The effect of red blood cell disorders on male fertility and reproductive health.

Male infertility is defined as a failure to conceive after 12 months of unprotected intercourse owing to suspected male reproductive factors. Non-malignant red blood cell disorders are systemic conditions that have been associated with male infertility with varying severity and strength of evidence. Hereditary haemoglobinopathies and bone marrow failure syndromes have been associated with hypothalamic-pituitary-gonadal axis dysfunction, hypogonadism, and abnormal sperm parameters. Bone marrow transplantation is a potential cure for these conditions, but exposes patients to potentially gonadotoxic chemotherapy and/or radiation that could further impair fertility. Iron imbalance might also reduce male fertility. Thus, disorders of hereditary iron overload can cause iron deposition in tissues that might result in hypogonadism and impaired spermatogenesis, whereas severe iron deficiency can propagate anaemias that decrease gonadotropin release and sperm counts. Reproductive urologists should be included in the comprehensive care of patients with red blood cell disorders, especially when gonadotoxic treatments are being considered, to ensure fertility concerns are appropriately evaluated and managed.

Functional and Taxonomic Dysbiosis of the Gut, Urine, and Semen Microbiomes in Male Infertility.

BACKGROUND: Little is known about the role of the genitourinary and gastrointestinal microbiota in the pathogenesis of male infertility. OBJECTIVE: To compare the taxonomic and functional profiles of the gut, semen, and urine microbiomes of infertile and fertile men. DESIGN, SETTING, AND PARTICIPANTS: We prospectively enrolled 25 men with primary idiopathic infertility and 12 healthy men with proven paternity, and we collected rectal swabs, semen samples, midstream urine specimens, and experimental controls. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed comprehensive semen analysis, 16S rRNA sequencing for quantitative high-resolution taxonomy, and shotgun metagenomics with a median of 140 million reads per sample for functional metabolic pathway profiling. RESULTS AND LIMITATIONS: We identified a diverse semen microbiome with modest similarity to the urinary microbiome. Infertile men harbored increased seminal α-diversity and distinct ß-diversity, increased seminal Aerococcus, and decreased rectal Anaerococcus. Prevotella abundance was inversely associated with sperm concentration, and Pseudomonas was directly associated with total motile sperm count. Vasectomy appeared to alter the seminal microbiome, suggesting a testicular or epididymal contribution. Anaerobes were highly over-represented in the semen of infertile men with a varicocele, but oxidative stress and leukocytospermia were associated with only subtle differences. Metagenomics data identified significant alterations in the S-adenosyl-L-methionine cycle, which may play a multifaceted role in the pathogenesis of infertility via DNA methylation, oxidative stress, and/or polyamine synthesis. CONCLUSIONS: This pilot study represents the first comprehensive investigation into the microbiome in male infertility. These findings provide the foundation for future investigations to explore causality and identify novel microbiome-based diagnostics and therapeutics for men with this complex and emotionally devastating disease. PATIENT SUMMARY: We explored the resident populations of bacteria living in the gut, semen, and urine of infertile and fertile men. We found several important bacterial and metabolic pathway differences with the potential to aid in diagnosing and treating male infertility in the future.

Microscopic spermatic cord denervation for chronic orchialgia/chronic scrotal content pain: operative outcomes and predictors of failure.

BACKGROUND: To describe our institutional outcomes with microscopic spermatic cord denervation (MSCD) for chronic scrotal content paint (CSCP) and identify predictors of treatment failure. METHODS: Retrospective chart review was performed to identify all MSCD performed by two surgeons at a single institution from 2010-2019. Patient demographic data and operative outcomes were collected. Patients were excluded from analysis if no post-operative follow up was available. Success was defined as complete resolution of bothersome pain. Multivariable logistic regression was utilized to identify predictors of treatment failure. RESULTS: During the study period, 101 patients were identified in which 113 MSCD procedures were performed. Final analysis included 103 procedures across 93 patients. Mean age was 41.8 years (SD 13.2), mean BMI was 29.2 kg/m2 (SD 5.96) and median months of pain preceding surgery were 24 (range, 3-300 months). Overall, 75/103 (73%) MSCD were successful. Of the failures, 5 patients had recurrence of pain greater than 6 months after surgery. Only the presence of pelvic floor muscle spasm (PFMS) independently predicted MSCD failure (OR 3.95, P=0.02). 9 of 19 (47%) patients with PFMS experienced treatment failure, while 19 of 84 (23%) without PFMS experienced failure. CONCLUSIONS: MSCD offers a therapeutic option for patients with refractory CSCP. The presence of PFMS is associated with lower surgical success rates. Patients with pre-operatively identified PFMS should be counseled regarding a higher risk of treatment failure.

Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy.

BACKGROUND: Polycythemia (erythrocytosis) is a known side effect of testosterone (T) replacement therapy (TRT) and appears to correlate with maximum T levels. There is also a well-established association between obstructive sleep apnea (OSA) and the development of polycythemia, which confers additional long-term cardiovascular morbidity. Synergy between TRT and OSA in the development of polycythemia remains poorly understood. AIM: The objective of this study was to retrospectively assess the relationship of OSA and secondary polycythemia in hypogonadal men receiving TRT. METHODS: We performed a retrospective chart review of all men treated by a single provider from 2015 to 2019 for the diagnosis of hypogonadism. Patients who developed a hematocrit of 52% or greater were classified as having polycythemia. OSA was identified via clinical documentation or use of nocturnal continuous positive airway pressure. Demographics, laboratory values, treatment details, and comorbidities were recorded. Data were reported as mean ± SD for parametric variables and median [interquartile range] for non-parametric values. OUTCOME: The primary outcome of this study was the association between OSA and polycythemia in hypogonadal men on TRT. RESULTS: 474 men were included in this study. 62/474 (13.1%) men met the criteria for the diagnosis of polycythemia with a median hematocrit of 53.6 [interquartile range 52.6, 55.5]. Univariate analysis demonstrated a strong positive association between polycythemia and the concomitant diagnosis of OSA in hypogonadal men (P = .002). Even after correcting for age, body mass index (BMI), and peak T levels in the multivariate analysis (P = .01), this relationship remained significant with an odds ratio of 2.09 [95% CI 1.17, 3.76]. 37 men on TRT with polycythemia and OSA were included in the final cohort with a mean age of 59.2 ± 11.4 years, mean BMI of 32.4 ± 6.0, and median time from TRT initiation to polycythemia diagnosis of 3 years. All patients diagnosed with OSA were prescribed continuous positive airway pressure with poor compliance noted in 52.8% of men. 37.8% were managed via phlebotomy and 59.5% were managed via dose de-escalation of TRT. In hypogonadal men on TRT with polycythemia, BMI was the only risk factor strongly associated with OSA (P = .013). CLINICAL TRANSLATION: In hypogonadal men (particularly those with elevated BMI) on TRT who develop secondary polycythemia, a diagnosis of OSA should be strongly considered. STRENGTHS & LIMITATIONS: This is a single provider retrospective study and further studies are needed to assess generalizability. CONCLUSIONS: In this retrospective single-center cohort, the development of polycythemia in hypogonadal men on TRT was associated with an increased prevalence of OSA. Lundy SD, Parekh NV, Shoskes DA. Obstructive Sleep Apnea Is Associated With Polycythemia in Hypogonadal Men on Testosterone Replacement Therapy. J Sex Med 2020;17:1297-1303.

Fertility considerations in men with testicular cancer.

The modern approach to cancer management has evolved into a multidisciplinary initiative focused not only on cancer specific and overall survival, but also patient quality of life and survivorship. Future fertility is often a major concern for young patients undergoing cancer therapy. Fertility preservation has emerged as a viable but significantly underutilized option. Patients and families should be aware of the varying effects of antineoplastic therapy on their future fertility to allow for an informed decision regarding their fertility preservation options. In this review we discuss the epidemiology, pathophysiology, and management of fertility in the setting of testicular cancer diagnosis and treatment.

Childless Men at the Time of Vasectomy are Unlikely to Seek Fertility Restoration.

OBJECTIVE: To examine whether men who were childless at the time of vasectomy sought consultation for fertility restoration. METHODS: Retrospective chart review was performed to determine if patients without children at the time of vasectomy sought consultation for fertility restoration (defined as vasectomy reversal or sperm retrieval). If the patient had not been seen in our healthcare system within the previous 12 months, he was contacted by phone to determine whether he had sought consultation for fertility restoration. RESULTS: Of 1656 men, 68 men (4.1%) were childless at the time of vasectomy. Fifteen patients were excluded as they were not followed in our hospital system and were unreachable by phone. Zero patients sought consultation for fertility restoration. CONCLUSION: Our single institution study demonstrated that no men who were childless at the time of vasectomy sought consultation for fertility restoration. Given that there are no other FDA approved methods for nonbarrier sterilization for males, men with no children at the time of vasectomy should receive the same AUA guideline-recommended counseling that men with children receive.