Reversible effects of the SARS-CoV-2 on semen parameters.

Despite that the SARS-CoV-2 pandemic has been controlled, it has affected a large proportion of the population, raising some concerns about potential sequelae in men at reproductive age. To contribute to the clarification of this issue, we performed a retrospective study comparing semen parameters values before and after confirmed SARS-CoV-2 infection in a large cohort of infertile men, compared to a control group that did not undergo SARS-CoV-2 infection. Wilcoxon test on paired samples and general linear regression model showed that SARS-CoV-2 infection has a detrimental effect on semen volume values (p < 0.005). However, semen volume seems to be significantly lower only during the first spermatogenic cycle after SARS-COV-2 infection (p < 0.005) and mainly in unvaccinated patients (p < 0.05). In addition, we detected alterations in progressive motility in patients infected with the alpha SARS-COV-2 strain (p < 0.05). In conclusion, our results show that although SARS-CoV-2 has a small effect on semen volume and sperm motility in infertile men, depending on the infectious strain or vaccination status, pre-infection values of semen parameters appear to be restored over one spermatogenic cycle after infection.

SARS-CoV-2 impairs male fertility by targeting semen quality and testosterone level: A systematic review and meta-analysis.

BACKGROUND: Since the discovery of COVID-19 in December 2019, the novel virus has spread globally causing significant medical and socio-economic burden. Although the pandemic has been curtailed, the virus and its attendant complication live on. A major global concern is its adverse impact on male fertility. AIM: This study was aimed to give an up to date and robust data regarding the effect of COVID-19 on semen variables and male reproductive hormones. MATERIALS AND METHODS: Literature search was performed according to the recommendations of PRISMA. Out of the 852 studies collected, only 40 were eligible for inclusion in assessing the effect SARS-CoV-2 exerts on semen quality and androgens. More so, a SWOT analysis was conducted. RESULTS: The present study demonstrated that SARS-CoV-2 significantly reduced ejaculate volume, sperm count, concentration, viability, normal morphology, and total and progressive motility. Furthermore, SARS-CoV-2 led to a reduction in circulating testosterone level, but a rise in oestrogen, prolactin, and luteinizing hormone levels. These findings were associated with a decline in testosterone/luteinizing hormone ratio. CONCLUSIONS: The current study provides compelling evidence that SARS-CoV-2 may lower male fertility by reducing semen quality through a hormone-dependent mechanism; reduction in testosterone level and increase in oestrogen and prolactin levels.

Male Tract Microbiota and Male Infertility.

In recent years, several studies have analyzed the composition of the male genital tract microbiota and its changes in infertility or in different situations associated with infertility. The aim of this narrative review is to obtain more insight on this topic; in particular, to describe actual evidence about changes in the semen microbiota in patients with infertility, male tract infections, or HPV infections. In semen, an increase in semen Prevotella spp. is associated with oligozoospermia and with obesity-associated asthenozoospermia; an increase in Pseudomonas is more frequently associated with asthenozoospermia and oligozoospermia; a reduction in Lactobacilli spp. (namely in Lactobacillus crispatus) may represent a marker of low semen quality. However, an increase in Lactobacillus iners is considered a risk factor for a reduced sperm concentration. In patients with prostatitis, there is a reduction in Lactobacillus spp. and an increase in Streptococcus spp., opening important perspectives about the role of probiotic treatments in these patients. Finally, an increase in Fusobacteria spp. was observed in patients with an HPV infection. In the conclusion, we underline the interactions between the seminal and vaginal microbiota, so that further studies should focus on the "couple genital microbiota".

Correlation between viral infections in male semen and infertility: a literature review.

Infertility affects approximately one-sixth of couples globally, with the incidence of male infertility steadily increasing. However, our understanding of the impact of viral infections on fertility remains limited. This review consolidates findings from previous studies, outlining 40 viruses identified in human semen and summarizing their key characteristics, modes of transmission, and their effects on both the reproductive and endocrine systems. Furthermore, it elucidates potential pathogenic mechanisms and treatment prospects of viruses strongly associated with male infertility. This synthesis will enhance our comprehension of how viral infections influence male reproductive health, offering valuable insights for future research as well as the diagnosis and treatment of infectious infertility.

The short-term effect of COVID-19 infection history on semen parameters in men referred to infertility centres.

Context In recent years, the COVID-19 pandemic became a threat to human health and induced global concern. The SARS-CoV-2 virus causes various disorders in the body's systems, and the reproductive system is no exception. Further, the rate of infertile couples is increasing and part of this is related to male infertility. Aims The aim of the present study was to investigate the impacts of COVID-19 infection history on semen quality in men referred to public and private infertility centres. Methods In this research, patients were divided into two groups: 88 men with a history of COVID-19 (Covid+) and 51 men without (Covid-). After semen collection, sperm parameters, fertilisation rate and oxidative stress were investigated. Key results Sperms with normal morphology and mature chromatin in patients with COVID-19 infection history decreased, and seminal oxidative stress and sperm DNA fragmentation were increased; moreover, the fertilisation rate in the Covid+ group decreased in compare to the Covid- group. Conclusion COVID-19 infection increases oxidative stress in the semen, so has a negative effect on some sperm parameters and fertilisation rate. Implications COVID-19 infection impairs semen quality by increasing in oxidative stress, thus reducing the fertility potential.

Association between post-COVID-19 conditions and male semen quality in Japan: A descriptive investigation.

Some reports suggest that coronavirus disease 2019 (COVID-19) may affect male reproductive function. There is also concern in Japan that COVID-19 may contribute to the pre-existing decline in male fertility; however, no studies have investigated the effects of COVID-19 on male reproductive function. In this study, we aimed to analyze the semen quality of men who had recovered from COVID-19. Male patients who had recovered from COVID-19 between February 2020 and September 2021 were recruited for this study. Participants were sent a semen collection kit; they were asked to collect semen at home and deliver it to a laboratory at Osaka University. We used these samples to analyze sperm concentration, total sperm count, and semen volume. In total, 125 participants were included in this study. The median age of all patients was 46 years (interquartile range (IQR): 38-52 years). The severity of COVID-19 was mild in 80 patients; 19 were moderate I, 22 were moderate II, and four were severe. The median semen volume was 2.5 mL (IQR: 1.8-3.1), the median sperm concentration was 98.9 million/mL (IQR: 43.8-162.2), and the median total sperm count was 212.1 million (IQR: 89.7-368.2). In a previous study in Japan, the median sperm count in adult men was reported to be 201 million. Participants in our study did not have lower sperm counts than this, despite their older age. Our results suggest that the long-term effects of COVID-19 on spermatogenesis are minimal.

The impact of COVID-19 on male reproductive health: a Systematic Review.

OBJECTIVE: This systematic literature review aims to assess the impact of COVID-19 on male fertility. DATA SOURCES: The study draws upon data extracted from PubMed, SciELO, and LILACS databases. STUDY SELECTION: The review incorporates cross-sectional studies, cohort studies, and clinical trials, encompassing investigations related to the subject matter. The studies included were published between June 2020 and March 2023, and encompassed content in English, Portuguese, and Spanish. Exclusion criteria encompassed review articles, case reports, abstracts, studies involving animal models, duplicate articles, and letters to the editor. DATA COLLECTION: Data extracted included the author's name and publication year, the number of patients studied, patient age, the presence of COVID-19 in semen, observed hormonal changes, and alterations in seminal quality. CONCLUSIONS: While hormonal changes and a decline in seminal quality were observed in COVID-19 patients, the virus itself was not detected in semen in the analyzed articles, which contradicts certain findings in the existing literature. It is essential to note that methodologies in the studies were diverse, and, due to the novelty of this infection, it is premature to definitively ascertain its long-term effects on male fertility or whether fertility can recover after a period of convalescence. This underscores the necessity for further research, utilizing more robust methodologies such as cohort studies.

Acute murine-betacoronavirus infection impairs testicular steroidogenesis and the quality of sperm production.

Although several testicular alterations promoted by coronavirus infection have been demonstrated, the extent, causes, and players of testicular pathogenesis are not totally understood. The present study aimed to investigate the short-term effects on male fertility of intranasally administered murine hepatitis virus strain 3 (MHV-3), a member of the genus Betacoronavirus, which causes a severe systemic acute infection. This mouse model might be used as a in vivo prototype for investigating the impact of betacoronavirus on the endocrine and exocrine testicular functions with the advantage to be performed in a biosafety level 2 condition. Herein, we performed virological, histopathological, and molecular studies regarding the testicular spermatogenesis and the spermatic quality analyses in an MHV-3-infected C57BL/6 mice. The main outcomes showed that MHV-3 infects mouse testis and induces a testicular inflammatory state, impairing the steroidogenic pathway. The infection led to several alterations in the testicular parenchyma, such as: seminiferous epithelium sloughing, retention of residual bodies, germ cell apoptosis, alterations in intercellular junction proteins, and worse spermatogenic parameters. Moreover, the levels of plasmatic testosterone as well as the quality of sperm production reduced. Therefore, the present data suggest that the viral/inflammatory impairment of the steroidogenic pathway and the consequent imbalance of androgen levels is critical in testicular pathology, disturbing the SC barrier function and the germ cell differentiation. Our study is important for comprehending the effects of beta coronavirus infections on testis function in order to develop treatments that could prevent virus-mediated male infertility.

ORF8 protein of SARS-CoV-2 reduces male fertility in mice.

As one of the most rapidly evolving proteins of the genus Betacoronavirus, open reading frames (ORF8's) function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by reactive oxygen species scavenger and endoplasmic reticulum-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion, we examined the plasma samples of coronavirus disease 2019 (COVID-19) convalescent patients and found that the patients aged from 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail-vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle- and ORF8-treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in 5-week-old male mice. Furthermore, the analysis of gene expression in the testes between vehicle- and ORF8-treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the human reproductive system.

Sperm quality and absence of SARS-CoV-2 RNA in semen after COVID-19 infection: a prospective, observational study and validation of the SpermCOVID test.

OBJECTIVE: To study the contagiousness of sperm and its influence on fertility after recovery from COVID-19 infection. DESIGN: Prospective cohort study. SETTING: University medical center. PATIENT(S): One hundred twenty Belgian men who had recovered from proven COVID-19 infection. INTERVENTION(S): No intervention was performed. MAIN OUTCOME MEASURE(S): Semen quality was assessed using the World Health Organisation criteria. DNA damage to sperm cells was assessed by quantifying the DNA fragmentation index and the high density stainability. Finally antibodies against SARS-CoV2 spike-1 antigen, nuclear and S1-receptor binding domain were measured by Elisa and chemilumenscent microparticle immunoassays, respectively. RESULT(S): SARS-CoV-2 RNA was not detected in semen during the period shortly after infection nor at a later time. Mean progressive motility was reduced in 60% of men tested shortly (<1 month) after COVID-19 infection, 37% of men tested 1 to 2 months after COVID-19 infection, and 28% of men tested >2 months after COVID-19 infection. Mean sperm count was reduced in 37% of men tested shortly (<1 month) after COVID-19 infection, 29% of men tested 1 to 2 months after COVID-19 infection, and 6% of men tested >2 months after COVID-19 infection. The severity of COVID-19 infection and the presence of fever were not correlated with sperm characteristics, but there were strong correlations between sperm abnormalities and the titers of SARS-CoV-2 IgG antibody against spike 1 and the receptor- binding domain of spike 1, but not against nucleotide, in serum. High levels of antisperm antibodies developed in three men (2.5%). CONCLUSION(S): Semen is not infectious with SARS-CoV-2 at 1 week or more after COVID-19 infection (mean, 53 days). However, couples with a desire for pregnancy should be warned that sperm quality after COVID-19 infection can be suboptimal. The estimated recovery time is 3 months, but further follow-up studies are under way to confirm this and to determine if permanent damage occurred in a minority of men.

Actualización sobre COVID-19 e histofisiología del sistema reproductor masculino / Update on COVID-19 and histophysiology of the male reproductive system

RESUMEN: La reciente pandemia de la COVID-19 ha sacudido a la sociedad teniendo una importante repercusión en el campo de la salud y de la investigación. Dada su relevancia, se han llevado a cabo estudios sobre los efectos del SARS-CoV-2 en la fisiología humana. En concreto, sobre la posible presencia y transmisión del virus a través del sistema reproductor masculino y su posible efecto en el éxito reproductivo. Conocer si la presencia del virus altera los órganos responsables del desarrollo y maduración de las células de la serie espermatogénica podría revelarnos su implicación en la calidad seminal. Por ello, nos planteamos esta revisión, con el fin de analizar las principales evidencias científicas sobre los efectos del SARS-CoV-2 en la histofisiología del sistema reproductor masculino y sobre la capacidad fecundante de los espermatozoides.

SUMMARY: The recent COVID-19 pandemic has shaken up society, having a significant impact on the field of health and research. Given its relevance, studies have been performed on the effects of SARS-CoV-2 on human physiology. In particular, the possible presence and transmission of the virus through the male reproductive system could affect reproductive success. Knowing if the presence of the virus disrupts the organs responsible for the development and maturation of the cell lines involved in spermatogenesis could reveal its implications in sperm quality. For that reason, we proposed this review, in order to analyze the main scientific evidence on the effects of SARS-CoV-2 on the histophysiology of the male reproductive system and sperm fertilizing capacity.

Androgens in SARS-CoV-2 coronavirus infections.

Recent molecular biology findings have shown that for the penetration of the SARS-CoV-2 coronavirus into host cells, a key role is played by protease serine 2, the activity of which is dependent on androgens. The important role of androgens is also evidenced by clinical observations that men in some age categories are infected by this novel coronavirus up to two times more frequently than women. In addition, men with androgenic alopecia tend to have more serious clinical courses, while men with androgen deprivation as a result of prostate cancer treatments tend to have milder courses. This is in line with the fact that preadolescent children are only rarely sickened with serious forms of SARS-CoV-2 infections. Even though these observations may be explained by other factors, many authors have hypothesized that lowered androgen levels and blocking their activity using anti-androgen medication may moderate the course of the viral infection in intermediately- to critically-affected cases. Clearly, it would be important for androgen deprivation to block not just gonadal androgens, but also adrenal androgens. On the other hand, low androgen levels are considered to be a risk factor for the course of SARS-CoV-2 infections, either because low androgen levels have a general effect on anabolic-catabolic equilibrium and energy metabolism, or because of the ability of testosterone to modify the immune system. It is not yet clear if infection with this novel coronavirus might induce hypogonadism, leading to undesirable side effects on male fertility.

Activation of PTH1R alleviates epididymitis and orchitis through Gq and ß-arrestin-1 pathways.

Inflammation in the epididymis and testis contributes significantly to male infertility. Alternative therapeutic avenues treating epididymitis and orchitis are expected since current therapies using antibiotics have limitations associated to side effects and are commonly ineffective for inflammation due to nonbacterial causes. Here, we demonstrated that type 1 parathyroid hormone receptor (PTH1R) and its endogenous agonists, parathyroid hormone (PTH) and PTH-related protein (PTHrP), were mainly expressed in the Leydig cells of testis as well as epididymal epithelial cells. Screening the secretin family G protein-coupled receptor identified that PTH1R in the epididymis and testis was down-regulated in mumps virus (MuV)- or lipopolysaccharide (LPS)-induced inflammation. Remarkably, activation of PTH1R by abaloparatide (ABL), a Food and Drug Administration-approved treatment for postmenopausal osteoporosis, alleviated MuV- or LPS-induced inflammatory responses in both testis and epididymis and significantly improved sperm functions in both mouse model and human samples. The anti-inflammatory effects of ABL were shown to be regulated mainly through the Gq and ß-arrestin-1 pathway downstream of PTH1R as supported by the application of ABL in Gnaq± and Arrb1-/- mouse models. Taken together, our results identified an important immunoregulatory role for PTH1R signaling in the epididymis and testis. Targeting to PTH1R might have a therapeutic effect for the treatment of epididymitis and orchitis or other inflammatory disease in the male reproductive system.

Understanding the cross-talk between mediators of infertility and COVID-19.

COVID-19 is the ongoing health emergency affecting individuals of all ages around the globe. Initially, the infection was reported to affect pulmonary structures. However, recent studies have delineated the impacts of COVID-19 on the reproductive system of both men and women. Hence, the present review aims to shed light on the distribution of SARS-CoV-2 entry factors in various reproductive organs. In addition, impacts of COVID-19 mediators like disrupted renin angiotensin system, oxidative stress, cytokine storm, fever, and the mental stress on reproductive physiology have also been discussed. For the present study, various keywords were used to search literature on PubMed, ScienceDirect, and Google Scholar databases. Articles were screened for relevancy and were studied in detail for qualitative synthesis of the review. Through our literature review, we found a multitude of effects of COVID-19 mediators on reproductive systems. Studies reported expression of receptors like ACE-2, TMPRSS2, and CD147 in the testes, epididymis, prostrate, seminal vesicles, and ovarian follicles. These proteins are known to serve as major SARS-CoV-2 entry factors. The expression of lysosomal cathepsins (CTSB/CTSL) and/ neuropilin-1 (NRP-1) are also evident in the testes, epididymis, seminal vesicles, fallopian tube, cervix, and endometrium. The binding of viral spike protein with ACE-2 was found to alter the renin-angiotensin cascade, which could invite additional infertility problems. Furthermore, COVID-19 mediated cytokine storm, oxidative stress, and elevated body temperature could be detrimental to gametogenesis, steroidogenesis, and reproductive cycles in patients. Finally, social isolation, confinement, and job insecurities have fueled mental stress and frustration that might promote glucocorticoid-mediated subnormal sperm quality in men and higher risk of miscarriage in women. Hence, the influence of COVID-19 on the alteration of reproductive health and fertility is quite apparent.

In Silico Identification of miRNA-lncRNA Interactions in Male Reproductive Disorder Associated with COVID-19 Infection.

Coronavirus disease 2019 (COVID-19), a global pandemic, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2 and transmembrane serine protease 2 (TMPRSS2) facilitates ACE2-mediated virus entry. Moreover, the expression of ACE2 in the testes of infertile men is higher than normal, which indicates that infertile men may be susceptible to be infected and SARS-CoV-2 may cause reproductive disorder through the pathway induced by ACE2 and TMPRSS2. Little is known about the pathway regulation of ACE2 and TMPRSS2 expression in male reproductive disorder. Since the regulation of gene expression is mediated by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) at the post-transcriptional level, the aim of this study was to analyze the dysregulated miRNA-lncRNA interactions of ACE2 and TMPRSS2 in male reproductive disorder. Using bioinformatics analysis, we speculate that the predicted miRNAs including miR-125a-5p, miR-125b-5p, miR-574-5p, and miR-936 as regulators of ACE2 and miR-204-5p as a modulator of TMPRSS2 are associated with male infertility. The lncRNAs with a tissue-specific expression for testis including GRM7-AS3, ARHGAP26-AS1, BSN-AS1, KRBOX1-AS1, CACNA1C-IT3, AC012361.1, FGF14-IT1, AC012494.1, and GS1-24F4.2 were predicted. The identified miRNAs and lncRNAs are proposed as potential biomarkers to study the possible association between COVID-19 and male infertility. This study encourages further studies of miRNA-lncRNA interactions to explain the molecular mechanisms of male infertility in COVID-19 patients.

Does COVID-19 Worsen the Semen Parameters? Early Results of a Tertiary Healthcare Center.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) is a global pandemic which may affect multiple organs and systems including testes and disrupt the gonadal functions. The current study aimed to evaluate the effect of COVID-19 on the semen parameters and sex-related hormone levels in infertile men. METHODS: The study included 21 patients who were evaluated in Ankara City Hospital, Andrology Clinic, for male infertility and have had the diagnosis of COVID-19. All the patients were evaluated in terms of semen parameters. The follicle-stimulating hormone, luteinizing hormone, and testosterone (T) levels were also evaluated in 8 of the patients. The results were presented through 2 dependent group analyses, based on the data of the patients collected before and after the diagnosis of COVID-19. RESULTS: None of the patients needed to be hospitalized at any time through the course of COVID-19. There was a significant decrease in semen volume, percentage of total motility, percentage of progressive motility, and normal sperm morphology after COVID-19 (3 [1-8] vs. 2.5 [1.5-5], p = 0.005; 48.6 ± 22.1 vs. 34.7 ± 20.7, p = 0.001; 35.1 ± 21.7 vs. 21.8 ± 15.9, p < 0.001; 6 [3-24] vs. 5 [3-18], p = 0.015; respectively). There was also a significant decline in T level of the patients after the diagnosis of COVID-19 (350.1 ± 115.5 vs. 289.8 ± 103.3, p = 0.009). CONCLUSION: COVID-19 may have unfavorable effects on the gonadal functions and may lead to further deterioration of the semen parameters in infertile men, which should be considered through the evaluation for infertility.

The probable destructive mechanisms behind COVID-19 on male reproduction system and fertility.

PURPOSE: The present study aims to summarize the current understanding of probable mechanisms and claims of adverse effects of SARS-CoV-2 on male fertility potential. METHODS: Our search was including original articles, reviews, guidelines, letters to the editor, comments on guidelines, and editorials, regarding the male reproductive system. We used the words SARS-CoV-2, coronavirus, severe acute respiratory syndrome coronavirus 2, "2019 ncov," testis, sperm, male factor infertility, fertility treatment, semen, assisted reproductive technology (ART), sexual transmission, and ACE2. RESULTS: Data showed coronavirus affects men more than women because of more expression of 2019 nCoV receptors (ACE2 and TMPRSS2) in testicular cells. Also, "Bioinformatics Analysis" suggests that sperm production may be damaged, since "Pseudo Time Analysis" has shown disruption in spermatogenesis. "Gene Ontology" (GO) showed an increase in viral reproduction and a decrease in sperm production-related terms. Recently, SARS-COV-2 mRNA and protein were detected in the semen of patients that had recovered from SARS-CoV-2 infection. Therefore, the probable disruption of blood-testis barrier (BTB) in febrile diseases is suspected in the acute phase of the disease enabling viral entry into the testes. Not only is spermatogenesis disturbed, but also disturbs gonadotropin, androgens, and testosterone secretion during SARS-CoV-2 infection. No sexual transmission has been reported yet; however, detection of the virus in semen still makes the sexual transmission an open question. CONCLUSION: There is a concern that male fertility may be disturbed after the SARS-CoV-2 infection. Therefore, follow-up of the reproductive functions and male fertility may be necessary in recovered cases, especially in aged men.

COVID-19 and male reproductive function: a prospective, longitudinal cohort study.

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-1ß, IL-6, IL-8, IL-10, TGF-ß, 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.