Antioxidant Intervention against Male Infertility: Time to Design Novel Strategies.

Infertility is a highly prevalent condition, affecting 9-20% of couples worldwide. Among the identifiable causes, the male factor stands out in about half of infertile couples, representing a growing problem. Accordingly, there has been a decline in both global fertility rates and sperm counts in recent years. Remarkably, nearly 80% of cases of male infertility (MI) have no clinically identifiable aetiology. Among the mechanisms likely plausible to account for idiopathic cases, oxidative stress (OS) has currently been increasingly recognized as a key factor in MI, through phenomena such as mitochondrial dysfunction, lipid peroxidation, DNA damage and fragmentation and finally, sperm apoptosis. In addition, elevated reactive oxygen species (ROS) levels in semen are associated with worse reproductive outcomes. However, despite an increasing understanding on the role of OS in the pathophysiology of MI, therapeutic interventions based on antioxidants have not yet provided a consistent benefit for MI, and there is currently no clear consensus on the optimal antioxidant constituents or regimen. Therefore, there is currently no applicable antioxidant treatment against this problem. This review presents an approach aimed at designing an antioxidant strategy based on the particular biological properties of sperm and their relationships with OS.

Neoplasia intratubular testicular e infertilidad: azoospermia asociada a neoplasia intratubular testicular bilateral / Testicular intraepithelial neoplasia and infertility: azoospermia associated with bilateral testicular intraepithelial neoplasia

La neoplasia testicular intratubular es una lesión premaligna testicular asociada a tumores germinales primarios gonadales y extragonadales. La prevalencia de neoplasia testicular intratubular en pacientes infértiles llega al 2% en diferentes estudios. Presentamos el caso de un paciente azoospérmico con diagnóstico incidental de neoplasia testicular intratubular bilateral en la biopsia testicular realizada durante la recuperación quirúrgica de espermatozoides. En pacientes infértiles, las técnicas de recuperación espermática deben incluir el estudio anatomopatológico de parénquima testicular para descartar enfermedad maligna asociada. Los pacientes con alteración de la espermatogénesis tienen mayor riesgo de presentar otras alteraciones del desarrollo gonadal (neoplasias, hipogonadismo, entre otros) en el contexto de un síndrome de disgenesia testicular (AU)

Testicular intraepithelial neoplasia is a premalignant lesion associated to gonadal and extragonadal germ cell tumors. Testicular intraepithelial neoplasia prevalence in infertile men has reached 2% in some studies. This report presents the case of an azoospermic man with an incidental diagnosis of bilateral testicular intraepithelial neoplasia after testicular sperm extraction. In infertile men, sperm retrieving techniques have to include histological analysis of testicular tissue, to discard any chance of malignant component. Patients with spermatogenesis alterations have an increased risk to present other disruptions in gonadal development (neoplasms, hypogonadism, among others) in the context of testicular dysgenesis syndrome (AU)

Concordance of renal stone culture: PMUC, RPUC, RSC and post-PCNL sepsis-a non-randomized prospective observation cohort study.

INTRODUCTION: Between 5 and 10% of patients undergoing percutaneous nephrolithotomy (PCNL) develop postoperative sepsis 1, 2. Strategies to prevent infectious complications are based on information provided by preoperative midstream urine cultures (PMUC). The aim of this study is to evaluate the concordance of the microbiologic findings of PMUC, cultures of the renal stone (RSC) and urine obtained directly from the renal pelvis (RPUC) in patients undergoing PCNL. MATERIALS AND METHODS: This is a multicenter prospective study. The study included all patients who underwent PCNL from May 2013 to July 2015 in three academic hospitals. All patients underwent a PMUC. Samples for RPUC were obtained by renal puncture for PCNL. Stone fragments extracted during the procedure were sent for culture (RSC). Clinical variables, stone configuration, burden and microbiology reports of cultures were recorded. We analyzed concordance between cultures and association with infectious complications. RESULTS: One hundred and twenty-two patients underwent PCNL. Twenty-four percent had positive culture, 3.2% (4/122) PMUC, 14.7% (18/122) RPUC and 13.9% (17/122) RSC. Positive PMUC demonstrated multidrug-susceptible Escherichia coli and Staphylococcus aureus, while RPUC showed multidrug-resistant pathogens and/or fungus. Seven patients (5.7%) developed postoperative infectious complications prior to discharge. There was a weak correlation between PMUC and intraoperative urine cultures (RPUC and RSC). Concordance rate between RPUC and RSC was 83.3%. The most common isolated pathogens were multidrug-resistant bacteria or fungus. CONCLUSIONS: PMUC did not reflect the microbiological environment found in stones and urine directly obtained from the renal pelvis. Patients with postoperative infectious complications had negative PMUC with positive RPUC or RSC. RPUC and RSC can help guide prompt and appropriate antibiotic treatment for patients who develop postoperative infectious complications after PCNL.

El urocultivo preoperatorio no refleja el status microbiólogico de pacientes sometidos a nefrolitotomía percutánea: mayor estudio multicéntrico en América Latina / Preoperative urine culture does not refledt the microbiological status of patiens undegoing percutaneous nephrolithotomy: Most comprehensive clinical trial in Latin America

Introducción: Entre el 50 por ciento a 10 por ciento de los pacientes sometidos a nefrolitotomía percutánea (NLP) presentará sepsis. Las estrategias de prevención de complicaciones infecciosas actuales, se basan en la información entregada por los cultivos de orina preoperatorios. El objetivo de este estudio es comparar los perfiles microbiológicos entre los cultivos de orina tradicionales preoperatorios, con cultivos del microambiente del cálculo renal (orina de pelvis renal y del cálculo) de pacientes sometidos a NLP.(AU)

Introduction. Between 50 pertcent to 10 pertcent of patients undergoing percutaneous nephrolithotomy (PCNL) will present sepsis. Current strategies for preventing infectious complications are based on the information provided by preoperative urine cultures. The aim of this study is to compare the microbiological profiles from traditional preoperative urine cultures with cultures from renal microenvironment (renal pelvis urine and kidney stone) of patients undergoing PCNL. Material y Methods. International multicenter prospective clinical trial. The study was conducted from December 2012 to May 2014 in three teaching hospitals, two from Chile and one from Argentina. All patients undergoing PCNL during that period were included. In a prospective fashion, preoperative urine culture, microbiological study of extracted urinary stones and cultures from renal pelvis urine were requested. In each hospital, data regarding patients was submitted through an online questionnaire: Age, sex, comorbidities, type of stone (staghorn or not), size of the stone, isolated bacteria, resistance profile and postoperative infectious complications were filled.(AU)

Prevalencia de microdeleciones del cromosoma Y en hombres chilenos infértiles / Y chromosome microdeletion prevalence in infertile Chilean men

Objetivo. El objetivo de este estudio es determinar la prevalencia de microdeleciones del cromosomaY en hombres chilenos infértiles. Material y métodos. Se incluyeron 102 hombres con diagnóstico de azoospermia u oligozoospermia severa que consultaron en la Unidad de Andrología por infertilidad. Se llevó a cabo análisis de microdeleciones de la región del factor de azoospermia (AZF) del cromosomaY a través de reacción en cadena de la polimerasa, utilizando ADN genómico extraído de leucocitos de sangre periférica. Cada paciente fue analizado utilizando sequence tagged sites para las regiones AZFa, AZFb y AZFc. Resultados. Sesenta y siete pacientes presentaron azoospermia y 35 oligozoospermia severa. Se encontraron microdeleciones del cromosomaY en el 9,8% de los pacientes. La mutación más prevalente fue AZFc, afectando al 3,9% de la muestra, seguida por AZFbc (2,9%), AZFa (2,0%) y AZFb (1,0%). Solo los hombres azoospérmicos presentaron las mutaciones. Conclusiones. La prevalencia de microdeleciones del cromosomaY en hombres chilenos infértiles es similar a la presentada en estudios internacionales. Estas mutaciones deben ser buscadas cuando se enfrenta a un paciente infértil con alteraciones cuantitativas severas del seminograma, ya que AZFa y AZFb están asociados con ausencia completa de gametos viables, y la portación de AZFc tiene importantes consecuencias en el potencial de fertilidad de la descendencia masculina (AU)

Objective. The aim of this study is to determine the prevalence of Ychromosome microdeletions in infertile Chilean men. Material and methods. A group of 102 infertile men with azoospermia or severe oligozoospermia were screened while attending a fertility clinic for microdeletions in the azoospermia factor (AZF) region of Ychromosome by multiplex polymerase chain reaction. Genomic DNA was extracted from peripheral blood samples. Each patient was analysed for the presence of sequence tagged sites in the AZFa, AZFb, and AZFc regions. Results. Azoospermia and severe oligozoospermia was found in 67 and 35 patients, respectively. Microdeletions were found in 9.8% of patients. The most prevalent mutation was AZFc, affecting 3.9% of the sample. This was followed by AZFbc with 2.9%, AZFa with 2.0%, and AZFb with 1.0%. Only azoospermic men were found to have these genetic alterations. Conclusions. Prevalence of Ychromosome microdeletions in infertile Chilean men is similar to the prevalence presented in international studies. As AZFa and AZFb mutations are associated with complete absence of viable gametes, and AZFc has important consequences in the fertility potential of the offspring, these mutations have to be searched when presented with an infertile patient with severe sperm alterations (AU)

Azoospermia y fertilización asistida: rol de la histología testicular en el éxito de icsi / Azoospermia and assisted reproduction: role of testicular histology in the success of ICSI

Introducción: La infertilidad masculina afecta aproximadamente al 7por ciento de los hombres, presentándose hasta el 15 por ciento de ellos con azoospermia. El conocimiento del tipo de azoospermia (obstructiva o no obstructiva) y la localización de la falla (pre-testicular, testicular o post-testicular) es vital para conocer el pronóstico de fertilidad de la pareja y plantear un plan terapéutico adecuado. Actualmente, la extracción de espermatozoides desde epidídimo o testículo de pacientes azoospérmicos, y la posterior inyección intracitoplásmática de éstos (ICSI, por sus siglas en inglés) ha permitido obtener embriones viables para su posterior transferencia. Materiales y métodos: Estudio descriptivo retrospectivo de 42 parejas infértiles con diagnóstico de azoospermia; que se sometieron a biopsia testicular, ICSI y posterior transferencia de embriones, entre los años 2004 y 2012. Se lleva a cabo un análisis de la edad de los pacientes, resultados de la histopatología testicular y su asociación con los resultados de la fertilización asistida. Resultados: 42 pacientes azoospérmicos se sometieron a biopsia testicular y extracción de espermatozoides en el mismo acto quirúrgico. La edad promedio de los pacientes fue de 36 años para los hombres y 32 años para las mujeres. En el análisis histológico de los tejidos testiculares, el 31por ciento de los pacientes presentaban espermatogénesis conservada (EC), el 35.7 por ciento atrofia mixta (AM), el 14.3 por ciento hipoespermatogénesis (HE), el 14.3 por ciento detención de la maduración (DM) y un 4.8 por ciento presentaba otras histologías. Lograron embarazo clínico 14 de 42 parejas (33,3 por ciento), siendo la tasa de embarazo específica por patología de 38,5 por ciento para EC, 26.7 por ciento para AM, 50 por ciento para HE, 16,7 por ciento para DM y 50 por ciento para las otras histologías. 12 de las 42 parejas realizaron más de un ciclo de transferencias...

Introduction: Male infertility affects approximately 7percent of men, presenting up to 15 percent with azoospermia. Knowing the type of azoospermia (obstructive or non-obstructive) and the location of the problem (pre-testicular, testicular and post-testicular) is vital to recognize the fertility prognosis of the couple and present a proper treatment plan. Currently, the extraction of sperm from epididymis or testis of azoospermic patients, and subsequent intracytoplasmic sperm injection (ICSI) has yielded viable embryos for transfer. Materials and Methods: Retrospective study of 42 infertile couples diagnosed with azoospermia, who underwent testicular biopsy, ICSI and subsequent embryo transfer, between 2004 and 2012. We performed an analysis of the patients’ age, testicular histopathology results and their association with assisted fertilization outcome. Results: 42 azoospermic patients underwent testicular biopsy and sperm extraction in the same surgery. The average age of patients was 36 years for men and 32 years for women. Histologic analysis of testicular tissue showed that 31 percent of patients had normal spermatogenesis (NS), 35.7 percent mixed atrophy (MA), 14.3 percent hypospermatogenesis (HS), 14.3 percent maturation arrest (MTA) and 4.8 percent had other histologies. 14 of 42 couples achieved clinical pregnancy (33.3 percent), with a specific pregnancy rate of 38.5 percent for NS, 26.7 percent for MA, 50 percent for HS, 16.7 percent for MTA and 50 percent for other histologies. 12 of 42 couples underwent more than one transfer cycle. Conclusions: The use of ICSI is a suitable alternative for infertile couples with severe male factor. The results of this technique are favorable for most histologies. Patients with MA exhibit sertoli solo syndrome and / or tubular sclerosis foci associated to regions with normal spermatogenesis, enabling the sperm extraction for ICSI.