Early Pharmacologic Approaches to Avert Anabolic Steroid-induced Male Infertility: A Narrative Review.

PURPOSE: To review the impact of testosterone and other androgenic-anabolic steroids (AASs) on male fertility, exploring potential drugs that can be used to preserve or restore male fertility upon AAS use or prior contact. METHODS: A review was performed to provide a unifying clinical link between drugs used to preserve or restore male fertility (ie, clomiphene citrate, human chorionic gonadotropin, selective estrogen receptor modulators, recombinant luteinizing and follicle-stimulating hormones, and human menopausal gonadotrophin) in the context of AAS-induced infertility and related aspects. FINDINGS: Human chorionic gonadotropin (125-500 IU every other day), clomiphene citrate (12.5-50 mg/d), recombinant luteinizing hormone (125-500 IU every other day), recombinant follicle-stimulating hormone (75-150 IU 1-3×/wk), and human menopausal gonadotrophin (75-150 IU 1-3×/wk) are promising early pharmacologic approaches to avert AAS-induced male infertility. Additionally, a full partner assessment is crucial to the success of a couple planning to have children. The partner's age and gynecopathies must be considered. Egg or sperm cryopreservation can also be alternatives for future fertility. Reinforcing AAS cessation is imperative to achieving better success in misusers. IMPLICATIONS: The exponential increase in AAS misuse raises concerns about the impact on male fertility. This review suggests that gonadotropin analogs and selective androgen receptor modulators (clomiphene citrate) are viable approaches to early preserve or restore fertility in men on AAS use or with previous contact. However, proper standardization of doses and combinations is required and hence physicians should also be aware of patients' and partners' fertility.

Potential effect of Zika virus infection on human male fertility?

BACKGROUND: Zika virus (ZIKV) sexual transmission and prolonged viral shedding in semen have been previously reported, suggesting a strong viral affinity for genital tissues. A transient impact of ZIKV on male fertility was shown in animal and human studies. METHODS: Adult male patients with confirmed ZIKV infection diagnosed in the city of Araraquara, Brazil during the epidemic season of 2016 were invited one year after the acute infection to respond to a questionnaire of genital symptoms and to provide a semen sample for molecular ZIKV testing and spermogram analysis, as well as a serum sample for hormonal testing. RESULTS: 101 of 187 tested patients had positive ZIKV RT-PCR in plasma and/or urine samples (54%, 72 women and 29 men). Of 15 adult male participants for whom telephone contact was successful, 14 responded to the questionnaire of genital symptoms and six consented to provide a semen sample at a median of 12 months after the acute infection. We report abnormal spermogram results from patients one year after confirmed ZIKV infection. CONCLUSIONS: Our findings suggest a possible long-term detrimental effect of ZIKV infection on human male fertility that has to be further explored in well-characterized samples from cohort studies conducted in ZIKV-endemic areas.

The epidemiology and etiology of azoospermia.

The misconception that infertility is typically associated with the female is commonly faced in the management of infertile men. It is uncommon for a patient to present for an infertility evaluation with an abnormal semen analysis report before an extensive female partner workup has been performed. Additionally, a man is usually considered fertile based only on seminal parameters without a physical exam. This behavior may lead to a delay in both the exact diagnosis and in possible specific infertility treatment. Moreover, male factor infertility can result from an underlying medical condition that is often treatable but could possibly be life-threatening. The responsibility of male factor in couple's infertility has been exponentially rising in recent years due to a comprehensive evaluation of reproductive male function and improved diagnostic tools. Despite this improvement in diagnosis, azoospermia is always the most challenging topic associated with infertility treatment. Several conditions that interfere with spermatogenesis and reduce sperm production and quality can lead to azoospermia. Azoospermia may also occur because of a reproductive tract obstruction. Optimal management of patients with azoospermia requires a full understanding of the disease etiology. This review will discuss in detail the epidemiology and etiology of azoospermia. A thorough literature survey was performed using the Medline, EMBASE, BIOSIS, and Cochrane databases. We restricted the survey to clinical publications that were relevant to male infertility and azoospermia. Many of the recommendations included are not based on controlled studies.

The epidemiology and etiology of azoospermia

The misconception that infertility is typically associated with the female is commonly faced in the management of infertile men. It is uncommon for a patient to present for an infertility evaluation with an abnormal semen analysis report before an extensive female partner workup has been performed. Additionally, a man is usually considered fertile based only on seminal parameters without a physical exam. This behavior may lead to a delay in both the exact diagnosis and in possible specific infertility treatment. Moreover, male factor infertility can result from an underlying medical condition that is often treatable but could possibly be life-threatening. The responsibility of male factor in couple's infertility has been exponentially rising in recent years due to a comprehensive evaluation of reproductive male function and improved diagnostic tools. Despite this improvement in diagnosis, azoospermia is always the most challenging topic associated with infertility treatment. Several conditions that interfere with spermatogenesis and reduce sperm production and quality can lead to azoospermia. Azoospermia may also occur because of a reproductive tract obstruction. Optimal management of patients with azoospermia requires a full understanding of the disease etiology. This review will discuss in detail the epidemiology and etiology of azoospermia. A thorough literature survey was performed using the Medline, EMBASE, BIOSIS, and Cochrane databases. We restricted the survey to clinical publications that were relevant to male infertility and azoospermia. Many of the recommendations included are not based on controlled studies.

Preservação da fertilidade em homens jovens com câncer: conceitos atuais e o futuro / Fertility preservation in young men with cancer: current concepts and future

Nos últimos 40 anos, o perfil mundial do câncer vem mudando. Encarado inicialmente como uma doença dos países ricos, nota-se atualmente que a maior parte de seu ônus global provêm de países de poucos recursos ou em desenvolvimento. Nas últimas décadas o câncer se tornou um problema de saúde pública mundial, com estimativas alarmantes para as décadas subseqüentes. No Brasil, as estimativas para o ano de 2012 serão válidastambém para o ano de 2013 e revelam a ocorrência de aproximadamente 518.510 casos novos de câncer,incluindo os casos de pele não melanoma. São esperados um total de 257.870 casos novos para o sexo masculino. A grande questão é que cerca de 10% destes casos serão na faixa etária inferior a 45 anos e 1% abaixo de 20 anos de idade. Embora o tratamento atual do câncer tenha aumentado consideravelmente as taxas de sobrevida em 5 anos de pacientes jovens, ele quase que invariavelmenteestará associado a enorme risco de infertilidade, levando a impacto negativo importante na vida destes jovens homens. Este artigo de revisão aborda os mais atuais conceitos empreservação de fertilidade em homens jovens tratados de câncer, o crescimento deste campo dentro da oncologia e da urologia e o futuro deste tema tão relevante para nossapopulação. Até hoje existe uma importante desconexão entre os guidelines mundiais e a prática médica, quando o assunto é preservação da fertilidade em homens com câncer em idade reprodutiva...

Over the past 40 years, the global profile of cancer is changing. Initially regarded as a disease of the richcountries, it is noted that currently most of its global burden comes from poor or developing countries. In recent decades cancer has become a public health problem worldwide, withalarming estimates for subsequent decades. In Brazil, the estimates for the year 2012 will be valid for the year 2013 and reveals the occurrence of approximately 518,510 new cases of cancer, including cases of non-melanoma skin. Are expected a total of 257,870 new cases for males. The greatthing is that about 10% of these cases are in the age group below 45 years and 1% below 20 years of age. Although the current treatment of cancer has increased considerablysurvival rates at 5 years young patients, it is almost invariably associated with great risk of infertility, leading to significant negative impact in the lives of these young men. This review article discusses the most current concepts in preserving fertility in young men treated for cancer, thegrowth of this field within the oncology and urology and the future of this topic so relevant to our population. Eventoday there is a important disconnect between the world and medical practice guidelines, when it comes to fertility preservation in men with cancer of reproductive age...

Grade 3 varicocele in fertile men: a different entity.

PURPOSE: Although varicocele size has an inverse relationship with baseline semen parameters and a direct relationship with seminal reactive oxygen species in infertile patients, to our knowledge the effect of varicocele grade in fertile men is unknown. We evaluated the impact of varicocele grade on seminal parameters, testicular size and seminal reactive oxygen species in fertile men. MATERIALS AND METHODS: We prospectively evaluated 194 men from July 2004 to April 2010. Of the men 156 were fertile and classified by presence of varicocele. A total of 38 infertile patients with varicocele as the only identifiable cause of infertility comprised the control group. Physical examination, semen parameters and seminal reactive oxygen species were compared between the groups. RESULTS: Of 156 fertile men 43 (24.3%) had clinical varicocele, which was grade 1 to 3 in 22, 11 and 10, respectively. The remaining 113 men (72.7%) had no varicocele. Infertile men had smaller testes, decreased semen parameters and higher seminal reactive oxygen species than the fertile groups. Testicular size, reactive oxygen species and semen parameters did not differ between fertile men with vs without varicocele. Fertile men with varicocele grade 3 had higher seminal reactive oxygen species than those with lower grade varicocele. As varicocele grade increased, seminal reactive oxygen species increased and sperm concentration decreased. CONCLUSIONS: Although fertile men have more efficient defense mechanisms to protect against the consequences of varicocele on testicular function, these mechanisms may not be sufficient in those with varicocele grade 3. Further research is needed to clarify whether they are at increased risk for future infertility.

Improving lymph node yield in retroperitoneal lymph node dissection using fluorescent molecular imaging: a novel method of localizing lymph nodes in Guinea pig model.

OBJECTIVES: To propose that fluorescent molecular imaging has utility in specifically identifying the lymph nodes, thereby enabling more definitive lymph node visualization and dissection. Retroperitoneal lymph node dissection (RPLND) is an invasive procedure with significant morbidity. A minimally invasive approach would be of great clinical benefit but has been limited by the extensive perivascular dissection required to remove all lymphatic tissue. Directed lymph node visualization would allow a limited dissection, making a laparoscopic approach more feasible. METHODS: Ten male Hartley guinea pigs underwent nonsurvival RPLND, 5 with the protease activatable in vivo fluorescent molecular imaging agent, ProSense and 5 without image guidance (control). ProSense was administered 24 hours before surgery and detected 24 hours later using a photodynamic detector. In group 1, RPLND was first performed without molecular imaging followed by image-guided lymph node dissection for residual nodes. In group 2, the near infrared detector was used initially for lymph node excision followed by traditionally unassisted extraction of the residual lymph nodes. The lymph nodes were extracted, counted, and sent for histopathologic analysis. RESULTS: With the assistance of molecular imaging, no additional lymph nodes were identified after complete dissection, and all tissue identified by ProSense was confirmed by histopathologic analysis to be lymph nodes. Without molecular imaging, all lymph nodes were not identified, and in 2 instances, the tissue was incorrectly thought to be lymphatic tissue. CONCLUSIONS: Molecular image-guided RPLND is a promising technique to improve in vivo, live visualization and dissection of lymph nodes and has the potential for application in improving the diagnosis and treatment of other urologic malignancies.

Microsatellite instability in solitary and sporadic gastric cancer.

UNLABELLED: Recently, the presence of microsatellite instability (MSI) has been reported in gastric cancer and associated with older age of presentation, distal tumor location, early disease staging, and better overall prognosis. Different characteristics in presentation and in tumor behavior may be explained by different genetic alterations during carcinogenesis of gastric cancer. Identification of specific genetic pathways in gastric cancer may have direct impact on prognosis and selection of treatment strategies. PATIENTS AND METHODS: All 24 patients were treated by radical surgery. Fragments of normal and tumor tissues were extracted from the specimen and stored at -80 degrees C before DNA purification and extraction. PCR amplification utilizing microsatellite markers was performed. Tumors presenting PCR products of abnormal sizes were considered positive for microsatellite instability (MSI+). RESULTS: Five patients (21%) had tumors that were MSI+ in at least 1 marker. In the group of patients with Lauren's intestinal-type gastric carcinoma, 3 had tumors that were MSI+ (23%), while in the group of diffuse-type gastric cancer, 2 patients had tumors that were MSI+ (19%). The mean age of presentation and the male:female ratio was similar in both groups. Tumors that were MSI+ were more frequently located in proximal portion of the stomach compared to microsatellite-stable (MSS) tumors (40% vs. 16%). Although there was a trend of patients with MSI+ tumors towards a proximal gastric tumor location, early staging, and negative lymph node metastasis, there was no statistical significance compared to those with MSS tumors (P >.1). Comparison of overall and disease-free survival between gastric tumors that were MSI+ and those that were MSS found no statistically significant differences (P >.1). CONCLUSIONS: Microsatellite instability is a frequent event in gastric carcinogenesis and shows a trend towards distinct clinical and pathological characteristics of gastric cancer.

Microsatellite instability in solitary and sporadic gastric cancer

A presença de Instabilidade de microsatellites (IMS) tem sido relatada no cancer gastrico e associada a pacientes com idade mais avançada, localização mais distal do tumor, estadios mais precoces e melhor prognostico. Relatamos neste prospectivo estudo envolvendo 24 pacientes com cancer gastrico solitario e esporadico, a incidencia de IMS, sua correlação com parametros epidemiologicos, clinicos e anatomo patológicos e o seu impacto sobre a sobrevida geral e livre de doença. PACIENTES E MÉTODOS: Todos os pacientes haviam sido tratados com cirurgia radical. Fragmentos de tecido normal e tumoral eram extraidos das peças e armazenados a ù80ºC antes da extração e purificação DNA. Realizava-se então a amplificação com PCR utilizando marcadores específicos de microsatelites. Os tumores que apresentavam produtos de amplificação anormais foram considerados positivos para IMS. RESULTADOS: Cinco pacientes (21%) apresentaram Instabilidade de microsatelites (IMS+) com pelo menos um marcador (primer) No grupo de pacientes com adenocarcinomas gástricos do tipo histológico de Lauren, três apresentavam IMS (23%) enquanto no grupo portador de cancar gástrico difuso, dois pacientes mostraram IMS (19%).. Embora haja uma tendência dos pacientes IMS+ apresentarem tumores de localização mais proximal, estadios mais precoces e ausência de metástases linfonodais, não se observou diferenças estatisticamente significativas (p > 0,1). A comparação entre as taxas de sobrevida geral e livre de doença não mostrou significância estatistica (p > 0,1). CONCLUSÕES: IMS é um evento frequente na carcinogese gástrica e pode estar associado a caracteristicas clinicas e anátomo-patológicas do câncer gástrico.

Bile duct-duodenal fistula caused by AIDS/HIV-associated tuberculosis.

Although infrequent, digestive fistulae in HIV/AIDS patients have been reported throughout the digestive tract from the esophagus to the anus, with predominance of esophageal fistulae. AIDS/HIV-associated opportunistic infections may invade the digestive system and lead to fistula formation. Tuberculosis is the most common infection associated with these esophageal fistulae. We report here one case of bile duct-duodenal fistula in a female AIDS patient with associated abdominal Mycobacterium tuberculosis infection compromising lymph nodes of the hepatic pedicle where the fistula was found. According to the reviewed literature, this is the third case of bile duct-duodenal fistula associated with abdominal tuberculosis in AIDS patient, and the first where both the fistula and the tuberculosis infection were diagnosed at laparotomy for acute abdomen. Whether the AIDS patient with abdominal pain needs or not a laparotomy to treat an infectious disease is often a difficult matter for the surgeon to decide, as most of the times appropriate medical treatment will bring more benefit.

Bile duct-duodenal fistula caused by AIDS/HIV-associated tuberculosis

Allthough infrequent, digestive fistulae in HIV/AIDS patients have been reported throughout the digestive tract from the esophagus to the anus, with predominance of esophageal fistulae. AIDS/HIV-associated opportunistic infections may invade the digestive system and lead to fistula formation. Tuberculosis is the most common infection associated with these esophageal fistulae. We report here one case of bile duct-duodenal fistula in a female AIDS patient with associated abdominal Mycobacterium tuberculosis infection compromising lymphnodes of the hepatic pedicle where the fistula was found. According to the reviewed literature, this is the third case of bile duct-duodenal fistula associated with abdominal tuberculosis in AIDS patient, and the first where both the fistula and the tuberculosis infection were diagnosed at laparotomy for acute abdomen. Whether the AIDS patient with abdominal pain needs or not a laparotomy to treat an infectious disease is often a difficult matter for the surgeon to decide, as most of the times appropriate medical treatment will bring more benefit