SARS-CoV-2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services.

The prolonged lockdown of health facilities providing non-urgent gamete cryopreservation-as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS-CoV-2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and propose that the same permissive approach for sperm banking granted for men with cancer is expanded to other groups of vulnerable patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto-immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. In both scenarios, the "fertility window" may be transitory; postponing diagnostic semen analysis and sperm banking in these men could compromise the prospects of biological parenthood. Moreover, we provide recommendations on how to continue the provision of andrological services in a considered manner and a safe environment. Our opinion is timely and relevant given the fact that fertility services are currently rated as of low priority in most countries.

Varicocele-Associated Infertility and the Role of Oxidative Stress on Sperm DNA Fragmentation.

Varicocele has been extensively described and studied as the most important reversible cause of male infertility. Its impact on semen parameters, pregnancy rates, and assisted reproductive outcomes have been associated with multifactorial aspects, most of them converging to increase of reactive oxygen species (ROS). More recently, sperm DNA fragmentation has gained significant attention and potential clinical use, although the body of evidence still needs further evolution. The associations between sperm DNA damage and a variety of disorders, including varicocele itself, share common pathways to ROS increase. This mini-review discusses different aspects related to the etiology of ROS and its relation to varicocele and potential mechanisms of DNA damage.

Bariatric Surgery Impact on Reproductive Hormones, Semen Analysis, and Sperm DNA Fragmentation in Men with Severe Obesity: Prospective Study.

PURPOSE: Growing evidence in the literature suggests that obesity is capable of altering reproductive hormone levels and male fertility. Effects on classic semen parameters and sperm DNA fragmentation (SDF), however, have not been properly established. Additionally, the impact of bariatric surgery (BS) on those parameters is still controversial. MATERIALS AND METHODS: In Phase 1, 42 patients with obesity and 32 fertile controls were submitted to reproductive hormone evaluation, semen analysis, and SDF testing. In Phase 2, patients with obesity were submitted to BS or clinical follow-up and were invited to 6-month revaluation. RESULTS: Phase 1: Men with obesity have higher levels of estradiol, LH, and FSH and lower levels of total testosterone (TT) when compared with eutrophic fertile men. Additionally, they present worse semen parameters, with reduction in ejaculated volume and sperm concentration, worse sperm motility and morphology, and higher SDF. Phase 2: 32 patients returned to revaluation. Eighteen were submitted to BS (group S) and 14 were not submitted to any specific therapeutic regimen (group NS). In group S, TT more than doubled after surgery (294.5 to 604 ng/dL, p < 0.0001). Worsening of sperm concentration and total ejaculated sperm count were also noticed, and 2 patients became azoospermic after BS. SDF, however, improved after the procedure. No changes in the variables studied were observed in non-operated patients. CONCLUSION: In this prospective study, we have found that BS results in improvements in reproductive hormone levels and SDF after 6-month follow-up. Sperm concentration, however, reduced after the procedure.

Gonadal Function and Reproductive System Anatomy in Postpubertal Prune-Belly Syndrome Patients.

OBJECTIVE: To gain insight into the causes of infertility in Prune Belly Syndrome (PBS) by evaluating reproductive system anatomy and gonadal function in a cohort of postpubertal PBS patients. METHODS: We contacted all PBS patients 14 years old or older treated and followed at our institution. Age at orchiopexy, type of orchiopexy (with or without ligation of gonadal vessels), testicular volumes and positions were evaluated. Pelvic magnetic resonance imaging (to assess prostate size, seminal vesicles, and vas) and hormonal profile were ordered. Sperm analysis and analysis of urine after masturbation were performed after informed consent. RESULTS: Fifteen patients were included in this study. Mean age was 19.2 years. Mean age at orchiopexy was 18 months. Fourteen patients (93.3%) had normal and orthotopic testes. Mean testicular volume was 6.9 cc. Eight patients collected semen, 5 of them (62.5%) had spermatozoa in the specimen and motile sperm was found in 4 (50%). Mean hormone levels were LH: 5.3 mg/dL, FSH: 6.9 mg/dL, testosterone 531 mg/dL. Magnetic resonance imaging revealed hypoplastic prostates in 66.6% and unilateral seminal vesicle absence in 66.6%. No vasal abnormality was noted. CONCLUSION: Patients with PBS may have normal sexual hormonal levels. Motile spermatozoa were found in half of the patients. Our study highlights a high prevalence of prostate and seminal vesicle abnormalities that may represent an important cause for their infertility.

Diagnostic accuracy of physical examination compared with color Doppler ultrasound in the determination of varicocele diagnosis and grading: Impact of urologists' experience.

BACKGROUND: Treatment of palpable varicocele in infertile men with abnormal semen parameters is widely accepted, and physical examination (PE) remains a cornerstone for recommending varicocele repair. However, identification of clinical varicocele during PE can be challenging for both urology residents and consultants. OBJECTIVE: To compare the diagnostic accuracy of PE to color Doppler ultrasonography (CDU) for the diagnosis of varicocele in experienced and non-experienced examiners. MATERIALS AND METHODS: Diagnostic accuracy study involving 78 patients attending a university-based infertility unit. Patients underwent scrotal PE by both experienced (over 10 years experience in male infertility) and non-experienced urologists (senior residents), and were subjected to CDU. varicocele diagnosis and varicocele grading were compared between examiner groups and to CDU. Accuracy measures were evaluated, and interobserver agreement was estimated using unweighted kappa statistics. A subgroup analysis for normal and high body mass index (BMI) was also performed for the same variables. RESULTS: Accuracy of PE for varicocele diagnosis was 63.5% with a positive predictive value (PPV) of 75.5%. The specificity and PPV of PE were higher among experienced than non-experienced urologists (82.0% CI: 74.27-88.26 and 81.1% CI: 74.39-86.44% vs 67.2% CI: 58.33-75.22 and 70.6% CI: 64.52-76.08, respectively). Agreements on varicocele diagnosis (k: 0.625 vs 0.517) and grading (k: 0.548 vs 0.418) by PE were higher among experienced than non-experienced urologists. Differences between eutrophic and overweight/obese patients were also suggested. DISCUSSION AND CONCLUSIONS: PE performed by infertility specialists identify patients with varicocele more precisely than non-specialists. However, PE alone has suboptimal accuracy for varicocele diagnosis. Our results indicate that PE should be followed by CDU to decrease the number of false positives and increase the diagnostic accuracy of varicocele diagnosis.

Optimizing male fertility: oxidative stress and the use of antioxidants.

PURPOSE: Management of male infertility is always a difficult task, with pathophysiology and available treatments often poorly understood. The purpose of this review was to summarize current evidence regarding the use of protective agents against reactive oxygen species (ROS), such as antioxidants that may be useful in the treatment of male factor infertility. METHODS: For this publication, a search of studies concerning oxidative stress, male infertility and antioxidant therapy was performed using the search engines ScienceDirect, OVID, PubMed and MEDLINE. Articles published in languages other than English were not considered. RESULTS: An interest in the physiologic and pathologic effects of ROS has grown. Nevertheless, use of antioxidants is challenging, considering the balance between physiological ROS activity and detrimental oxidative stress level. Several studies have shown positive outcomes in terms of semen parameters, with others having failed to do so. Available evidence is still limited in pregnancy and live birth rates. CONCLUSIONS: Protective agents against ROS, such as antioxidants, may have positive effects on semen parameters in some patients, although a widespread indication is still restricted by practical aspects, including unknown physiological levels of ROS and controversy regarding different concentrations and combinations of drugs.

Positive rheotaxis extended drop: a one-step procedure to select and recover sperm with mature chromatin for intracytoplasmic sperm injection.

PURPOSE: The purpose of this study was to develop a novel one-step ICSI approach to select sperm with better chromatin maturity than the conventional method. METHODS: This was a pilot diagnostic study, which prospectively recruited men during a 6-month period in a University-affiliated infertility centre. Forty consecutive semen samples were provided for analysis. The positive rheotaxis extended drop (PRED) was set up creating a pressure and viscosity gradient. Each semen sample was divided into four aliquots: one aliquot for density gradient centrifugation (DGC), two aliquots for PRED (fresh semen (PRED-FS) and processed semen (PRED-DGC)), and one aliquot as the control (FS). In PRED, a mean of 200 spermatozoa were collected consecutively without selection from the outlet reservoir. The aniline blue assay was used to assess chromatin immaturity. RESULTS: The mean channel length, measured from inlet to outlet, was 32.55 ± 0.86 mm, with a mean width of 1.04 ± 0.21 mm. In 82.5% of cases (33/40), at least 50 spermatozoa were captured between 15 and 30 min. Improved chromatin maturity after the DGC preparation and the PRED approach was observed in all samples. This was reflected by a mean reduction from 28.65 ± 8.97% uncondensed chromatin in the native ejaculates to 17.29 ± 7.72% in DGC and 0.89 ± 1.31% in the PRED approach (P < 0.01). CONCLUSIONS: The PRED method may improve the current ICSI technique by providing it with its own sperm selection process. ICSI would probably become an even more complete technique comprising selection, capture and injection of the male gamete.

Ozone decreases sperm quality in systemic lupus erythematosus patients.

OBJECTIVE: To investigate the deleterious effects of air pollutants exposure in the Sao Paulo metropolitan region on semen quality in systemic lupus erythematosus (SLE). METHODS: A seven-years longitudinal repeated-measures panel study was performed at the Laboratory of Experimental Air Pollution and Rheumatology Division. Two semen samples from 28 post-pubertal SLE patients were analyzed. Daily concentrations of air pollutants exposure: PM10, SO2, NO2, ozone, CO, and meteorological variables were evaluated on 90 days before each semen collection dates using generalized estimating equation models. RESULTS: Intravenous cyclophosphamide (IVCYC) and ozone had an association with a decrease in sperm quality of SLE patients. IVCYC was associated with decreases of 64.3 million of spermatozoa/mL (95% CI 39.01-89.65; p=0.0001) and 149.14 million of spermatozoa/ejaculate (95% CI 81.93-216.38; p=0.017). With regard to ozone, the most relevant adverse effects were observed from lags 80-88, when the exposure to an interquartile range increase in ozone 9-day moving average concentration led to decreases of 22.9 million of spermatozoa/mL (95% CI 5.8-40.0; p=0.009) and 70.5 million of spermatozoa/ejaculate (95% CI 12.3-128.7; p=0.016). Further analysis of 17 patients that never used IVCYC showed association between exposure to ozone (80-88 days) and decrease of 30.0 million of spermatozoa/mL (95% CI 7.0-53.0; p=0.011) and 79.0 million of spermatozoa/ejaculate (95% CI 2.1-155.9; p=0.044). CONCLUSION: Ozone and IVCYC had a consistent adverse effect on semen quality of SLE patients during spermatogenesis. Minimizing exposure to air pollution should be taken into account, especially for patients with chronic systemic inflammatory diseases living in large cities.

Ozone decreases sperm quality in systemic lupus erythematosus patients / O ozônio diminui a qualidade do sêmen em pacientes com lúpus eritematoso sistêmico

Abstract Objective To investigate the deleterious effects of air pollutants exposure in the Sao Paulo metropolitan region on semen quality in systemic lupus erythematosus (SLE). Methods A seven-years longitudinal repeated-measures panel study was performed at the Laboratory of Experimental Air Pollution and Rheumatology Division. Two semen samples from 28 post-pubertal SLE patients were analyzed. Daily concentrations of air pollutants exposure: PM10, SO2, NO2, ozone, CO, and meteorological variables were evaluated on 90 days before each semen collection dates using generalized estimating equation models. Results Intravenous cyclophosphamide (IVCYC) and ozone had an association with a decrease in sperm quality of SLE patients. IVCYC was associated with decreases of 64.3 million of spermatozoa/mL (95% CI 39.01–89.65; p = 0.0001) and 149.14 million of spermatozoa/ejaculate (95% CI 81.93–216.38; p = 0.017). With regard to ozone, the most relevant adverse effects were observed from lags 80–88, when the exposure to an interquartile range increase in ozone 9-day moving average concentration led to decreases of 22.9 million of spermatozoa/mL (95% CI 5.8–40.0; p = 0.009) and 70.5 million of spermatozoa/ejaculate (95% CI 12.3–128.7; p = 0.016). Further analysis of 17 patients that never used IVCYC showed association between exposure to ozone (80–88 days) and decrease of 30.0 million of spermatozoa/mL (95% CI 7.0–53.0; p = 0.011) and 79.0 million of spermatozoa/ejaculate (95% CI 2.1–155.9; p = 0.044). Conclusion Ozone and IVCYC had a consistent adverse effect on semen quality of SLE patients during spermatogenesis. Minimizing exposure to air pollution should be taken into account, especially for patients with chronic systemic inflammatory diseases living in large cities.

Resumo Objetivo Investigar os efeitos deletérios da exposição aos poluentes do ar na Região Metropolitana de São Paulo sobre a qualidade do sêmen de pacientes com lúpus eritematoso sistêmico (LES). Métodos Foi feito um estudo longitudinal de painel com medidas repetidas de sete anos no Laboratório de Poluição Atmosférica Experimental e Reumatologia. Foram analisadas duas amostras de sêmen de 28 pacientes com LES pós‐púberes. Foram avaliadas as concentrações diárias de exposição aos poluentes do ar PM10, SO2, NO2, ozônio e CO e variáveis meteorológicas 90 dias antes de cada data de coleta de sêmen com o uso do método de equações de estimativas generalizadas. Resultados A ciclofosfamida intravenosa (CICIV) e o ozônio estiveram associados a uma diminuição na qualidade do sêmen dos pacientes com LES. A CICIV esteve associada a um decréscimo de 64,3 milhões de espermatozoides/mL (IC 95% 39,01‐89,65; p = 0,0001) e 149,14 milhões de espermatozoides/ejaculado (IC 95% 81,93‐216,38; p = 0,017). Em relação ao ozônio, os efeitos adversos mais relevantes foram observados entre os lags (intervalo de tempo) 80 e 88, quando a exposição a uma concentração média de ozônio um intervalo interquartil maior em nove dias móveis levou a um decréscimo de 22,9 milhões de espermatozoides/mL (IC 95% 5,8‐40; p = 0,009) e 70,5 milhões de espermatozoides/ejaculado (IC 95% 12,3‐128,7; p = 0,016). Uma análise mais aprofundada dos 17 pacientes que nunca usaram CICIV mostrou associação entre a exposição ao ozônio (80‐88 dias) e o decréscimo de 30 milhões de espermatozoides/mL (IC 95% 7‐53; p = 0,011) e 79 milhões de espermatozoides/ejaculado (IC 95% 2,1‐155,9; p = 0,044). Conclusão O ozônio e a CICIV tiveram um efeito adverso consistente sobre a qualidade do sêmen de pacientes com LES durante a espermatogênese. Deve‐se considerar a minimização da exposição à poluição do ar, especialmente para pacientes com doenças inflamatórias sistêmicas crônicas que vivem nas grandes cidades.

Male fertility potential alteration in rheumatic diseases: a systematic review.

BACKGROUND: Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. MATERIALS AND METHODS: A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. RESULTS: A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. CONCLUSIONS: Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy.

Male fertility potential alteration in rheumatic diseases: a systematic review

ABSTRACT Background Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. Materials and Methods A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. Results A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Conclusions Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy.

Summary evidence on the effects of varicocele treatment to improve natural fertility in subfertile men.

The objective of this review was to summarize the evidence concerning the benefit of varicocele treatment to improve natural fertility in subfertile males. We also analyzed the effect of varicocele treatment on conventional semen parameters and sperm functional tests. An electronic search to collect the data was performed using the PubMed/MEDLINE databases until July 2015. Data pooled from a variety of study designs indicate that varicocelectomy improves semen parameters in the majority of the treated men with clinical varicocele and abnormal semen parameters regardless of the chosen surgical method. Surgical varicocele repair was beneficial not only for alleviating oxidative stress-associated infertility but also to improve sperm nuclear DNA integrity. However, given the low magnitude of the effect size in sperm DNA integrity, further research is needed to elucidate its clinical significance. Conflicting results on the effect of varicocele treatment on natural fertility seem to be due to heterogeneous study designs and, more importantly, patient selection criteria. When these issues are controlled, current evidence indicates that treatment of subclinical varicocele is not warranted, as it does not seem to improve fertility. On the contrary, fair evidence indicates that varicocele treatment should be offered to infertile patients with palpable varicocele and abnormal semen parameters. This evidence supports the current guidelines issued by the American Urological Association and European Association of Urology, which state that varicocele treatment should be offered to male partners of infertile couples presenting for evaluation with clinical varicocele and semen parameters alterations.