Associations between Sperm Epigenetic Age and Semen Parameters: An Evaluation of Clinical and Non-Clinical Cohorts.

The well-documented relationship between chronological age and the sperm methylome has allowed for the construction of epigenetic clocks that estimate the biological age of sperm based on DNA methylation, which we previously termed sperm epigenetic age (SEA). Our lab demonstrated that SEA is positively associated with the time taken to achieve pregnancy; however, its relationship with semen parameters is unknown. A total of 379 men from the Longitudinal Investigation of Fertility and Environment (LIFE) study, a non-clinical cohort, and 192 men seeking fertility treatment from the Sperm Environmental Epigenetics and Development Study (SEEDS) were included in the study. Semen analyses were conducted for both cohorts, and SEA was previously generated using a machine learning algorithm and DNA methylation array data. Association analyses were conducted via multivariable linear regression models adjusting for BMI and smoking status. We found that SEA was not associated with standard semen characteristics in SEEDS and LIFE cohorts. However, SEA was significantly associated with higher sperm head length and perimeter, the presence of pyriform and tapered sperm, and lower sperm elongation factor in the LIFE study (p < 0.05). Based on our results, SEA is mostly associated with defects in sperm head morphological factors that are less commonly evaluated during male infertility assessments. SEA shows promise to be an independent biomarker of sperm quality to assess male fecundity.

Analysis of 12 kinds of cytokines in seminal plasma by flow cytometry and their correlations with routine semen parameters.

OBJECTIVE: To investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters. METHODS: The remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated. RESULTS: The r2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1ß and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05). CONCLUSION: There are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches.

Does COVID-19 affect sperm quality in males? the answer may be yes, but only temporarily.

BACKGROUND: The Corona Virus Disease 2019 (COVID-19) pandemic has raised concerns regarding its potential impact on male reproductive health. However, the impact of COVID-19 on sperm quality remains uncertain. This retrospective study aimed to investigate the short-term and relatively long-term effects of COVID-19 infection on sperm quality. METHODS: A total of 85 males with fertility requirements, who underwent semen evaluation at Guilin People's Hospital between June 2022 and July 2023, were included in the study. Changes in semen parameters were analyzed across three specific timeframes: within 6 months before COVID-19 infection, within 3 months after COVID-19 infection, and 3-6 months after COVID-19 recovery. RESULTS: The results revealed that the sperm concentration and total sperm number were significantly lower after infection compared to before, while in the recovery period, the sperm concentration, total sperm count, progressive motility, and normal morphology significantly increased. Comparing the three periods, the most significant difference was observed in sperm concentration, which exhibited a significant decrease after infection but returned to normal levels after recovery from COVID-19. CONCLUSIONS: These findings suggest that COVID-19 may exert some impact on sperm quality, particularly evidenced by decreased sperm concentration post-infection. Fortunately, these effects on semen parameters appear to be temporary, with gradual restoration of semen parameters within 3-6 months after recovery. However, further research is needed to explore the underlying mechanisms and long-term implications of these observed changes in semen parameters.

Ambient air pollution decreased normal fertilization rate via the mediation of seminal prosaposin.

OBJECTIVE: This study focuses on the association between seminal concentration of prosaposin and ambient air pollutants and whether the association affects the normal fertilization rate in vitro fertilization (IVF) treatment. METHODS: The cohort of 323 couple participants aged 22-46 was recruited from Jan. 2013 to Jun. 2018. At enrollment, resident address information was obtained and semen parameters of male counterparts were evaluated according to WHO criteria. We used inverse distance weighting interpolation to estimate the levels of ambient pollutants (SO2, O3, CO, NO2, PM2.5, and PM10) in the surrounding area. The exposure of each participant was estimated based on the data gathered from air quality monitoring stations and their home address over various periods (0-9, 10-14, and 0-90 days) before semen sampling. The generalized linear regression model (GLM) and the Bayesian kernel machine regression (BKMR) were used to analyze the associations between pollutants, semen parameters, prosaposin, and normal fertilization. Additionally, the mediating effect of prosaposin and semen parameters on the link between pollutants and normal fertilization was investigated. RESULTS: GLM and BKMR showed exposure to ambient air pollutants was all associated with the concentration of seminal prosaposin, among them, O3 and CO were also associated with normal fertilization (-0.10, 95 %CI: -0.13, -0.06; -26.43, 95 %CI: -33.79, -19.07). Among the semen parameters, only the concentration of prosaposin and total motile sperm count (TMC) was associated with normal fertilization (0.059, 95 %CI: 0.047, 0.071; 0.016, 95 %CI: 0.012, 0.020). Mediation analysis showed that prosaposin played a stronger mediating role than TMC in the relationship between short-term exposure to O3 and fertilization (66.83 %, P<0.001 versus 3.05 %, P>0.05). CONCLUSION: Seminal plasma prosaposin showed a stronger meditating effect reflect the correlation between ambient air pollutants and normal fertilization rate than conventional semen parameters, which may be used as one of the indicators between pollution and fertilization in IVF.

Association between semen parameters and recurrent pregnancy loss: An umbrella review of meta-analyses.

AIM: Recurrent pregnancy loss (RPL) is a common clinical reproductive problem. With research advancements, an increasing number of studies have suggested that male factors play an important role in RPL. However, the evaluation results of male sperm quality in published meta-analyses are inconsistent. We aimed to summarize the evidence of the association between semen factors and RPL and evaluate the level and validity of the evidence. METHODS: We searched PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases for systematic reviews or meta-analyses to evaluate the association between male semen parameters and RPL. The methodological quality of the included meta-analyses was assessed, and data and evidence were re-synthesized and stratified using a random-effects model. RESULTS: Seven meta-analyses and nine semen parameters were included in the final analysis. The methodological quality of all publications was considered low or very low. There was highly suggestive evidence for the association between sperm DNA fragmentation (SDF), sperm progressive motility rate, and RPL (class II). The evidence level for the association between sperm concentration, normal sperm morphology, sperm deformity rate, total motility, and RPL was suggestive evidence (class III). The evidence level for the association between sperm volume and sperm count and RPL was weak (class IV). There was no significant association between sperm pH and RPL (class NS). CONCLUSIONS: Our results suggest level II evidence for the association between male SDF and RPL, while the evidence level for the association between conventional semen routine parameters and RPL was low (classes III and IV).

Effects of inactivated SARS-CoV-2 vaccination on male fertility: A retrospective cohort study.

Numerous studies have revealed severe damage to male fertility from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, raising concerns about the potential adverse impact on reproductive function of the coronavirus disease 2019 (COVID-19) vaccine developed based on the virus. Interestingly, there are several researchers who have studied the impact of the COVID-19 mRNA vaccine since then but have come up with conflicting results. As a near-ideal candidate for mass immunization programs, inactivated SARS-CoV-2 vaccine has been widely used in many countries, particularly in less wealthy nations. However, little is known about its effect on male fertility. Here, we conducted a retrospective cohort study at a single large center for reproductive medicine in China between December 2021 and August 2022. Five hundred and nineteen fertile men with no history of laboratory-confirmed COVID-19 were included and categorized into four groups based on their vaccination status: unvaccinated group (n = 168), one-dose vaccinated group (n = 8), fully vaccinated group (n = 183), and booster group (n = 160). All of them underwent a semen analysis and most had serum sex hormone levels tested. There were no significant differences in all semen parameters and sex hormone levels between the unvaccinated group and either vaccinated group. To account for possible vaccination-to-test interval-specific changes, sub-analyses were performed for two interval groups: ≤90 and >90 days. As expected, most of the semen parameters and sex hormone levels remained unchanged between the control and vaccinated groups. However, participants in vaccinated group (≤90 days) have decreased total sperm motility and increased follicle-stimulating hormone level compared with the ones in unvaccinated group. Moreover, some trends similar to those found during COVID-19 infection and recovery were observed in our study. Fortunately, all values are within the normal range. In addition, vaccinated participants reported few adverse reactions. No special medical intervention was required, and no serious adverse reactions happened. Our study suggests that inactivated SARS-CoV-2 vaccination does not impair male fertility, possibly due to the low frequency of adverse effects. This information reassures young male population who got this vaccine worldwide, and helps guide future vaccination efforts.

Comparison of semen parameters in the same patients before and after diagnosis of COVID-19.

Clinical and histopathological evidence suggest that the male reproductive system may be negatively impacted in patients with coronavirus disease (COVID-19). The objective of this study is to investigate the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on semen parameters by comparing semen analyses before and after COVID-19 diagnosis in the same patient. We retrospectively analyzed 342 semen analyses by reviewing medical records. The study included two groups of patients: (i) those who underwent two consecutive semen analyses within 6 months, one before (n = 114) and one after (n = 114) COVID-19 diagnosis, and (ii) a control group (n = 114) that was age-matched and did not receive a diagnosis of COVID-19. The study results indicated a significant decrease in semen volume, total sperm count per ejaculate, progressive motile sperm count, total motile sperm count, and normal sperm morphology after SARS-CoV-2 infection in comparison to their respective values before the infection. Subgroup analyses showed that the duration of COVID-19 diagnosis (short-term vs. long-term) did not impact the changes in semen parameters. However, fever during the COVID-19 process had a negative effect on semen parameters, particularly sperm concentration, unlike in patients without fever. In conclusion, our findings suggest that SARS-CoV-2 infection is associated with a decline in semen quality, which may potentially impact male fertility. Furthermore, it's important to note that the negative effects on semen parameters may persist in the long-term. Our results also indicate that fever during active infection could be a significant risk factor that negatively affects spermatogenesis.

Occupational factors and markers of testicular function among men attending a fertility center.

STUDY QUESTION: Are occupational factors associated with markers of testicular function among men attending a fertility center? SUMMARY ANSWER: Men working non-daytime/rotating shifts and those with physically demanding jobs have higher sperm concentration and total sperm count as well as higher estradiol and total testosterone concentrations. WHAT IS KNOWN ALREADY: Semen quality has declined during recent decades and has been negatively correlated with higher risks of common chronic diseases and mortality, highlighting its public health importance beyond fertility and reproduction. While most of the previous epidemiology literature on male fertility has focused on environmental exposures, dietary factors, and other related variables, little attention has been paid to occupational factors. STUDY DESIGN, SIZE, DURATION: This observational study included 377 men who were male partners in couples seeking infertility treatment at a fertility center, who enrolled in the Environment and Reproductive Health (EARTH) study between 2005 and 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Self-reported information on lifting/moving heavy objects, typical shift, and physical level of exertion at work was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone concentrations. Linear regression models were used to evaluate the association between occupational factors and measures of testicular function, while adjusting for covariates such as age, BMI, education, race, smoking, and abstinence time, and accounting for multiple semen samples (mean = 2, min-max = 1-9) in analyses for semen parameters. MAIN RESULTS AND THE ROLE OF CHANCE: Men had a median (interquartile range) age of 36 (33, 39) years and were predominantly Caucasian (87%). Of the men who completed the survey, 12% reported often lifting or moving heavy objects at work, 6% reported heavy physical exertion at work, and 9% reported evening or rotating shifts. Men who reported often lifting or moving heavy objects at work had 46% higher sperm concentrations (P = 0.01) and 44% higher total counts (P = 0.01) compared with men who reported never lifting or moving heavy objects at work. Similar results were found for men working in rotating shifts compared to those in day shifts, as well as for men involved in heavy levels of physical exertion compared to those with light levels at work. We also found that men involved in heavy/moderate levels of physical exertion at work had higher circulating testosterone concentrations compared to those with lighter exertion (adjusted means of 515 and 427 ng/dl, respectively, P = 0.08), and men who often moved/lifted heavy objects at work had higher estradiol concentrations, compared to those who never did (adjusted means of 36.8 and 27.1 pg/ml, respectively, P = 0.07). Men working evening/rotating shifts had 24% higher testosterone (P = 0.04) and 45% higher estradiol concentrations (P = 0.01), compared to men working day shifts. No associations were observed for ejaculated volume, total motility, morphologically normal sperm, or serum FSH and LH concentrations. LIMITATIONS, REASONS FOR CAUTION: Due to our study design which recruited men from couples seeking fertility treatment, it may not be possible to generalize our findings to men from the general population. Also, as is the case of all studies based on self-reported questionnaires, measurement error and misclassification of the exposure are potential concerns. WIDER IMPLICATIONS OF THE FINDINGS: Physically demanding jobs and rotating or evening shift occupations may be associated with higher testicular function in men measured as higher sperm concentrations and counts as well as higher serum testosterone and estradiol levels. Confirmation of these findings in other non-fertility clinic study populations is warranted. STUDY FUNDING/COMPETING INTEREST(S): NIH grants R01ES022955, R01ES009718, R01ES033651, and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and Legacy, Inc. R.A.G. works part time for Legacy, Inc., which provided funds to perform this analysis. There are no other conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

The effects of male anxiety and depression on IVF outcomes.

STUDY QUESTION: What are the effects of male anxiety and depression on IVF outcomes? SUMMARY ANSWER: Men with anxiety had lower final total motile sperm counts (fTMSC) during IVF compared to men without anxiety; however, there were no differences in live birth rates (LBRs). WHAT IS KNOWN ALREADY: Studies have shown that male anxiety causes low sperm motility, worse sperm morphology, and increased DNA fragmentation, which are known to be influential factors on fertilization rates and embryo quality during IVF. However, data are lacking on whether there is a direct association between male anxiety and/or depression and IVF outcomes. STUDY DESIGN, SIZE, DURATION: This was a survey-based, retrospective cohort study completed at a single, large hospital-affiliated fertility center with 222 respondents who underwent IVF with or without ICSI. The study was conducted between 6 September 2018 and 27 December 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Male partners of couples who underwent IVF or IVF/ICSI completed a Hospital Anxiety and Depression Scale (HADS) questionnaire. They were separated into two groups for both anxiety (HADS-A ≥ 8 or HADS-A < 8) and depression (HADS-D ≥ 8 or HADS-D < 8). Men with an elevated HADS-A or HADS-D score ≥8 were considered to have anxiety or depression, respectively. The primary outcome was LBR. Secondary outcomes included semen parameters at the time of IVF, cycle outcomes, pregnancy outcomes, and prevalence of erectile dysfunction and low libido. MAIN RESULTS AND THE ROLE OF CHANCE: There were a total of 222 respondents, of whom 22.5% had a HADS-A ≥ 8 and 6.5% had a HADS-D ≥ 8. The average age of respondents was 37.38 ± 4.90 years old. Antidepressant use was higher in the respondents with a HADS-A or HADS-D ≥ 8 (P < 0.05). Smoking use was similar between groups for both HADS-A and HADS-D (P > 0.05). When adjusted for male BMI, antidepressant use and smoking, men with a HADS-A or HADS-D ≥ 8 had similar rates of erectile dysfunction (adjusted relative risk (aRR) = 1.12 (95% CI 0.60, 2.06)) and low libido (aRR = 1.70 (95% CI 0.91, 3.15)) compared to those with a HADS-A or HADS-D ≤ 8. Men with a HADS-A ≥ 8 were more likely to have a lower fTMSC on the day of oocyte retrieval (11.8 ≥ 8 vs 20.1 < 8, adjusted ß = -0.66 (95% CI -1.22, -0.10)). However, the LBR per embryo transfer (ET) was similar between the HADS-A groups (43.2% ≥8 vs 45.1% <8, adjusted relative risk = 0.90 (95% CI 0.65, 1.06)). Although depression was uncommon in the entire cohort, the HADS-D groups were clinically similar for fTMSC (18.7 ≥ 8 vs 16.0 < 8) and LBR per ET (46.7% ≥8 vs 45.4% <8). LIMITATIONS, REASONS FOR CAUTION: Limitations of our study are the survey-based design, the lack of sperm morphology assessment at the time of IVF, our inability to fully assess the HADS-D ≥ 8 cohort due to the small sample size and the large Caucasian demographic. WIDER IMPLICATIONS OF THE FINDINGS: Couples undergoing IVF have an increased likelihood of suffering from anxiety and/or depression. There is currently a debate on whether or not men should be treated with antidepressants while attempting to conceive due to potential detrimental effects on sperm quality. Our study shows that, regardless of antidepressant use, couples with men who did or did not report anxiety and/or depression have similar LBRs when undergoing IVF. Therefore, it is important to assess both partners for mental health and to not withhold treatment due to a concern about a potential impact of antidepressants or anxiety/depression on sperm quality. STUDY FUNDING/COMPETING INTEREST(S): There was no funding to report for this study. Z.W. is a contributing author for UptoDate. S.S.S. is on the advisory board for Ferring Pharmaceuticals. E.G. was a medical consultant for Hall-Matson Esq, Teladoc, and CRICO and is a contributing author for UptoDate. The remaining authors have nothing to report. TRIAL REGISTRATION NUMBER: N/A.

Machine learning-based clustering to identify the combined effect of the DNA fragmentation index and conventional semen parameters on in vitro fertilization outcomes.

BACKGROUND: Previous studies have demonstrated an association between male sperm quality and assisted reproduction outcomes, focusing on the effects of individual parameters and reaching controversial conclusions. The WHO 6th edition manual highlights a new semen assay, the sperm DNA fragmentation index, for use after routine semen examination. However, the combined effect of the sperm DNA fragmentation index (DFI) and routine semen parameters remains largely unknown. METHODS: We assessed the combined effect of the sperm DFI and conventional semen parameters on single fresh conventional IVF outcomes for infertile couples from January 1, 2017, to December 31, 2020. IVF outcomes were obtained from the cohort database follow-up records of the Clinical Reproductive Medicine Management System of the Third Affiliated Hospital of Guangzhou Medical University. An unsupervised K-means clustering method was applied to classify participants into several coexposure pattern groups. A multivariate logistic regression model was used for statistical analysis. RESULTS: A total of 549 live births among 1258 couples occurred during the follow-up period. A linear exposure-response relationship was observed among the sperm DFI, sperm motility, and IVF outcomes. In multivariable adjustment, increased sperm DFI values and decreased sperm motility and semen concentration levels were associated with reduced odds of favourable IVF outcomes. Four coexposure patterns were generated based on the sperm DFI and the studied semen parameters, as follows: Cluster 1 (low sperm DFI values and high sperm motility and semen concentration levels), Cluster 2 (low sperm DFI values and moderate sperm motility and semen concentration levels), Cluster 3 (low sperm DFI values and low sperm motility and semen concentration levels) and Cluster 4 (high sperm DFI values and low sperm motility and semen concentration levels). Compared with those in Cluster 1, participants in Cluster 3 and Cluster 4 had lower odds of a live birth outcome, with odds ratios (95% confidence intervals [CIs]) of 0.733 (0.537, 0.998) and 0.620 (0.394, 0.967), respectively. CONCLUSIONS: When combined with low sperm DFI values, there was no significant difference between high or moderate sperm concentration and motility levels, and both were associated with favourable IVF outcomes. Low sperm parameter levels, even when DFI values remain low, may still lead to poor IVF outcomes. Participants with high sperm DFI values and low sperm motility and semen concentration levels had the worst outcomes. Our findings offer a novel perspective for exploring the joint effects of sperm DFI and routine semen parameter values.

Effect of semen collection location on semen parameters and fertility outcomes and implications for practice in the COVID-19 era: a systematic review and meta-analysis of randomized and observational studies.

OBJECTIVE: During the COVID-19 era, semen collection at infertility centers might increase the risk of spreading SARS-CoV-2. Seminal fluid collection at home is an alternative method for preventing this spread. However, there is no conclusion about the effect of home vs clinic semen collection on semen parameters and assisted reproductive technology outcomes. This systematic review and metaanalysis aimed to assess the effect of semen collection location on semen parameters and fertility outcomes. DATA SOURCES: A literature search was conducted using the major electronic databases including MEDLINE via Ovid, EMBASE, Scopus, CINAHL, OpenGrey, and CENTRAL from their inception to September 2021. CLINICALTRIALS: gov was searched to identify the ongoing registered clinical trials. STUDY ELIGIBILITY CRITERIA: We included all human randomized controlled trials and observational studies that investigated the effect of at-home semen collection vs in-clinic semen collection on semen parameters and fertility outcomes. METHODS: We pooled the mean difference and risk ratio using Review Manager software version 5.4.1 (The Cochrane Collaboration, 2022). The Grading of Recommendations, Assessment, Development and Evaluations approach was applied to assess the quality of evidence. RESULTS: Seven studies (3018 semen samples) were included. Overall, at-home semen collection results made little to no difference in semen volume (mean difference, 0.37; 95% confidence interval, -0.10 to 0.85; low-quality evidence), sperm count (mean difference, -6.02; 95% confidence interval, -27.26 to 15.22; very low-quality evidence), and sperm motility (mean difference, 0.76; 95% confidence interval, -4.39 to 5.92; very low-quality evidence) compared with in-clinic semen collection. There was no difference in fertilization rate (risk ratio, 1.00; 95% confidence interval, 0.97-1.03; very low-quality evidence) and pregnancy rate in in vitro fertilization (risk ratio, 1.04; 95% confidence interval, 0.86-1.25; very low-quality evidence). CONCLUSION: At-home semen collection had no adverse effects on semen parameters or fertility outcomes compared with in-clinic collection. However, higher-quality evidence is needed.

Effect of COVID-19 on sperm parameters: pathologic alterations and underlying mechanisms.

The rapid outbreak of the coronavirus disease 2019 (COVID-19) pandemic has brought challenges to different medical fields, especially reproductive health. To date, most studies on the effects of COVID-19 on male reproduction have some limitations. In addition, there is little research on the mechanisms underlying by which severe acute respiratory syndrome coronavirus 2 infection affects semen quality. Here, we revealed the possible impact of COVID-19 on sperm parameters and the potential mechanisms. At present, it is still controversial whether COVID-19-induced fever adversely affects sperm parameters. Severe acute respiratory syndrome coronavirus 2 can induce up-regulation of pro-inflammatory cytokine, which leads to the destruction of blood-testis barrier and impairment of spermatogenesis. Moreover, severe viral infection of the respiratory system could induce systemic oxidative stress. Sperm are highly vulnerable to it due to their limited levels of antioxidant defense, unsophisticated DNA damage detection and repair mechanisms. Our review prompt medical staff and patients to consciously check the reproductive function of COVID-19 male patients. Moreover, opening our prospective beyond the direct infection could be the key to better understand the COVID-19 short and long-term effects and provide a new idea for future treatment of patients with reproductive function injury.

Clomiphene Citrate in the Management of Infertility in Oligospermic Obese Men with Hypogonadism: Retrospective Pilot Study.

Background and Objectives: Obesity is a significant risk factor for hypogonadism and infertility that is further associated with reduced semen quality. The aim of this study is to evaluate the effect of clomiphene citrate (CC), prescribed for treating infertility, on serum testosterone and semen parameters, particularly in oligospermic obese hypogonadal men. Materials and Methods: A retrospective analysis of data related to men (n = 53) who underwent CC treatment for infertility and hypogonadism (testosterone < 300 ng/dL) was performed. Patients with obesity (BMI ≥ 30 kg/m2) and sperm concentration ≤ 15 × 106/mL were included for analysis. Results: The overall results showed that, in oligospermic obese men (n = 31), treatment with CC significantly improved baseline sperm concentration (4.5 ± 6.8 × 106/mL vs. 11.4 ± 15.5 × 106/mL, p < 0.05) and motility (31.5% ± 21.5% vs. 42.6% ± 14.7%, p < 0.05). Furthermore, subsequent examination of oligospermic hypogonadal obese men treated with CC (n = 13) revealed substantial improvements in baseline serum testosterone levels (193.8 ± 59.3 ng/dL vs. 332.7 ± 114.8 ng/dL, p < 0.05) along with an increase in sperm concentration, total motility, and normal morphology. Conclusions: The results of this retrospective study suggest that CC treatment not only improves chances of fertility outcomes by substantially improving semen parameters but also increases total serum testosterone levels in oligospermic obese men without any supplemental and expensive testosterone replacement therapy.

Impact of GLP-1 Agonists on Male Reproductive Health-A Narrative Review.

Background and objective-Obesity is a prevalent health concern that notably impairs male fertility through hormonal disruptions and other pathophysiological alterations. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can significantly reduce weight. This narrative review synthesizes the existing literature discussing the impact of glucagon-like peptide-GLP-1 RAs on the male reproductive system, particularly on the hypothalamic-pituitary-gonadal axis and spermatogenesis, highlighting their potential impact on male fertility. Material and methods-PubMed database was used for the retrieval of English-language articles published up to November 2023. This non-systematic literature review predominantly concentrates on both pre-clinical and clinical studies pertaining to GLP-1 RAs, specifically exploring their impact on male reproductive hormones and sperm parameters. Results-GLP-1 receptors have been identified within the male reproductive system according to the existing literature. While the exact mechanisms are not well understood, they appear to be involved in glucose homeostasis and energy metabolism, both vital processes in spermatogenesis. Multiple clinical trials have demonstrated the efficacy of GLP-1 RAs for promoting weight loss. Recent studies show that the use of GLP-1 RAs in obese males may enhance sperm metabolism, motility, and insulin secretion in vitro, along with positive effects on the human Sertoli cells. Recent clinical trials discussed in this review demonstrate weight loss associated with GLP-1 RAs is correlated with improvements in sperm count, concentration, and motility. However, the direct impact of GLP-1 RAs on male reproductive hormones remains unclear, necessitating further research to confirm their potential role in treating male infertility. Conclusions-This narrative review summarizes the existing literature discussing the potential impact of GLP-1 RA on the male reproductive system, emphasizing their potential therapeutic role in addressing idiopathic infertility in obese men. Despite numerous studies exploring the influence of GLP-1 and GLP-1 RAs on reproductive hormones, testicular function, and spermatogenesis, further clinical trials are crucial to validate initial evidence. Longer follow-up periods are essential to address uncertainties regarding the long-term repercussions and outcomes of GLP-1 RA use. While this holds true, the current literature suggests that GLP-1RAs show promise as a potential therapeutic approach for improving sperm parameters in obese men.

Steroid Hormones in Seminal Plasma: the Relationship with Sperm Quality.

The purpose of this study was to find out whether the seminal testosterone and/or estradiol levels could serve as prognostic criteria for normal spermatogenesis and whether they are able to characterize the sperm pathology. The study involved healthy young male volunteers (n=269); serum and seminal steroid hormones were measured; the sperm concentration, mobility, and morphology were evaluated. The results indicate that the seminal testosterone concentration is lower (p<0.05) and the seminal estradiol is higher than the corresponding parameters in the serum (p<0.05). The seminal testosterone and estradiol concentrations negatively correlated with the sperm concentration, and the seminal estradiol concentration was higher in pathozoospermic than in normospermic men (p<0.05). It is assumed that the seminal estradiol level can be an indicator of sperm quality and serve as a biological predictor of normal spermatogenesis; in addition, this parameter can be used for diagnostic purposes in patients with impaired spermatogenesis induced by excess of estrogens.

[Correlation of serum and seminal plasma HCY levels with semen parameters in men and its effect on recurrent spontaneous abortion].

OBJECTIVE: To investigate the correlation of serum and seminal plasma homocysteine (Hcy) levels with semen parameters in men and its effect on recurrent spontaneous abortion (RSA) in their spouses. METHODS: The study included 103 males subjects undergoing preconception examination in the reproduction center from March 2022 to June 2023. According to whether their spouses had a history of RSA or not, we divided their subjects into an RSA (n = 43) and a non-RSA group (NRSA, n = 60), obtained their serum and seminal plasma Hcy levels and semen parameters, and analyzed their correlation. RESULTS: The serum Hcy level was significantly correlated with the sperm DNA fragmentation index (DFI) (r = 0.316, P = 0.005), but not with the seminal plasma Hcy level (r = －0.041, P = 0.723) and other semen parameters of the subjects (P > 0.05). There was no significant correlation between seminal plasma Hcy and semen parameters (P > 0.05). The median serum Hcy was significantly higher in the RSA than in the NRSA group (18.39 ï¼»13.02, 42.84ï¼½ vs 14.65 ï¼»12.00, 18.20ï¼½ µmol/L), with statistically significant difference in the overall distribution of serum Hcy between the two groups (Ｚ=－2.20, P = 0.028), so was the median sperm DFI in the former than in the latter group (25.00% ï¼»12.50%, 37.25%ï¼½ vs 13.00% ï¼»11.00%, 18.50%ï¼½), with statistically significant difference in the overall sperm DFI distribution between the two groups (Ｚ=－2.74, P = 0.006). CONCLUSION: The serum Hcy level was positively correlated with sperm DFI, and both serum Hcy and sperm DFI were significantly elevated in men with spousal RSA, which is expected to be used as a clinical screening indicator for males with spousal RSA.

Association of peripubertal blood lead levels with reproductive hormones and semen parameters in a longitudinal cohort of Russian men.

STUDY QUESTION: Are peripubertal blood lead levels (BLLs) associated with semen parameters and serum reproductive hormones among young Russian men? SUMMARY ANSWER: We observed a suggestion of lower ejaculate volume with higher peripubertal BLL but no associations of BLLs with reproductive hormones measured throughout adolescence or with other sperm parameters measured at adulthood. WHAT IS KNOWN ALREADY: Lead is a known reproductive toxicant and endocrine disruptor. Previous literature has shown associations between high lead exposure and poorer semen quality both in occupationally and environmentally exposed men. However, to our knowledge, no longitudinal studies have explored the association of childhood lead exposure with semen parameters and reproductive hormones in young men. STUDY DESIGN, SIZE, DURATION: The Russian Children's Study is a prospective cohort study that enrolled 516 boys at age 8-9 years in 2003-2005 and followed them annually for 10 years. BLLs were measured at entry and lifestyle and health questionnaires were completed. Reproductive hormones were measured in blood samples collected every 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 516 boys enrolled, 481 had BLLs measured at entry. Of these, 453 had at least one measurement of serum testosterone, follicle stimulating hormone (FSH) or luteinizing hormone (LH) (median = 5 samples per boy) and 223 had semen samples collected ∼10 years after enrolment. Semen assessment included ejaculated volume, sperm concentration, progressive motility and total sperm count, and parameters were categorized using published andrology standards for low semen quality based on sperm count and motility. Linear mixed models were used to examine the associations of log-transformed BLLs (and BLL categories) with reproductive hormones and semen parameters, adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 223 young men with peripubertal BLLs and at least one semen sample (total samples = 438), the median (interquartile range) BLL was 3 (2, 5) µg/dl and 27% had BLL ≥5 µg/dl. Overall, 49% of the semen samples fell below reference levels for sperm count and/or motility. Men with peripubertal BLL ≥5 µg/dl had significantly lower ejaculated volume than those with BLL <5 µg/dl (mean = 2.42 vs 2.89 ml, P = 0.02), but this difference was attenuated in adjusted models (mean = 2.60 vs 2.83 ml, P = 0.25). No associations were observed between BLL measured at age 8-9 years and reproductive hormone levels or sperm parameters, including sperm concentration, total count, progressive motility and total progressive motile sperm count, or with the probability of having low semen quality based on sperm count/motility. LIMITATIONS, REASONS FOR CAUTION: Only a subset of the original cohort participated in the semen quality portion of the study, although inverse probability weighting was used to account for possible selection bias. BLLs were only measured at a single time in peripuberty, and other exposure time periods, including later or longer-term childhood exposure, may be more predictive of semen quality. The young men were also exposed to other chemical contaminants before and during pubertal development. WIDER IMPLICATIONS OF THE FINDINGS: While semen volume often receives less attention than other sperm parameters, it is an important component of male fertility. Additional prospective studies covering different exposure windows and including other seminal plasma biomarkers are warranted to explore our finding of potentially lower ejaculated volume with higher BLLs and to confirm the lack of associations for other semen parameters among youth exposed to environmental BLLs. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided through grants R01ES0014370 and P30ES000002 from the National Institute of Environmental Health Sciences, grant R82943701 from the U.S. Environmental Protection Agency, and grant 18-15-00202 from the Russian Science Foundation (O.S and Y.D.). All authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Does mRNA SARS-CoV-2 vaccine detrimentally affect male fertility, as reflected by semen analysis?

RESEARCH QUESTION: Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters? DESIGN: A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1-2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology. RESULTS: The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 â€¯×  106/ml, with only a single participant (1.3%) with a sperm count of 12.5 â€¯×  106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO. CONCLUSIONS: The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.

Women's and men's intake of omega-3 fatty acids and their food sources and assisted reproductive technology outcomes.

BACKGROUND: Long-chain omega-3 fatty acids and their food sources have garnered interest as a potential nutrient with wide-range health benefits, including fertility. OBJECTIVE: This study aimed to investigate the association of women's and men's intake of omega-3 fatty acids and omega-3 rich-foods with semen quality and outcomes of infertility treatment with assisted reproductive technologies. STUDY DESIGN: Couples presenting to the Massachusetts General Hospital were invited to enroll in a prospective cohort study (2007-2020). Male and female diets were assessed using a validated 131-item food frequency questionnaire. The primary outcomes were implantation, clinical pregnancy, and live birth probabilities. The secondary outcomes included total and clinical pregnancy loss and conventional semen parameters, for males only. We estimated the relationship between intakes of omega-3 fatty acids, nuts, and fish and the probability (95% confidence interval) of study outcomes using generalized linear mixed models to account for repeated treatment cycles per participant while simultaneously adjusting for age, body mass index, smoking status, education, dietary patterns, total energy intake, and male partner diet. RESULTS: A total of 229 couples and 410 assisted reproductive technology cycles were analyzed for primary and secondary outcomes. Of note, 343 men contributing 896 semen samples were included in analyses for semen quality measures. Women's docosahexaenoic acid + eicosapentaenoic acid intake was positively associated with live birth. The multivariable-adjusted probabilities of live birth for women in the bottom and top quartiles of eicosapentaenoic acid + docosahexaenoic acid intake were 0.36 (95% confidence interval, 0.26-0.48) and 0.54 (95% confidence interval, 0.42-0.66) (P trend=.02). Eicosapentaenoic acid + docosahexaenoic acid intake was inversely related to the risk of pregnancy loss, which was 0.53 among women in the lowest quartile of eicosapentaenoic acid + docosahexaenoic acid intake and 0.05 among women in the highest quartile (P trend=.01). Men's intake of total omega-3 fatty acids was positively related to sperm count, concentration, and motility, but unrelated to any assisted reproductive technology outcomes. Similar associations were observed when evaluating the intake of primary food sources of these fatty acids. CONCLUSION: Women's consumption of omega-3 fatty acids and omega-3-rich foods may improve the probability of conception by decreasing the risk of pregnancy loss. In addition, men's intake of omega-3 fatty acids may influence semen quality.

Sperm mitochondrial DNA copy numbers in normal and abnormal semen analysis: A systematic review and meta-analysis.

BACKGROUND: Normal mature sperm have a considerably reduced number of mitochondria, which provide the energy required for progressive sperm motility. Literature suggests that disorders of sperm motility may be linked to abnormal sperm mitochondrial number and function. OBJECTIVES: To summarise the evidence from literature regarding the association of mitochondrial DNA copy numbers and semen quality with a particular emphasis on the sperm motility. SEARCH STRATEGY: Standard methodology recommended by Cochrane. SELECTION CRITERIA: All published primary research reporting on the association between mitochondrial DNA copy numbers and semen quality. DATA COLLECTION AND ANALYSIS: Using standard methodology recommended by Cochrane we pooled results using a random effects model and the findings were reported as a standardised mean difference. MAIN RESULTS: We included ten studies. The primary outcome was sperm mitochondrial DNA copy numbers. A meta-analysis including five studies showed significantly higher mitochondrial DNA copy numbers in abnormal semen analysis compared with normal semen analysis (standardised mean difference 1.08, 95% CI 0.74-1.43). Seven studies included in the meta-analysis showed a significant negative correlation between mitochondrial DNA copy numbers and semen parameters. The quality of evidence was assessed as good to very good in 60% of studies. CONCLUSIONS: Our review demonstrates significantly higher mitochondrial DNA in human sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis. TWEETABLE ABSTRACT: There is significantly higher mitochondrial DNA in sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis.