Eligibility for the medical therapy among men with non-obstructive azoospermia-Findings from a multi-centric cross-sectional study.

BACKGROUND: Existing literature does not provide accurate epidemiological data regarding the true prevalence of men with non-obstructive azoospermia (NOA) who would be eligible for hormonal optimization therapy, according to specific pre-treatment criteria. OBJECTIVES: To investigate the characteristics of those men with NOA who would qualify for the medical therapy prior to any SR procedure in a large multi-centric cross-sectional study. MATERIALS AND METHODS: Complete data from 1644 NOA patients seeking medical help for primary infertility at three tertiary referral centers from USA, Brazil, and Italy were analyzed. Baseline serum hormone levels were collected for all patients. NOA was confirmed after two consecutive semen analyses. Genetic tests, including karyotype analysis and Y microdeletions, were performed on all patients. Patients with secondary hypogonadism (total testosterone (T) levels less than 300 ng/dL and luteinizing hormone (LH) levels less than 8 mIU/mL) were earmarked as potential candidates for receiving clomiphene citrate (CC) and/or human chorionic gonadotropin (hCG). Patients with a T to 17ß-estradiol (E2) ratio < 10 were classified as eligible for aromatase inhibitors (AIs) therapy (e.g., anastrazole). A third sub-cohort was created by combining the criteria of the first two sub-cohorts. Descriptive statistics was used to detail overall characteristics and differences between the different sub-cohorts. RESULTS: Among the 1,644 men, 28% (n = 460) had T < 300 ng/dL and LH < 8 mIU/mL, thereby being potentially suitable for CC and/or hCG, while 37% (n = 607) had a T to E2 ratio < 10 thus potentially suitable for AIs. Lastly, 17.7% (n = 280) met the criteria for potential eligibility for both CC and/or hCG and AIs. CONCLUSIONS: Findings from this multicentric cross-sectional study reveal that about 30% of men with NOA were eligible for hormonal treatment with CC and/or hCG while 37% were found to be potential candidates for AIs, and 17% for both therapies. Therefore, these findings show that a only a small subset of NOA patients can benefit from medical therapy prior to considering any SR procedures.

Male obesity: Associated effects on fertility and the outcomes of offspring.

Obesity rates are increasing globally, making it imperative to comprehend the effects of parental obesity on human reproduction. This review aims to highlight the impact of male obesity on reproductive and offspring outcomes. Male obesity has been shown to affect fertility through various mechanisms, including changes in semen quality, difficulty with natural conception, and worsened assisted reproductive technology outcomes. The evidence regarding the impact of male obesity on success of sperm retrieval is conflicting, but all aforementioned adverse effects may be modifiable with weight loss. Moreover, paternal obesity may influence atypical offspring outcomes, such as placental abnormalities and disruptions in fetal development, which may be moderated by epigenetic pathways. Further research is needed to fully understand the complex relationships and underlying mechanisms involved. Gaining more insight into the impact of male obesity on fertility and offspring outcomes can aid in the development of targeted interventions to improve family planning and the health of future generations.

The Impact of Obesity on Sperm Parameters in Young Adult Males: A Retrospective Study of Sperm Donors.

OBJECTIVE: To utilize a large cohort of healthy sperm bank donors to evaluate the association between body mass index and individual sperm parameters. METHODS: Sperm parameters from donors across the United States were obtained between 2013 and 2022. Donors were healthy men aged 18-46years old. Semen samples were analyzed in a certified lab following guidelines by the World Health Organization. A multivariable interaction model between age, body mass index, and sperm parameters was conducted. RESULTS: There were 117,357 sperm donations included in our study. In our sample, 98,397 (83.84%) men were classified as young donors (ages 18-32years) and 18,960 (16.16%) were classified as old donors (ages 33-46years). We identified 1032 (0.88%) men as underweight, 76,635 (65.30%) as normal weight, 36,686 (31.26%) as overweight, and 3004 (2.56%) as obese. Participants had a median total motile sperm count (TMSC) of 186 (interquartile ranges [IQR]: 128 million), volume of 3.36 (IQR: 1.82 mL), sperm concentration of 56 (IQR: 34 million/mL) and a progressive motility of 59.84% (IQR: 16.95%). Older obese donor had lower TMSC (ß = -22.98 ±â€¯4.66, P < .001), semen volumes (ß = -0.85 ±â€¯0.06, P < .001), and progressive motility (ß = -3.94 ±â€¯0.56, P < .001) compared to younger, healthy weight donors. CONCLUSION: We observed lower TMSC, semen volumes, and progressive motility in older obese donors. Although these values are within the normal expected ranges for individual sperm parameters, our ability to detect differences within this healthy population highlights the importance of maintaining a healthy diet and exercise regimen for preserving high sperm counts.

Fertility outcomes in men with prior history of anabolic steroid use.

OBJECTIVE: To study sperm parameters recovery and fertility outcomes in men with azoospermia or severe oligospermia caused by anabolic steroid use who underwent a standardized treatment regimen for spermatogenesis recovery. DESIGN AND SUBJECTS: A retrospective analysis of a cohort of men with a prior history of anabolic steroid use and infertility complaints (between 2018 and 2022) was conducted. EXPOSURE: The standardized treatment approach involved discontinuing testosterone replacement therapy and administering a combination regimen of clomiphene citrate and human chorionic gonadotropin for a minimum of 3 to 6 months. MAIN OUTCOME MEASURES: The main outcome measures included changes in sperm parameters, predominantly sperm concentration, and subsequent pregnancy outcomes. RESULTS: A total of 45 men (median age 37 years, IQR 32-45) met the inclusion criteria for this analysis. Median duration of prior T use was 4 years (IQR 1.3-10), with the 2 most common modalities consisting of injection therapy (43.5%) and oral therapy (34.8%). The median initial sperm concentration was 0 million/cc (IQR 0-1.15), and 23 (51.1%) men initially presented with azoospermia. The median duration of combination human chorionic gonadotropin/clomid therapy was 5 months (IQR 3-12). In initially azoospermic men (N: 23), 5 were lost to follow-up, 6 (33.3%) progressed to severe oligospermia (<5 million/cc), 6 (33.3%) to oligospermia (<15 million/cc), 1 (5.6%) to normozoospermia (>15 million/cc), and 5 (27.8%) remained azoospermic after medical treatment for 6 months. Among the 24 couples who responded to the follow-up call, a total of 9 (37.5%) achieved a successful subsequent pregnancy. Of these, 33.3% (3 couples) used assisted reproductive technology, whereas 66.7% (6 couples) conceived naturally. On logistic regression analysis, no significant predictors for improved sperm parameters or successful pregnancy were identified. CONCLUSION: Despite appropriate treatment regimens, a significant proportion of men with a prior history of anabolic steroid use continue to exhibit severe oligospermia, with more than half showing limited improvement in semen parameters after 6 months of treatment. Only a fraction of men achieves normozoospermia after treatment. Further research is needed to explore predictors for improved sperm parameters and successful pregnancy outcomes in men with a history of anabolic steroid use.

Surgical management of brain metastasis from ovarian cancer: a systematic review and case series.

OBJECTIVE: Ovarian cancer is a rare origin of brain metastasis (BM), with an incidence of only 1%-3%. Consequently, the literature is sparse, and no treatment consensus guideline is available for ovarian BM. The authors conducted a systematic review of ovarian BM and performed a combined pooled cohort survival analysis with their case series. METHODS: A systematic review of PubMed, Scopus, and Web of Science consistent with PRISMA guidelines along with an institutional retrospective chart review was conducted. Inclusion criteria for the systematic review included patients with confirmed BM and primary ovarian cancer, reported perioperative complications and outcomes, differentiated histology, and explicitly reported individual patient data. Reviews, commentaries, technical notes, and articles without English-language translations were excluded. The Newcastle-Ottawa Quality Assessment Scale was used independently by the first and second authors to assess the quality of each article. The authors performed univariate and multivariate analyses of several survival prognostic factors. Kaplan-Meier curves were generated for significant prognostic factors in the univariate analysis. RESULTS: A total of 48 patients with individual data across 34 studies and 8 patients from the authors' institution were included. All patients (n = 56) underwent resection for BM; 83.9% received adjuvant radiotherapy following surgery and 41.1% of patients received adjuvant chemotherapy. The median progression-free survival was 12 months (range 2-43 months). The median overall survival was 9 months (range 1-49 months). On univariate analysis, a single BM and no extracranial metastasis conferred a survival benefit, while clear cell carcinoma as the primary histology corresponded to worsened OS. Multivariable analysis showed that age > 50 years (p = 0.002) and > 1 BM (p < 0.001) were risk factors for poor prognosis. Protective factors included the addition of the following multimodal adjuvant therapy with surgery: radiotherapy (p = 0.002), chemotherapy and radiotherapy (p = 0.005), and stereotactic radiosurgery (p = 0.002). CONCLUSIONS: Although the scarcity of published individual patient data hinders the determination of optimal management, the authors' analysis highlights that multimodal therapies, a single cranial lesion, and age < 50 years are associated with increased survival for patients with ovarian BMs.

The gut microbiome contributes to somatic morphine withdrawal behavior and implicates a TLR2 mediated mechanism.

The ongoing opioid epidemic has left millions of people suffering from opioid use disorder due to the over-prescription of highly addictive substances. Chronic opioid exposure leads to dependence, where the absence of the drug results in negative symptoms of withdrawal, often driving patients to continue drug use; however, few therapeutic strategies are currently available to combat the cycle of addiction and the severity of morphine withdrawal. This study investigates the microbiome as a potential therapeutic target for morphine withdrawal, as gut dysbiosis caused by morphine use has been proven to contribute to other aspects of opioid use disorders, such as tolerance. Results show that although the microbiome during morphine withdrawal trends toward recovery from morphine-induced dysbiosis, there continues to be a disruption in the alpha and beta diversity as well as the abundance of gram-positive bacteria that may still contribute to the severity of morphine withdrawal symptoms. Germ-free mice lacking the microbiome did not develop somatic withdrawal symptoms, indicating that the microbiome is necessary for the development of somatic withdrawal behavior. Notably, only TLR2 but not TLR4 whole-body knockout models display less withdrawal severity, implicating that the microbiome, through a gram-positive, TLR2 mediated mechanism, drives opioid-induced somatic withdrawal behavior.

Factors Associated With Restarting Androgenic Anabolic Steroids After Cessation in Men With Infertility: A Retrospective Analysis.

Introduction The use of androgenic anabolic steroids (AAS) negatively affects male fertility by disrupting hormone release and reducing testosterone levels. Despite this, many men using steroids are unaware of fertility-related consequences. We aimed to determine the factors associated with AAS resumption during fertility treatment, specifically focusing on the duration, age, and dosage of AAS use prior to treatment. Our study, the first of its kind, investigated risk factors for resuming AAS following fertility assessment. Methods We conducted a retrospective review of adult men diagnosed with infertility due to chronic AAS use between 2012 and 2022 at the University of Miami. The study included men with azoospermia or severe oligospermia who were instructed to stop using AAS. Excluded were those who underwent orchiectomy for benign or malignant conditions. We collected data on demographic characteristics, AAS route details, fertility treatments, and AAS resumption. We hypothesized that risk factors for restarting AAS would include duration of AAS use, type of AAS, pre-treatment testosterone levels, and increased age. Results We identified 94 men with infertility caused by AAS use. Among them, 31 (33.0%) resumed AAS therapy within eight months after cessation. The median age of men who restarted AAS was 40 years. Those who resumed AAS had used it for a longer duration prior to fertility assessment compared to those who did not (60 months vs. 17 months, respectively). However, we found no statistically significant differences in age, duration of AAS use, AAS administration details, or serum testosterone levels at the time of initial assessment. Conclusion In conclusion, most men seeking fertility assessment due to AAS abuse did not resume testosterone therapy. However, those who did restart AAS had a longer history of AAS use. Future high-quality prospective studies are needed to better understand the risk factors associated with resuming AAS in male infertility caused by anabolic steroids.

Vasectomy has No Impact on Future Lower Urinary Tract Symptoms Diagnoses: A Retrospective Cohort Claims Database Analysis.

Purpose: The aim of this study was to assess whether there is an association between vasectomy and benign prostatic hyperplasia with associated lower urinary tract symptoms (BPH/LUTS) due to inflammatory etiology. Materials and Methods: We assessed the incidence of BPH/LUTS in men who had undergone vasectomy in a matched cohort analysis using the TriNetX Research Network. We identified men aged 30 to 60 years who underwent vasectomy and had a follow-up visit within 6 months to 5 years after vasectomy from January 2010 through December 2022 and compared them with matched controls. Outcomes recorded include diagnoses of BPH (N40, N40.1), BPH-related medication prescriptions, and BPH-related procedures. We accounted for confounding variables through propensity score-matching for age; race; and history of comorbid medical conditions: hyperlipidemia (International Classification of Disease-10: E78), metabolic syndrome (E88.81), overweight or obesity (E66), testicular hypofunction (E29.1), hypertension (I10-I16), nicotine dependence (F17), and obstructive sleep apnea (G47.33). Results: There was no significant difference in BPH diagnosis between postvasectomy men vs controls (0.84% vs 0.80%, RR: 0.95, 95% CI 0.86-1.05) or BPH/LUTS diagnosis (0.48% vs 0.44%, RR: 0.92, 95% CI 0.81-1.05) within 6 months to 5 years after vasectomy, respectively. No differences in BPH medication prescription (0.94% vs 0.84%) or rate of BPH procedures (0.022% vs 0.017%) were detected between the 2 groups. Conclusions: This study suggests that vasectomy does not increase the risk of BPH development and/or LUTS worsening compared with the general population, providing assurance to both patients and health care providers who may consider vasectomy as a safe family planning option.

Linking the gut microbiome to microglial activation in opioid use disorder.

Substance use disorder (SUD) is a physical and psychological disorder globally prevalent today that has resulted in over 107,000 drug overdose deaths in 2021 in the United States alone. This manuscript reviews the potential relationship between opioid use disorder (OUD), a prevalent subset of SUD, and the microglia, the resident macrophages of the central nervous system (CNS), as they have been found to become significantly more activated during opioid exposure. The inflammatory response mediated by the microglia could contribute to the pathophysiology of SUDs, in particular OUD. Further understanding of the microglia and how they respond to not only signals in the CNS but also signals from other areas of the body, such as the gut microbiome, could explain how the microglia are involved in drug use. Several studies have shown extensive communication between the gut microbiome and the microglia, which may be an important factor in the initiation and development of OUD. Particularly, strategies seeking to manipulate and restore the gut microbiome have been shown to reduce microglial activation and attenuate inflammation. In this review, we discuss the evidence for a link between the microglia and OUD and how the gut microbiome might influence microglial activation to drive the disorder and its associated behaviors. Understanding this connection between microglia and the gut microbiome in the context of drug use may present additional therapeutic targets to treat the different stages of drug use.