Persistent oligonecrozoospermia after asymptomatic SARS-CoV-2 infection. A case report and literature review.

COVID-19 is known to have deleterious effects on different systems such as the respiratory, cardiovascular, central nervous, and gastrointestinal. However, conflicting data about the possible implications for male reproductive health and fertility have been reported. In addition, the long-term consequences of SARS-CoV-2 infection remain unclear. Herein, we report a case of a 42-year-old man with no known co-morbidities and normal baseline semen quality, who subsequently suffered an asymptomatic SARS-CoV-2 infection. Shortly after, the patient developed sudden oligoasthenozoospermia, even reaching azoospermia, which gradually evolved into persistent severe oligonecrozoospermia, accompanied by semen inflammation and oxidative stress. Remarkably, the latter occurred in the absence of urogenital infections, hormonal imbalances, tissue/organ obstruction/damage, medication or drug treatment, smoking, or exposure to toxins/pollutants, radiation, or high temperature. This case constitutes valuable clinical evidence that adds to the current knowledge in the field and highlights the need for further and longer follow-up studies to better understand the putative long-term consequences of SARS-CoV-2 infection on male fertility.

COVID-19 associates with semen inflammation and sperm quality impairment that reverses in the short term after disease recovery.

Introduction: COVID-19 exerts deleterious effects on the respiratory, cardiovascular, gastrointestinal, and central nervous systems, causing more severe disease in men than in women. However, cumulative reported data about the putative consequences on the male reproductive tract and fertility are controversial. Furthermore, the long-term effects of SARS-CoV-2 infection are still uncertain. Methods: In this study, we prospectively evaluated levels of inflammatory cytokines and leukocytes in semen and sperm quality parameters in a cohort of 231 reproductive-aged male patients, unvaccinated, who had recovered from mild or severe COVID-19 and in 62 healthy control individuals. Sperm quality was assessed early (less than 3 months) and long (more than 3 and up to 6 months) after having COVID-19. Interestingly, and unlike most reported studies, available extensive background and baseline data on patients' sperm quality allowed performing a more accurate analysis of COVID-19 effects on sperm quality. Results: Significantly higher levels of IL-1ß, TNF and IFNγ were detected in semen from patients recently recovered from mild and/or severe COVID-19 with respect to control individuals indicating semen inflammation. Moreover, patients recovered from mild and/or severe COVID-19 showed significantly reduced semen volume, lower total sperm counts, and impaired sperm motility and viability. Interestingly, all observed alterations returned to baseline values after 3 or more months after disease recovery. Discussion: These results indicate that COVID-19 associates with semen inflammation and impaired semen quality early after disease. However, long COVID-19 seems not to include long-term detrimental consequences on male fertility potential since the observed alterations were reversible after 1-2 spermatogenesis cycles. These data constitute compelling evidence allowing a better understanding of COVID-19 associated sequelae, fundamental for semen collection in assisted reproduction.

Chronic epididymitis due to Chlamydia trachomatis LGV-L2 in an HIV-negative heterosexual patient: a case report.

Chlamydia trachomatis is an obligate intracellular pathogen and the leading bacterial cause of sexually transmitted infections worldwide. Chlamydia trachomatis genovars L1-L3 are responsible for lymphogranuloma venereum (LGV), an invasive sexually transmitted disease endemic in tropical and subtropical regions of Africa, South America, the Caribbean, India and South East Asia. The typical signs and symptoms of C. trachomatis LGV urogenital infections in men include herpetiform ulcers, inguinal buboes, and/or lymphadenopathies. Since 2003, endemic cases of proctitis and proctocolitis caused by C. trachomatis LGV emerged in Europe, mainly in HIV-positive men who have sex with men (MSM). Scarce data have been reported about unusual clinical presentations of C. trachomatis LGV urogenital infections. Herein, we report a case of a 36-year-old heterosexual, HIV-negative male declaring he did not have sex with men or trans women, who presented to the Urology and Andrology outpatient clinic of a healthcare center from Cordoba, Argentina, with intermittent testicular pain over the preceding 6 months. Doppler ultrasound indicated right epididymitis and funiculitis. Out of 17 sexually transmitted infections (STIs) investigated, a positive result was obtained only for C. trachomatis. Also, semen analysis revealed oligoasthenozoospermia, reduced sperm viability as well as increased sperm DNA fragmentation and necrosis, together with augmented reactive oxygen species (ROS) levels and the presence of anti-sperm IgG autoantibodies. In this context, doxycycline 100 mg/12 h for 45 days was prescribed. A post-treatment control documented microbiological cure along with resolution of clinical signs and symptoms and improved semen quality. Strikingly, sequencing of the ompA gene revealed C. trachomatis LGV L2 as the causative uropathogen. Remarkably, the patient did not present the typical signs and symptoms of LGV. Instead, the infection associated with chronic testicular pain, semen inflammation and markedly reduced sperm quality. To our knowledge, this is the first reported evidence of chronic epididymitis due to C. trachomatis LGV L2 infection in an HIV-negative heterosexual man. These findings constitute important and valuable information for researchers and practitioners and highlight that C. trachomatis LGV-L2 should be considered as putative etiologic agent of chronic epididymitis, even in the absence of the typical LGV signs and symptoms.

Interferon γ, IL-17, and IL-1ß impair sperm motility and viability and induce sperm apoptosis.

Urogenital inflammation is a known cause of male infertility. Increased levels of inflammatory cytokines, leukocyte counts and oxidative stress are highly detrimental for sperm quality thus compromising male fertility. Although cytokines affect sperm by recruiting and activating leukocytes consequently inducing tissue inflammation and oxidative stress, scarce to absent data have been reported about the putative direct effects of inflammatory cytokines on spermatozoa. Herein, we analyzed whether IFNγ, IL-17A, IL-1ß, and IL-8 can alter human sperm motility and viability per se. Fractions of viable and motile spermatozoa from normospermic healthy donors were in vitro incubated with recombinant human IFNγ, IL-17A, IL-1ß or IL-8 and sperm ROS production, motility, viability and apoptosis were analyzed. Sperm exposed to different concentrations of IFNγ, IL-17A and IL-1ß, or a combination of them, for either 1 or 3 h showed significantly increased levels of mitochondrial ROS production and reduced motility and viability with respect to sperm incubated with vehicle. Moreover, the exposure to IFNγ, IL-17A and IL-1ß resulted in significantly higher levels of early and/or late apoptotic and/or necrotic spermatozoa. Interestingly, no significant differences in sperm motility, viability and apoptosis were observed in sperm incubated with the concentrations of IL-8 analyzed, for either 1 or 3 h, with respect to sperm incubated with vehicle. In conclusion, our results indicate that IFNγ, IL-17A and IL-1ß per se impair sperm motility and decreases viability by triggering increased mitochondrial ROS production and inducing sperm apoptosis. Our results suggest that screening inflammatory cytokines in semen would be an additional helpful tool for the diagnostic workup of male infertility.

Results from a large cross-sectional study assessing Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma hominis urogenital infections in patients with primary infertility.

Female and male infertility have been associated to Chlamydia trachomatis, Ureaplasma spp. and Mycoplasma hominis urogenital infections. However, evidence from large studies assessing their prevalence and putative associations in patients with infertility is still scarce. The study design was a cross-sectional study including 5464 patients with a recent diagnosis of couple's primary infertility and 404 healthy control individuals from Cordoba, Argentina. Overall, the prevalence of C. trachomatis, Ureaplasma spp. and M. hominis urogenital infection was significantly higher in patients than in control individuals (5.3%, 22.8% and 7.4% vs. 2.0%, 17.8% and 1.7%, respectively). C. trachomatis and M. hominis infections were significantly more prevalent in male patients whereas Ureaplasma spp. and M. hominis infections were more prevalent in female patients. Of clinical importance, C. trachomatis and Ureaplasma spp. infections were significantly higher in patients younger than 25 years. Moreover, Ureaplasma spp. and M. hominis infections were associated to each other in either female or male patients being reciprocal risk factors of their co-infection. Our data revealed that C. trachomatis, Ureaplasma spp. and M. hominis are prevalent uropathogens in patients with couple's primary infertility. These results highlight the importance of including the screening of urogenital infections in the diagnostic workup of infertility.

Association between meteorological variables and semen quality: a retrospective study.

Spermatogenesis is a temperature-dependent process, and high summer temperatures have been linked to lower sperm concentration and count. However, reports describing the association between other meteorological variables and semen quality are scarce. This study evaluated the association between semen quality and temperature, humidity, pressure, apparent temperature (AT), temperature-humidity index (THI), simplified wet-bulb global temperature (sWBGT), and sunshine duration. Semen samples were obtained at the Laboratorio de Andrología y Reproducción (LAR, Argentina), from men undergoing routine andrology examination (n=11657) and computer-assisted sperm analysis (n=4705) following WHO 2010 criteria. Meteorological variables readings were obtained from the Sistema Meteorológico Nacional. Sperm quality parameters were negatively affected in summer when compared to winter. Additionally, there was a significant decrease in sperm kinematics between winter and spring. Branch and bound variable selection followed by multiple regression analysis revealed a significant association between semen quality and meteorological variables. Specifically, changes in sunshine duration and humidity reinforced the prognosis of semen quality. Highest/lowest sunshine duration and humidity quantiles resulted in decreased sperm concentration, count, motility, vitality and membrane competence, nuclear maturity, and sperm kinematics associated to highest sunshine duration and lowest humidity. Findings from this report highlight the relevance of environmental studies for predicting alterations in male reproductive health associated to variations in meteorological variables, especially considering the current climate changes around the planet due to global warming and its consequences for human health.

Impact of age, clinical conditions, and lifestyle on routine semen parameters and sperm kinematics.

OBJECTIVE: To assess the impact of aging on routine semen and computer-assisted sperm analysis (CASA) motility parameters according to the current World Health Organization guidelines; and to evaluate the effect of obesity and lifestyle (alcohol consumption, cigarette smoking) in older men's semen. DESIGN: Blind cross-sectional study. SETTING: Research laboratory and andrology and reproduction laboratory. PATIENT(S): A population of 11,706 men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis: routine (semen volume, sperm concentration and count, motility, vitality, morphology, hypo-osmotic swelling test, round and peroxidase-positive cell concentration) and CASA (straight-line velocity, curvilinear velocity, average path velocity, linearity, straightness, beat cross frequency, wobble, amplitude of lateral head displacement, and mean angular displacement) parameters; and body mass index. RESULT(S): A negative correlation was found between age and routine semen parameters: volume, sperm count, motility, vitality, total motile spermatozoa and normal-motile spermatozoa, round cell concentration, and hypo-osmotic swelling test values. Several CASA variables (straight-line velocity, curvilinear velocity, average path velocity, beat cross frequency, amplitude of lateral head displacement, and mean angular displacement) were also negatively affected. Using 40 years as a cut-off value, significant differences in most parameters correlated to age. In a selected subpopulation of men unexposed to known fertility-compromising factors, the same evaluations were performed, finding some parameters still decreased. Although obesity exerted a significant deleterious effect on older patients' semen quality, alcohol consumption and cigarette smoking mildly affected it. CONCLUSION(S): Male aging, with the contribution of unhealthy conditions, are paramount effectors of sperm quality deterioration.

Incidence of Sperm Surface Autoantibodies and Relationship with Routine Semen Parameters and Sperm Kinematics.

PROBLEM: Antisperm antibodies (ASA) are associated with male subfertility. However, results on sperm surface autoantibodies are controversial, the relationship between ASA and semen parameters (WHO, 2010) is unknown, and data on ASA and sperm kinematics are scarce. METHOD OF STUDY: A retrospective study carried out in men undergoing routine semen analysis (WHO 2010), ASA evaluation (direct SpermMAR(™) (IgG) test), and computer-assisted sperm analysis (CASA). RESULTS: A 2.6% and a 5.9% incidence of ASA-positive cases were found (cut-off 50% and 10%, respectively; n = 7492). ASA-positive samples had lower (P < 0.0001) sperm concentration, count, motility, and hypo-osmotic swelling (HOS) test score. HOS results did not correlate with sperm vitality in normozoospermic samples with high ASA levels. In unselected samples, ASA-positive samples (cut-off 50%) showed decreased sperm kinematics (VSL, VAP, LIN, ALH, STR, BCF, WOB), but in normozoospermic samples, ASA-positive and ASA-negative subgroups had similar CASA results. CONCLUSIONS: ASA evaluation is highly relevant in full semen assessment.

The impact of obesity on male reproduction: its biological significance.

Since obesity and male subfertility have increased in parallel during the last decades, the hypothesis of an association between these two phenomena has been explored by several researchers. Although there is no consensus apparently obesity impacts men's reproductive potential by several mechanisms, like alterations on the hypothalamus-pituitary-testicular axis, modifications of spermatogenesis and semen quality and/or impairment of men's sexual health. This review intends to summarize the underlying bases of such alterations and propose new ones, without miscalculating their biological significance. Obesity is not rigorously related to subfertility; in addition, the existence of a genetic predisposition to obesity-linked sterility is currently under investigation. Nonetheless, the impact of obesity on male reproductive potential must be fully elucidated since the prevalence of obesity is increasing and consequently, the number of obese men with reduced fertility will also rise.

Semen quality and aging: analysis of 9.168 samples in Cordoba. Argentina.

OBJECTIVES: Concomitantly with the actual trend towards later fathering, more detailed studies are necessary to establish the relationship between male age and seminal features. The objective of the present paper was to evaluate the relationship of men age with semen quality and with the seminal levels of epididymal and accessory gland markers. METHODS: The study was conducted as a retrospective study of 9168 cases obtained from the Andrology and Reproduction Laboratory in Cordoba, Argentina for 10 years (1995-2004) (men ages 20 to 77). An important number of factors such as abstinence time, toxic habits, work conditions and drugs consumption has been statistically considered. The parameters measured were: seminal volume, sperm concentration, total sperm count, sperm motility, morphology and viability. Seminal levels of alpha-glucosidase, fructose and citric acid were also evaluated. RESULTS: We detected a significant decrease in seminal volume, sperm count, motility, viability and normal morphology, and a reduction in alpha-glucosidase and fructose levels in relation to age. CONCLUSIONS: Since semen quality is a tool for fertility prognosis estimation, the weight of evidence indicates that men may become progressively less fertile as they get older. Couples who decide to delay childbearing should be warned about this matter.

Envejecimiento y calidad seminal: un análisis en 9.168 casos en Córdoba. Argentina / Semen quality and aging: a 9.168 sample study in Cordoba. Argentina

OBJETIVO: En coincidencia con la actual tendencia hacia la paternidad tardía, son necesarios más estudios para establecer la relación entre la edad del varón y las características seminales.El objetivo del presente trabajo fue evaluar la relación de la edad con la calidad espermática y con los niveles seminales de marcadores funcionales del epidídimo y de glándulas anexas.MÉTODOS: este estudio retrospectivo fue realizado sobre 9168 casos obtenidos de hombres miembros de parejas con problemas de fertilidad que se presentaron en el Laboratorio de Andrología y Reproducción, en Córdoba, Argentina durante 10 años (1995-2004) (en pacientes entre 20 y 77 años). Se controló estadísticamente un importante número de posibles factores de confusión tales como tiempo de abstinencia sexual, hábitos tóxicos, condiciones laborales y consumo de medicamentos. Los parámetros evaluados fueron: volumen seminal, concentración espermática, número total de espermatozoides, motilidad, morfología y vitalidad espermática. Se cuantificaron además las concentraciones seminales de alfa-glucosidasa, fructosa y ácido cítrico.RESULTADOS: en el presente estudio detectamos un descenso significativo en el volumen seminal, el recuento espermático, la motilidad, la vitalidad y el porcentaje de espermatozoides morfológicamente normales, así como una reducción en los niveles de alfa-glucosidasa y fructosa seminales en relación con la edad.CONCLUSIONES: dado que la calidad seminal constituye un factor de pronóstico para la fertilidad masculina, las evidencias indican que los hombres podrían disminuir su fertilidad a medida que envejecen. Aquellas parejas que decidan postergar su paternidad deben ser advertidas acerca de este hecho(AU)

OBJECTIVES: Concomitantly with the actual trend towards later fathering, more detailed studies are necessary to establish the relationship between male age and seminal features.The objective of the present paper was to evaluate the relationship of men age with semen quality and with the seminal levels of epididymal and accessory gland markers.METHODS: The study was conducted as a retrospective study of 9168 cases obtained from the Andrology and Reproduction Laboratory in Cordoba, Argentina for 10 years (1995-2004) (men ages 20 to 77). An important number of factors such as abstinence time, toxic habits, work conditions and drugs consumption has been statistically considered. The parameters measured were: seminal volume, sperm concentration, total sperm count, sperm motility, morphology and viability. Seminal levels of alpha-glucosidase, fructose and citric acid were also evaluated.RESULTS: We detected a significant decrease in seminal volume, sperm count, motility, viability and normal morphology, and a reduction in alpha-glucosidase and fructose levels in relation to age.CONCLUSIONS: Since semen quality is a tool for fertility prognosis estimation, the weight of evidence indicates that men may become progressively less fertile as they get older. Couples who decide to delay childbearing should be warned about this matter(AU)