygotes showed a lower potential in developing into blastocysts when cultured in vitro. Thus, fresh cleavage transfer was tried and two live births were successfully achieved thereafter. In conclusion, this study provided novel mutations in PLCZ1 gene to expand the pathogenic mutational spectrum in male infertility and demonstrated that PLCZ1 was a crucial sperm-related genetic factor for early embryonic arrest. We also proposed that cleavage transfer after ICSI and AOA treatment could be a potential treatment method for male patients carrying bi-allelic mutations in PLCZ1.

MP43-16 VARICOCELE INDUCED TESTICULAR HYPERTHERMIA: INFRARED DIGITAL THERMOGRAPHIC ASSESSMENT EXPLORING THE EFFECT OF SURGICAL VARICOCELE CORRECTION ON POSTOPERATIVE TESTICULAR TEMPERATURE AND REPRODUCTIVE OUTCOME

You have accessJournal of UrologyCME1 Apr 2023MP43-16 VARICOCELE INDUCED TESTICULAR HYPERTHERMIA: INFRARED DIGITAL THERMOGRAPHIC ASSESSMENT EXPLORING THE EFFECT OF SURGICAL VARICOCELE CORRECTION ON POSTOPERATIVE TESTICULAR TEMPERATURE AND REPRODUCTIVE OUTCOME Mohammed Mahdi, Kareim Khalafalla, Ahmed Al Saeedi, Mohamed Arafa, Haitham Elbardisi, Sami Alsaid, and Ahmad Majzoub Mohammed MahdiMohammed Mahdi More articles by this author , Kareim KhalafallaKareim Khalafalla More articles by this author , Ahmed Al SaeediAhmed Al Saeedi More articles by this author , Mohamed ArafaMohamed Arafa More articles by this author , Haitham ElbardisiHaitham Elbardisi More articles by this author , Sami AlsaidSami Alsaid More articles by this author , and Ahmad MajzoubAhmad Majzoub More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003289.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Testicular hyperthermia is considered as one of the main pathophysiological mechanisms of spermatogenic dysfunction in patients with varicocele. The aim is to compare scrotal & inguinal temperature measurements between varicocele patients and normal controls linking such measurements with semen parameters, in addition to the evaluation of changes in such variables after varicocele repair. METHODS: Patients with clinical varicocele were included. They were classified into normal semen (group I; n=25); & abnormal semen (group II; n=34). Controls (group III; n=30 ) with no varicocele & normal semen parameters were recruited. Initial conventional semen analysis (WHO 2010) and oxidation reduction potential (ORP) test (MiOXSYS) were performed. Bilateral inguinoscrotal infrared digital thermographic imaging (FLIR E6, Wilsonville, USA) was done.21 patients from group II underwent microsurgical varicocelectomy, temperature measurements & semen analysis were repeated 3 months post-surgery.Temperature were compared between all groups using ANOVA. Paired t-test was used to evaluate changes in temperature & semen parameters after the procedure. Pearson’s correlations were used to explore the association between temperature measurements & different variables and between changes in post-operative temperature with the changes in semen parameters. RESULTS: Bilateral scrotal temperatures, ORP and semen DNA fragmentation were significantly higher in group II compared with the other 2 groups.Left scrotal temperature was significantly negatively correlated with sperm concentration (-0.268, p=0.004), total motility (-0.337, p<0.001), normal morphology (-0.282, p=0.003) & left testicular size (-0.292, p=0.002). While it was significantly positively correlated with ORP (0.374, p=0.01). After varicocelectomy, there was a significant decrease in bilateral testicular temperature (p=0.01), and a significant increase in the sperm count (p= 0.03) & Normal morphology (p≤0.001), however, no significant correlation was identified between changes in testicular temperature & changes in all semen parameters. CONCLUSIONS: Increased scrotal temperature is detected in patients with testicular dysfunction secondary to clinical varicocele. Varicocele repair results in improvements in testicular temperature & semen parameters. Further studies with larger samples are needed to support correlations between post-operative outcomes. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e607 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohammed Mahdi More articles by this author Kareim Khalafalla More articles by this author Ahmed Al Saeedi More articles by this author Mohamed Arafa More articles by this author Haitham Elbardisi More articles by this author Sami Alsaid More articles by this author Ahmad Majzoub More articles by this author Expand All Advertisement PDF downloadLoading ...

PD42-08 PRELIMINARY RESULTS OF A FIRST IN HUMAN DOSE-RANGING CLINICAL TRIAL OF ADAM®, A NONHORMONAL HYDROGEL-BASED MALE CONTRACEPTIVE

You have accessJournal of UrologyCME1 Apr 2023PD42-08 PRELIMINARY RESULTS OF A FIRST IN HUMAN DOSE-RANGING CLINICAL TRIAL OF ADAM®, A NONHORMONAL HYDROGEL-BASED MALE CONTRACEPTIVE Paul Anderson, Damien Bolton, and Nathan Lawrentschuk Paul AndersonPaul Anderson More articles by this author , Damien BoltonDamien Bolton More articles by this author , and Nathan LawrentschukNathan Lawrentschuk More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003352.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Since the introduction of modern contraception in 1960, the focus has been on women, with a large assortment of hormonal and nonhormonal contraceptive options available for females. In contrast, male contraceptive options currently include only condoms, vasectomy, and the withdrawal method. Here we present the initial results from a first in human clinical trial of ADAM, a nonhormonal, nonpermanent, hydrogel-based contraceptive. METHODS: The preliminary safety and efficacy of ADAM® (Contraline, Inc.), a highly biocompatible nonhormonal, nonpermanent hydrogel designed for injection into the vas deferens, was assessed in an open-label, single-arm, prospective, multi-center, dose-ranging clinical trial with up to 30 male subjects with normal semen parameters, ages 25-65 years. After institutional review and ethics board approval, an initial cohort of 4 men were implanted with the first dose and rate of the ADAM® hydrogel (120 uL at 800 uL/min) under general anesthesia at the time of this writing. A no scalpel vasectomy (NSV) approach was used to identify and externalize the vas deferens, followed by cannulation with a 24G over-the-needle catheter, and ADAM® injection using a proprietary, automated injection device. An additional 26 men will be implanted with variable doses pending initial safety and efficacy data. Participants will be monitored for changes in semen parameters and for adverse events for up to 36 months, or until the average of two semen analyses demonstrates ≥15 million sperm/mL. Men who do not achieve azoospermia within 6 months, and all men at 36 months, will be offered a vasectomy. RESULTS: A volume of 120 uL of ADAM® was implantated intravasally into 4 men with a mean±SD age 41.3±7.3 years and baseline semen parameters of volume 2.15±0.81 mL, pH 8.14±0.13, concentration 78.45±28.12 M/mL, motility 56.8±7.5%, morphology 13.5±3.7% normal forms, TMC 70.0±15.7 M sperm. Implantations resulted in no serious adverse events within 2 weeks of the procedure, with post-procedure recovery characteristics similar to those in men receiving vasectomy. Post-procedure semen analyses at 14±3 days demonstrated volume 1.9±1.0 mL, pH 8.3±0.2, concentration 1.1±1.2 M/mL, motility 0.0±0.0%, and TMC of 0.5±0.6 sperm. Two patients had azoospermia and a third only 5 motile and 6 immotile sperm / 30 HPF in the initial post-procedure sample. CONCLUSIONS: Intravasal injection of ADAM® into human male vas deferens is feasible, and initially safe and effective at rapidly inducing near-azoospermia. Additional data will define the longer-term safety and efficacy of ADAM® and its feasibility as a male contraceptive. Source of Funding: Contraline, Inc., Charlottesville, VA; Male Contraceptive Initiative, Durham, NC © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1114 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paul Anderson More articles by this author Damien Bolton More articles by this author Nathan Lawrentschuk More articles by this author Expand All Advertisement PDF downloadLoading ...

Metabolomics profiling of seminal plasma in obesity-induced asthenozoospermia.

Asthenozoospermia is one of the essential causes of male infertility, and its incidence is significantly higher in obese men. Due to its complex etiology and unknown pathomechanism, the diagnosis and treatment of obesity-induced asthenozoospermia is a prevalent problem in reproductive medicine. This study aims to explore major differential metabolites and metabolic pathways in seminal plasma and pathological mechanisms for obesity-induced asthenozoospermia. We performed non-target metabolomic studies on the seminal plasma of healthy men with normal semen parameters (HN group, n=20), obese men with normal semen parameters (ON group, n=20), and men with obesity-induced asthenozoospermia (OA group, n=20) based on gas chromatography-mass spectrometry. Metabolic profilings and related pathway analyses were conducted to discriminate differential metabolites and metabolic pathways. A total of 20 differential metabolites including fructose, succinic acid, aconitic acid, methylmaleic acid, glucopyranose, serine, valine, leucine, phenylalanine, glycine, glutamic acid, alanine, proline and threonine were identified in HN group and ON group; 24 differential metabolites including glucose, fructose, pyruvic acid, citric acid, succinic acid, aconitic acid, glucopyranose, glutamic acid, valine, leucine, glycine, phenylalanine, lysine, citrulline, proline and alanine were produced in OA group and ON group; and 28 differential metabolites including glucose, fructose, citric acid, succinic acid, glucopyranose, valine, glycine, serine, leucine, phenylalanine, alanine, threonine, proline, glutamic acid, citrulline, lysine and tyrosine were produced in OA group and HN group. In addition, abnormal energy metabolism including carbohydrate metabolism (TCA cycle, glycolysis/gluconeogenesis, and pyruvate metabolism) and amino acid metabolism (phenylalanine, tyrosine, and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism; phenylalanine metabolism, etc.) were found in ON group and OA group. Obesity could affect the metabolite composition in seminal plasma and abnormal energy metabolism in seminal plasma mainly including carbohydrate metabolism and amino acid metabolism were closely related to obesity-induced asthenozoospermia.

Efficacy of Artificial Oocyte Activation in Improving the Reproductive Outcome in Poor Responders: A Single Centre Cohort Study.

Achieving pregnancy in poor ovarian response patients is a challenge. Failed fertilization after ICSI, despite normal semen parameters is due to defects in oocyte activation. In-vitro activation of oocytes using Ca+2 agents can be useful in increasing the fertilization rates in these patients. This study aimed to evaluate the efficacy of artificial oocyte activation by calcium ionophores in poor responders in improving fertilization, cleavage, implantation and clinical pregnancy rates. This is a prospective, cohort study conducted on 120 patients having poor ovarian response, (POSEIDON criteria) undergoing in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment at Southend Fertility and IVF, New Delhi from 1st August 2019 to 31st March 2020. Exclusion criterion was patients with partners with abnormal semen parameters. After OPU patients were randomized into two groups, study group (n=50) underwent ICSI-AOA (ICSI followed by artificial oocyte activation) using calcium ionophore- GM508 Cult-Active Solution) while the controls (n=57) were subjected to ICSI only. Comparison of ICSI-AOA and ICSI groups showed: (i) number of fertilized oocytes - 2.42 vs. 2.16, p = 0.049 (ii) No. of cleavage stage embryos 2.32 vs. 1.96, p = 0.008 (iii) No. of grade A embryos 1.52 vs. 1.04, p = 0.009 (iv) fertilization rate - 89.00% vs. 83.04%, p = 0.093 (v) cleavage rate - 96.33% vs. 92.55%, p = 0.165 (vi) implantation rate - 27.14% vs. 11.74%, p = 0.098 (vii) clinical pregnancy rate - 34.3% vs. 20.5%, p = 0.167. The number of fertilized oocytes, grade A embryos and cleavage stage embryos formed after ICSI-AOA were statistically significantly more than ICSI. ICSI-AOA has not shown improvement in fertilization, cleavage, implantation and clinical pregnancy rate. From the present study the conclusive evidence cannot be drawn due to small sample size hence further studies are needed on a larger population.

The impact of varicocelectomy on sperm DNA fragmentation and pregnancy rate in subfertile men with normal semen parameters: A pilot study

The impact of varicocelectomy on sperm DNA fragmentation and pregnancy rate in subfertile men with normal semen parameters: A pilot study

Semen Thresholds of Normality Established by the WHO Do Not Reveal Genome Instability-A Potential Occult Male Factor.

Semen parameters are unable to inform on the function or fertilizing capacity of the male gamete. Standardized methods are provided by the WHO but, the lower reference limits have reduced sensitivity to predict chances of conception. Subfertile men may be falsely classified as "normal" and a male factor contributing to genome instability may be overlooked. Semen parameters, sperm DNA fragmentation (SDF), sperm chromatin maturity and stability, and sperm aneuploidy were assessed in fertile (F), subfertile normozoospermic (SN) and subfertile non-normozoospermic males (SN-N). Standardized assays employing flow cytometry were used to detect genome instability. Sperm DNA fragmentation did not differ significantly whether the semen samples were from a fertile (F), subfertile normozoospermic (SN) or subfertile non-normozoospermic male (SN-N). Chromatin decondensation was significantly reduced and hyperstability significantly increased in the SN group as compared to the F group. The frequency of diploidy was significantly different in the three study groups with significance between F and SN and between F and SN-N groups. Subfertile men with normal semen parameters are often excluded from extensive genetic testing. Genome instability might be an independent attribute of semen quality detecting problems not seen with semen analysis alone.

Effect of paternal age on assisted reproductive outcomes in ICSI donor cycles.

Despite growing evidence suggesting age-related molecular changes in gametes, the impact of paternal age on clinical outcomes during infertility treatments has not been adequately assessed. This study aims to assess the correlation of paternal age to clinical pregnancy and live birth rates in egg donation cycles undergoing intracytoplasmic sperm injection. This retrospective cohort study includes 4930 fresh oocyte donation cycles from 3995 couples between April 2005 and February 2020 in a private IVF hospital. Clinical pregnancy and live birth rates were the primary outcome measures. The results were also assessed according to the paternal age groups, donor characteristics, semen parameters, fertilization rate, and quality of the transferred embryos. The age and body mass index of the donors, oocyte maturation, fertilization rates, and the mean number of transferred embryo quality were comparable on day-3 but not on day-5 embryo transfers between paternal age groups (p>0.05). Paternal age was found to be negatively correlated to the number of oocytes utilized, normal semen parameters, fertilization, clinical pregnancy, and live birth rates (p<0.05). In day-5 embryo transfer cycles, only the rate of cycles with normal spermatozoa, number of allocated oocytes, and pregnancy were found to be statistically significant. Paternal age may influence reproductive outcomes and should be considered during infertility evaluations in intracytoplasmic sperm injection donor cycles. Further research is needed to confirm these findings.

A narrative review of sperm selection technology for assisted reproduction techniques.

In-vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) has become increasingly prevalent even in cases without significant male factor infertility; however, stagnant live-birth rates, both nationally and internationally, have driven more research into sperm selection. To date, nothing has replaced swim-up and density-gradient preparation methods and therefore we sought to review the state of the science. A PubMed search was performed between years of 1989 and 2024 for English research articles reporting data on sperm selection technology in assisted reproductive technology. IVF with ICSI is increasingly prevalent even in men with normal semen parameters. Despite technologic advances and widespread use, reproductive outcomes with ICSI have been stagnant. This market for opportunity growth has allowed for sperm selection techniques to grow exponentially with heterogeneity in utilization and a paucity of positive reproductive outcomes. Swim-up and density-gradient centrifugation remain the most utilized sperm selection techniques. Various future technologies show promise including epigenetics, sperm biomarkers and a potential role of artificial intelligence; however, more research is needed. Given unchanged IVF success rates, sperm selection technologies hold promise to improve reproductive outcomes beyond traditional ICSI. At present, no technique has shown superiority to swim up and density centrifugation.

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

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

Genome-Wide Association Screening Determines Peripheral Players in Male Fertility Maintenance

Deciphering the functional relationships of genes resulting from genome-wide screens for polymorphisms that are associated with phenotypic variations can be challenging. However, given the common association with certain phenotypes, a functional link should exist. We have tested this prediction in newly sequenced exomes of altogether 100 men representing different states of fertility. Fertile subjects presented with normal semen parameters and had naturally fathered offspring. In contrast, infertile probands were involuntarily childless and had reduced sperm quantity and quality. Genome-wide association study (GWAS) linked twelve non-synonymous single-nucleotide polymorphisms (SNPs) to fertility variation between both cohorts. The SNPs localized to nine genes for which previous evidence is in line with a role in male fertility maintenance: ANAPC1, CES1, FAM131C, HLA-DRB1, KMT2C, NOMO1, SAA1, SRGAP2, and SUSD2. Most of the SNPs residing in these genes imply amino acid exchanges that should only moderately affect protein functionality. In addition, proteins encoded by genes from present GWAS occupied peripheral positions in a protein-protein interaction network, the backbone of which consisted of genes listed in the Online Mendelian Inheritance in Man (OMIM) database for their implication in male infertility. Suggestive of an indirect impact on male fertility, the genes focused were indeed linked to each other, albeit mediated by other interactants. Thus, the chances of identifying a central player in male infertility by GWAS could be limited in general. Furthermore, the SNPs determined and the genes containing these might prove to have potential as biomarkers in the diagnosis of male fertility.

A Metabolomic Profile of Seminal Fluid in Extremely Severe Oligozoopermia Suggesting an Epididymal Involvement.

Male infertility has increased in the last decade. Pathophysiologic mechanisms behind extreme oligospermia (EO) are not yet fully understood. In new "omics" approaches, metabolomic can offer new information and help elucidate these mechanisms. We performed a metabolomics study of the seminal fluid (SF) in order to understand the mechanisms implicated in EO. We realized a targeted quantitative analysis using high performance liquid chromatography and mass spectrometry to compare the SF metabolomic profile of 19 men with EO with that of 22 men with a history of vasectomy (V) and 20 men with normal semen parameters (C). A total of 114 metabolites were identified. We obtained a multivariate OPLS-DA model discriminating the three groups. Signatures show significantly higher levels of amino acids and polyamines in C group. The sum of polyunsaturated fatty acids and free carnitine progressively decrease between the three groups (C &gt; EO &gt; V) and sphingomyelins are significantly lower in V group. Our signature characterizing EO includes metabolites already linked to infertility in previous studies. The similarities between the signatures of the EO and V groups are clear evidence of epididymal dysfunction in the case of testicular damage. This study shows the complexity of the metabolomic dysfunction occurring in the SF of EO men and underlines the importance of metabolomics in understanding male infertility.

The effect of aging on semen parameters in normozoospermic men: A cross-sectional study.

Semen parameters change with age and are reported differently worldwide. This retrospective cross-sectional study aimed to investigate the semen quality pattern among aging men and the age thresholds for semen parameters. The records of men who had normal semen parameters from January 2015-June 2020 were retrospectively evaluated for andrological outpatient at Samsun Training and Research hospital and Gazi hospital in Samsun, Turkey. Adult men meeting the inclusion criteria were divided into 3 groups of I) 18-29 yr (n = 629), II) 30-39 yr (n = 775), and III) 40-49 yr (n = 190). Correlations between age and sperm parameters were then analyzed. A total of 1594 men were enrolled in the study. Significant differences were observed in total sperm numbers, total motility rates, progressive motility rates, nonprogressive motility rates, normal morphology rates, mean semen volume, and sperm concentrations. The parameters of total sperm number, progressive motility rate, and normal morphology rate were significantly higher in group I than in the other 2 groups (p 0.001, p 0.001, and p 0.001, respectively) and in group II compared to group III (p = 0.001, p = 0.003, and p 0.001), respectively. Mean semen volume and total motility rate were significantly higher in group I than in the other groups (p = 0.001 and p 0.001, respectively). However, no difference was observed between group II and group III (p = 0.61 and p = 0.04, respectively). Age has a significant impact on semen parameters capable of affecting male fertility, particularly total sperm numbers, the progressive motility rate, and the normal morphology rate.

Profiling the male germline genome to unravel its reproductive potential

To identify specific germline mutations related to sperm reproductive competence, in couples with unexplained infertility. In this retrospective study, couples were divided according to whether they had successful intracytoplasmic sperm injection outcomes (fertile) or not (infertile). Ancillary sperm function tests were performed on ejaculates, and whole exome sequencing was performed on spermatozoal DNA. Sperm aneuploidy and gene mutation profiles were compared between the 2 cohorts as well as according to the specific reasons for reproductive failure. Center for reproductive medicine at a major academic medical center. Thirty-one couples with negative infertility workups and normal semen parameters. Couples with mutations on fertilization- or embryo development-related genes were subsequently treated by assisted gamete treatment or microfluidics, respectively. Intracytoplasmic sperm injection cycle outcomes including fertilization, clinical pregnancy, and delivery rates. Sperm aneuploidy was lower in the fertile group (4.0% vs. 8.4%). Spermatozoa from both cohorts displayed mutations associated with sperm-egg fusion (ADAM3A) and acrosomal development (SPACA1), regardless of reproductive outcome. The infertile cohort was then categorized according to the reasons for reproductive failure: absent fertilization, poor early embryo development, implantation failure, or pregnancy loss. Spermatozoa from the fertilization failure subgroup (n = 4) had negligible PLCζ presence (10% ± 9%) and gene mutations (PLCZ1, PIWIL1, ADAM15) indicating a sperm-related oocyte-activating deficiency. These couples were successfully treated by assisted gamete treatment in their subsequent cycles. Spermatozoa from the poor early embryo development subgroup (n = 5) had abnormal centrosomes (45.9% ± 5%), and displayed mutations impacting centrosome integrity (HAUS1) and spindle/microtubular stabilization (KIF4A, XRN1). Microfluidic sperm processing subsequently yielded a term pregnancy. Spermatozoa from the implantation failure subgroup (n = 7) also had abnormal centrosomes (53.1% ± 13%) and carried mutations affecting embryonic implantation (IL9R) and microtubule and centrosomal integrity (MAP1S, SUPT5H, PLK4), whereas those from the pregnancy loss subgroup (n = 5) displayed mutations on genes involved in trophoblast development (NLRP7), cell cycle regulation (MARK4, TRIP13, DAB2IP, KIF1C), and recurrent miscarriage (TP53). By assessing the sperm genome, we identified specific germline mutations related to various reproductive processes. This information may clarify elusive factors underlying reproductive competence and enhance treatment for couples with unexplained infertility.

Analysis of 2 men with t(8;22)(q13;q13) and t(8;14)(q13;q22) chromosomal translocation karyotypes.

Male infertility is a multifactorial condition that is closely associated with chromosomal abnormalities. Reciprocal chromosomal translocation (RCT) is a significant structural genetic abnormality. The specific mechanisms of forms of RCT affecting male infertility include the product of chromosomally unbalanced gametes, thereby disrupting the structure and function of important genes responsible for spermatogenesis. RCT breakpoints have been found to disrupt gene structure and function in many medical fields However, the relationship between RCT breakpoints and male infertility remains to be determined. The purpose of this study is to describe 2 male carriers of RCTs 46,XY,t(8;22)(q13;q13) and 46,XY,t(8;14)(q13;q22). Both patients were collected from the second hospital of Jilin University. Semen parameters were detected using the computer-aided semen analysis system. Cytogenetic analysis was performed using standard operating procedure. Related genes on chromosomal breakpoints were searched using Online Mendelian Inheritance in Man. One man had semen parameters within the normal range, but the couple was infertile after 5 years of marriage. The other man showed normal semen parameters, and his wife had experienced 2 spontaneous miscarriages. Using a literature search, the association between chromosome 22q13 breakpoint and fertility were investigated. The results suggest that physicians should focus on the clinical phenotype of the patients and the breakpoints of RCT in genetic counseling. An important gene related to human male infertility is clearly located in chromosome region 22q13, and its function is worthy of further study.

Altered non-coding RNA profiles of seminal plasma extracellular vesicles of men with poor semen quality undergoing in vitro fertilization treatment.

Currently, the precise mechanisms that underline male infertility are still unclear. Accumulating data implicate non-coding RNA cargo of seminal plasma extracellular vesicles due to their association with poor semen quality and higher expression levels relative to vesicle-free seminal plasma. We assessed sperm-free seminal plasma extracellular vesicle non-coding RNA profiles from 91 semen samples collected from male participants of couples seeking infertility treatment. Men were classified into two groups (poor, n=32; normal, n=59) based on World Health Organization semen cutoffs. Small RNA sequencing reads were mapped to standard biotype-specific transcriptomes in the order micro RNA>transfer RNA>piwi-interacting RNA>ribosomal RNA >ribosomal RNA>circular RNA>long non-coding RNA using STAR. Differential expression of normalized non-coding RNA read counts between the two groups was conducted by EdgeR (Fold change ≥1.5 and (false discovery rate [FDR]<0.05). Small RNA sequencing identified a wide variety of seminal plasma extracellular vesicle non-coding RNA biotypes including micro RNA, ribosomal RNAs, piwi-interacting RNAs, transfer RNA, long non-coding RNAs as well as circular RNAs, and fragments associated with pseudogenes, and nonsense-mediated decay. The expression levels of 57 seminal plasma extracellular vesicle non-coding RNAs (micro RNA: 6, piwi-interacting RNA: 4, ribosomal RNA: 6, circular RNA: 34, and long non-coding RNA: 7) were altered in men with poor semen quality relative to normal semen parameters, many (60%) of which were circular RNA species. Ontology analysis of differentially expressed micro RNAs and circular RNAs showed enrichment in functional terms related to cellular communication and early development. This is the first study to generate comprehensive seminal plasma extracellular vesicle non-coding RNA profiles in a clinical setting and to determine the differences between men with normal and abnormal semen parameters. Thus, our study suggests that seminal plasma extracellular vesicle non-coding RNAs may represent novel biomarkers of male reproductive phenotypes.

The impact of different WHO reference criteria for semen analysis in clinical practice: Who will benefit from the new 2021 thresholds for normal semen parameters?

BackgroundIn 2021, the World Health Organization (WHO) has provided the latest update on processing and evaluating semen analysis.ObjectivesTo assess (i) the rate of discordance in semen parameters categorization across three different WHO reference values (namely WHO21, 2010 and 1999) and (ii) the clinical differences among discordant semen analyses from a cohort of primary infertile men.Materials and methodsData from 788 infertile men were analyzed. Semen parameters were interpreted based on WHO21, WHO10, and WHO99 reference criteria. Pregnancy outcomes with assisted reproductive techniques (ART) were available for 110 (14%) patients. Descriptive statistics was applied to describe potential differences among the three consecutive WHO references criteria.ResultsSemen parameters categorizations were highly different across the three groups (p < 0.001). Of all, 271 (42.2%) patients had normal semen parameters according to WHO10 but were pathologic when considered with WHO21 reference criteria (namely, men with increased semen abnormalities). Infertile men with increased semen abnormalities had lower testicular volume (p < 0.001) but higher FSH (p < 0.01) and LH (p < 0.001) values than those who had no change in terms of semen parameters categorization. Negative ART outcomes were more frequently reported in men with worsening semen parameters compared with those with confirmed semen parameters at WHO21 versus WHO10 (26.8% vs. 49%, p = 0.03). Conversely, infertile men with worsening semen parameters at WHO21 versus WHO99 were similar in terms of clinical and hormonal characteristics compared with those with the same rate of semen abnormalities.ConclusionsOne out of three infertile men showed worsened semen categorization according to WHO21 versus WHO10. Infertile men with worsening of semen parameters had worse clinical and hormonal characteristics than those with confirmed numbers of semen abnormalities. Moreover, live birth rates were lower in men with worsening semen abnormalities as for WHO21.

P-229 Has rampant use of ICSI wiped out Conventional IVF for non male factor infertility, or can Conventional IVF hold its ground

Abstract Study question Can ICSI completely replace and produce higher implantation rates as compared to conventional IVF for non-male factor infertility patients? Summary answer ICSI has no advantage over Conventional IVF in improving fertilization and implantation rates in non-male factor infertility. Rampant use of ICSI is not recommended. What is known already ICSI is the technique of choice for male factor infertility, no argument there. But in the recent times, the unbridled use of ICSI for non male factor patients worldwide has pushed Conventional IVF out of the picture. The evidence states otherwise, ICSI holds no significant advantage over Conventional IVF in couples with normal semen parameters when it comes to fertilization and implantation rates. The mechanical damage as a result of ICSI to oocytes cannot be ignored. Conventional IVF holds a certain advantage in allowing the oocyte to choose the sperm, mimicking in vivo selection. Study design, size, duration Prospective randomized study conducted in 140 patients, undergoing IVF &amp; ICSI with non-male factor infertility. The oocytes recovered for all the patients included in the study underwent split insemination, and were divided into 2 groups: Group 1: Insemination by Conventional IVF, and Group 2: Insemination by ICSI. Fertilization and Implantation rates were recorded. Participants/materials, setting, methods 140 patients with non-male factor cause of infertility were undergoing IVF/ICSI cycle were included in this study. Post ovum pick-up, the oocytes recovered for each patient were split into 2 separate groups and inseminated using Conventional IVF (413) and ICSI (679). The fertilization check was done at 17±1 hours. The implantation rates were noted 14 days after embryo transfer using the beta HCG values. The results were noted and compared. Main results and the role of chance In the Conventional IVF(C-IVF) group, fertilization rates were 69.23% compared to 71.44% in the ICSI group. The implantation rates were 26.50% in C-IVF group vs 22.10% in ICSI group. Limitations, reasons for caution A major limitation is the time constraint which did not allow us to track the live birth rates along with the small sample size, the lack of data showing clinical outcomes of this study can be improved upon in the future and with similar studies. Wider implications of the findings While ICSI holds the gold standard as the technique of choice for male factor infertility, it is not superior to C-IVF in patients with normal semen parameters. ICSI for all cannot be justified at this moment. Larger RCTs are required to establish superiority of one technique over the other Trial registration number not applicable

O-137 Evaluation of the effect of seminal plasma exosomes from unexplained infertile men on the expression of implantation-related genes

Abstract Study question Do exosomes from seminal plasma of men with unexplained infertility affect endometrial receptivity? Summary answer Seminal plasma exosomes from unexplained infertile men alter the expression of genes and signaling pathways related to endometrial receptivity. What is known already Unexplained infertile Men are a challenging group with no obvious cause of infertility. Many Complicated mechanisms play a crucial role in preparing the receptive endometrium for embryo implantation. The exosomes of seminal plasma are a heterogeneous cargo of nucleic acids, proteins, and lipids that participate in sperm maturation and function by binding to sperm. It is now apparent that the seminal plasma and its exosomes play a complex role in controlling the female reproductive system. There is no study investigating the effect of Unexplained seminal plasma exosomes on endometrial receptivity. Study design, size, duration Samples were collected from 10 men with normal semen parameters from couples undergoing infertility treatment and from 10 donor men with proven fertility and analyzed according to WHO -2010 criteria. Endometrial biopsy tissue was collected from 6 women in the proliferative phase of a natural menstrual cycle. Endometrial epithelial cells were cultured immediately after tissue processing and treated with 100 μg/ml seminal exosomes for (6 and 24 hours); then analyzed for gene expression. Participants/materials, setting, methods Exosomes isolated by an ultracentrifuge and characterized size and ultrastructure with dynamic light scattering and transmission electron microscopy. Western blot analysis showed the presence of the exosome markers. After incubation of exosomes with DiI dye, cytoplasmic localization of exosomes detected by fluorescence microscopy. The endometrial receptivity and signaling pathway genes were analyzed by qRT-PCR and immunocytochemistry. Image J and Prism software were used to quantify and analyze the data. P-value &amp;lt;0.05 was considered statistically significant. Main results and the role of chance Compared with the embryo donation group, the mRNA levels of MUC1, LIF, G-CSF, CX3CL1, and VEGF were significantly downregulated in the endometrium treated with unexplained infertile exosomes, especially after 24 hours of treatment. Mean mRNA levels of IL6, IL8, and TGFB genes in the unexplained infertile group changed compared with the embryo donation group but were not significant (p &amp;gt; 0.05). Immunocytochemical analysis showed that MUC1 and LIFR protein levels were increased in endometrial epithelial cells. Limitations, reasons for caution larger sample size and exosomal compositions assessment will be useful to identify the effect of exosomes on the endometrium. Wider implications of the findings Alterations in the expression of genes associated with endometrial receptivity by exosomes of the unexplained infertile men compared with embryo donation could be one of the causes of infertility in these individuals. Presumably, the atypical composition of exosomes has a different effect on sperm functions and endometrial genes expression. Trial registration number Not applicable