Showing papers on "Semen analysis published in 2020"

Some of the Factors Involved in Male Infertility: A Prospective Review

Abstract: Infertility is defined as the inability of couples to have a baby after one year of regular unprotected intercourse, affecting 10 to 15% of couples. According to the latest WHO statistics, approximately 50-80 million people worldwide sufer from infertility, and male factors are responsible for approximately 20-30% of all infertility cases. The diagnosis of infertility in men is mainly based on semen analysis. The main parameters of semen include: concentration, appearance and motility of sperm. Causes of infertility in men include a variety of things including hormonal disorders, physical problems, lifestyle problems, psychological issues, sex problems, chromosomal abnormalities and single-gene defects. Despite numerous efforts by researchers to identify the underlying causes of male infertility, about 70% of cases remain unknown. These statistics show a lack of understanding of the mechanisms involved in male infertility. This article focuses on the histology of testicular tissue samples, the male reproductive structure, factors affecting male infertility, strategies available to find genes involved in infertility, existing therapeutic methods for male infertility, and sperm recovery in infertile men.

Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial.

Abstract: Importance Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth. Objective To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth. Design, Setting, and Participants The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019. Interventions Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months. Main Outcomes and Measures The co–primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization. Results Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, −0.9% [95% CI, −4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]). Conclusions and Relevance Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples’ live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility. Trial Registration ClinicalTrials.gov Identifier:NCT01857310

Male Infertility is a Women's Health Issue-Research and Clinical Evaluation of Male Infertility Is Needed.

Abstract: Infertility is a devastating experience for both partners as they try to conceive. Historically, when a couple could not conceive, the woman has carried the stigma of infertility; however, men and women are just as likely to contribute to the couple’s infertility. With the development of assisted reproductive technology (ART), the treatment burden for male and unexplained infertility has fallen mainly on women. Equalizing this burden requires reviving research on male infertility to both improve treatment options and enable natural conception. Despite many scientific efforts, infertility in men due to sperm dysfunction is mainly diagnosed by a semen analysis. The semen analysis is limited as it only examines general sperm properties such as concentration, motility, and morphology. A diagnosis of male infertility rarely includes an assessment of internal sperm components such as DNA, which is well documented to have an impact on infertility, or other components such as RNA and centrioles, which are beginning to be adopted. Assessment of these components is not typically included in current diagnostic testing because available treatments are limited. Recent research has expanded our understanding of sperm biology and suggests that these components may also contribute to the failure to achieve pregnancy. Understanding the sperm’s internal components, and how they contribute to male infertility, would provide avenues for new therapies that are based on treating men directly for male infertility, which may enable less invasive treatments and even natural conception.

Sperm DNA Integrity and Male Fertility in Farm Animals: A Review

Abstract: The accurate prediction of male fertility is of major economic importance in the animal breeding industry However, the results of conventional semen analysis do not always correlate with field fertility outcomes There is evidence to indicate that mammalian fertilization and subsequent embryo development depend, in part, on the inherent integrity of the sperm DNA Understanding the complex packaging of mammalian sperm chromatin and assessment of DNA integrity could potentially provide a benchmark in clinical infertility In the era of assisted reproduction, especially when in-vitro fertilization or gamete intrafallopian transfer or intracytoplasmic sperm injection is used, assessment of sperm DNA integrity is important because spermatozoa are not subjected to the selection process occurring naturally in the female reproductive tract Although sperm DNA integrity testing measures a significant biological parameter, its precise role in the infertility evaluation in farm animals remains unclear In this review, the earlier findings on sperm DNA integrity in relation to male fertility are compiled and analyzed Furthermore, the causes and consequences of sperm DNA damage are described, together with a review of advances in methods for detection of sperm DNA damage, and the prognostic value of sperm DNA quality on male fertility

Sperm DNA fragmentation on the day of fertilization is not associated with embryologic or clinical outcomes after IVF/ICSI.

Abstract: To evaluate if sperm DNA fragmentation (SDF) in the sample used for intracytoplasmic sperm injection (ICSI) impacts outcomes after euploid blastocyst transfer. Prospective cohort study of couples undergoing IVF with preimplantation genetic testing for aneuploidy from December 2014–June 2017. Sperm collected on the day of ICSI was analyzed for SDF using the sperm chromatin structure assay (SCSA®). Semen analysis parameters, embryologic outcomes, and clinical outcomes after euploid blastocyst transfer were compared between groups with DNA fragmentation index (DFI) ≤ 15% and DFI > 15% using Mann–Whitney U, t tests, and generalized linear mixed effects models. Two hundred thirty-four patients were included. One hundred seventy-nine men had DFI ≤ 15% (low DFI group) and 55 men had DFI > 15% group (high DFI group). Total motile sperm and sperm concentration were significantly lower in the group with DFI > 15% vs. DFI ≤ 15%. There was no difference in fertilization (86.3 vs. 84.2%, adjusted OR (95% CI) 0.86 (0.63–1.18)), blastulation (49.5 vs. 48.8%, adjusted OR 1.02 (0.75–1.36)), or euploidy (55.7 vs. 52.1%, adjusted OR 0.96 (0.7–1.31)) between the low and high DFI groups, respectively. Clinical outcomes were similar between low and high DFI groups, including implantation rate (68.8 vs. 79.8%), ongoing pregnancy rate (65.9 vs. 72.6%), and miscarriage rate (4.2 vs. 8.8%), respectively. Sperm DNA fragmentation on the day of ICSI is not associated with embryologic or clinical outcomes after euploid blastocyst transfer. Increasing levels of SDF are associated with low sperm concentration and total motile sperm count.

Disruption in ACTL7A causes acrosomal ultrastructural defects in human and mouse sperm as a novel male factor inducing early embryonic arrest

Abstract: Early embryonic arrest is a challenge for in vitro fertilization (IVF). No genetic factors were previously revealed in the sperm-derived arrest of embryonic development. Here, we reported two infertile brothers presenting normal in conventional semen analysis, but both couples had no embryos for transfer after several IVF and intracytoplasmic sperm injection (ICSI). Whole-exome sequencing identified a homozygous missense mutation of ACTL7A in both brothers. This mutation is deleterious and causes sperm acrosomal ultrastructural defects. The Actl7a knock-in mouse model was generated, and male mutated mice showed sperm acrosomal defects, which were completely consistent with the observations in patients. Furthermore, the sperm from ACTL7A/Actl7a-mutated men and mice showed reduced expression and abnormal localization of PLCζ as a potential cause of embryonic arrest and failure of fertilization. Artificial oocyte activation could successfully overcome the Actl7a-mutated sperm-derived infertility, which is meaningful in the future practice of IVF/ICSI for the ACTL7A-associated male infertility.

Metabolomics analysis of seminal plasma in patients with idiopathic Oligoasthenoteratozoospermia using high-resolution NMR spectroscopy.

Abstract: BACKGROUND Male infertility is a global health issue caused by a combination of different factors. Specialists generally rely on semen analysis to diagnose male infertility. However, it is known that diagnostic semen analysis fails to identify about 50% of male infertility disorders. Recently, metabolomics has been proven to be a powerful technique for the diagnosis of different diseases. OBJECTIVE To determine whether metabolites could be used as potential biomarkers for the diagnosis of male factor infertility through comparing seminal plasma samples from infertile men with oligoasthenoteratozospermia (OAT) and samples from normozoospermic controls. MATERIALS AND METHODS This study utilized high-resolution 1 H NMR spectroscopy to reveal whether the metabolomic changes of seminal plasma obtained from 31 patients with oligoasthenoteratozospermia (OAT) are different from the ones obtained from 28 normozoospermic controls. RESULTS Multivariate statistical analysis of NMR data concluded that the metabolomic profile of samples from patients with OAT exhibits statistically significant differences when compared to the controls. The differences were based on the metabolites lactate, citrate, lysine, arginine, valine, glutamine, creatinine, α-ketoglutaric acid, spermine, putrescine, and tyrosine. Except the tyrosine, levels of the above metabolites were significantly decreased in patients with OAT compared to the controls. The levels of citrate, choline, spermine, putrescine, α-ketoglutaric acid, valine, and tyrosine were significantly different (p < 5 × 10-4 ) between two groups. On the other hand, levels of lactate, creatinine, lysine, arginine, and glutamine were also statistically significant (0.001 < p < 0.05). However, considering the p-values, the physiological relevance of these metabolites may be lower when compared to the others. A PLS-DA model built on the NMR data achieved 89.29% sensitivity and 93.55% specificity results in a leave-one-out cross-validation process. DISCUSSION AND CONCLUSION 1 H NMR spectroscopy-based metabolomic analysis could be used as a diagnostic tool for the diagnosis of oligoasthenoteratozospermia.

The effects of aging on semen parameters and sperm DNA fragmentation.

Abstract: Introduction This study aimed to look into possible correlations between male age and different sperm parameters derived from semen analysis and sperm deoxyribonucleic acid (DNA) fragmentation. Methods This retrospective descriptive study included 2681 male patients who underwent semen analysis at Clinica Las Condes (CLC), Santiago, Chile, between January 2014 and May 2017; correlations between age and sperm parameters were analyzed. Results Males above the age of 50 were significantly more likely to present anomalies in semen volume, sperm concentration, and sperm DNA fragmentation; males aged 41+ years were more likely to have lower sperm concentration levels; males aged 31+ years were more likely to have decreased sperm motility; when concentration was constant, more volume and motility anomalies were seen as age increased; when volume was kept constant, more motility and concentration anomalies were seen as age increased; and when motility was constant, normal semen volumes decreased as age increased. Conclusion Our study showed that male age significantly affects sperm parameters that might have an impact on male fertility.

Patients with chronic prostatitis/chronic pelvic pain syndrome show T helper type 1 (Th1) and Th17 self-reactive immune responses specific to prostate and seminal antigens and diminished semen quality.

Abstract: Objectives To assess the presence of self-reactive immune responses to seminal and prostate antigens (PAg), biomarkers of inflammation of the male genital tract, and semen quality parameters in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Patients, subjects and methods Peripheral blood and semen samples were collected from patients with CP/CPPS and age-matched healthy control volunteers. We analysed the lymphoproliferative responses of peripheral blood mononuclear cells (PBMC) to different seminal plasma (SP)-derived and purified PAg, serum autoantibodies specific to PAg, leucocyte subpopulations, and inflammatory cytokines in semen, sperm apoptosis/necrosis, and semen quality parameters. Results Significantly greater PBMC proliferative responses specific to PAg, with elevated secretion of interferon (IFN)γ and interleukin (IL)-17, were detected in the patients with CP/CPPS vs the controls. Moreover, the patients with CP/CPPS had significantly greater serum immunoglobulin G immune reactivity to SP proteins, such as prostate-specific antigen and prostatic acid phosphatase, than the controls. Inflammation of the male genital tract was exemplified by high levels of IFNγ, IL-17, IL-1β and IL-8, as well as higher counts of leukocytes, mainly CD4 T lymphocytes and macrophages, in the semen. In addition, this local inflammation was associated with an overall diminished semen quality, i.e., reduced sperm concentration, motility and viability; and higher levels of sperm apoptosis/necrosis in patients with CP/CPPS vs controls. Conclusion Patients with CP/CPPS show T helper type 1 (Th1) and Th17 immune responses specific to PAg associated with chronic inflammation of the male genital tract and reduced semen quality. These immune responses may underlie the induction and development of chronic pelvic pain and inflammation of the male genital tract, which in turn could alter normal prostate functioning and impair semen quality.

A novel homozygous mutation in WDR19 induces disorganization of microtubules in sperm flagella and nonsyndromic asthenoteratospermia

Abstract: Asthenoteratospermia with multiple morphological abnormalities in the sperm flagella (MMAF) is a significant cause of male infertility. WDR19 is a core component in the IFT-A complex and has a critical role in intraflagellar transport. However, the role of WDR19 mutations in male infertility has yet to be examined. We performed whole exome sequencing (WES) for 65 asthenoteratospermia individuals and identified a proband who carried a homozygous WDR19 (c.A3811G, p.K1271E) mutation from a consanguineous family. Systematic examinations, including CT scanning and retinal imaging, excluded previous ciliopathic syndromes in the proband. Moreover, semen analysis of this patient showed that the progressive rate decreased to zero, and the sperm flagella showed multiple morphological abnormalities. Scanning and transmission electron microscopy assays indicated that the ultrastructure of sperm flagella in the patient was completely destroyed, while immunofluorescence revealed that WDR19 was absent from the sperm neck and flagella. Moreover, IFT140 and IFT88, predicted to interact with WDR19 directly, were mis-allocated in the WDR19-mutated sperm. Notably, the MMAF subject harboring WDR19 variant and his partner successfully achieved clinical pregnancy through intracytoplasmic sperm injection (ICSI). We identified WDR19 as a novel pathogenic gene for male infertility caused by asthenoteratospermia in the absence of other ciliopathic phenotypes, and that patients carrying WDR19 variant can have favorable pregnancy outcomes following ICSI.

Membrane Potential Determined by Flow Cytometry Predicts Fertilizing Ability of Human Sperm.

Abstract: Infertility affects 10 to 15% of couples worldwide, with a male factor contributing up to 50% of these cases. The primary tool for diagnosing male infertility is traditional semen analysis, which reveals sperm concentration, morphology, and motility. However, 25% of infertile men are diagnosed as normozoospermic, meaning that, in many cases, normal-appearing sperm fail to fertilize an egg. Thus, new information regarding the mechanisms by which sperm acquire fertilizing ability is needed to develop a clinically feasible test that can predict sperm function failure. An important feature of sperm fertilization capability in many species is plasma membrane hyperpolarization (membrane potential becoming more negative inside) in response to signals from the egg or female genital tract. In mice, this hyperpolarization is necessary for sperm to undergo the changes in motility (hyperactivation) and acrosomal exocytosis required to fertilize an egg. Human sperm also hyperpolarize during capacitation, but the physiological relevance of this event has not been determined. Here, we used flow cytometry combined with a voltage-sensitive fluorescent probe to measure absolute values of human sperm membrane potential. We found that hyperpolarization of human sperm plasma membrane correlated positively with fertilizing ability. Hyperpolarized human sperm had higher in vitro fertilization (IVF) ratios and higher percentages of acrosomal exocytosis and hyperactivated motility than depolarized sperm. We propose that measurements of human sperm membrane potential could be used to diagnose men with idiopathic infertility and predict IVF success in normozoospermic infertile patients. Patients with depolarized values could be guided toward intracytoplasmic sperm injection, preventing unnecessary cycles of intrauterine insemination or IVF. Conversely, patients with hyperpolarized values of sperm membrane potential could undergo only conventional IVF, avoiding the risks and costs associated with intracytoplasmic sperm injection.

Reduced semen quality in patients with testicular cancer seminoma is associated with alterations in the expression of sperm proteins.

Abstract: Testicular cancer seminoma is one of the most common types of cancer among men of reproductive age. Patients with this condition usually present reduced semen quality, even before initiating cancer therapy. However, the underlying mechanisms by which testicular cancer seminoma affects male fertility are largely unknown. The aim of this study was to investigate alterations in the sperm proteome of men with seminoma undergoing sperm banking before starting cancer therapy, in comparison to healthy proven fertile men (control group). A routine semen analysis was conducted before cryopreservation of the samples (n = 15 per group). Men with seminoma showed a decrease in sperm motility (P = 0.019), total motile count (P = 0.001), concentration (P = 0.003), and total sperm count (P = 0.001). Quantitative proteomic analysis identified 393 differentially expressed proteins between the study groups. Ten proteins involved in spermatogenesis, sperm function, binding of sperm to the oocyte, and fertilization were selected for validation by western blot. We confirmed the underexpression of heat shock-related 70 kDa protein 2 (P = 0.041), ubiquinol-cytochrome C reductase core protein 2 (P = 0.026), and testis-specific sodium/potassium-transporting ATPase subunit alpha-4 (P = 0.016), as well as the overexpression of angiotensin I converting enzyme (P = 0.005) in the seminoma group. The altered expression levels of these proteins are associated with spermatogenesis dysfunction, reduced sperm kinematics and motility, failure in capacitation and fertilization. The findings of this study may explain the decrease in the fertilizing ability of men with seminoma before starting cancer therapy.

Fetal Programming of Semen Quality (FEPOS) Cohort - A DNBC Male-Offspring Cohort.

Abstract: Background: Prenatal exposures may contribute to male infertility in adult life, but large-scale epidemiological evidence is still lacking. The Fetal Programming of Semen quality (FEPOS) cohort was founded to provide means to examine if fetal exposures can interfere with fetal reproductive development and ultimately lead to reduced semen quality and reproductive hormone imbalances in young adult men. Methods: Young adult men at least 18 years and 9 months of age born to women in the Danish National Birth Cohort living in relative proximity to Copenhagen or Aarhus and for whom a maternal blood sample and two maternal interviews during pregnancy were available were invited to FEPOS. Recruitment began in March 2017 and ended in December 2019. The participants answered a comprehensive questionnaire and underwent a physical examination where they delivered a semen, urine, and hair sample, measured their own testicular volume, and had blood drawn. Results: In total 21,623 sons fulfilled eligibility criteria of whom 5697 were invited and 1058 participated making the response rate 19%. Semen characteristics did not differ between sons from the Copenhagen and Aarhus clinics. When comparing the FEPOS semen parameters to similar cohorts, the median across all semen characteristics was slightly lower for FEPOS participants, although with smaller variation. Conclusion: With its 1058 young adult men, the FEPOS cohort is the largest population-based male-offspring cohort worldwide specifically designed to investigate prenatal determinants of semen quality. Wide-ranging information on maternal health, lifestyle, socioeconomic status, occupation, and serum concentrations of potential reproductive toxicants during pregnancy combined with biological markers of fertility in their sons collected after puberty allow for in-depth investigations of the ‘fetal origins of adult disease hypothesis’. (Less)

Bovine Sperm Sexing Alters Sperm Morphokinetics and Subsequent Early Embryonic Development

Abstract: In artificial insemination the use of sex-sorted bovine sperm results in reduced conception, the causes of which are only partly understood. Therefore, we set out to investigate the effects of sexing on bovine sperm function and early embryonic development. Computer-assisted semen analysis (CASA) of sperm of the same bulls (n = 5), before and after sexing, demonstrated significantly reduced fast (A) and slow (B) progressively motile sperm (p < 0.05) after sexing. Sexed-sperm also revealed significantly less hyperactivated sperm (p < 0.05). As shown by time-lapse videomicroscopy of in vitro produced embryos (n = 360), embryos derived from sexed-sperm displayed significantly increased incidences of arrest at the 4-cell stage (p < 0.05). The relative risk for shrinkage/fusion of blastomeres with subsequent lysis was 1.71 times higher in the embryos derived from sexed-sperm as compared to conventional embryos (p < 0.05) resulting in significantly reduced blastocyst rates (p < 0.001). The relative risk for cleavage was 2.36 times lower in the embryos derived from sex-sorted sperm (p < 0.001). Additionally, sexed-sperm-derived embryos showed reduced survival times (hazard ratio HR = 1.54, p < 0.001) which were bull dependent (p < 0.001). However, the percentage of apoptotic cells was similar to conventional embryos. Furthermore, embryos derived from sexed-sperm were found to reach developmental stages at similar timings as conventional embryos. Our results suggest that reduced conception rates after sexing are due to altered sperm morphokinetics, decreasing the chance of sperm to reach and fertilise the oocyte, and aberrant early embryonic development.

Sperm DNA fragmentation: causes and identification

Abstract: Sperm DNA fragmentation is referred to as one of the main causes of male infertility. Failures in the protamination process, apoptosis and action of reactive oxygen species (ROS) are considered the most important causes of DNA fragmentation. Action of ROS or changes in sperm protamination would increase the susceptibility of sperm DNA to fragmentation. Routine semen analysis is unable to estimate sperm chromatin damage. Sperm DNA integrity influences sperm functional capability, therefore tests that measure sperm DNA fragmentation are important to assess fertility disorders. Actually, there is a considerable number of methods for assessing sperm DNA fragmentation and chromatin integrity, sperm chromatin stability assay (SCSA modified), sperm chromatin dispersion (SCD), comet assay, transferase dUTP nick end labelling (TUNEL); and protamine evaluation in sperm chromatin assay, such as toluidine blue, CMA3, protamine expression and evaluation of cysteine radicals. This review aims to describe the main causes of sperm DNA fragmentation and the tests commonly used to evaluate sperm DNA fragmentation.

Sperm Cohort-Specific Zinc Signature Acquisition and Capacitation-Induced Zinc Flux Regulate Sperm-Oviduct and Sperm-Zona Pellucida Interactions

Abstract: Building on our recent discovery of the zinc signature phenomenon present in boar, bull, and human spermatozoa, we have further characterized the role of zinc ions in the spermatozoa's pathway to fertilization. In boar, the zinc signature differed between the three major boar ejaculate fractions, the initial pre-rich, the sperm-rich, and the post-sperm-rich fraction. These differences set in the sperm ejaculatory sequence establish two major sperm cohorts with marked differences in their sperm capacitation progress. On the subcellular level, we show that the capacitation-induced Zn-ion efflux allows for sperm release from oviductal glycans as analyzed with the oviductal epithelium mimicking glycan binding assay. Sperm zinc efflux also activates zinc-containing enzymes and proteases involved in sperm penetration of the zona pellucida, such as the inner acrosomal membrane matrix metalloproteinase 2 (MMP2). Both MMP2 and the 26S proteasome showed severely reduced activity in the presence of zinc ions, through studies using by gel zymography and the fluorogenic substrates, respectively. In the context of the fertilization-induced oocyte zinc spark and the ensuing oocyte-issued polyspermy-blocking zinc shield, the inhibitory effect of zinc on sperm-borne enzymes may contribute to the fast block of polyspermy. Altogether, our findings establish a new paradigm on the role of zinc ions in sperm function and pave the way for the optimization of animal semen analysis, artificial insemination (AI), and human male-factor infertility diagnostics.

The association between ambient temperature and sperm quality in Wuhan, China

Abstract: Few epidemiological investigations have focused on the influence of environmental temperature on human sperm quality. Here, we evaluated the potential association between ambient temperature and human sperm quality in Wuhan, China, and examined the interactive effect of particulate matter (PM2.5) and temperature. 1780 males who had been living in Wuhan for no less than three months and received semen analysis at the Department of Reproductive Medicine in Renmin Hospital of Wuhan University between April 8, 2013 and June 30, 2015 were recruited. Daily mean meteorological data and air pollution data (PM2.5, O3 and NO2) in Wuhan between 2013 and 2015 were collected. A generalized linear model was used to explore the associations between ambient temperature and sperm quality (including sperm concentration, percentage of normal sperm morphology, and progressive motility) at 0–9, 10–14, 15–69, 70–90, and 0–90 days before semen examination, and the interaction between temperature and PM2.5. The associations between ambient temperature and sperm quality were an inverted U-shape at five exposure windows, except for a lag of 0–9 days for sperm concentration. A 1 °C increase in ambient temperature above the thresholds was associated with a 2.038 (1.292 ~ 2.783), 1.814 (1.217 ~ 2.411), 1.458 (1.138 ~ 1.777), 0.934(0.617 ~ 1.251) and 1.604 (1.258 ~ 1.951) decrease in the percentage of normal sperm morphology at lag 0–9, lag 10–14, lag 15–69, lag 70–90, and lag 0–90 days, respectively. The interaction p-values of PM2.5 and temperature were mostly less than 0.05 at five exposure windows. When ambient temperature exposure levels were above the thresholds, a 0.979 (0.659–1.299) and 3.559 (0.251 ~ 6.867) decrease in percentage of normal sperm morphology per 1 °C increase in temperature at lag 0–90 days was observed in the PM2.5 ≤ P50 group and PM2.5 > P50 group, respectively. Our results indicate that exposure to ambient temperature has a threshold effect on sperm quality, and PM2.5 enhances the effect of temperature on sperm quality when temperatures are above the threshold.

Exogenous melatonin advances the ram breeding season and increases testicular function.

Abstract: Governed by melatonin, ovine reproductive seasonality limits production outcomes due to periods of decreased reproductive efficiency. Though it is established that slow-release melatonin implants improve out of season reproductive performance in the ewe, the comprehensive effects of exogenous melatonin in the ram remain inconclusive. This study aimed to ultimately clarify the ability of exogenous melatonin to alter ram reproductive function during the non-breeding season and the subsequent breeding season. Hence, we investigated the effect of exogenous melatonin on reproductive endocrinology, semen quality and production, testicular size and libido in Merino and Poll Dorset rams (n = 31, using a subset of 18 rams for analysis of semen production and quality). Melatonin treatment resulted in elevation of melatonin in seminal plasma from 1–8 weeks post-implantation and in blood plasma at 6 weeks post-implantation. The blood plasma testosterone of implanted rams was greater than controls at both 6 weeks post-implantation and during the following breeding season. Implanted rams exhibited increased testicular size and number of sperm per ejaculate from 3–12 weeks post-implantation but did not demonstrate any change in sperm motility or morphology in response to treatment. Compared to their control counterparts, melatonin-treated Poll Dorset rams exhibited a lower percentage of sperm DNA fragmentation during several weeks of the non-breeding season. Though melatonin increased the likelihood of ejaculate collection in Poll Dorset rams (P < 0.05), libido was otherwise unaffected by treatment. Melatonin did not alter seminal plasma concentrations of inhibin A or Anti-Mullerian hormone, however, for the first time in the ram we have shown Anti-Mullerian hormone to be positively correlated with the number of sperm per ejaculate and sperm motility (r = 0.464 and 0.3242 respectively, P < 0.001), and inhibin A to be correlated to the number of sperm per ejaculate (r = 0.1786, P = 0.0135). These results indicate that melatonin is able to both systemically upregulate reproduction and act directly upon testicular function in the ram.

Predictive value of oxidative stress testing in semen for sperm DNA fragmentation assessed by sperm chromatin dispersion test

Abstract: BACKGROUND Although standard semen analysis is a cornerstone of male infertility investiation, it has significant limitations. Seminal oxidative stress and DNA damage have shown potential to better predict male fertility potential and provide improved diagnostic and management strategies. OBJECTIVE The aim of this study was to investigate whether seminal oxidation-reduction potential (ORP), a new parameter to measure oxidative stress directly, can accurately predict the percentage of sperm DNA fragmentation (SDF) and thereby serve as a surrogate marker in the evaluation of male infertility. MATERIALS AND METHODS ORP was evaluated in 3968 patients using the MiOXSYS system and SDF in 1147 patients using the Halosperm G2 test kit. Both parameters were analyzed in 1068 patients, along with seminal analysis, according to WHO guidelines 2010 (5th edition). RESULTS SDF correlated positively with seminal ORP normalized for sperm concentration (n = 1068; r = .218; P < .0001) as well as with ORP normalized for the motile sperm concentration (motORP; n = 1068; r = .387; P < .0001). MotORP can significantly (P < .0001) better predict SDF than ORP normalized for the sperm concentration (area under the curve (AUC): 0.719 vs 0.623) (specificity: 71.5%; sensitivity: 61.9%; PPV: 47.1%; NPV: 82.1%). Moreover, motORP can significantly (P < .0001) better predict (AUC: 0.826 vs 0.771) normozoospermia with high sensitivity (82.75%) and specificity (68.5%). DISCUSSION Unlike other oxidative stress (OS) markers, ORP provides a global vision of the redox balance in semen. Moreover, SDF can also be induced by mechanisms different from OS, which could explain why its predictive power was low. The higher predictive power of motORP reflects the impact of seminal ROS on motility rather than inherent DNA breaks present in immature and aborted apoptotic spermatozoa. CONCLUSION The evaluation of motORP seems a more promising parameter than ORP normalized for sperm concentration for the prediction of SDF and normozoospermia. However, even if ORP and SDF are inter-related, they measure independent sperm functions and one test cannot replace the other in the evaluation of sperm function defects.

Seminal SIRT1-oxidative stress relationship in infertile oligoasthenoteratozoospermic men with varicocele after its surgical repair.

Abstract: This work assessed seminal SIRT1-oxidative stress (OS) relationship in infertile oligoasthenoteratozoospermic (OAT) men after varicocele repair. Overall, thirty OAT men with varicocele were investigated. Inclusion criteria were infertile males (males who were unable to initiate a pregnancy within 1 year of regular unprotected intercourse), confirmed OAT and normal female factor. These cases were subjected to history taking, clinical checkup and semen analysis. In their semen, seminal SIRT1, malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were assessed. These men were subjected to varicocele surgical repair and were followed up for 3 months. Post-operatively, the mean seminal SIRT1, GPx levels showed significant increases and the mean MDA level showed significant decrease compared to the pre-operative levels linked to improved sperm parameters. The mean seminal SIRT1, GPx, MDA levels showed more significant improvement in grade III varicocele cases compared to grade II cases after surgical repair. Seminal SIRT1 levels showed significant positive correlations with sperm concentration, sperm motility, sperm normal morphology, seminal GPx levels and a significant negative correlation with seminal MDA levels. It could be concluded that seminal SIRT1 is significantly decreased in infertile OAT men with varicocele after its surgical repair linked to improved sperm parameters as well as seminal OS.

The potential role of central obesity in male infertility: body mass index versus waist to hip ratio as they relate to selected semen parameters.

Abstract: Little is known about the potential role of central obesity among men. Our first aim was to confirm what is already known from prior research, namely that both BMI and WHR are inversely associated with selected semen parameters. Our second aim was to examine the potential role of central obesity by assessing if there was a difference between BMI and WHR regarding their relationships to these selected semen parameters. In this cross-sectional study between January 2011 to January 2018, we analyzed semen samples from 1169 patients who visited an andrology clinic in Budapest for infertility reasons. Variables assessed were: body measurements (height, weight, waist circumference, and hip circumference), and the results of semen analysis (sperm concentration, total sperm count, progressive sperm motility, and normal sperm morphology). The mean height and weight were 180.6 cm and 87.3 kg, respectively – the mean BMI was 26.8. The mean waist and hip circumferences were 100.9 cm and 94.8 cm, respectively – the mean waist to hip ratio was 0.94. The mean sperm concentration, total sperm count, and percents of progressive motility and normal morphology were 48.7 M/ml, 165 million, 21.2, and 4.8%, respectively. Both BMI and WHR were significant correlates in all semen parameter regression models. When comparing the parameter estimates for BMI with those for WHR for each semen parameter, the parameter estimate for WHR was significantly lower (indicating a stronger negative association) than that for BMI for progressive motility and total sperm count, but not for normal morphology or concentration. Our study is the first to examine, using a large patient sample, the potential role of central obesity by comparing the difference between BMI and WHR as they relate to selected semen parameters. Our findings indicate a potential role of central obesity for progressive motility and total sperm count, but not for normal morphology and concentration. Despite the limitations and the exploratory nature of this study, we can conclude that our results point to a potential role of central obesity in male infertility, but this finding should be confirmed and further explored in future research. The trial was retrospectively authorized after the data collection on September 24, 2018. Registration number: SE RKEB: 169/2018.

Bariatric Surgery Impact on Reproductive Hormones, Semen Analysis, and Sperm DNA Fragmentation in Men with Severe Obesity: Prospective Study

Abstract: Growing evidence in the literature suggests that obesity is capable of altering reproductive hormone levels and male fertility. Effects on classic semen parameters and sperm DNA fragmentation (SDF), however, have not been properly established. Additionally, the impact of bariatric surgery (BS) on those parameters is still controversial. In Phase 1, 42 patients with obesity and 32 fertile controls were submitted to reproductive hormone evaluation, semen analysis, and SDF testing. In Phase 2, patients with obesity were submitted to BS or clinical follow-up and were invited to 6-month revaluation. Phase 1: Men with obesity have higher levels of estradiol, LH, and FSH and lower levels of total testosterone (TT) when compared with eutrophic fertile men. Additionally, they present worse semen parameters, with reduction in ejaculated volume and sperm concentration, worse sperm motility and morphology, and higher SDF. Phase 2: 32 patients returned to revaluation. Eighteen were submitted to BS (group S) and 14 were not submitted to any specific therapeutic regimen (group NS). In group S, TT more than doubled after surgery (294.5 to 604 ng/dL, p < 0.0001). Worsening of sperm concentration and total ejaculated sperm count were also noticed, and 2 patients became azoospermic after BS. SDF, however, improved after the procedure. No changes in the variables studied were observed in non-operated patients. In this prospective study, we have found that BS results in improvements in reproductive hormone levels and SDF after 6-month follow-up. Sperm concentration, however, reduced after the procedure.

MicroRNAs association with azoospermia, oligospermia, asthenozoospermia, and teratozoospermia: a systematic review

Abstract: Infertility is a major health problem across the world. One of the main reasons for male infertility are defects in sperm. Semen analysis is the most common test utilized to evaluate male fertility and since it suffers from multiple drawbacks, reproduction scientists have tried to find new molecular markers for detecting sperm defects. MicroRNAs (miRNAs) are small molecules in cells which take part in regulating gene expression. Various studies have confirmed miRNAs to have a role in defining multiple sperm characteristics, including sperm count, motility, and morphology. In this paper, we have systematically reviewed the role of miRNAs in infertile men with sperm defects including azoospermia, oligospermia, asthenozoospermia, and teratozoospermia. Also, we have assembled various bioinformatics tools to come up with a pipeline for predicting novel miRNAs which could possibly participate in sperm count, motility, and morphology. Also, related KEGG and GO terms for predicted miRNAs have been included in order to highlight their role in sperm function. Our study emphasizes the potential role of miRNAs in male infertility and provides a general overview for future studies aiming to find robust molecular markers for this condition.

Seminal oxidation-reduction potential and sperm DNA fragmentation index increase among infertile men with varicocele.

Abstract: Varicocele is a common cause of male infertility. It is reported that low sperm concentration, motility and morphology are indicative of increased sperm DNA fragmentation index (DFI) in men with va...

Sperm DNA fragmentation in Chinese couples with unexplained recurrent pregnancy loss

Abstract: We aimed to study the association between sperm DNA fragmentation and recurrent pregnancy loss (RPL) in the Chinese population via a retrospective observational study of Chinese couples who had experienced RPL between May 2013 and August 2018. The study population included 461 men from couples with RPL and 411 men from a control group (couples with clinical pregnancy via in vitro fertilization owing to female causes). Routine semen analysis, sperm chromatin analysis, and microscopic (high-power) morphological analysis were performed using semen samples. Semen samples were assessed for volume, sperm count, and motility. The sperm DNA fragmentation index (DFI) was calculated, and the median DFI was obtained. Men were categorized as having normal (37.8%; DFI ≤ 15.0%), moderate (33.6%; 15.0% < DFI < 30.0%), or severe (28.6%; DFI ≥ 30.0%) DNA fragmentation levels. The percentage of men with severe DNA fragmentation was significantly higher in the RPL (42.3%) group than that in the control group (13.1%), whereas the percentage of men with normal levels of DNA fragmentation was significantly lower in the RPL group (22.8%) than that in the control group (54.7%). Subsequent analysis also demonstrated that the sperm DNA fragmentation rate had a moderate reverse correlation with the sperm progressive motility rate (r = -0.47, P < 0.001) and the total motile sperm count (r = -0.31, P < 0.001). We found a positive correlation between RPL and sperm DNA fragmentation. The results suggest that increased sperm DNA damage is associated with RPL.

Metabolic syndrome and semen quality in adult population

Abstract: BACKGROUND Male obesity is suggested to impact negatively on male fertility and semen quality in numerous studies. However, previous literatures regarding health effects of the metabolic syndrome (MetS) on semen quality are rare and inconsistent. The aim of this study is to investigate the relationship between MetS and sperm parameters in a Taiwanese reproductive-age male population. METHODS A total of 8395 men who attended a private medical screening program in Taiwan from 2010 to 2016 were included in this cross-sectional study. Semen analysis was assessed in accordance with the WHO guidelines and included sperm concentration, total motility, progressive motility, and morphology. MetS was defined by the modified National Cholesterol Education Program Third Adult Treatment Panel (NCEP ATP III) criteria with the Asian cutoff for waist circumference (WC). The associations between MetS and semen analysis were examined by multivariable linear regressions. RESULTS After fully adjusting for pertinent covariables, MetS was significantly associated with a reduced percentage of sperm normal morphology. Blood pressure, WC, and serum glucose had a significantly negative association with sperm normal morphology. Individuals with an increased number of MetS components had a closer association with reduced sperm progressive motility and the percentage of normal morphology. CONCLUSION MetS and its components exhibited deleterious effects on semen quality among reproductive-age men. Further studies are warranted to explore these pathophysiologic relationship and underlying mechanisms.

Presence of The NLRP3 Inflammasome Components in Semen of Varicocele Patients.

Abstract: Background Varicocele is a common cause of male infertility with multifactorial etiology. Inflammation is a characteristic pathological event that occurs in the testis tissue following the varicocele. The aim of this study was to investigate expression of nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome components and cytokines in semen of varicocele and control subjects. Materials and methods In this case-control study, seminal plasma was collected from 32 varicocele patients (with grades 2 and 3) and 20 fertile men as control group. Semen analysis was performed in all subjects. Concentrations of interleukin-1b (IL-1b), IL-18 and caspase-1 in seminal plasma were measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis-associated speck-like protein containing a caspase activation and recruitment domain, in addition to NALP3 were identified in seminal plasma by Western blot. Statistical significance between the mean values was determined by student's t test. Results According to our data, the level of IL-1b was significantly (P=0.03) increased in the seminal plasma of varicocele patients, compared to the control subjects. We analyzed amount of IL-18 in the both groups. The level of this interleukin was markedly (P=0.002) decreased in varicocele patients. No change was observed in the level of caspase-1 in both groups. Western blot analysis revealed that apoptosis associated speck-like protein (ASC, P=0.0002) and NLRP3 (P=0.005) were significantly elevated in the semen of varicocele patients. Conclusion This study provides the first evidence of activation of NLRP3 components in semen of men with varicocele.