SARS-CoV-2 effects on male reproduction: should men be worried??

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has placed a global challenge on both healthcare and society. So far, studies have shown that men are more prone to become ill than women and are more likely to die compared to female patients. Higher rates of positive cases and fatality in men than women have drawn the attention of scientists to investigate the possible impacts of SARS-CoV-2 on the male reproductive system. In this review, we tried to summarise so far findings on the effect of the SARS-CoV-2 on the male reproductive function to further assess the potential risks of this novel coronavirus on male reproductive health.

SARS-CoV-2 infection (COVID-19) and male fertility: Something we should be worried about?

As of 2021, roughly 5 million deaths were linked to SARS-CoV-2 infection based on World Health Organization estimates. The pandemic takes its staggering death toll, severely affecting the healthcare systems and leading to detrimental implications globally. While the severe impact on the respiratory system is well-established, the exact effect on male reproduction is still largely uncharted territory. When it comes to gender, men appear more vulnerable compared to women. Increasing evidence suggests that COVID-19 adversely affects spermatogenesis and hormonal balance in diverse ways. Semen parameters seem to be compromised at least temporarily, while long-term worsening needs to be clarified in studies with extended follow-up. For the time being, no data support the adverse effect of COVID-19 vaccines on a male's reproductive health. In the present article, we examine the available literature and briefly discuss the impact of the virus on reproduction and fertility. We further provide a comprehensive overview of the current status of vaccination and its potential effect on male fertility. Ultimately, we address the need for future well-designed large-scale trials before drawing definite conclusions on the exact impact of the virus on a male's fecundity.

Mild Androgen Insensitivity Syndrome presenting in male with infertility and sexual difficulties

Androgen insensitivity syndrome has a wide spectrum of presentations. It results from a mutation in androgen receptor (AR) gene. It ranges from mild androgen insensitivity syndrome (MAIS) which is the mildest form to complete androgen insensitivity syndrome (CAIS). In case of MAIS, the abnormality that can be observed appears to be male infertility and sexual difficulties including premature ejaculation and erectile dysfunction. In this case report, we discuss a case of MAIS in a 37-year-old male who presented with infertility, premature ejaculation, and secondary erectile dysfunction.Copyright © 2023, Ibn Sina Trust. All rights reserved.

Misinformation on Tiktok About the Effect of Covid-19 Infections and Vaccinations on Male Fertility

INTRODUCTION AND OBJECTIVE: The effect of the SARSCoV- 2 infection and vaccine on male fertility has been a cause of controversy. Studies have found that while COVID-19 disease can be associated with decreased sperm counts and quality, the vaccine is not. Despite evidence about the lack of association between the COVID-19 vaccine and male fertility, social media platforms, including TikTok, continue to spread misleading information. Objective(s): To identify how TikTok contributes to misinformation regarding the COVID-19 virus, vaccination, and male infertility. METHOD(S): After excluding unrelated videos, 58 videos using the terms #covidvaccine and #malefertility were identified on Tiktok from January 1 to December 31, 2021. Videos were reviewed by five independent researchers. Information collected included video publication date, length, views, likes, comments, presence of US certified medical professional, demographic details, scientific article cited, belief held on COVID-19 vaccine, infection and infertility, modified DISCERN score and Patient Materials Assessment Tool (PEMAT). The PEMAT score evaluated 17 items regarding understandability and actionability. The modified DISCERN based reliability score ranked quality from 1=poor, to 5=excellent. Data was analyzed using SPSS statistics software v24. RESULT(S): The average video was 51 seconds long, received 34,678 views, 3,301 likes, and 160 comments. A majority of videos featured a medical professional (67.2%). Most videos were of the opinion that the COVID-19 infection causes infertility in men (48.3%) but not the vaccine (37.9%). Few videos believed that the vaccine was responsible for male infertility (6.9%). The average DISCERN score for the 58 videos was 2.93, PEMAT Understandability score was 76.1%, and PEMAT Actionability score was 25.7%. With the presence of a certified US Medical Professional in the TikTok video, the average DISCERN score (2.00 vs. 3.38, p=.001), PEMAT Understandability Score (67.68 vs. 80.26, p=.015), and PEMAT Actionability Score (13.16 vs. 31.82, p=.024) increased significantly. Videos with medical professionals present had a lower average number of views (31,996 vs. 40179, p=.691), fewer likes (1,902 vs. 6,173, p=.290), and fewer comments (150 vs. 182, p=.737), but none of these differences were statistically significant. CONCLUSION(S): This study demonstrates that TikTok videos endorsing misinformation are popularly viewed. Among all the misinformation in social media, it is reassuring to see that there are medical professionals interested in promoting medically accurate information.

Male fertility: summary overview of the publications January - March 2022.

The article presents an overview of the most significant publications on the topic of male infertility. The main selection criteria were the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 papers published in the first quarter (January - March) of 2022 was compiled. The review includes articles on the following issues: the role of coronavirus infection in male infertility, the effectiveness of aromatase inhibitors in infertile men, the effect of assisted reproductive technologies on the reproductive health of descendants, recurrent miscarriage, the effect of antibiotic therapy on the DNA fragmentation index, the role of antisperm antibodies in male infertility, the incidence of idiopathic male infertility, the Sixth Edition WHO guidelines for the ejaculate processing, as well as the relationship of depression with male infertility.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Cholesterol-Amino-Phosphate (CAP) Derived Lipid Nanoparticles for Delivery of Self-Amplifying RNA and Restoration of Spermatogenesis in Infertile Mice.

Male infertility caused by genetic mutations is an important type of infertility. Currently, there is no reliable method in the clinic to address this medical need. The emergence of mRNA therapy provides a possible strategy for restoring mutant genes in the reproductive system. However, effective delivery of mRNA to spermatocytes remains a formidable challenge. Here a series of cholesterol-amino-phosphate (CAP) lipids are reported by integrating three bioactive moieties into a geometric structure, which is favorable for mRNA delivery. The results demonstrate that CAP-derived lipid nanoparticles (CAP LNPs) can deliver RNA including traditional mRNA and self-amplifying RNA (saRNA) encoding DNA Meiotic Recombinase 1 (Dmc1) protein in spermatocytes and treat male infertility caused by the Dmc1 gene mutation. Notably, the delivery efficiency of CAP LNPs is significantly higher than that of the MC3 and ALC-0315 LNPs, which is consistent with the design of CAP molecules. More importantly, a single injection of CAP LNPs-saRNA can produce Dmc1 protein for an extended period, which restores the spermatogenesis in the Dmc1 gene knockout mouse model. Overall, this study proves the concept of LNPs for the delivery of mRNA to spermatocytes, which provides a unique method to probe male infertility caused by the genetic mutation.

Effects of mild/asymptomatic COVID-19 on semen parameters and sex-related hormone levels in men: a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) has yet to be proven to alter male reproductive function, particularly in the majority of mild/asymptomatic patients. The purpose of this study was to explore whether mild/asymptomatic COVID-19 affects semen quality and sex-related hormone levels. To find suitable comparative studies, a systematic review and meta-analysis was done up to January 22, 2022, by using multiple databases (Web of Science, PubMed, and Embase). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify and choose the studies. Meta-analysis was used to examine the semen parameters and sex-related hormones of mild/asymptomatic COVID-19 patients before and after infection. The effects of semen collection time, fever, and intensity of verification on semen following infection were also investigated. A total of 13 studies (n = 770) were included in the analysis, including three case-control studies, six pre-post studies, and four single-arm studies. A meta-analysis of five pre-post studies showed that after infection with COVID-19, sperm concentration (I2 = 0; P = 0.003), total sperm count (I2 = 46.3%; P = 0.043), progressive motility (I2 = 50.0%; P < 0.001), total sperm motility (I2 = 76.1%; P = 0.047), and normal sperm morphology (I2 = 0; P = 0.001) decreased. Simultaneously, a systematic review of 13 studies found a significant relationship between semen collection time after infection, inflammation severity, and semen parameter values, with fever having only bearing on semen concentration. Furthermore, there was no significant difference in sex-related hormone levels before and after infection in mild/asymptomatic patients. Mild/asymptomatic COVID-19 infection had a significant effect on semen quality in the short term. It is recommended to avoid initiating a pregnancy during this period of time.

SARS-CoV-2, fertility-related autoantibodies and reproductive injury

As the critical risk of the short-term SARS-CoV-2 infection is severe lung inflammation with a hypercoagulative state that could escalate to multiorgan failure, many possible long-term implications are still under investigation. This article will review the most recent findings related to the potential contribution of SARS-CoV-2 to male infertility. Viral-induced male infertility has been studied widely and in much detail in the past. Numerous viral infections have a well-known ability to induce orchitis, resulting in impaired testicular functions and male infertility. SARS-CoV-2 may be an additional virus that is related to male infertility for several reasons that will be dealt with in this review: [1] the strong affinity of SARS-CoV-2 for the human ACE2 receptor, [2] SARS-CoV-2 induced sex steroid hormonal abnormalities, [3] increased levels of oxidative stress in COVID-19, and [4] molecular mimicry between humans and components of SARS-CoV-2 leading to antigenic cross-reactivity phenomena. As these mechanisms might be responsible for SARS-CoV-2-induced male infertility, new evidence demonstrates testicular damage and semen abnormalities following the viral infection. Pathological findings of patients who died of COVID-19 exhibit injury to Sertoli cells and seminiferous tubules with a reduction in Leydig cells, which all are critical components of spermatogenesis. Moreover, impairment of sperm quality was found in SARS-CoV-2-infected patients. Those manifestations found in COVID-19-ill patients, parallel to sex steroid hormonal abnormalities, might critically influence spermatogenesis and SARS-CoV-2-induced male infertility. © 2023 Elsevier Inc. All rights reserved.

Morphological changes in testicles of patients with idiopathic infertility after novel coronavirus infection (COVID-19)

Introduction. SARS-CoV-2 causes several negative processes in the body and complicates the course of chronic somatic diseases, causing dysfunction and having a negative effect on many organs and systems of the body, including organs of the reproductive system. Objective. To study morphological changes in testicles of patients who have undergone a new coronavirus infection. Materials and methods. Objects of morphological research were testicular tissues obtained by intraoperative biopsy under intravenous anesthesia served. Material sampling was carried out in 12 patients aged 25–29 years with idiopathic infertility who underwent COVID-19. Patients showed ultrasound signs of fibrosis in the testicles, which were absent before infection with SARS-CoV-2. The biopsy was performed 12 months after COVID-19. Results. In all observations, changes were observed that are characteristic of the inflammatory process, nonbacterial autoimmune genesis. Histio-lymphocytic infiltration of testicular tissue with destruction of single tubules and parenchyma atrophy, combined with varying degrees of sclerosis, was verified. Conclusion. In testicular biopsy specimens from patients who have undergone COVID-19, an autoimmune inflammatory process is recorded, manifested by lymphocytic infiltration of testicular tissue, which was combined with varying degrees of sclerosis. © Vestnik Urologii 2022.

Male fertility: summary overview of the publications January - March 2022.

The article presents an overview of the most significant publications on the topic of male infertility. The main selection criteria were the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 papers published in the first quarter (January - March) of 2022 was compiled. The review includes articles on the following issues: the role of coronavirus infection in male infertility, the effectiveness of aromatase inhibitors in infertile men, the effect of assisted reproductive technologies on the reproductive health of descendants, recurrent miscarriage, the effect of antibiotic therapy on the DNA fragmentation index, the role of antisperm antibodies in male infertility, the incidence of idiopathic male infertility, the Sixth Edition WHO guidelines for the ejaculate processing, as well as the relationship of depression with male infertility.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Male fertility: summary overview of the publications January - March 2022.

The article presents an overview of the most significant publications on the topic of male infertility. The main selection criteria were the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 papers published in the first quarter (January - March) of 2022 was compiled. The review includes articles on the following issues: the role of coronavirus infection in male infertility, the effectiveness of aromatase inhibitors in infertile men, the effect of assisted reproductive technologies on the reproductive health of descendants, recurrent miscarriage, the effect of antibiotic therapy on the DNA fragmentation index, the role of antisperm antibodies in male infertility, the incidence of idiopathic male infertility, the Sixth Edition WHO guidelines for the ejaculate processing, as well as the relationship of depression with male infertility.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Male fertility: a summary overview of the publications April - September 2022.

The article provides an overview of the most significant publications on male infertility. The main selection criteria were the practical relevance of the article, as well as the impact factor of the journal it was published, according to the ScImago Journal Rank (SJR). As a result, a list of 10 papers published in Q2 - Q3 (April - September) 2022 was formed. The summary overview includes articles on the following topics: role of coronavirus infection in disorders of spermatogenesis, efficacy of hormonal stimulation before surgical sperm extraction, therapy consequences of diabetes mellitus on progeny reproductive health, new methods for selecting spermatozoa in IcSI, the efficacy of antioxidants, the safety of vaccines against SARS-coV-2, the importance of genetic tests and predictive factors for micro-TESE success.Copyright © 2022 Authors. All rights reserved.

Male fertility: Review of the publications of July-September 2020.

The article provides an overview of the most significant publications on the male infertility topic. The main selection criteria were considered the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 works published in the third quarter (July-September) of 2020 was formed. The review included articles on the following issues: Redox balance in the male reproductive system, advanced paternal age, the effect of a new nasal form of testosterone on fertility, the correlation of PSA levels with infertility, as well as new data on the effect of COVID-19 on male fertility.Copyright © 2021 Vestnik Urologii. All rights reserved.

Male fertility: A review of the publications from April - June 2021.

The article provides an overview of the most significant publications on the topic of male infertility. The main selection criteria were considered the practical significance of the article, as well as the impact factor of the journal in which it was published, according to the SCImago Journal Rank (SJR). As a result, a list of 10 works published in the II quarter (April - June) of 2021 was formed. The review includes articles on the following issues: the effectiveness of repeated micro-TESE in non-obstructive azoospermia, the role of COVID-19 in male fertility, the effect of testosterone therapy on spermatogenesis, testicular microlithiasis, electroejaculation as a method of obtaining spermatozoa, harm from carrying cell phones near the genitals, prediction of the effectiveness of intrauterine insemination, the effect of advanced paternal age on sperm aneuploidy, and the importance of the microbiome for male fertility.Copyright © 2021 Rostovskii Gosudarstvennyi Meditsinskii Universitet. All Rights Reserved.

Male fertility: a review of the publications July - September 2021.

The article provides an overview of the most significant publications on the topic of male infertility. The main selection criteria were considered the practical significance of the article, as well as the impact factor of the journal in which it was published according to the SCImago Journal Rank (SJR). As a result, we formed a list of 10 articles published in the III quarter (July - September) of 2021. The review included articles concerning the following issues: the ability of oocytes to repair damaged DNA-chains of sperm cells, the effectiveness of ICSI in AZF-c microdeletions, the advanced paternal age, artificial intelligence in reproductive clinics, genetic causes of infertility, the effect of surgical treatment of varicocele concerning DNA fragmentation, the role of ICSI in the frequency of chromosomal abnormalities in offspring, the safety of COVID-19 vaccination for spermatogenesis, as well as the novel WHO 6 manual for semen investigation.Copyright © 2021 Vestnik Urologii. All rights reserved.

Male fertility: Review of the publications of April - June 2020.

The article provides an overview of the most significant publications on the topic of male infertility. The main selection criteria are the practical relevance of the article, as well as the impact factor of the journal in which it was published, according to the ScImago Journal Rank (SJR). as a result, a list of 10 works published in the II quarter (april - June) of 2020 was formed. The review includes articles on the following topics: the effect of asymptomatic genital tract infection on male fertility, methods of spermatogonia transplantation, the effect of alcohol on fertility, the role of folate status in male fertility, lumicrine regulation of spermatogenesis, oxidative-reductive balance in the male reproductive system, comparison of testicular sperm extraction (TESE) and micro-TESE results, natural conception and intrauterine insemination (IUI) at high MaR test values, and the first data on the effect of cOVID-19 on male fertility.Copyright © 2020 Rostovskii Gosudarstvennyi Meditsinskii Universitet. All rights reserved.

Psychological status of infertile men during the Coronavirus Disease 2019 Pandemic in China: a cross-sectional investigation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has had a widespread and profound impact on people's mental health. The factors associated with mental symptoms among men diagnosed with infertility, a disease closely related to psychological conditions, remain unclear. The aim of this study is to investigate the risk factors associated with mental symptoms among infertile Chinese men during the pandemic. RESULTS: A total of 4,098 eligible participants were recruited in this cross-sectional, nationwide study, including 2,034 (49.6%) with primary infertility and 2,064 (50.4%) with secondary infertility. The prevalence of mental health conditions was 36.3%, 39.6%, and 6.7% for anxiety, depression, and post-pandemic stress, respectively. Sexual dysfunction is associated with a higher risk with adjusted odds ratios (ORs) of 1.40 for anxiety, 1.38 for depression, and 2.32 for stress. Men receiving infertility drug therapy displayed a higher risk for anxiety (adjusted OR, 1.31) and depression (adjusted OR, 1.28) symptoms, while those receiving intrauterine insemination had a lower risk of anxiety (adjusted OR, 0.56) and depression (adjusted OR, 0.55) symptoms. CONCLUSION: The COVID-19 pandemic has had a significant psychological impact on infertile men. Several psychologically vulnerable populations were identified, including individuals with sexual dysfunction, respondents receiving infertility drug therapy, and those experiencing control measures for COVID-19. The findings provide a comprehensive profile of the mental health status of infertile Chinese men during the COVID-19 outbreak and provide potential psychological intervention strategies.

RéSUMé: CONTEXTE: L'épidémie de maladie à coronavirus 2019 (COVID-19) a eu un impact étendu et profond sur la santé mentale des gens. Les facteurs associés aux symptômes mentaux chez les hommes diagnostiqués comme infertiles, une maladie étroitement liée aux conditions psychologiques, restent flous. L'objectif de cette étude est d'étudier les facteurs de risque associés aux symptômes mentaux chez les hommes chinois infertiles pendant la pandémie. RéSULTATS: Au total, 4 098 participants admissibles ont été recrutés dans cette étude transversale à l'échelle nationale, dont 2 034 (49,6%) présentaient une infertilité primaire et 2 064 (50,4%) une infertilité secondaire. La prévalence des problèmes de santé mentale était respectivement de 36,3 %, 39,6 % et 6,7 % pour l'anxiété, la dépression, et le stress postpandémique. La dysfonction sexuelle est associée à un risque plus élevé avec des odds ratios ajustés (OR) de 1,40 pour l'anxiété, 1,38 pour la dépression et 2,32 pour le stress. Les hommes recevant un traitement médicamenteux contre l'infertilité présentaient un risque plus élevé de symptômes d'anxiété (OR ajusté, 1,31) et de dépression (OR ajusté, 1,28), alors que ceux dont le traitement consistait à faire des inséminations intra-utérines présentaient un risque plus faible de symptômes d'anxiété (OR ajusté, 0,56) et de dépression (OR ajusté, 0,55). CONCLUSIONS: La pandémie de COVID-19 a eu un impact psychologique important sur les hommes infertiles. Plusieurs populations psychologiquement vulnérables ont été identifiées, notamment les personnes souffrant de dysfonction sexuelle, les hommes recevant un traitement médicamenteux contre l'infertilité, et ceux subissant des mesures de contrôle de la COVID-19. Les résultats fournissent un profil complet de l'état de santé mentale des hommes Chinois infertiles pendant l'épidémie de COVID-19 et fournissent des stratégies potentielles d'intervention psychologique.

SARS-CoV-2 and male infertility: from short- to long-term impacts.

PURPOSE: The coronavirus 2019 (COVID-19) pandemic-caused by a new type of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-has posed severe impacts on public health worldwide and has resulted in a total of > 6 million deaths. Notably, male patients developed more complications and had mortality rates ~ 77% higher than those of female patients. The extensive expression of the SARS-CoV-2 receptor and related proteins in the male reproductive tract and the association of serum testosterone levels with viral entry and infection have brought attention to COVID-19's effects on male fertility. METHODS: The peer-reviewed articles and reviews were obtained by searching for the keywords SARS-CoV-2, COVID-19, endocrine, spermatogenesis, epididymis, prostate, and vaccine in the databases of PubMed, Web of Science and Google Scholar from 2020-2022. RESULTS: This review summarizes the effects of COVID-19 on the male reproductive system and investigates the impact of various types of SARS-CoV-2 vaccines on male reproductive health. We also present the underlying mechanisms by which SARS-CoV-2 affects male reproduction and discuss the potentially harmful effects of asymptomatic infections, as well as the long-term impact of COVID-19 on male reproductive health. CONCLUSION: COVID-19 disrupted the HPG axis, which had negative impacts on spermatogenesis and the epididymis, albeit further investigations need to be performed. The development of vaccines against various SARS-CoV-2 variations is important to lower infection rates and long-term COVID risks.

Exploration of the common genetic landscape of COVID-19 and male infertility.

Background: COVID-19 has spread widely across continents since 2019, causing serious damage to human health. Accumulative research uncovered that SARS-CoV-2 poses a great threat to male fertility, and male infertility (MI) is a common comorbidity for the COVID-19 pandemic. The aim of the study was to explore the cross-talk molecular mechanisms between COVID-19 and MI. Materials and methods: A total of four transcriptome data regarding COVID-19 and MI were downloaded from the Gene Expression Omnibus (GEO) repository, and were divided for two purposes (initial analysis and external validation). Differentially expressed genes (DEGs) analysis, GO and pathway annotation, protein-protein interaction (PPI) network, connectivity ranking, ROC analysis, immune infiltration, and translational and post-translational interaction were performed to gain hub COVID-19-related DEGs (CORGs). Moreover, we recorded medical information of COVID-19 patients with MI and matched healthy controls, and harvested their sperm samples in the university hospital. Expressions of hub CORGs were detected through the qRT-PCR technique. Results: We identified 460 overlapped CORGs in both the COVID-19 DEGs and MI DEGs. CORGs were significantly enriched in DNA damage and repair-associated, cell cycle-associated, ubiquitination-associated, and coronavirus-associated signaling. Module assessment of PPI network revealed that enriched GO functions were closely related to cell cycle and DNA metabolism processes. Pharmacologic agent prediction displayed protein-drug interactions of ascorbic acid, biotin, caffeine, and L-cysteine with CORGs. After connectivity ranking and external validation, three hub CORGs (ENTPD6, CIB1, and EIF3B) showed good diagnostic performance (area under the curve > 0.75). Subsequently, three types of immune cells (CD8+ T cells, monocytes, and macrophages M0) were dominantly enriched, and 24 transcription factor-CORGs interactions and 13 miRNA-CORGs interactions were constructed in the network. Finally, qRT-PCR analysis confirmed that there were significant differences in the expression of hub CORGs (CIB1 and EIF3B) between the patient and control groups. Conclusion: The present study identified and validated hub CORGs in COVID-19 and MI, and systematically explored molecular interactions and regulatory features in various biological processes. Our data provide new insights into the novel biomarkers and potential therapeutic targets of COVID-19-associated MI.