SARS-CoV-2 infection reduces quality of sperm parameters: prospective one year follow-up study in 93 patients.

BACKGROUND: Short- and long-term implications of SARS-CoV-2 on the quality of the sperm and the results of this on fertility remain largely unknown due to lack of longitudinal studies. In this longitudinal observational cohort study, we aimed to analyse the differential effect and the impact of SARS-CoV-2 infection on different semen quality parameters. METHODS: Sperm quality was assessed using the World Health Organization criteria, DNA damage to sperm cells by quantifying the DNA fragmentation index (DFI) and the high-density stainability (HDS), IgA- and IgG-anti-sperm antibodies (ASA) were assessed with light microscopy. FINDINGS: SARS-CoV-2 infection was associated with sperm parameters that were independent of spermatogenic cycle like progressive motility, morphology, DFI and HDS, as well as spermatogenic cycle dependent parameters such as sperm concentration. Detection of IgA- and IgG-ASA allowed classification of patients in three different groups according to its sequence of appearance in sperm during post-COVID-19 follow-up. The maximum progressive motility was lowest during follow-up in patients without ASA (41.9%), intermediate in patients with only IgA-ASA (46.2%) and highest inpatients who had both IgA- and IgG-ASA (54.9%). INTERPRETATION: SARS-CoV-2 infection was associated with changes of all analysed sperm parameters to a different degree which is also observed in their return to normality and is suggestive of individual variations in the patient's immune system performance. Firstly, sperm production is decreased through temporal immune mediated arrest of active meiosis, and secondly immune induced sperm DNA damage prevents fertilization if transferred to the oocyte. Both mechanisms are temporal, and most sperm parameters return to baseline after infection. FUNDING: AML (R20-014), Femicare.

Deleterious impact of COVID-19 pandemic: Male fertility was not out of the bag.

BACKGROUND: The emergence and the spread of coronavirus disease (COVID-19) induced by the SARS-CoV-2 virus has multiple consequences in all countries around the world. Male germ cells of infertile patients which are shown to be vulnerable to many environmental conditions, could be particularly vulnerable to such an exceptional pandemic situation. We aimed through the current study to investigate the potential variations in sperm quality of infertile patients during the COVID-19 pandemic in Tunisia. METHODS: This was a cohort study including 90 infertile patients addressed to Laboratory of Cytogenetics and Reproductive Biology of Monastir Department of Maternity and Neonatology in Monastir, during the two first COVID-19 waves in Tunisia and who already have a spermogram before the pandemic period. RESULTS: We have pointed out a significant decrease in both total and progressive sperm motility during COVID-19 pandemic (p<0.0001 and p = 0.001 respectively). The percentage of morphologically abnormal spermatozoa increased from 90.99±7.38 to 93.67±4.55% during the pandemic (p< 0.001). The remaining sperm parameters were similar between the two compared timepoints. Interestingly, the univariate analysis didn't show any other associated factor to the observed impairment in sperm mobility and morphology. CONCLUSION: These data highlight the severe impact of the pandemic of the male reproductive health of hypofertile patients. Delaying infertility investigations and management after pandemic waves is recommended to hope a better gamete quality and hence to improve conception potential.

The bibliometric analysis of studies on intracytoplasmic sperm injection from 2002 to 2021.

Background: Infertility is estimated to occur in 1 out of every 4-7 couples. Intracytoplasmic sperm injection (ICSI), a type of assisted reproduction introduced in 1992, has been used across the world for almost all indications of infertility, yielding high pregnancy rates. There is a growing concern worldwide about ICSI since semen quality has declined in recent years, accompanied with the potential risks of this technology. This study aims to analyze the current status and hotspots of ICSI via a bibliometric analysis. Methods: We retrieved publications on ICSI from the Web of Science Core Collection database from 2002 to 2021. CiteSpace was used to summarize knowledge mapping of subject categories, keywords, and co-citation relationships with the strongest citation bursts. VOSviewer was used to explore co-citation and co-occurrence relationships for countries, organizations, references, authors, and keywords. Results: A total of 8271 publications were analyzed between 2002 and 2021. The major findings are as follows: the USA, China, Italy, Japan, and Belgium are the top five prolific countries. The Free University of Brussels, University of Copenhagen, University of Valencia, Ghent University, and the University of California San Francisco are the top five contributing organizations. Fertility and Sterility and Human Reproduction are the most productive and cited journals. The hotspot topics are risks of ICSI, oocyte preservation, live birth rate, infertile men, and embryo quality in the past two decades. Conclusion: This study presents a research overview of ICSI from different perspectives. These findings will contribute to a better understanding of the current status of ICSI research and provide hotspots and trends for future studies.

Recovery of sperm quality after COVID-19 disease in male adults under the influence of a micronutrient combination: A prospective study.

OBJECTIVE: This study aims to evaluate the safety and efficacy of a standard micronutrient preparation to improve semen parameters and seminal oxidative stress in adult male subjects after Coronavirus Disease 2019 (COVID-19) disease. METHODS: For this prospective pilot study, 30 males aged 20-50 years who had recently recovered from a symptomatic SARS-CoV-2 infection were recruited from June to October 2021 through a public call for participation. Participants of the study group (n = 30) received two semen analyses according to WHO criteria at an interval of 12 weeks, during which they daily received a micronutrient preparation (L-carnitine, L-arginine, coenzyme Q10, vitamin E, zinc, folic acid, glutathione and selenium). Changes in major semen variables and seminal oxidative stress levels before and after therapy were analyzed and compared to a control group (n = 10) adhering to the same inclusion criteria, including subjects who recently recovered from symptomatic COVID-19 disease without micronutrient supplementation within the 12 weeks between the two semen analyses. RESULTS: After 3 months of micronutrient supplementation the rate of normal semen analysis results in the study group increased significantly (p = 0.009) by 66.7%: from 50.0% before to 83.3% after therapy. There was a significant increase in progressive (p = 0.014) and overall motility (p = 0.05) as well as in the vitality (p = 0.0004) of semen cells after 12 weeks of micronutrient intake. In the control group there were no significant changes in any semen parameter or in the rate of normal semen analysis results over the 3-month observation period. In both groups, sperm density, morphology and oxidative stress did not improve significantly. CONCLUSIONS: Our data suggests that supplementation of certain micronutrients may be a safe way to support recovery of impaired semen parameters in male adults recovered from COVID-19 disease.

SARS-CoV-2 effects on sperm parameters: a meta-analysis study.

AIM: The rapid outbreak of the coronavirus disease 2019 (COVID-19) pandemic posed challenges across different medical fields, especially reproductive health, and gave rise to concerns regarding the effects of SARS-CoV-2 on male infertility, owing to the fact that the male reproductive system indicated to be extremely vulnerable to SARS-CoV-2 infection. Only a small number of studies have investigated the effects of SARS-CoV-2 on male reproduction, but the results are not consistent. So, we performed this meta-analysis to draw a clearer picture and evaluate the impacts of COVID-19 on male reproductive system. METHOD: We searched Embase, Web of Science, PubMed, and Google Scholar databases to identify the potentially relevant studies. Standardized mean difference (SMD) with 95% confidence interval (CI) was applied to assess the relationship. Heterogeneity testing, sensitivity analysis, and publication bias testing were also performed. RESULTS: A total of twelve studies including 7 case control investigations and 5 retrospective cohort studies were found relevant and chosen for our research. Our result showed that different sperm parameters including semen volume [SMD = - 0.27 (- 0.46, - 1.48) (p = 0.00)], sperm concentration [SMD = - 0.41 (- 0.67, - 0.15) (p = 0.002)], sperm count [SMD = - 0.30 (- 0.44, - 0.17) (p = 0.00)], sperm motility [SMD = - 0.66 (- 0.98, - 0.33) (p = 0.00)], and progressive motility [SMD = - 0.35 (- 0.61, - 0.08) (p = 0.01)] were negatively influenced by SARS-CoV-2 infection. However, sperm concentration (p = 0.07) and progressive motility (p = 0.61) were not found to be significantly associated with SARS-CoV-2 infection in case control studies. No publication bias was detected. CONCLUSION: The present study revealed the vulnerability of semen quality to SARS-CoV-2 infection. Our data showed a strong association of different sperm parameters with SARS-CoV-2 infection. The results suggested that SARS-CoV-2 infection in patients may negatively influence their fertility potential in a short-term period, but more studies are needed to decide about the long-term effects.

SARS-CoV-2 Vaccine Effects on Semen Parameters: A Systematic Review and Meta-Analysis.

OBJECTIVE: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitomizes the best preventative SARS-CoV-2 infection strategy to counteract the severe consequences of infection. However, concerns have been raised that the vaccines could have an adverse effect on sperm function and overall reproductive health. This combined systematic review and meta-analysis aimed to investigate the effects of different available SARS-CoV-2 vaccines on semen parameters. METHODS: A systematic PubMed, Scopus, Google Scholar, ScienceDirect, LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), and Scilit database literature search until mid-June 2022 was conducted. Prospective and retrospective studies were eligible. No limitation was placed on language. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were thereafter obtained. RESULTS: Upon search completion, 122 studies were identified and retrieved and 110 were excluded, while the remaining 12 independent studies evaluating the effects of coronavirus disease 2019 (COVID-19) vaccines on semen parameters were included in this review. The total number of men included was 1551, aged 22.4-48 years. Following meta-analysis, the SMD summary measure with 95% CI for each semen parameter included a concentration of 0.22 (0-0.22); Total sperm count of 0.11 (0.18-0.24); Total motility of 0.02 (0.05-0.09); Volume of 0.02 (-0.1-0.14); Vitality of 0.55 (-0.19-0.29), progressive motility of -0.43 (-0.54 to -0.32); Total motile sperm count of -0.38 (-0.44 to -0.31); And normal morphology of 0.42 (-0.54 to -0.3). In brief, the total sperm count was slightly increased post-vaccination, while progressive motility, total motile sperm count, and normal morphology were marginally reduced post-vaccination, according to the meta-analysis. CONCLUSIONS: No effects were observed regarding sperm viability and semen volume since the results of all the studies crossed the line of no effect. All seminal parameters analyzed showed a negligible or small change in relation to the vaccination effect. Furthermore, the parameters remained within the normal World Health Organization reference ranges, making the clinical significance unclear. Therefore, based on these results, it appears that vaccination does not have negative effects on semen quality. The individual study findings suggested that COVID-19 vaccines are not associated with decreased semen parameters.

Investigation of the relationship between COVID-19 disease and semen parameters in idiopathic male infertility patients.

OBJECTIVE: Recent studies have shown that there may be a deterioration in sperm parameters in patients who had recovered from COVID-19 disease. We aimed to investigate the relationship between COVID-19 disease and semen parameters in idiopathic male infertility patients. PATIENTS AND METHODS: The study was conducted among male patients who applied with infertility between June 2021 and February 2022 following the approval of the Ethics Committee. Idiopathic infertility patients who could give semen analysis were included in the study. Detailed medical history of all patients was obtained. The presence of detectable causes of infertility was defined as exclusion criteria. The patients who had COVID-19 disease history (Reverse Transcriptase-PCR or Computed Tomography findings) in the last year were divided into two groups COVID-19 (+) and COVID-19 (-). The semen samples obtained from patients after a 3 day sexual abstinence in accordance with the WHO 2021 criteria were recorded. RESULTS: A total of 42 male idiopathic infertility patients who met the criteria were included in the study. It was analyzed that both groups were similar in terms of sociodemographic characteristics, comorbidities, and habits (p>0.05). It was determined that 40.4% (n=17) had COVID-19 disease. The mean duration time after COVID-19 was 9.6 (4-17) months. Mean sperm concentration was found to be statistically significantly lower than the COVID-19 (-) group (41.59±17.4 vs. 58.8±21.9; p=0.021). Semen volume (3.05±0.7 vs. 3.32±0.6 mL; p>0.05), progressive sperm motility (34.05±20.96 vs. 43.00±16.94; p=0.12) and normal sperm morphology (3.47±1.42 vs. 3.08±1.41; p=0.41) were similar in both groups.The mean sperm concentration of the patients who recovered in the last 6 months (25.37±9.07 vs. 56.03±29.67 million/ml; p=0.013) compared to patients with >6 months after recovery (n=9) was found to be significantly lower. CONCLUSIONS: The COVID-19 disease can cause a significant decrease in sperm concentration in idiopathic infertility patients, especially in the first 6 months, and the rates of oligospermia and asthenospermia are higher.

Do the Covid-19 vaccines affect the reproductive parameters of men?-A Northern Saudi experience.

Background: The COVID-19 vaccine acceptance is a psychological behavior influenced by many factors, including fear of an adverse effect on the reproductive system. Aims: The aim of this study is to assess the COVID-19 vaccines effect on reproductive parameters among the male population of northern Saudi Arabia. Patients and Methods: We conducted a prospective cohort study among 100 volunteers who received two doses of COVID-19 vaccines. A pre- and post-vaccination blood sample was collected and analyzed for testosterone, prolactin, and follicle-stimulating hormone (FSH). Semen samples were also collected and analyzed. The Wilcoxon signed-rank test was used to compare the values between pre- and post-vaccination. Results: Of the 100 samples analyzed, there was a significant increase in progressive sperm motility after the second dose of vaccination, but the increase was within the physiological limits (pre-55.03 [42.00-61.75] vs. post-57.50 [42.25-63.00], P = 0.008). Similarly, a significant increase in serum testosterone level after the second vaccination dose was observed (pre-380.65 [301.60-485.73] vs. post-410 [318.18-505.35], P = 0.016). Conclusion: These preliminary results show that the COVID-19 vaccines do not have any adverse effect on the reproductive parameters of men. A prospective long-term follow-up study will be necessary on all WHO -approved COVID vaccines to determine their long-term effect on men's reproductive health. The future follow-up study could strengthen our findings and encourage the men who have vaccine hesitancy to take due to fear of its effect on reproductive parameters.

Validation of a SARS-CoV-2 RT-PCR assay: a requirement to evaluate viral contamination in human semen.

RESEARCH QUESTION: Is it possible to validate an accurate and reliable method for direct detection of SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) in human semen fractions? DESIGN: This qualitative improvement study aimed to provide a prospective validation of SARS-CoV-2 detection in male semen. The SARS-CoV-2 genome was detected by multiplex real-time RT-PCR on patient samples that underwent routine semen analyses for infertility at the Center for Reproductive Medicine at the University Hospital of Clermont-Ferrand. Samples comprised surplus semen collected for treatment with assisted reproductive technology. Seminal fluid and spermatozoa fractions were isolated with density gradient centrifugation and cryopreserved. Positive samples were prepared with a standard of inactivated SARS-CoV-2 particles. RESULTS: The analytical method was validated in both seminal fluid and spermatozoa fractions. In both semen fractions, the assay was repeatable, reproducible and showed high sensitivity with a limit of detection of 0.33 SARS-CoV-2 genome copies/µl. The limit of quantification was 1 copy of the SARS-CoV-2 genome/µl. The method was effective regardless of semen quality (normal and altered sperm parameters), number of spermatozoa or the cryoprotectant media used to freeze spermatozoa. CONCLUSION: This validated RT-PCR assay provided accurate and reliable screening of SARS-CoV-2 in seminal fluid and spermatozoa fractions. This method is essential to ensure protection against viral contamination in the cryobanking process.

Examining changes on testicular structure and sperm analysis of COVID-19 patients.

This study aimed to examine the testicular functions with sperm analysis of patients with COVID-19. The study was carried out with male patients aged between 18 and 50 years with positive RT-PCR test and SARS-CoV-2 virus between December 2020 and April 2021. A total of 103 participants were included in the study. The mean age was 31.24 ± 5.67 (19-45) years and the mean body mass index of the participants was 28.41 ± 4.68 kg/m2 . The patients were divided into two groups, group-1 was patients who had COVID-19, group-2 was healthy men. A semen analysis of both groups was performed, and the serum total testosterone, FSH, LH, anti-mullerian hormone and Inhibin-B tests were analysed and recorded. The testicular dimensions and testicular densities were examined by ultrasound and elastography for both groups. Comparing the patient and control groups results, this study found that the sperm count per 1 cc (p = 0.01) and total motility (p = 0.01) in group-1 was lower than in the control group, the testicular dimensions decreased (for right testis group-2 was 15.39 ± 4.78 ml versus group-1 was 12.11 ± 4.62 cm3 p < 0.01, for left testis group-2 was 16.01 ± 5.12 versus group-1 was 11.92 ± 4.78 cm3 ; p < 0.01), and the shear wave velocities were significantly higher in group-1 patients. In conclusion, sperm parameters deteriorate in men who have symptomatic disease with SARS-CoV-2 infection. The fact that the cause of this deterioration is characterized by changes at the cellular level in the testis raises doubts about the persistence of this condition.

Semen parameters and sex hormones as affected by SARS-CoV-2 infection: A systematic review.

BACKGROUND: Impaired semen quality and reproductive hormone levels were observed in patients during and after recovery from coronavirus disease 2019 (COVID-19), which raised concerns about negative effects on male fertility. Therefore, this study systematically reviews available data on semen parameters and sex hormones in patients with COVID-19. METHODS: Systematic search was performed on PubMed and Google Scholar until July 18th, 2022. We identified relevant articles that discussed the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male fertility. RESULTS: A total number of 1,684 articles were identified by using a suitable keyword search strategy. After screening, 26 articles were considered eligible for inclusion in this study. These articles included a total of 1,960 controls and 2,106 patients. When all studies were considered, the results showed that the semen parameters and sex hormone levels of patients infected with SARS-CoV-2 exhibited some significant differences compared with controls. Fortunately, these differences gradually disappear as patients recover from COVID-19. CONCLUSION: While present data show the negative effects of SARS-CoV-2 infection on male fertility, this does not appear to be long-term. Semen quality and hormone levels will gradually increase to normal as patients recover.

Effect of Coronavirus Disease (COVID-19) on Human Semen: No Evidence of Coronavirus in Semen of Patients.

Background: In December 2019, a severe acute respiratory syndrome (SARS-COV-2) was found in China. The coronavirus can impact different organs, as shown by the virus having been detected in urine, blood, oropharyngeal, and feces. This study was done to assess the impact of COVID-19 on semen analysis and to evaluate the existence of the virus in the semen of infected men. Methodology. Forty fertile men with COVID-19 were confirmed by an oropharyngeal sample. The men were divided into two groups. The semen of twenty men in the acute stage of COVID-19 and twenty men in the clinical recovery stage was analyzed, and the parameters of semen were compared between two groups. In addition, a PCR test of patients' semen was done. Result: The analysis showed that all patients' semen specimens tested negative. Semen analysis revealed no significant difference in sperm count, concentration, or motility, and the sperm of both groups was found to be normal. However, viability and morphology parameters were significantly lower in men with the acute disease. Conclusion: Coronavirus (COVID-19) was not secreted in the semen of infected men but had a negative effect on the morphology and viability of the sperm of men in the acute stage.

COVID-19 vaccination and male fertility issues: Myth busted. Is taking COVID-19 vaccine the best choice for semen protection and male fertility from risky infection hazards?

The emerging coronavirus illness (COVID-19) pandemic is posing a global health hazard, with men being at a larger risk than women. There have been few publications on the andrological consequences of COVID-19 and its vaccines so far. To assuage vaccine fear stemming from concerns about fertility, the effect of inactivated whole-virus and viral vector vaccines on semen quality was investigated in 100 Egyptian men. The safety of COVID-19 vaccines on semen parameters was validated with no significant change in pre- and post-vaccination semen analyses in either type of vaccine. Following COVID-19 vaccination, we can declare male semen parameters as unaffected.

Oxidative Stress Markers and Sperm DNA Fragmentation in Men Recovered from COVID-19.

SARS-CoV-2 negatively affects semen characteristics, impairs various biochemical processes in seminal fluid and within spermatogenic cells ultimately leading to male fertility decline. However, the distinct mechanisms, in particular, the role of oxidative stress on the consequences of coronavirus infection, have not been well investigated, which is the purpose of the present study. The standard semen parameters, its pro- and antioxidant system state, as well as the level of sperm DNA fragmentation, were assessed in 17 semen samples of men five months after the coronavirus infection and in 22 age-matched control patients. We determined that the DNA fragmentation rate negatively correlated with the period after coronavirus recovery, as well as seminal fluid superoxide dismutase activity and uric acid level. It was demonstrated that COVID-19 is not always associated with increased DNA fragmentation, allowing them to be considered as two independent factors. Thus, the most significant changes were noted in the samples of men after COVID-19 and abnormal TUNEL results: increased round cell number, decreased seminal fluid's nitrotyrosine level, and total antioxidant capacity and Zn, as well as an increased 8-hydroxy-2'-deoxyguanosine level within spermatozoa. The data obtained indicate that increased DNA fragmentation and diminished semen quality in men can be the result of an imbalance in semen pro- and antioxidant components after COVID-19.

Ability and accuracy of the smartphone-based O`VIEW-M® sperm test: Useful tool in the era of Covid-19.

Male infertility affects up to 12% of men. Although manual testing using microscope examination and computer-assisted semen analysis are standard methods of measuring sperm count and motility, these methods are limited by being laboratory based. To investigate the usefulness of a novel semen analysis device using a smartphone camera. This prospective multicenter randomized parallel design trial enrolled 200 men aged ≥19 years of age between August and December 2018. Each subject was advised to use the Smart Sperm Test for OVIEW-M at home after 5 days of abstinence. The accuracy of the OVIEW-M test relative to the in-hospital test was determined. A questionnaire was administered to assess subject likelihood of using the OVIEW-M. Measurements using standard methods and the OVIEW-M showed similar sperm counts and similar motile sperm counts. Correlation analysis showed significant correlations between sperm count and sperm motility when measured by OVIEW-M tests (r = 0.893, p < 0.01) and standard microscope examination (r = 0.883, p < 0.01). Of the subjects who responded to questionnaires, 43% regarded the results of the OVIEW-M tests as reliable and 18% as unreliable. Semen analysis with the smartphone-based application and accessories yielded results not inferior to those of laboratory tests. Men who visit the hospital for evaluation of infertility can easily perform OVIEW-M semen tests at home.

The influence of SARS-CoV-2 on semen parameters of infected infertile male in comparison with those that noninfected.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by SARS COV-2 that has spread globally, the virus can cause different pathological alterations in many organs, such as the lung, kidney, and testis. The study aimed to determine the effect of COVID-19 on the seminal fluid parameters of infected infertile males compared with those who are noninfected. METHODS: The study was performed in Al-Hussein Teaching Hospital during the period from September to November, 2021 and it involved 318 patients. The patients' info included age, address, and vaccination. The sperm count, activity, and morphology were detected using Computer-assisted semen analysis CASA (Microptic-Spain) according to the WHO manual. RESULTS: There were high significant differences between the infertile males who were infected with COVID- 19 and those who were vaccinated (X2  = 12.509, p = 0.001). A high significant relation (p < 0.001) was recorded between types of infection severity and volume of semen (p < 0.001) and nonprogress life sperm (C) (p < 0.001). While significant differences were shown in the moderate progression sperm (B) (p = 0.012), and morphology (p = 0.02), respectively. High significant differences were reported between the types of infection severity (count of the sperm, presence of pus, B, C and D), (p < 0.001), while a significant difference was shown between severity types in relation to A and morphology of the sperms (p = 0.021 and 0.015), respectively. CONCLUSION: The severity of COVID-19 has a significant impact on infertility and sperm parameters, particularly progression and sperm morphology, despite the fact that these parameters are unrelated to vaccination.