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Showing papers on "Semen published in 2021"


Journal ArticleDOI
TL;DR: This study presents an abnormal sex hormone secretion among COVID‐19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow-up, and compared the sex‐related hormone levels between 119 reproductive‐aged men with SARS‐CoV‐2 infection and 273 age‐matched control men.
Abstract: In the past several months, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated infection (coronavirus disease 2019 [COVID-19]) developed rapidly and has turned into a global pandemic Although SARS-CoV-2 mainly attacks respiratory systems, manifestations of multiple organs have been observed A great concern was raised about whether COVID-19 may affect male reproductive functions In this study, we collected semen specimens from 12 male COVID-19 patients for virus detection and semen characteristics analysis No SARS-CoV-2 was found in semen specimens Eight out of 12 patients had normal semen quality We also compared the sex-related hormone levels between 119 reproductive-aged men with SARS-CoV-2 infection and 273 age-matched control men A higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID-19 group Multiple regression analysis indicated that serum T: LH ratio was negatively associated with white blood cell counts and C-reactive protein levels in COVID-19 patients It's the first report about semen assessment and sex-hormone evaluation in reproductive-aged male COVID-19 patients Although further study is needed to clarify the reasons and underlying mechanisms, our study presents an abnormal sex hormone secretion among COVID-19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow-up

184 citations


Journal ArticleDOI
TL;DR: Recent bioinformatics evidence suggested that angiotensin‐converting enzyme 2—the main cell entry target of SARS‐CoV‐2—was predominantly enriched in spermatogonia, Leydig and Sertoli cells, which suggests the potential vulnerability of the male reproductive system to SARS-CoV-2 infection.
Abstract: Background Since SARS-CoV-2 infection was first identified in December 2019, the novel coronavirus-induced pneumonia COVID-19 spread rapidly and triggered a global pandemic Recent bioinformatics evidence suggested that angiotensin-converting enzyme 2-the main cell entry target of SARS-CoV-2-was predominantly enriched in spermatogonia, Leydig and Sertoli cells, which suggests the potential vulnerability of the male reproductive system to SARS-CoV-2 infection Objectives To identify SARS-CoV-2 RNA in seminal plasma and to determine semen characteristics from male patients in the acute and recovery phases of infection Methods From February 26 to April 2, 2020, 23 male patients with COVID-19 were recruited The clinical characteristics, laboratory findings and chest computed tomography scans of all patients were recorded in detail We also investigated semen characteristics and the viral RNA load in semen from these patients in the acute and recovery phases of SARS-CoV-2 infection using approved methods Results The age range of the 23 patients was 20-62 years All patients tested negative for SARS-CoV-2 RNA in semen specimens Among them, the virus had been cleared in 11 patients, as they tested negative The remaining 12 patients tested negative for SARS-CoV-2 RNA in semen samples, but were positive in sputum and fecal specimens The median interval from diagnosis to providing semen samples was 32 days, when total sperm counts, total motile sperm counts, and sperm morphology of the patients were within normal ranges Discussion and conclusion In this cohort of patients with a recent infection or recovering from COVID-19, there was no SARS-CoV-2 RNA detected in semen samples, which indicates the unlikely possibility of sexual transmission through semen at about 1 month after first detection

133 citations


Journal ArticleDOI
TL;DR: In this paper, a prospective cross-sectional study on 43 sexually active men who were known to have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was performed.
Abstract: Study question How is the semen quality of sexually active men following recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection? Summary answer Twenty-five percent of the men with recent SARS-Cov-2 infections and proven healing were oligo-crypto-azoospermic, despite the absence of virus RNA in semen. What is known already The presence of SARS-CoV-2 in human semen and its role in virus contagion and semen quality after recovery from coronavirus disease 2019 (COVID-19) is still unclear. So far, studies evaluating semen quality and the occurrence of SARS-CoV-2 in semen of infected or proven recovered men are scarce and included a limited number of participants. Study design, size, duration A prospective cross-sectional study on 43 sexually active men who were known to have recovered from SARS-CoV2 was performed. Four biological fluid samples, namely saliva, pre-ejaculation urine, semen and post-ejaculation urine, were tested for the SARS-CoV-2 genome. Female partners were retested if any specimen was found to be SARS-CoV-2 positive. Routine semen analysis and quantification of semen leukocytes and interleukin-8 (IL-8) levels were performed. Participants/materials, setting, methods Questionnaires including International Index of Erectile Function and Male Sexual Health Questionnaire Short Form were administered to all subjects. The occurrence of virus RNA was evaluated in all the biological fluids collected by RT-PCR. Semen parameters were evaluated according to the World Health Organization manual edition V. Semen IL-8 levels were evaluated by a two-step ELISA method. Main results and the role of chance After recovery from COVID-19, 25% of the men studied were oligo-crypto-azoospermic. Of the 11 men with semen impairment, eight were azoospermic and three were oligospermic. A total of 33 patients (76.7%) showed pathological levels of IL-8 in semen. Oligo-crypto-azoospermia was significantly related to COVID-19 severity (p Limitations, reasons for caution Although crypto-azoospermia was found in a high percentage of men who had recovered from COVID-19, clearly exceeding the percentage found in the general population, the previous semen quality of these men was unknown, nor is it known whether a recovery of testicular function was occurring. The low number of enrolled patients may limit the statistical power of study. Wider implications of the findings SARS-CoV-2 can be detected in saliva, urine and semen in a small percentage of men who recovered from COVID-19. One-quarter of men who recovered from COVID-19 demonstrated oligo-crypto-azoospermia indicating that an assessment of semen quality should be recommended for men of reproductive age who are affected by COVID-19. Study funding/competing interest(s) None. Trial registration number n/a.

115 citations


Journal ArticleDOI
TL;DR: The coronavirus disease 2019 (COVID‐19) has been spreading all over the world since December 2019, however, medical information regarding the urogenital involvement in recovered CO VID‐19 patients is limited or unknown.
Abstract: Background The coronavirus disease 2019 (COVID-19) has been spreading all over the world since December 2019. However, medical information regarding the urogenital involvement in recovered COVID-19 patients is limited or unknown. Objectives To comprehensively evaluate urogenital involvement in recovered COVID-19 patients. Materials and methods Men aged between 20 years and 50 years who were diagnosed with SARS-CoV-2 infection and recovered when the study was conducted were enrolled in our study. Demographic and clinical characteristics, and history of hospitalization were collected and analyzed. Urine, expressed prostatic secretions (EPSs), and semen samples were collected for SARS-CoV-2 RNA detection. Semen quality and hormonal profiles were analyzed. Results Among 74 male recovered COVID-19 patients, 11 (14.9%) were asymptomatic, classified into mild type, and 31 (41.9%) were classified into moderate type. The remaining patients (32/74, 43.2%) had severe pneumonia. No critically ill recovered COVID-19 patient was recruited in our cohort. The median interval between last positive pharyngeal swab RT-PCR test and semen samples collection was 80 days (IQR, 64-93). The median age was 31 years (IQR, 27-36; range, 21-49), and the median body mass index (BMI) was 24.40 (IQR, 22.55-27.30). Forty-five (61.6%) men were married, and 28 (38.4%) were unmarried. Fifty-three (72.6%) patients denied cigarette smoking, 18 (24.7%) were active smokers, and 2 of them were past smokers. The majority of our participants (53/74, 72.6%) did not consume alcohol. Fever occurred in most of the patients (75.3%), and 63 of them had abnormal chest CT images. Only one patient complained of scrotal discomfort during the course of COVID-19, which was ruled out orchitis by MRI (data not shown). A total of 205 samples were collected for SARS-CoV-2 detection (74 urine samples, 70 semen samples, and 61 EPS samples). However, viral nucleic acid was not detected in body fluids from the urogenital system. In terms of hormonal profiles, the levels of FSH, LH, testosterone, and estradiol were 5.20 [4.23] mIU/mL, 3.95 [1.63] mIU/mL, 3.65 [1.19] ng/mL, and 39.48 [12.51] pg/mL, respectively. And these values were within the normal limits. The overall semen quality of recovered COVID-19 patients was above the lower reference limit released by the WHO. While compared with healthy control, sperm concentration, total sperm count, and total motility were significantly declined. In addition, different clinical types of COVID-19 have no significant difference in semen parameters, but total sperm count showed a descending trend. Interestingly, subjects with a longer recovery time showed worse data for sperm quality. Small sample size and lacking semen parameters before the infection are the major limitations of our study. Discussion and conclusions To the best of our knowledge, it is the largest cohort study with longest follow-up for urogenital evaluation comprehensively so far. Direct urogenital involvement was not found in the recovered COVID-19 male patients. SARS-CoV-2 RNA was undetectable in the urogenital secretions, and semen quality declined slightly, while hormonal profiles remained normal. Moreover, patients with a long time (≥90 days) since recovery had lower total sperm count. Great attention and further study should be conducted and follow-up on the reproductive function in the following months.

91 citations


Journal ArticleDOI
TL;DR: In the patients before treatment, decreased serum of T, FSH and LH levels was consistent with acute patient stress due to COVID‐19, and it seems that decreased sperm morphology was associated with the acute fever.
Abstract: The study investigated whether there is a male reproductive system coronavirus disease-2019 (COVID-19) phenomenon. Thirty participants who met the inclusion criteria were enrolled in the study between April and May 2020. The participants were assigned in one of the three groups including COVID-19 patients before and after treatment, and controls. Presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the semen samples was investigated. Additionally, participant's demographics, semen parameters and serum sex hormone levels were compared between the groups. SARS-CoV-2 was not detected within the semen samples. Sperm morphology and serum sex hormone levels were significantly different between the groups. In the post hoc analysis, sperm morphology was significantly lower in the COVID-19 patients. Patients before treatment had significantly lower serum FSH, LH and T levels than controls. However, patients after treatment had similar serum FSH, LH and T levels with controls and patients before treatment. In our opinion, COVID-19 and its treatment had no specific deteriorative effect on male sexual health at a short-time period. In the patients before treatment, decreased serum of T, FSH and LH levels was consistent with acute patient stress due to COVID-19. Similarly, it seems that decreased sperm morphology was associated with the acute fever.

84 citations


Journal ArticleDOI
TL;DR: In this paper, the connection between changes in multiple seminal biomarkers and reproductive function in male patients recovering from COVID-19 infection was addressed, and the direct experimental evidence that the male reproductive system could be targeted and damaged by the infection was provided.
Abstract: The existing evidence suggests that the human reproductive system may be potentially vulnerable to COVID-19 infection. However, little is known about the virus-host interaction of COVID-19 in sperm cells. We are the first to address the connection between changes in multiple seminal biomarkers and reproductive function in male patients recovering from COVID-19. In a prospective longitudinal cohort study, seminal ACE2 activity, markers of inflammation and oxidative stress, apoptotic variables, and semen quality parameters were evaluated at 10-day intervals for a maximum follow-up time of 60 days among male patients with laboratory-confirmed COVID-19 (n = 84) and healthy controls (CON; n = 105). At the baseline and the subsequent follow-ups, the COVID-19 group revealed significantly higher levels of seminal plasma ACE2 enzymatic activity, IL-1β, IL-6, IL-8, IL-10, TGF-β, TNF-α, IFN-α, IFN-γ, ROS, caspase-8, caspase-9, and caspase-3 activity as well as lower levels of SOD activity than those in the CON group (P < 0.05). These perturbations tended to persist over time and were correlated with significant impairments in semen volume, progressive motility, sperm morphology, sperm concentration, and the number of spermatozoa. We provide the direct experimental evidence that the male reproductive system could be targeted and damaged by the COVID-19 infection. These findings go beyond our current understanding of the disease, suggesting that the reproductive function of the patients recovering from the disease should be precisely followed and evaluated to detect and avoid more serious reproductive problems in the future, as they may develop a transient state of male subfertility like those with oligoasthenoteratozoospermia.

68 citations


Journal ArticleDOI
TL;DR: The use of next‐generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health.
Abstract: BACKGROUND Male factor is attributable in up to 50% of cases of infertility. In vitro studies demonstrate that bacteria can negatively impact sperm function. The use of next-generation sequencing techniques has provided a better understanding of the human microbiome, and dysbiosis has been reported to impact health. Evidence regarding the impact of the semen microbiome on sperm function and fertility remains conflicting. MATERIALS AND METHODS A systematic search was conducted in accordance with the Preferred Reporting Items for Reviews and Meta-analysis (PRISMA) statement. The databases MEDLINE, OVID and PubMed were searched to identify English language studies related to the identification of bacteria in the semen of infertile and fertile men, between 1992 and 2019. Fifty-five observational studies were included, with 51 299 subjects. We included studies identifying bacteria using next-generation sequencing, culture or polymerase chain reaction. RESULTS The semen microbiome was rich and diverse in both fertile and infertile men. Three NGS studies reported clustering of the seminal microbiome with a predominant species. Lactobacillus and Prevotella were dominant in respective clusters. Lactobacillus was associated with improvements in semen parameters. Prevotella appeared to exert a negative effect on sperm quality. Bacteriospermia negatively impacted sperm concentration and progressive motility, and DNA fragmentation index (DFI; MD: 3.518, 95% CI: 0.907 to 6.129, P = .008). There was an increased prevalence of ureaplasma urealyticum in infertile men (OR: 2.25, 95% CI: 1.47-3.46). Ureaplasma urealyticum negatively impacted concentration and morphology. There was no difference in the prevalence of chlamydia trachomatis between fertile and infertile men and no significant impact on semen parameters. Enterococcus faecalis negatively impacted total motility, and Mycoplasma hominis negatively impacted concentration, PM and morphology. DISCUSSION AND CONCLUSIONS Ureaplasma urealyticum, Enterococcus faecalis, Mycoplasma hominis and Prevotella negatively impact semen parameters, whereas Lactobacillus appears to protect sperm quality. These findings may facilitate the development of novel therapies (eg probiotics), although the evidence regarding the impact of the seminal microbiome on fertility is inconclusive and further studies are needed to investigate this association.

63 citations


Journal ArticleDOI
TL;DR: In this paper, the role of the genitourinary and gastrointestinal microbiota in the pathogenesis of male infertility was investigated in a pilot study with 25 men with primary idiopathic infertility and 12 healthy men with proven paternity.

59 citations


Journal ArticleDOI
Yanfei He1, Jie Wang1, Junlin Ren1, Yubo Zhao1, Jing Chen1, Xuejiao Chen1 
TL;DR: In this paper, the authors reviewed the relevant publications on the possible impact of Coronavirus Disease 2019 (COVID-19) on male reproductive system and summarized the latest and most important research results so far.
Abstract: Background Angiotensin-converting enzyme II (ACE2), a receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to enter host cells, is widely expressed in testes and prostate tissues. The testis and prostate produce semen. At present, there are contradictory reports about whether SARS-CoV-2 can exist in the semen of infected men. Objective To provide a comprehensive overview of the topic of whether COVID-19 can impact on male reproductive system. Methods We reviewed the relevant publications on the possible impact of Coronavirus Disease 2019 (COVID-19) on male reproductive system and summarized the latest and most important research results so far. Literature published in English from December 2019 to January 31, 2021 regarding the existence of SARS-CoV-2 in semen, testis, and prostatic fluid and the effects of COVID-19 on male reproductive were included. Results We identified 28 related studies, only one of which reported the presence of SARS-CoV-2 in semen. The study found that the semen quality of patients with moderate infection was lower than that of patients with mild infection and healthy controls. The impaired semen quality may be related to fever and inflammation. Pathological analysis of the testis/epididymis showed that SARS-CoV-2 viral particles were positive in 10 testicular samples, and the spermatogenic function of the testis was impaired. All 94 expressed prostatic secretion (EPS) samples were negative for SARS-CoV-2 RNA. Conclusion The likelihood of SARS-CoV-2 in the semen of COVID-19 patients is very small, and semen should rarely be regarded as a carrier of SARS-CoV-2 genetic material. However, COVID-19 may cause testicular spermatogenic dysfunction via immune or inflammatory reactions. Long-term follow-up is needed for COVID-19 male patients and fetuses conceived during the father's infection period.

48 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigated the presence of viral RNA in semen of men with SARS-CoV-2 infection and evaluated its effect on semen parameters in ejaculate.
Abstract: PURPOSE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a surge of research to help better understand the breadth of possible sequelae. However, little is known regarding the impact on semen parameters and fertility potential. We sought to investigate for presence of viral RNA in semen of men with SARS-CoV-2 infection and to evaluate its effect on semen parameters in ejaculate. MATERIALS AND METHODS: We prospectively recruited thirty men diagnosed with acute SARS-CoV-2 infection using real-time reverse transcriptase polymerase chain reaction (RT-PCR) of pharyngeal swab specimens. Semen samples were collected from each individual using mailed kits. Follow-up semen samples were done with mailed kits or in-person in office setting. Semen analysis and PCR was performed after samples were received. RESULTS: Thirty semen samples from recovered men were obtained 11-64 days after testing positive for SAR-CoV-2 infection. The median duration between positive SAR-CoV-2 test and semen collection was 37 days (interquartile range [IQR]=23). The median total sperm number (TSN) in ejaculate was 12.5 million (IQR=52.1). When compared with age-matched SARS-CoV-2(-) men, TSN was lower among SARS-CoV-2(+) men (p=0.0024). Five men completed a follow-up sperm analysis (median 3 months) and had a median TSN of 18 million (IQR=21.6). No RNA was detected by means of RT-PCR in the semen in 16 samples tested. CONCLUSIONS: SARS-CoV-2 infection, though not detected in semen of recovered men, can affect TSN in ejaculate in the acute setting. Whether SARS-CoV-2 can affect spermatogenic function long-term remains to be evaluated.

47 citations


Journal ArticleDOI
TL;DR: In this paper, the consequences of COVID-19 on sperm parameters after recovery were investigated, and the results indicated an adverse but potentially reversible consequence of the coronavirus disease on sperm quality.
Abstract: The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

Journal ArticleDOI
TL;DR: Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands.
Abstract: Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines and enzymes, cholesterol, DNA and RNA-the latter often protected within epididymis- or prostate-derived extracellular vesicles. It is beyond question that the SP participates in diverse aspects of sperm function pre-fertilization events. The SP also interacts with the various compartments of the tubular genital tract, triggering changes in gene function that prepares for an eventual successful pregnancy; thus, it ultimately modulates fertility. Despite these concepts, it is imperative to remember that SP-free spermatozoa (epididymal or washed ejaculated) are still fertile, so this review shall focus on the differences between the in vivo roles of the SP following semen deposition in the female and those regarding additions of SP on spermatozoa handled for artificial reproduction, including cryopreservation, from artificial insemination to in vitro fertilization. This review attempts, including our own results on model animal species, to critically summarize the current knowledge of the reproductive roles played by SP components, particularly in our own species, which is increasingly affected by infertility. The ultimate goal is to reconcile the delicate balance between the SP molecular concentration and their concerted effects after temporal exposure in vivo. We aim to appraise the functions of the SP components, their relevance as diagnostic biomarkers and their value as eventual additives to refine reproductive strategies, including biotechnologies, in livestock models and humans.

Journal ArticleDOI
TL;DR: CoQ10 supplementation for three months could improve semen parameters, oxidative stress markers and reduce SDF in infertile men with idiopathic OA.
Abstract: PURPOSE Oxidative stress and sperm DNA fragmentation (SDF) are potential contributing factors for idiopathic male infertility. Coenzyme Q10 (CoQ10) have been reported to be effective in the treatment of idiopathic male infertility, in general, owing to its antioxidant properties. Thus, the present study intends to investigate the effects of CoQ10 therapy on semen parameters, oxidative stress markers and SDF in infertile men, specifically with idiopathic oligoasthenozoospermia (OA). MATERIALS AND METHODS In this case-control study, sixty-five infertile patients with idiopathic OA and forty fertile men (control) were included. All participants underwent semen analysis based on the World Health Organization guidelines (5th edition, 2010). Patients received CoQ10 at the dose of 200 mg/d orally for three months. Seminal plasma CoQ10, total antioxidant capacity (TAC), total reactive oxygen species (ROS), glutathione peroxidase (GPx), and SDF levels were measured in controls (baseline) and infertile patients pre- and post-CoQ10 treatment. RESULTS CoQ10 treatment for three months significantly improved sperm concentration (p<0.05), progressive motility (p<0.05), total motility (p<0.01), seminal fluid CoQ10 concentration (p<0.001), TAC (p<0.001), and GPx (p<0.001) levels in infertile men with OA. Further, ROS level (p<0.05) and SDF percentage (p<0.001) were reduced in OA patients as compared to the baseline. CoQ10 levels also correlated positively with sperm concentration (r=0.48, p=0.01) and total motility (r=0.59, p=0.003) while a negative correlation was recorded between SDF and sperm motility (r=-0.54, p=0.006). CONCLUSIONS CoQ10 supplementation for three months could improve semen parameters, oxidative stress markers and reduce SDF in infertile men with idiopathic OA.

Journal ArticleDOI
TL;DR: The recent report of SARS‐CoV‐2 presence in semen samples of six patients, including two subjects who were recovering from the clinical disease, re‐opened the discussion on possible male genital tract infection, virus shedding in semen, sexual transmission and safety of fertility treatments during the pandemic period.
Abstract: BACKGROUND: The recent report of SARS-CoV-2 presence in semen samples of six patients, including two subjects who were recovering from the clinical disease, re-opened the discussion on possible male genital tract infection, virus shedding in semen, sexual transmission and safety of fertility treatments during the pandemic period. OBJECTIVES: To explore current data and hypothesis on the possible sites of SARS-CoV-2 infection in the male reproduction system. MATERIALS AND METHODS: We reviewed the current literature to describe: a) the evidences on angiotensin-converting enzyme 2 (AC2E) and transmembrane serine protease 2 (TMPRSS2) expression in the testes, accessory glands (including prostate) and the urinary tract; b) other coronaviruses' (SARS and MERS) ability to infect these sites. RESULTS: The co-expression of both ACE2 and TMPRSS2 genes was reported in spermatogonial stem cells, elongated spermatids, in at least a small percentage of prostate hillock cells and in renal tubular cells. Testicular damage was described in autopsies of SARS patients, without evidence of the virus in the specimens. Prostate is a known infection site for MERS-CoV. SARS-CoV-2 was detected in urines. DISCUSSION: There are still al lot of open questions on the effects of SARS-CoV-2 infection on the male reproductive tract. The presence of receptors is not a proof that the testis provides a site for viral infection and it is still unknown if SARS-CoV-2 is capable to pass the blood-testis barrier. The possibility of a prostate involvement has not been investigated yet: we have no data, but theoretically it cannot be excluded. Moreover, the RNA detected in semen could have been just a residual of urinary shedding. CONCLUSION: Opening our prospective beyond the testis could be the key to better understand the possibility of a semen-related viral transmission as well as COVID19 short and long-term effects on male reproductive function.

Journal ArticleDOI
TL;DR: In this paper, a prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021, where semen samples from 75 fertile men were analyzed 1-2 months following their second dose of Pfizer's COVID-19 vaccine.
Abstract: 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 × 106/ml, with only a single participant (1.3%) with a sperm count of 12.5 × 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.

Journal ArticleDOI
TL;DR: Though several computer‐assisted sperm analysis (CASA) systems have been developed, conventional methods for semen analysis are still widely accepted in clinical practice and their diagnostic value in clinical andrology is summarized.
Abstract: Infertility is a major health issue affecting over 48.5 million couples around the world, with the male factor accounting for about 50% of the cases. The conventional semen analysis recommended by the World Health Organization (WHO) is the cornerstone in the evaluation of male fertility status. It includes macroscopic and microscopic evaluation of the ejaculate, which reflects the production of spermatozoa in the testes, the patency of the duct system and the glandular secretory activity. Evaluation of seminal fructose, sperm vitality and leucocytes (Endtz test) are useful adjuncts to semen analysis that provide information on specific clinical conditions. Though several computer-assisted sperm analysis (CASA) systems have been developed, conventional methods for semen analysis are still widely accepted in clinical practice. This review summarises the conventional techniques used in routine semen analysis and their diagnostic value in clinical andrology.

Journal ArticleDOI
TL;DR: In this article, the impact of SARS-CoV-2 infection on semen parameters in a cohort of men who had recently recovered from COVID-19 was investigated, and the results showed that sperm motility and total motile sperm count were the semen parameters which showed a significant reduction in cases with a history of mild CoV-19 infection.
Abstract: In this prospective study, we investigated the impact of SARS-CoV-2 infection on semen parameters in a cohort of men who had recently recovered from COVID-19. A total of 24 men who had recently recovered from mild COVID-19 were included in the study. Their semen parameters were normal before COVID-19 according to the World Health Organization 2010 reference values. Semen samples were collected from these participants in the recovery phases of COVID-19. To determine the effect of SARS-CoV-2 infection on semen parameters, the patients' pre-COVID-19 and post-COVID-19 semen analyses were compared. The mean age of the participants was 34.7 ± 6.4 years. The median interval between the positive nasopharyngeal swab test and obtaining semen samples was 111.5 (158) days. There was no significant difference in semen parameters before and after COVID-19 in terms of semen volume (p = .56), sperm concentration (p = .06), and progressive motility (p = .14). Total motility (p = .01) and total motile sperm count (p = .02) decreased significantly after SARS-CoV-2 infection compared to the pre-infection values. This study demonstrated that sperm motility and total motile sperm count were the semen parameters which showed a significant reduction in cases with a history of mild COVID-19.

Journal ArticleDOI
TL;DR: This is the first report to identify DEPs in seminal plasma of unilateral varicocele patients compared to fertile donors and shows that KIF5B and ANXA2 can be utilized as potential biomarkers of infertility in unilateral varICOcele patients.
Abstract: Purpose Aberrant expression of seminal plasma proteins are associated with altered homeostasis that may affect the fertilizing ability of spermatozoa. However, the precise roles of seminal exosomes on sperm function remain unclear. The objective of this study was to identify the differentially expressed proteins (DEPs) associated with varicocele-mediated infertility by comparing seminal plasma protein profile of unilateral varicocele patients with proven fertile donors. Materials and methods Semen samples were obtained from 10 proven fertile donors with normal semen parameters and 33 infertile patients with unilateral varicocele. For proteomic analysis, 5 samples from each group were pooled and run in triplicate. Key DEPs (ANXA2, TF, CD63, KIF5B, SEMG1) associated with the exosome function were selected by bioinformatic tools and validated using Western blotting. Results A total of 47 seminal plasma proteins were differentially expressed in unilateral varicocele patients compared to fertile donors. Validation of exosome-associated DEPs in unilateral varicocele patients (n=7) and fertile donors (n=7) revealed significant upregulation of ANXA2 (p=0.0016) and downregulation of KIF5B (p=0.009). The main upstream regulators of the DEPs in seminal plasma of unilateral varicocele group were androgen receptor, YB1 and NRF2. Conclusions This is the first report to identify DEPs in seminal plasma of unilateral varicocele patients compared to fertile donors. Based on the detection of DEPs associated with exosomal function, Western blotting was used to validate the presence of defective exosome machinery in seminal plasma of unilateral varicocele patients. KIF5B and ANXA2 can be utilized as potential biomarkers of infertility in unilateral varicocele patients.

Journal ArticleDOI
TL;DR: This first comparative study to address the issue of serum vitamin D3content between normozoospermic patients and those with sperm abnormalities clearly demonstrates a direct and positive relationship between serumitamin D level and overall semen quality, male reproductive potential, and testosterone levels.
Abstract: The present study aimed to evaluate the influence of serum vitamin D levels on semen quality and testosterone levels. This is a cross-sectional study conducted at Androscience, Science and Innovation Center in Andrology and High-Complex Clinical and Andrology Laboratory in Sao Paulo, Brazil, with 508 male patients, aged 18-60 years, from 2007 to 2017. Seminal parameters and serum sexual hormones were correlated with serum vitamin D concentrations in 260 men selected by strict selection criteria. Patients were divided into normozoospermic group (NZG, n = 124) and a group with seminal abnormalities (SAG, n = 136). Evaluation included complete physical examination, past medical history, habits and lifestyle factors, two complete seminal analysis with sperm functional tests, serum levels of 25-hydroxy-vitamin D3(25(OH)VD3), total and free testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), total cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR) index, and karyotype. The mean concentration of 25(OH)VD3was significantly lower in the SAG (P < 0.001) and positively correlated with all baseline seminal parameters and total testosterone levels. In addition, serum vitamin D3concentration was found to be positively correlated with sperm concentration (β= 2.103; P < 0.001), total number of spermatozoa with progressive motility (β = 2.069; P = 0.003), total number of motile spermatozoa (β = 2.571; P = 0.015), and strict morphology (β = 0.056; P = 0.006), regardless of other variables. This is the first comparative study to address the issue of serum vitamin D3content between normozoospermic patients and those with sperm abnormalities. It clearly demonstrates a direct and positive relationship between serum vitamin D level and overall semen quality, male reproductive potential, and testosterone levels.

Journal ArticleDOI
TL;DR: In this paper, the impact of exposure to multiple metals/metalloids at environmental levels on the conventional human semen-quality parameters was investigated, and the Spearman's correlation was used to investigate the correlation and interactions between blood/seminal plasma and semen metal-metalloid levels.

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TL;DR: Research is needed to understand the presence of the SARS‐CoV‐2 virus in semen, sexual transmissibility, and impact on sperm quality.
Abstract: Research is needed to understand the presence of the SARS-CoV-2 virus in semen, sexual transmissibility, and impact on sperm quality. Several studies have examined men recovering from COVID-19, but large-scale community-based testing is needed to ascertain the effects on the male reproductive tract, and the potential for prolonged transmission.

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TL;DR: In this article, the authors examined semen from men with a recent diagnosis of COVID-19 as well as those in the convalescent phase to determine if SARS-CoV-2 can be detected and its relationship, if any, with the severity of the disease.
Abstract: Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in semen and transmitted sexually is a vital question that has, thus far, been inconclusive. Prior studies, with limited numbers, have included men in various stages of infection with most in the recovery phase of the illness. The timing of test results and severity of illness has made recruiting study participants a significant challenge. Our pilot study will examine semen from men with a recent diagnosis of COVID-19 as well as those in the convalescent phase to determine if SARS-CoV-2 can be detected and its relationship, if any, with the severity of the disease. Eighteen men with a median age of 32 (range, 24-57) who tested positive for COVID-19 by rt-PCR analysis were enrolled and provided a semen sample. The study group demonstrated symptoms of COVID-19 ranging from asymptomatic to moderate and none required hospitalization. Samples were subjected to viral RNA extraction and then processed by real-time RT-PCR using the US Centers for Disease Control and Prevention (CDC, USA) panel of 2019-Novel Coronavirus (2019-nCoV) primers and probes to detect the presence of SARS-CoV-2 RNA. Length of time from diagnosis to providing a specimen ranged from 1 to 28 days (median, 6 days). Fifteen participants were symptomatic and three were asymptomatic, including recovering men, at the time of semen collection. No SARS-CoV-2 was detected in any of the semen samples. Based on these preliminary results and consistent with prior findings, we suggest SARS-CoV-2 is not present in semen during the acute or convalescent phase of COVID-19.

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TL;DR: Attention is drawn to recognise a disturbed epididymal environment as a potential cause of male infertility because the data are limited regarding critical markers of sperm maturation and studies that can identify such markers for diagnosis and managing epididcyal dysfunction are scarce.
Abstract: The diagnosis and treatment of male infertility, excluding assisted conception, are limited because of, but not limited to, poor understanding of sperm post-testicular development and storage. Many may think that sperm dysfunction is only self-contained in the sperm cell itself as a result of defective spermatogenesis. However, it can also be a consequence of inadequate epididymal maturation following disorders of the epididymis. Improper epididymal functions can disturb semen parameters and sperm DNA integrity, result in high leucocyte concentrations and high numbers of immature germ cells and debris or even cause idiopathic infertility. To date, the data are limited regarding critical markers of sperm maturation and studies that can identify such markers for diagnosis and managing epididymal dysfunction are scarce. Therefore, this article aims to draw attention to recognise a disturbed epididymal environment as a potential cause of male infertility.

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TL;DR: In this article, the effect of a lifestyle intervention on semen quality of healthy young men living in highly polluted areas of Italy was evaluated using a randomized controlled trial, where the intervention group followed a 4-mo Mediterranean diet and moderate physical activity program, at which the participants showed an improvement of semen quality parameters.
Abstract: Background Human semen quality is affected by lifestyle and environmental factors. Objective To evaluate the short-term effects of a diet and physical activity intervention on semen quality of healthy young men living in highly polluted areas of Italy. Design, setting, and participants A randomized controlled trial was conducted. Healthy young men were assigned to an intervention or a control group. Intervention A 4-mo Mediterranean diet and moderate physical activity program. Outcome measurements and statistical analysis The primary outcomes were sperm concentration, motility and morphology, concentration of round cells, and semen total antioxidant capacity. Secondary outcomes were adherence to Mediterranean diet and physical activity. All outcomes were measured twice, at the enrollment (t0) and at the end of the intervention (t4). Results and limitations A total of 263 individuals attended all visits, and underwent examinations and laboratory analyses: 137 in the intervention group and 126 in the control group. The adherence to Mediterranean diet and physical activity level increased more in the intervention group than in the control group from t0 to t4. Sperm concentration, total and progressive motility, and proportion of normal morphology cells increased in the intervention group but decreased in the control group, with statistically significant differences between the two groups at t4. The total antioxidant capacity increased in the intervention group but decreased in the control group, from t0 to t4. Conclusions Study results showed that an intervention based on Mediterranean diet and regular physical activity can determine an improvement of semen quality in healthy young men. Patient summary Our study aimed to evaluate the effect of a lifestyle intervention on semen quality of healthy young men. We assigned the 263 enrolled individuals to an intervention or a control group. The intervention group followed a 4-mo Mediterranean diet and moderate physical activity program, at the end of which the participants showed an improvement of semen quality parameters.

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TL;DR: Different methods used to evaluate sperm chromatin integrity and condensation are discussed and compared, and their inclusion in the routine evaluation of the male infertility is compared.
Abstract: Male infertility has a complex etiology, and many times, the cause is unknown. While routine semen analysis provides an overview of basic semen parameters, such as sperm concentration, motility, viability and morphology, a significant overlap of these parameters has been reported in fertile and infertile men. Moreover, conventional semen parameters do not reveal the cellular or molecular mechanisms of sperm dysfunctions leading to infertility. Therefore, sperm functional parameters, including sperm chromatin integrity, are evaluated to provide information on subtle sperm defects that are not routinely identified. Incomplete or defective sperm chromatin condensation increases the susceptibility of the sperm DNA to oxidative damage or other factors. To evaluate sperm chromatin integrity, different methods with varying degrees of diagnostic and prognostic capabilities are available. Among these assays, SCSA, TUNEL and SCD assays are most commonly used. While these assays rather evaluate the DNA directly for damages, the aniline blue and chromomycin A3 stains test for the quality of chromatin condensation. Thus, this review discusses and compares different methods used to evaluate sperm chromatin integrity and condensation, and their inclusion in the routine evaluation of the male infertility.

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TL;DR: In this article, the effect of cysteamine addition to the sheep sperm extender during cooling storage on semen quality parameters was investigated, including motility parameters, membrane integrity, viability, lipid peroxidation, and mitochondrial activity of cooled semen.
Abstract: Physical and chemical changes caused by oxidative stress in the spermatozoa membrane can reduce spermatozoa function and even lead to death. Cystamine (NH2-CH2-CH2-SH, β-mercaptoethylamine) is a natural substance that modulates the endocrine and metabolic status of animals. This substance has antioxidant and anti-apoptotic effects by inducing intracellular cysteine accumulation. Cystamine is used to treat many diseases despite its many side effects. Sheep semen is sensitive to the stressful condition of chilling storage, which restricts semen storage for artificial insemination in commercial herds. The effect of cystamine on spermatogenesis is not yet fully understood. The present study aimed to investigate the effect of cysteamine addition to the sheep sperm extender during cooling storage on semen quality parameters. Sperm samples were collected from six Edilbayevskaya rams (2 and 3 years old, 70-85 kg). The samples were diluted by extender and supplemented with different concentrations of cysteamine (0, 1, 2, 5, and 10 mM) and cooled to 4oC for 50 h. Motility parameters, membrane integrity, viability, lipid peroxidation, and mitochondrial activity of cooled semen were evaluated at 0, 25, and 50 h of cooling storage. Although cysteamine failed to affect semen quality at start time (0 hrs), extender supplementation with cysteamine improved sperm total motility, progressive motility, and mitochondrial membrane potential during storage periods (P≤0.01). Moreover, using 1 and 2 mM cysteamine functionally and viably improved (P≤0.01) sperm membrane compared to other treatments. Antioxidant potential (AOP), lipid peroxidation (LPO), and total glutathione (tGSH) (except AOP at 50 h) were significantly different after semen storage at 4 °C. Therefore, levels of AOP and tGSH were significantly increased by using cysteamine. Cysteamine supplementation (1 and 2 mM cysteamine) leads to lower levels of LPO (p<0.01) at 0, 25, and 50 h. Therefore, finding and using the best concentrations of cysteamine in a cooling extender could be effective in saving sheep semen against damages of the cooling storage process.

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TL;DR: The impact of human papillomavirus on male fertility and associated reproductive outcomes has not been clarified and further research is needed to clarify the mechanism behind the association.
Abstract: BACKGROUND The impact of human papillomavirus (HPV) on male fertility and associated reproductive outcomes has not been clarified. OBJECTIVES To elucidate the prevalence of seminal HPV infection and assess the associated effects on seminal parameters, male infertility, and reproductive outcomes. MATERIALS AND METHODS A systematic review and meta-analysis was performed in accordance with PRISMA guidelines. A search was performed using PubMed, MEDLINE, SCOPUS, and Cochrane databases. Studies published until November 2019 were included. HPV prevalence, risk of infertility, seminal parameters, and reproductive outcomes were evaluated among the general population and infertile men. RESULTS Fifty studies met the inclusion criteria. The prevalence of seminal HPV infection is significantly higher in infertile compared to the general population (20.9% versus 8.2%). A significant association between seminal HPV infection and male infertility (OR 3.30, 95% CI 1.87-5.84), even when adjusting for female infertility (OR 3.02, 95% CI = 2.11-4.33) was founded. In addition, HPV infection is related to a significant decrease in progressive motility (DM -10.35, IC -13.75, -6.96), a low sperm morphology score (DM -2.46, 95% CI -3.83, -1.08), and a significant increase in the sperm DNA fragmentation index (7.24, 95% CI 4.44.10.03) compared with HPV-negative patients. It was also observed an increased risk of miscarriage (OR 5.13, 95% CI 2.40,10.94), and a reduced chance of ongoing pregnancy (OR 0.33, IC 95% 0.13,0,82) in patients undergoing ART with seminal HPV infection. DISCUSSION Infertile men have a higher prevalence of seminal HPV infection compared to the general population, regardless of the HPV genotype detected. CONCLUSIONS HPV in semen may have an impact in sperm quality and reproductive outcomes. Additional well-designed studies are warranted to improve the quality of evidence.

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TL;DR: In this paper, the effects of curcumin supplementation in freezing medium on preventing cryo-damage in human semen were assessed and it was shown that 20 μM Curcumin supplements increased sperm motility and reduced intracellular ROS and DNA fragmentation.
Abstract: Cryopreservation causes decreased sperm fertility potential due to reactive oxygen species (ROS) production and physical-chemical damage, resulting in reduced sperm viability and motility. The addition of antioxidants to freezing media could protect sperm from cryo-damage, counteracting the harmful effects of ROS. The aim of this study was to assess the effects of curcumin supplementation in freezing medium on preventing cryo-damage in human semen. Semen samples collected from fertile men were cryopreserved in freezing medium supplemented with different concentrations of curcumin (2.5, 5, 10, and 20 μM). After freezing-thawing, sperm parameters, DNA fragmentation, intracellular ROS, and glutathione peroxidase 4 (GPX4) gene expression were evaluated. Supplementation with 20 μM curcumin in freezing medium caused increases in progressive and nonprogressive motility and significant reductions in intracellular ROS and DNA fragmentation in frozen-thawed sperm cells. Following cryopreservation, GPX4 mRNA expression was significantly upregulated in thawed semen supplemented with 20 μM curcumin compared to the control. The results showed that curcumin supplementation in freezing medium was protective against human sperm parameters and sperm DNA, counteracting oxidative damage induced by the freeze-thaw process.

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TL;DR: In this paper, the effects of COVID-19 on semen oxidative status and parameters 14 and 120 days after diagnosis in patients presenting with moderate infection (defined as respiratory symptoms, with or without fever, with Spo2 90% and lung involvement <50%).
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus causing coronavirus disease 2019 (COVID-19). Because COVID-19 is a multisystem infection, there are some concerns regarding its possible effects on male fertility. This study aimed to investigate the effects of COVID-19 on semen oxidative status and parameters 14 and 120 days after diagnosis in patients presenting with moderate infection (defined as respiratory symptoms, with or without fever, with Spo2 90% and lung involvement <50%). Semen samples were obtained from 20 participants at two time points: the first sample on Day 14 and the second on Day 120 after diagnosis. Semen parameters (sperm concentration, motility, morphology, and viability) were evaluated, as were levels of seminal reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidant capacity (TAC) and sperm DNA fragmentation. Semen parameters, including sperm motility and DNA integrity, improved at 120 days after the COVID-19 diagnosis relative to values at 14 days. In addition, ROS and MDA levels were significantly reduced in patients 120 days after infection, and TAC increased at 120 days compared with 14 days (during the acute stage of infection). In conclusion, the present study shows that the detrimental effects of COVID-19 on sperm properties caused by oxidative stress decrease up to Day 120 after diagnosis.

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TL;DR: In vitro effect of zinc oxide (ZnO) nanoparticles on rabbit spermatozoa motility and viability parameters are evaluated to show the negative dose–dependent effect.