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Showing papers on "Semen analysis 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: 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
20 Jul 2021-JAMA
TL;DR: In this paper, the authors assessed sperm parameters before and after mRNA vaccine administration to address vaccine hesitancy based on concerns about fertility, and they found that MMR vaccine attenuated fertility.
Abstract: To address vaccine hesitancy based on concerns about fertility, this study assesses sperm parameters before and after mRNA vaccine administration.

102 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: 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: The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS‐CoV‐2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID‐19, possible formation of anti‐sperm antibodies (ASA) and subsequently immunological infertility as a complication of Sars‐Co V‐2 infection.
Abstract: The novel coronavirus was recognised in December 2019 and caught humanity off guard. The virus employs the angiotensin-converting enzyme 2 (ACE2) receptor for entry into human cells. ACE2 is expressed on different organs, which is raising concern as to whether these organs can be infected by the virus or not. The testis appears to be an organ enriched with levels of ACE2, while the possible mechanisms of involvement of the male reproductive system by SARS-CoV-2 are not fully elucidated. The major focus of the present studies is on the short-term complications of the coronavirus and gains importance on studying the long-term effects, including the possible effects of the virus on the male reproductive system. The aim of this review was to provide new insights into different possible mechanisms of involvement of male gonads with SARS-CoV-2 including investigating the ACE2 axis in testis, hormonal alterations in patients with COVID-19, possible formation of anti-sperm antibodies (ASA) and subsequently immunological infertility as a complication of SARS-CoV-2 infection. Finally, we suggest measuring the sperm DNA fragmentation index (DFI) as a determiner of male fertility impairment in patients with COVID-19 along with other options such as sex-related hormones and semen analysis. Invasion of SARS-CoV-2 to the spermatogonia, Leydig cells and Sertoli cells can lead to sex hormonal alteration and impaired gonadal function. Once infected, changes in ACE2 signalling pathways followed by oxidative stress and inflammation could cause spermatogenesis failure, abnormal sperm motility, DNA fragmentation and male infertility.

45 citations


Journal ArticleDOI
TL;DR: This largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment in men referred for fertility evaluation showed that a man's semen count is a marker of his general health.
Abstract: Background Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive. Objective We tested whether semen quality and reproductive function could represent a marker of general male health. Design, setting, and participants A retrospective study of 5177 individuals from a prospectively collected database of 11 516 males of infertile couples who had semen analysis in a tertiary university center. Outcome measurements and statistical analysis Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone 9.4 IU/l. Individuals with a total sperm count of Results and limitations Men with a low sperm count ( Conclusions This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health. Patient summary This large study evaluated semen quality, reproductive function, and metabolic risk in men referred for fertility evaluation, and showed that a man’s semen count is a marker of his general health. Men with low sperm counts are more likely than those with normal sperm counts to have greater body fat, higher blood pressure, higher “bad” (low-density lipoprotein) cholesterol and triglycerides, and lower “good” (high-density lipoprotein) cholesterol. They also have a higher frequency of metabolic syndrome and insulin resistance, a condition that can lead to diabetes. Men with low sperm counts had a 12-fold increased risk of hypogonadism or low testosterone levels, and half of them had osteoporosis or low bone mass. Fertility evaluation gives men the unique opportunity for health assessment and disease prevention.

45 citations


Journal ArticleDOI
TL;DR: The mechanisms of DNA damage as well as its impact in different scenarios of male infertility, associated with spontaneous and assisted reproduction and the clinical applicability of sperm DNA fragmentation testing are discussed.
Abstract: Male factor is responsible for up to 50% of infertility cases in the world Semen analysis is considered the cornerstone of laboratory evaluation of male infertility, but it has its own drawbacks and fails to predict the male fertility potential with high sensitivity and specificity Different etiologies have been linked with male infertility, of which sperm DNA damage has gained significant attention with extensive research on sperm function tests The associations between sperm DNA damage and a variety of disorders such as varicocele, obesity, cancer, radiation and lifestyle factors are explored in this review Furthermore, we discuss the mechanisms of DNA damage as well as its impact in different scenarios of male infertility, associated with spontaneous and assisted reproduction Finally, we review the clinical applicability of sperm DNA fragmentation testing in the management of male infertility

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: 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: The 6th edition of the manual was published in 2019 as mentioned in this paper and the most important change proposed was the adoption of decision limits to differentiate normal from abnormal ejaculate. But the decision limits are not applicable to assign normality in this case and proves unable to discriminate between fertile and infertile patients.
Abstract: Semen examination is the cornerstone of the evaluation of male fertility potential. Despite its apparent simplicity, it is a complex series of assessments with highly variable results that are subject to interpretation. The semen analysis is used to gauge reproductive potential and guide the clinician in management of the infertile couple. Over the past 40 years, the World Health Organization (WHO) Infertility Task Force has attempted to standardize the methodology of semen examination so as to bring uniformity and relevance to the test. The 1st edition of the “Laboratory Manual for the Examination and Processing of Human Semen” was published in 1980. Since then, four more editions of the WHO manual have been published, each attempting to reflect global male population demographics, to address limitations from previous versions, and to incorporate technological and scientific evolution in the field of reproduction. Currently, the 5th edition of the WHO manual, published in 2010, is implemented worldwide, and is considered one of the most used, yet contested documents in the field of male infertility [1]. In March 2021, the WHO released a preliminary draft of the 6th edition of its manual for public review and suggestions (https://www.who.int/publications/i/item/9789241547789). Essentially, the new manual comprises three parts: semen examination; sperm preparation and cryopreservation; and quality control and assurance. The procedures for semen examination include basic (routine) examinations, extended examinations (which may be used by laboratories or clinicians in certain situations), and advanced tests (which are not currently recommended for routine use and are primarily for research purposes). The 6th edition has presented the basic examination in a step-by-step and temporal manner, so that it can be reproduced precisely in any laboratory with the required equipment and expertise. The sections on extended and advanced examinations have been completely revamped in concordance with current clinical practice, with many older tests being abandoned and new tests being adopted. The purpose of this mini review and commentary is to familiarize fertility specialists with the principal changes proposed in the anticipated 6th edition of the WHO manual for human semen analysis. The advantages, limitations and clinical implications of these changes are discussed. 1. Use of decision limits to identify abnormal ejaculates The most important change proposed in the 6th edition is the adoption of decision limits to differentiate normal from abnormal ejaculates. The editors of the 6th edition acknowledge that the reference ranges described in the 5th edition should be abandoned as they are of limited value in differentiating fertile from infertile men. The 5th edition WHO manual utilized a population of 1,800 fertile men to obtain the reference distributions for semen parameters [1]. The lower 5th percentile was used to define the reference values for normal semen parameters. While the 5th percentile is commonly utilized as a statistical approach to determine cut-off norms in medical tests, this resulted in much controversy when applied to male fertility [2]. It has been argued that the 5th percentile is not applicable to assign normality in this case and proves unable to discriminate between fertile and infertile patients [3]. Several studies reported a shift of fertility status from abnormal to normal in 15% to 44% of patients by just using the 5th edition norms instead of the 4th edition [4,5,6,7]. It was therefore proposed that WHO reference ranges did not adequately reflect fertility dynamics of the male partner, with several investigators and clinicians believing that normal values were above the lower 5th percentile. With these limitations in mind, the editors of the 6th edition suggested using different reference limits because the previous reference ranges fail to differentiate fertile from infertile men [8]. Decision limits were introduced by Guzick et al [9], who proposed a two-level reference range narrative by defining an intermediate group of values. According to their data the sub-fertile population demonstrated a sperm concentration below 13.5×106/mL, sperm motility less than 32% and typical forms below 9%. Yet, the normal fertile subgroup had a sperm concentration greater than 48×106/mL, sperm motility over 63%, and normal morphology above 12%. Values between these two levels were categorized as intermediate fertility [9]. The 5th edition has been criticized for neglecting the female factor as an important confounder [3] and for both over- and under-representation of various regions of the world [4]. The editors of the 6th edition have acknowledged these limitations (Appendix 8.1 of the manual) and stipulated that semen examination cannot strictly differentiate between pathological and normal samples. Moreover, they recognize that using the lower 5th percentile is not the correct approach to identify normal or abnormal semen samples, and that semen analysis alone cannot predict fertility as this depends on multiple variables, particularly, female factors. Hence, the “normal” reference values of the 5th edition have been replaced by “decision limits” in the 6th edition. These are classified as “normal”, “borderline”, and “pathological”. A “normal” concentration is ≥20×106/mL, “borderline” lies between 10 to 20×106/mL, and “pathological” is <10×106/mL. For motility “normal” is defined as ≥50% progressively motile sperm, “borderline” is 35% to 49% progressively motile, while a “pathological” sample is defined as <35% progressively motile sperm. Morphology has been categorized as “normal” when typical forms are ≥14%, “borderline” is between 4% and 13% and “pathological” morphology is below 4%. Additionally, the 6th edition states that sperm antibodies are not the sole cause of agglutination as this may be caused by different pathologies. Therefore, sperm antibody binding below 50% is considered “normal”; it is “borderline” between 50% to 79%, and “pathological” when ≥80%. The introduction of the “decision limits” concept is an attempt to emphasize that the purpose of the semen examination is not to label a man as fertile or infertile, but rather to decide next steps in terms of further evaluation and treatment. The current limits are still arbitrary and future studies with clinical outcomes in the various groups will help refine these limits. The creation of a “borderline” group will have significant clinical implications as many men whose sample would previously have been labeled as normal using the 5th edition criteria, will now be classified as “borderline” and be eligible for therapeutic interventions. Clinicians can still offer hope for natural pregnancy in these cases before opting to pursue ART. The impact of this classification shift will likely be significant in clinical practice. If we now apply the new criteria and deem men with parameters below the new “normal” threshold (“borderline”+“pathological”) as infertile, we will suddenly increase the number of infertile men in our practices. Interestingly, the upcoming manual presents revised reference values based on combined data of fertile men (with time to pregnancy less than 12 months) from the 2010 manual (5th edition) and by including released data from studies published until 2020. The 6th edition has included data from 5 additional studies (with 1,789 more male subjects) to those used in the 5th edition. The five new studies have incorporated data from two regions in Europe, one from Africa and two from Asia, although notably 1,200 out of 1,789 participants originate from China alone, therefore skewing the reference values towards normality of specific geolocations that do not necessarily apply in different populations.

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 effect of coronavirus disease 2019 (COVID-19) on the semen parameters and sex-related hormone levels in infertile men was evaluated in terms of semen parameters.
Abstract: 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.

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: In this paper, the authors conducted a systematic review on the effects of COVID-19 on male reproductive health, including the presence of viral RNA in semen, and the impact on semen quality, testicular histology and male reproductive hormones.
Abstract: Objective The COVID-19 pandemic, caused by the acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), remains an ongoing public health challenge. Although males are affected slightly more than females, the impact of SARS-COV-2 on male reproductive system remains unclear. This systematic review aims to provide a concise update on the effects of COVID-19 on male reproductive health, including the presence of viral RNA in semen, and the impact on semen quality, testicular histology, testicular pain and male reproductive hormones. The global health is fronting an immediate as well as impending threat from the novel coronavirus (SARS-CoV-2) causing coronavirus disease (COVID-19), that inflicts more males than females. Evidence suggest that male reproductive system is susceptible to this viral infection. However, there are still several pertinent queries that remain to be fully explained regarding the mechanism in testicular SARS-CoV-2 dynamics and the exact mode of its actions. Thus, the present systematic review aims to provide a concise update on the effects of coronavirus disease 2019 (COVID-19) on male reproduction.. Methods A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines searching the PubMed database. Eligibility for inclusion were original human studies evaluating the impact of COVID-19 on male reproductive health. Specific outcomes required for inclusion were at least one of the following: i) seminal detection of mRNA virus, or evaluation of ii) semen analysis, iii) testicular histology or ultrasonography, iv) testicular clinical symptoms and/or v) male reproductive hormones in COVID-19-positive patients. Results Of 553 retrieved articles, 25 met the inclusion criteria. This included studies primarily investigating the presence of viral RNA in semen (n = 12), semen quality (n = 2), testicular histology (n = 5), testicular pain (n = 2) and male reproductive hormones (n= 4). Results show little evidence for the presence of viral RNA in semen, although COVID-19 seems to affect seminal parameters, induce orchitis, and cause hypogonadism. Mortality cases suggest severe histological disruption of testicular architecture, probably due to a systemic and local reproductive tract inflammatory response and oxidative stress-induced damage. Conclusions Clinical evaluation of the male reproductive tract, seminal parameters and reproductive hormones is recommended in patients with current or a history of COVID-19, particularly in males undergoing fertility treatment. Any long-term negative impact on male reproduction remains unexplored and an important future consideration.

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TL;DR: Investigation of the efficiency of CellROX Deep Red and Orange probes in detecting ROS in bovine sperm cells and their relationship with sperm fertility potential found both are both efficient and higher levels of ROS assessed by Red might be associated with low fertility samples.
Abstract: Detection of reactive oxygen species (ROS) is of great interest in semen analysis since their excess is detrimental to sperm function and male fertility. Fluorescence microscopy has achieved attention for providing broad possibilities of sperm evaluations and also for presenting substantial accessibility. In this context, this study investigated the efficiency of CellROX Deep Red® and Orange® probes in detecting ROS in bovine sperm cells and assessed their relationship with sperm fertility potential. First, 16 ejaculates were assigned in three treatments: T0 (no ROS production induced), T1x (ROS production induced once) and T2x (ROS production induced twice). Samples were incubated with Red and Orange probes and percentages of cells producing ROS were evaluated using fluorescence microscopy. Coefficient of determination was 0.61 for Red and 0.56 for Orange. Afterwards, frozen-thawed semen samples from high and low fertility bulls were evaluated regarding percentages of cells producing ROS detected by Red and Orange. Higher levels of ROS assessed by Red were detected in low fertility bovine samples. In conclusion, CellROX Red® and Orange® are both efficient in detecting ROS in bovine spermatozoa. Furthermore, higher sperm ROS detection by CellROX Red® might be associated with low fertility samples.

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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: The past 50 years have seen heated debate in the reproductive sciences about global trends in human sperm count, and the largest and most methodologically rigor study was published in 2017.
Abstract: The past 50 years have seen heated debate in the reproductive sciences about global trends in human sperm count. In 2017, Levine and colleagues published the largest and most methodologically rigor...

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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.

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TL;DR: In this review, different sperm selection strategies for retrieving spermatozoa with the highest fertilising potential and their impact on ART outcomes are discussed.
Abstract: The application of assisted reproductive technologies (ART) has revolutionised the treatment of human infertility, giving hope to the patients previously considered incapable of establishing pregnancy While semen analysis is performed to access whether a sample has an adequate number of viable, motile and morphologically normal sperm cells able to achieve fertilisation, sperm selection techniques for ART aim to isolate the most competent spermatozoon which is characterised by the highest fertilising potential Based on the semen analysis results, the correct sperm selection technique must be chosen and applied In this review, different sperm selection strategies for retrieving spermatozoa with the highest fertilising potential and their impact on ART outcomes are discussed In addition, advantages and disadvantages of each method and the best suited techniques for each clinical scenario are described

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TL;DR: Patients with varicocele have an increase in sperm DNA fragmentation levels, particularly in oxidative stress-induced sperm DNA damage, particularly on the basis of single- and double-stranded DNA fragmentation.
Abstract: Purpose: Sperm DNA fragmentation is a major cellular mechanism underlying varicocele-related male infertility. However, the type of DNA fragmentation - whether oxidative or of another nature - remains unknown. Thus, the aim of this study was to evaluate single- and double-stranded sperm DNA fragmentation, and oxidative-induced sperm DNA damage in men with varicocele. Materials and Methods: A cross-sectional study was performed, including 94 normozoospermic adults, of which 39 men without varicocele (controls) and 55 men with varicocele grades II or III, uni- or bilaterally. All men collected semen by masturbation. After semen analysis, the remaining volume was used for evaluation of three types of sperm DNA damage: (i) total DNA fragmentation, using an alkaline comet assay, (ii) double-stranded DNA fragmentation, using a neutral comet assay, and (iii) oxidative DNA damage, using an alkaline comet assay associated with the DNA glycosylase formamidopyrimidine enzyme. In each assay, percentage of sperm with any degree of DNA fragmentation, and with high DNA fragmentation were compared between the groups using an unpaired Student's t test or a Mann-Whitney test. Results: The varicocele group presented a higher rate of sperm with fragmented DNA (both any and high DNA fragmentation), considering single-stranded DNA fragmentation, double-stranded DNA fragmentation, or a combination of both, as well as oxidative- induced DNA fragmentation. Conclusions: Patients with varicocele have an increase in sperm DNA fragmentation levels, particularly in oxidative stress-induced sperm DNA damage.


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TL;DR: The couple was diagnosed with male factor infertility (Asthenoteratozoospermia), the couple was counselled and suggested for treatment of Intracytoplasmic Sperm Insemination with self-oocytes and donor sperms and Freeze all strategy for embryo transfer.
Abstract: Introduction: Approximately about 15%-20% of couples are affected by infertility. By the means of diagnosis and treatment both the partners male and female must be evaluated simultaneously, since male contributes as a factor for infertility in 40-60%. The primary step to diagnose male’s infertility in any case scenario is qualitative semen analysis. Urological evaluation and physical examination of male should be carried out as there are many factors which can affect semen quality. Widely, in assisted reproductive technology (ART) treatment, couples diagnosed with grievous male infertility (Non-Obstructive Azoospermia/OATz syndrome) as well as female patient deprived of male partners eager to have pregnancy are recommended to opt cryo-preserved donor spermatozoa. Main symptoms and important clinical findings: Qualitative semen analysis showed poor motility (94%-96% Immotility) and morphology (98% abnormality). The main diagnoses, therapeutic interventions, and outcomes: The couple was diagnosed with male factor infertility (Asthenoteratozoospermia), the couple was counselled and suggested for treatment of Intracytoplasmic Sperm Insemination with self-oocytes and donor sperms and Freeze all strategy for embryo transfer. Wife conceived in first treatment cycle. Conclusion: Frozen embryo transfer of 03 Grade A day 4 morula was done in March 2020, and patient conceived in 1st cycle. Later in November 2020 couple was blessed with a baby girl.

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TL;DR: In this paper, the authors evaluated whether conventional semen parameters could predict assisted reproductive technology success and found that sperm motility significantly predicted both pregnancy and live birth rates and a cut-off of 5.5% was identified as a threshold to predict clinical pregnancy.
Abstract: BACKGROUND An explosive increase in couples attending assisted reproductive technology has been recently observed, despite an overall success rate of about 20%-30%. Considering the assisted reproductive technology-related economic and psycho-social costs, the improvement of these percentages is extremely relevant. However, in the identification of predictive markers of assisted reproductive technology success, male parameters are largely underestimated so far. STUDY DESIGN Retrospective, observational study. OBJECTIVES To evaluate whether conventional semen parameters could predict assisted reproductive technology success. MATERIALS AND METHODS All couples attending a single third-level fertility center from 1992 to 2020 were retrospectively enrolled, collecting all semen and assisted reproductive technology parameters of fresh cycles. Fertilization rate was the primary end-point, representing a parameter immediately dependent on male contribution. Pregnancy and live birth rates were considered in relation to semen variables. Statistical analyses were performed using the parameters obtained according to the World Health Organization manual editions used for semen analysis. RESULTS Note that, 22,013 in vitro fertilization and intracytoplasmic sperm injection cycles were considered. Overall, fertilization rate was significantly lower in patients with abnormal semen parameters compared to normozoospermic men, irrespective of the World Health Organization manual edition. In the in vitro fertilization setting, both progressive motility (p = 0.012) and motility after capacitation (p = 0.002) significantly predicted the fertilization rate (statistical accuracy = 71.1%). Sperm motilities also predicted pregnancy (p < 0.001) and live birth (p = 0.001) rates. In intracytoplasmic sperm injection cycles, sperm morphology predicted fertilization rate (p = 0.001, statistical accuracy = 90.3%). Sperm morphology significantly predicted both pregnancy (p < 0.001) and live birth (p < 0.001) rates and a cut-off of 5.5% was identified as a threshold to predict clinical pregnancy (area under the curve = 0.811, p < 0.001). DISCUSSION Interestingly, sperm motility plays a role in predicting in vitro fertilization success, while sperm morphology is the relevant parameter in intracytoplasmic sperm injection cycles. These parameters may be considered reliable tools to measure the male role on ART outcomes, potentially impacting the clinical management of infertile couples.

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TL;DR: In this article, the authors investigated the long-term effects of SARS-CoV-2 infection (COVID-19) and its relative treatment on male reproductive health.
Abstract: PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily via respiratory droplets and enters host cells through angiotensin-converting enzyme 2 (ACE-2) receptors. ACE-2 receptors have been identified in many tissues including testes. The aim of the study has been to investigate the long-term effects of SARS-CoV-2 infection (COVID-19) and its relative treatment on male reproductive health. METHODS: Cross-sectional analysis has been performed on 49 recovered COVID-19 patients who had semen analysis prior to the COVID-19 pandemic. Those who had a recovery time lag of at least 3 months have been re-examined, and 29 eligible patients with no andrological problems have been enrolled in the study. Following a detailed physical examination and retrieval of medical history, the values of semen analysis and serum sex hormone parameters have been collected and compared before and after COVID-19 infection. The p value of <0.05 has been considered significant. RESULTS: The average age of the 29 patients has been 31.21 ± 5.48 (range: 18-41) years. Favipiravir has been co-administered with hydroxychloroquine in 17 patients, while the remaining 12 received favipiravir treatment without hydroxychloroquine. The average time between clinical recovery from COVID-19 and collection of semen has been 4.52 ± 1.36 (range: 3-8) months. Before and after COVID-19, serum follicle-stimulating hormone, luteinizing hormone, total testosterone, and prolactin levels, as well as all semen parameters, have been comparable. CONCLUSION: Our study demonstrated that COVID-19 and its treatment with favipiravir and hydroxychloroquine did not affect spermatogenesis and serum androgen levels in the long-term period. Further clinical studies with larger sample size are needed to confirm and support our findings.