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Andrologia Sep 2021The effect of COVID-19 on the male reproductive tract has been sparsely studied. This exploratory study was designed to determine the presence of SARS-CoV-2 in the semen...
The effect of COVID-19 on the male reproductive tract has been sparsely studied. This exploratory study was designed to determine the presence of SARS-CoV-2 in the semen of men recovering from COVID-19. A systematic literature review was also performed as per PRISMA guidelines to gather perspective on this topic. The prospective study included men 21 years and older recovering from COVID-19 with nasopharyngeal swab negative for SARS-CoV-2 or at least two weeks from the last COVID RT-PCR positivity. After clinical evaluation, freshly ejaculated semen sample by masturbation was collected in a sterile container. Samples were processed for the detection of SARS-CoV-2 by RT-PCR. Twenty-one patients were contacted for the study, 11 of which consented to provide a semen sample. The mean age of the cohort was 29.72 ± 4.52 years. None of the patients gave a history of epididymo-orchitis or sexual dysfunction at the time of assessment. None of the semen samples demonstrated SARS-CoV-2 on RT-PCR. Median duration of semen sample collection from the COVID positivity was 44 days (Range 19-59 days). Detailed literature review revealed that SARS-CoV-2 is not found in patients recovering from COVID-19 infection. We conclude that SARS-CoV-2 is not found in the semen of patients recovering from COVID-19.
Topics: Adult; COVID-19; Humans; Male; Prospective Studies; RNA, Viral; SARS-CoV-2; Semen
PubMed: 34115901
DOI: 10.1111/and.14136 -
Archivio Italiano Di Urologia,... Mar 2021The aim of this review is to summarize, following a timeline, the current knowledge regarding the effects of the Sars-cov2 virus on male fertility, researching the...
OBJECTIVES
The aim of this review is to summarize, following a timeline, the current knowledge regarding the effects of the Sars-cov2 virus on male fertility, researching the pathological and clinical results of the studies published in the last year.
METHODS
A systematic research was performed on the major international online databases; Thirty-five articles were selected.
RESULTS
A statistically significant reduction in testosterone levels and sperm quality in subjects with COVID-19 has been highlighted in several papers; however, in many cases the tests have been conducted in patients with active disease and long-term consequences are still not known. Some studies have confirmed the presence of the virus in the testis in a low percentage of patients; viral presence in sperm has only been found in one study. Testicular discomfort, which could indicate viral orchitis, was highlighted in several works, with an incidence of up to 19% percent of patients. The presence of inflammatory lymphocytic infiltrates, IgG and inflammatory cytokines have been documented in several works; pathological signs of inflammation were found in 60.9% of testicular biopsies performed in one study. The entry of the virus into the testis cells, both stromal and seminal cells appeared to be Angiotensin Converting Enzyme-2 (ACE2) mediated, as it also occurs in other tissues. DNA fragmentation, reactive oxygen species (ROS) formation, autoantibody production and ACE2 mediated effect have all been hypothesized as cause of cellular damage.
CONCLUSIONS
The results on effects of COVID-19 infection on the male reproductive system are currently insufficient as they are based on a small number of patients and therefore are often contradictory.Certain mechanisms of testicular damage are still to be assessed, as any risk categories like age, ethnicity, or others. As for the transmission of the virus through sperm, there is insufficient evidence to ensure that this cannot happen.
Topics: COVID-19; Fertility; Genitalia, Male; Humans; Infertility, Male; Male
PubMed: 33754623
DOI: 10.4081/aiua.2021.1.115 -
Archivio Italiano Di Urologia,... Mar 2021Severe Acute Respiratory Syndrome Coronavirus 2, (SARS-CoV-2) was first identified by the Chinese Centers for Disease Control and Prevention on January 8, 2020 and was...
INTRODUCTION
Severe Acute Respiratory Syndrome Coronavirus 2, (SARS-CoV-2) was first identified by the Chinese Centers for Disease Control and Prevention on January 8, 2020 and was declared as a global pandemic on March 11, 2020 by WHO. SARS-CoV-2 uses the Angiotensin-converting enzyme 2 (ACE2) receptor as an entry route, associated with the transmembrane serine protease protein (TMPRSS2), which makes the testis and particularly spermatogenesis potentially vulnerable, since this tissue has high expression of ACE2.
MATERIAL AND METHODS
We performed a systematic literature review by electronic bibliographic databases in Pubmed, Scopus and ScienceDirect up to August 2020 about the effect of SARS-CoV-2 on male sexual function and its transmission, to assess possible repercussions on sex organs and the existence of a sexual transmission path.
RESULTS
Although SARS-CoV-2 presence has not been found in testicle samples, it has been demonstrated that it causes histological changes compatible with orchitis, and sex hormone disturbances. TMPRSS2 is up-regulated in prostate cancer where it supports tumor progression, thus these patients may have a higher risk of SARS-CoV-2 infection. TMPRSS2 inhibitors may be useful for the treatment or prevention of COVID-19. No viral material has been found in blood or semen, however it has been proven to be present in stool and saliva.
CONCLUSION
The male reproductive system would be highly vulnerable and susceptible to infection by SARS-CoV-2 given the expression of the ACE2 receptor in somatic and germ cells. The seminal fluid would remain free of viral presence in patients with COVID-19. Regardless, non-genital sex could be an important source of viral transmission. In assisted reproduction techniques all necessary tests must be carried out to ensure the donor is free of the virus at the time of collection and handling of the seminal sample.
Topics: COVID-19; Humans; Male; Sexual Dysfunction, Physiological; Sexually Transmitted Diseases, Viral; Testis
PubMed: 33754609
DOI: 10.4081/aiua.2021.1.48 -
Journal of Medical Virology May 2021PubMed, Scopus, and ISI Web of Knowledge databases were searched to identify studies published up to December 2020 on the involvement of urinary and male genital systems...
PubMed, Scopus, and ISI Web of Knowledge databases were searched to identify studies published up to December 2020 on the involvement of urinary and male genital systems in COVID-19. Sixteen studies involving a total of 575 patients (538 males and 37 females) were included in this systematic review. The COVID-19 phase was available for 479 patients: 426 in the acute and 53 in the recovery phase. De novo lower urinary tract symptoms (LUTS) were observed in 43 patients and deterioration of pre-existing LUTS in 7. Bladder hemorrhage was observed in three patients and acute urinary retention in one. Regarding the male genital system, scrotal discomfort was observed in 8 patients, swelling in 14, pain in 16, and erythema in 1; low flow priapism was observed in 2 patients. Ultrasound examination identified acute orchitis in 10 patients, acute epididymitis in 7, and acute epididymo-orchitis in 16. A case-control study reported that patients with moderate COVID-19 show a significant reduction in sperm concertation, the total number of sperms per ejaculate, progressive motility, and complete motility. In contrast to what is known from the first studies on the subject, this review also includes subsequent studies that give evidence of the involvement of the lower urinary tract and male genital system in COVID-19.
Topics: COVID-19; Genitalia, Male; Humans; Male; SARS-CoV-2; Urinary Tract
PubMed: 33595134
DOI: 10.1002/jmv.26883 -
F&S Reviews Apr 2021To determine if SARS-CoV-2, which has led to the rapidly spreading COVID-19 global pandemic, is sexually transmitted. Since the putative receptor for the virus is... (Review)
Review
OBJECTIVE
To determine if SARS-CoV-2, which has led to the rapidly spreading COVID-19 global pandemic, is sexually transmitted. Since the putative receptor for the virus is identified in reproductive organs, it is also important to examine if COVID-19 may affect human fertility.
EVIDENCE REVIEW
A systematic review of English publications was conducted up to December 11, 2020 in PubMed, NIH iCite COVID-19 portfolio, Cochrane Library, and Google Scholar databases, searching for SARS-CoV-2 in the testes; seminal, prostatic, and vaginal fluids; and cervical smears. A total of 1,997 records were identified, duplicates were removed, and 1,490 records were reviewed for eligibility by examining titles and abstracts. Subsequently, 202 full-text relevant articles were reviewed by 2 independent reviewers. Forty-seven studies (literature reviews, editorials, and guidelines) were assessed qualitatively, and 23 studies that tested the male and female reproductive tracts of patients with COVID-19 for SARS-CoV-2 were quantitatively analyzed.
RESULTS
No epidemiological investigations to date have described evidence suggesting that COVID-19 is an STD. While angiotensin-converting enzyme 2 receptor is found in the reproductive organs, the lack of co-expression of the TMPRSS2 modulatory protein, required for SARS-CoV-2 cell entry, in testicular cells, sperm, or oocytes, argues against the hypothesis that gametes transmit SARS-CoV-2. Molecular detection studies of SARS-CoV-2 RNA in the male and female reproductive tracts were summarized: 98.0% (293/299) of the seminal fluids, 16/17 testicular biopsies, all 89 prostatic fluids, 98.3% (57/58) of the vaginal fluids, all 35 cervical smears, and all 16 oocyte samples tested negative for SARS-CoV-2. None of the studies confirmed sexual transmission of SARS-CoV-2. Nonetheless, COVID-19 may have detrimental effects on male reproduction by inducing orchitis and/or decreasing testosterone levels, sperm counts, and motility.
CONCLUSION
On the basis of the current worldwide published information, COVID-19 is not an STD. This information is important for clinicians, proposed guidelines for public health, U.S. Food and Drug Administration guidelines for gamete and tissue donor eligibility, and fertility treatments. Universal precautions, currently practiced worldwide, are adequate and sufficient at this time to prevent the transmission of known or unknown viral infections. We suggest that recovered patients of COVID-19, especially those with infertility, should be evaluated for their ovarian and testicular function.
PubMed: 33558864
DOI: 10.1016/j.xfnr.2021.01.002 -
Annals of Medicine and Surgery (2012) Jul 2020Acute scrotal pain is a urological emergency. While for testicular torsion and acute epididymitis clinical recommendations are well established, few is known about low... (Review)
Review
BACKGROUND
Acute scrotal pain is a urological emergency. While for testicular torsion and acute epididymitis clinical recommendations are well established, few is known about low incidence causes of acute scrotal pain. Our aim is to identify and characterise rare differential diagnoses of acute scrotal pain in order to give diagnostic and therapeutic recommendations.
MATERIALS AND METHODS
A systematic literature search was performed in PubMed, Web of Science and the Cochrane Library databases up to February 2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The systematic review protocol was registered on PROSPERO (CRD42018099472).
RESULTS
Eighty-four publications were selected for analysis. The databases provided mostly case reports, series and small studies, overall reporting on a cohort of 245 cases. Tumors, segmental testicular infarction, testicular vasculitis, pancreatitis, brucellosis, spermatic vein thrombosis, acute aortic syndrome and appendicitis were identified as rare underlying causes of acute scrotal pain and were characterised. As a result of our data analysis we were able to draw an overview of the rare differential diagnoses and diagnostic management of acute scrotal pain.
CONCLUSION
Rare differential diagnoses of acute scrotal pain are susceptible to misinterpretation as testicular torsion or acute epididymo-orchitis. Surgical management is indicated in case of suspicion for torsion or tumor. We herein present knowledge of the rare differential diagnoses and raise awareness for associated systemic disease in order to facilitate disease management and increase the potential for testicle-sparing treatment.
PubMed: 32547738
DOI: 10.1016/j.amsu.2020.05.031 -
Fertility and Sterility Jun 2020To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy.
OBJECTIVE
To summarize current understanding of the effects of novel and prior coronaviruses on human reproduction, specifically male and female gametes, and in pregnancy.
DESIGN
Review of English publications in PubMed and Embase to April 6, 2020.
METHOD(S)
Articles were screened for reports including coronavirus, reproduction, pathophysiology, and pregnancy.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
Reproductive outcomes, effects on gametes, pregnancy outcomes, and neonatal complications.
RESULT(S)
Seventy-nine reports formed the basis of the review. Coronavirus binding to cells involves the S1 domain of the spike protein to receptors present in reproductive tissues, including angiotensin-converting enzyme-2 (ACE2), CD26, Ezrin, and cyclophilins. Severe Acute Respiratory Syndrome Coronavirus 1 (SARS-CoV-1) may cause severe orchitis leading to germ cell destruction in males. Reports indicate decreased sperm concentration and motility for 72-90 days following Coronavirus Disease 2019 (COVID-19) infection. Gonadotropin-dependent expression of ACE2 was found in human ovaries, but it is unclear whether SARS-Coronavirus 2 (CoV-2) adversely affects female gametogenesis. Evidence suggests that COVID-19 infection has a lower maternal case fatality rate than SARS or Middle East respiratory syndrome (MERS), but anecdotal reports suggest that infected, asymptomatic women may develop respiratory symptoms postpartum. Coronavirus Disease 2019 infections in pregnancy are associated with preterm delivery. Postpartum neonatal transmission from mother to child has been reported.
CONCLUSION(S)
Coronavirus Disease 2019 infection may affect adversely some pregnant women and their offspring. Additional studies are needed to assess effects of SARS-CoV-2 infection on male and female fertility.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Female; Fertility; Host-Pathogen Interactions; Humans; Infertility, Female; Infertility, Male; Male; Orchitis; Pandemics; Pneumonia, Viral; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Reproduction; Risk Assessment; Risk Factors; SARS-CoV-2; Sperm Count; Sperm Motility
PubMed: 32482250
DOI: 10.1016/j.fertnstert.2020.04.025 -
Current Urology Mar 2020It is estimated that between 50 and 89% of non-gonococcal urethritis is not caused by . Associations between non-chlamydial non-gonococcal urethritis (NCNGU) with... (Review)
Review
BACKGROUND
It is estimated that between 50 and 89% of non-gonococcal urethritis is not caused by . Associations between non-chlamydial non-gonococcal urethritis (NCNGU) with balanoposthitis, epididymo-orchitis and reactive arthritis have been suggested, but evidence to support these often-theoretical relationships is sparse and further investigation is called for. Concerns over increasing antimicrobial resistance has rendered the need for clarity over this question ever more pressing in recent years. A review of the current evidence on the complications of NCNGU in men is therefore urgently warranted.
OBJECTIVE
This systematic review summarizes and evaluates the available evidence that NCNGU, whether symptomatic or asymptomatic, causes the significant complications that are already well-recognized to be associated with non-gonococcal urethritis. These significant complications are epididymo-orchitis, balanoposthitis, and sexually-acquired reactive arthritis (Reiter's syndrome) including arthritis or conjunctivitis.
SUMMARY
We conducted a systematic review and qualitative synthesis using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis framework. Five databases (PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and British Nursing Index) were searched. We included studies that measured clinical outcome after diagnosis of NCNGU in men. Bias was assessed using variations of the Newcastle-Ottawa scale. Data were extracted and entered into a pre-written data abstraction proforma. Seven peer-review studies were included. This included 2 retrospective cohort studies, 1 case series, 2 case reports and 2 cross-sectional studies. The studies described and analyzed 3 types of complication: balanitis, posthitis and/or meatitis; reactive arthritis and/or conjunctivitis; and epididymitis. All studies reported one or more complications.
KEY MESSAGES
This review identifies an important avenue for future research: while the available evidence suggests that NCNGU has the potential to cause significant complications in men, with the strongest evidence existing for balanitis, posthitis and/or meatitis, the nature and significance of these relationships is far from clear. The findings of this review suggest that prospective, adequately powered research into whether there is a causal link between NCNGU and significant clinical complications in men would be highly worthwhile. The findings of this review raise important questions about the utility of the term NCNGU in research and clinical practice.
PubMed: 32398991
DOI: 10.1159/000499266 -
BioMed Research International 2018. Brucellosis has a wide spectrum of clinical manifestations and it may last several days or even several years; however, it is often misdiagnosed and therefore may... (Meta-Analysis)
Meta-Analysis Review
. Brucellosis has a wide spectrum of clinical manifestations and it may last several days or even several years; however, it is often misdiagnosed and therefore may cause inadequate therapy and prolonged illness. Previous studies about meta-analysis of manifestations of brucellosis reported in English lacked the data published in Chinese, which did not provide details about the contact history, laboratory tests, and misdiagnosis. We undertake a meta-analysis of clinical manifestations of human brucellosis in China to identify those gaps in the literature. We have searched published articles in electronic databases up to December 2016 identified as relating to clinical features of human brucellosis in China. 68 studies were included in the analysis. The main clinical manifestations were fever, fatigue, arthralgia, and muscle pain (87%, 63%, 62%, and 56%, resp.). There are significant differences between adults and children. Rash, respiratory and cardiac complications, and orchitis/epididymitis were more prevalent in children patients. The common complications of brucellosis were hepatitis, followed by osteoarthritis, respiratory diseases, cardiovascular diseases, central nervous system dysfunction, hemophagocytic syndrome, and orchitis/epididymitis in male. In the nonpastoral areas, brucellosis has a high ratio of misdiagnosis. Our analysis provides further evidence for the accurate diagnosis, particularly in assessing severe, debilitating sequelae of this infection.
Topics: Adult; Brucellosis; Child, Preschool; China; Diagnostic Errors; Geography; Humans; Incidence
PubMed: 29850535
DOI: 10.1155/2018/5712920 -
Deutsches Arzteblatt International May 2017Infections of the genital tract are considered common causes of male fertility disorders, with a prevalence of 6-10%. Most of the affected men are asymptomatic. The... (Review)
Review
BACKGROUND
Infections of the genital tract are considered common causes of male fertility disorders, with a prevalence of 6-10%. Most of the affected men are asymptomatic. The diagnostic evaluation is based mainly on laboratory testing. Inconsistent diagnostic criteria have been applied to date, and this may explain the controversial debate about the role of infection and inflammation in the genital tract as a cause of infertility. The risk of an irreversible fertility disorder should not be underestimated.
METHODS
This review is based on pertinent publications retrieved by a selective literature search in PubMed, including guidelines from Germany and abroad and systematic review articles.
RESULTS
The main causes of inflammatory disease of the male genital tract are ascending sexually transmitted infections (STIs) and uropathogens. Chronic prostatitis has no more than a limited influence on ejaculate variables. By contrast, approximately 10% of men who have had acute epididymitis develop persistent azoospermia thereafter, and 30% have oligozoospermia. Obstruction of the excurrent ducts can ensue, as can post-infectious disturbances of spermatogenesis. The differential diagnostic evaluation includes the determination of testicular volumes, hormone concentrations, and ejaculate variables. Epidemiological data are lacking with regard to infertility after primary orchitis of infectious origin; however, up to 25% of testicular biopsies obtained from infertile men reveal focal inflammatory reactions. Multiple studies have suggested a deleterious effect of leukocytes and inflammatory mediators on sperm para - meters. On the other hand, the clinical significance of bacteriospermia remains unclear.
CONCLUSION
Any suspicion of an infectious or inflammatory disease in the male genital tract should prompt a systematic diagnostic evaluation and appropriate treatment. For patients with obstructive azoospermia, the etiology and site of the obstruction determine the surgical approach to be taken. In the near future, the elucidation of underlying pathophysiological mechanisms and the identification of suitable biomarkers may enable new strategies for conservative treatment.
Topics: Germany; Humans; Infertility, Male; Inflammation; Male; Risk Factors; Urinary Tract Infections
PubMed: 28597829
DOI: 10.3238/arztebl.2017.0339