Evolution of the basic semen analysis and processing sperm.

PURPOSE OF REVIEW: The sixth edition of the World Health Organization (WHO) laboratory manual for the examination and processing of human semen was recently published with specific step-by-step instructions for semen evaluation and sperm processing. Point-of-care (POC) testing for semen evaluation and microfluidics for sperm processing are rapidly evolving technologies that could impact how we evaluate and process sperm. Understanding the updated manual in the context of these novel technologies is important. RECENT FINDINGS: Proper standardization of semen evaluation and sperm processing will allow for consistent high-quality results among laboratories worldwide. POC testing could improve access to semen evaluations that generate referrals to male infertility specialists for further assessment. Microfluidics can select functional sperm with decreased DNA fragmentation in semen and testicular biopsy samples for assisted reproductive technology (ART). Clinical outcomes, such as pregnancy rates and live birth rates, have not been shown to be consistently improved with these technologies compared to conventional techniques, although high level evidence research in this area is limited. SUMMARY: POC testing and microfluidics have the potential to be combined with machine learning technologies to improve fertility care. If these technologies are appropriately optimized, they could change how we evaluate and process sperm, and potentially lead to improved ART outcomes.

Whole-organ decellularization of the human uterus and in vivo application of the bio-scaffolds in animal models.

PURPOSE: The aim of this investigation was to design a perfusion-based decellularization protocol to provide whole human uterine bio-scaffolds with preserved structural and componential characteristics and to investigate the in vivo properties of the decellularized tissues. METHODS: Eight human uteri, donated by brain-dead patients, were decellularized by perfusion of sodium dodecyl sulfate (SDS) through the uterine arteries using a peristaltic pump. The bio-scaffolds were evaluated and compared with native human uterus regarding histological, immunohistochemical, structural, and bio-mechanical properties, in addition to CT angiographies to examine the preservation of the vascular networks. Subsequently, we obtained acellular patches and implanted them on uterine defects of female Wistar rats to investigate the bio-compatibility and regenerative potential of the bio-scaffolds. Finally, we performed immunostaining to investigate the potential role of circulating stem cells in recellularization of the implanted bio-scaffolds. RESULTS: The outcomes of this investigation confirmed the efficacy of the proposed protocol to provide whole human uterine scaffolds with characteristics and extra-cellular matrix components similar to the native human uterus. Subsequent in vivo studies demonstrated the bio-compatibility and the regenerative potential of the scaffolds and suggested a signaling pathway as an underlying mechanism for the regenerative process. CONCLUSIONS: To the best of our knowledge, this investigation provides the first efficient perfusion-based decellularization protocol for the human uterus to obtain whole-organ scaffolds. The outcomes of this investigation could be employed in future human uterus tissue engineering studies which could ultimately result in the development of novel treatments for female infertile patients.

Comparing predictive values of carbohydrate antigen 19-9, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 in 161 patients with ureteropelvic junction obstruction.

BACKGROUND: To evaluate and compare the efficacy of urinary carbohydrate antigen 19-9 (CA19-9), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) biomarkers as predictive factors to determine the surgery requirement in patients with ureteropelvic junction obstruction. METHODS: We obtained urine samples from 161 patients at diagnosis and evaluated their levels of the three biomarkers. The patients were under observation for 2 years; subsequently, they were divided into two groups based on their requirement of pyeloplasty. We determined the correlation between the urinary concentration of the biomarkers and surgical interventions, as well as the kidney function deterioration and sonography outcomes. RESULTS: The non-surgery group included 60 male and 22 female patients with mean age of 21 months. The surgery group comprised 58 boys and 21 girls with mean age of 26.9 months with no significant difference of age and gender between the two groups. The outcomes were indicative of higher efficacy of CA19-9 level with a sensitivity and specificity of 84.2% and 73.2% at the cutoff point of 59.09 U/ml. Also, a significant negative correlation was detected between the kidney function and the concentrations of CA19-9 and NGAL. CONCLUSIONS: Our evaluations demonstrate the higher efficacy of CA19-9 to predict the requirement of surgical intervention in comparison with the other biomarkers, as well as a significant correlation between kidney function deterioration and urinary CA19-9 and NGAL. The outcomes of this investigation could pave the way for more extensive clinical application of these urinary biomarkers, besides future research determining the association between markers and kidney fibrosis.

In vivo application of decellularized rat colon and evaluation of the engineered scaffolds following 9 months of follow-up.

The aim of this study was to investigate the rat small intestine mesentery and colon as natural bio-reactors for rat colon-derived scaffolds. We decellularized eight whole rat colons by a perfusion-based protocol using 0.1% sodium dodecyl sulfate for 24 hr. The provided bio-scaffolds were examined by histological staining, scanning electron microscopy, and collagen and sulfated glycosaminoglycan quantification. Subsequently, we implanted 4 cm segments of the provided bio-scaffolds into two groups of animal models comprising tissue grafting into the mesenteric tissue (n: 10) and end-to-end anastomosis (n: 10) to the colon of host rats. Following 9 months of follow-up, we harvested the grafts and performed histological and immunohistochemical studies as well as real-time PCR evaluation for telomerase activity of the samples. Histological staining, scanning electron microscopy and protein content evaluation of the acellular tissues confirmed the complete removal of the cellular components and preservation of the extracellular matrix. Histopathological assessment of the implanted scaffolds was suggestive of a regenerative process in both groups. Moreover, immunohistochemical analysis of the samples confirmed the presence of smooth muscle cells, endothelial progenitor cells, and neural elements in both groups of grafted scaffolds. Our data confirmed the recellularization of the acellular colon grafts in both groups after 9 months of follow up. Also, the implanted tissues demonstrated different characteristics based on their implantation location. The outcomes of this investigation illustrate the capability of acellular tissues for in vivo application and regeneration.

Correction to: Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

This article was unintentionally published twice in this journal, by the same authors. Following should be considered the version of record and used for citation purposes.

Decellularised whole ovine testis as a potential bio-scaffold for tissue engineering.

The aim of this study was to determine an efficient whole-organ decellularisation protocol of a human-sized testis by perfusion through the testicular arteries. In the first step of this study, we determined the most efficient detergent agent, whereas the second phase delineated the optimal time required for the decellularisation process. Initially sheep testes were decellularised by one of three different detergent agents: sodium dodecyl sulphate (SDS), Triton X-100 and trypsin-ethylenediamine tetraacetic acid (EDTA) solutions, each perfused for 6h. In the second phase, the selected detergent agent was applied for different time periods. A total number of 20 organs were processed during this investigation. The efficacy of the decellularisation process and the preservation of the extracellular matrix components and structure were evaluated by histopathological examinations, 4',6'-diamidino-2-phenylindole (DAPI) staining, DNA quantification, hydroxyproline measurement, magnetic resonance imaging and scanning electron microscopy. Organ perfusion with 1% SDS solution for 6 to 8h demonstrated the most desirable outcomes regarding decellularisation and extracellular matrix preservation. The 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was used to determine the toxicity of the scaffold and its potential for further application in tissue-engineering investigations. This investigation introduces an efficient method to produce a three-dimensional testicular bio-scaffold resembling the properties of the native organ that could be employed in tissue-engineering studies.

Correction to: Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

The original version of this article unfortunately contained a mistake. The affiliation of Fariba Ghorbani should be Tracheal Diseases Research Center (TDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

PURPOSE: The main purpose of this investigation was to determine an efficient whole-organ decellularization protocol of a human-sized uterus and evaluate the in vivo properties of the bioscaffold. METHODS: Twenty-four ovine uteri were included in this investigation and were decellularized by three different protocols (n 6). We performed histopathological and immunohistochemical evaluations, 4,6-diamidino-2-phenylindole (DAPI) staining, DNA quantification, MTT assay, scanning electron microscopy, biomechanical studies, and CT angiography to characterize the scaffolds. The optimized protocol was determined, and patches were grafted into the uterine horns of eight female Wistar rats. The grafts were extracted after 10 days; the opposite horns were harvested to be evaluated as controls. RESULTS: Protocol III (perfusion with 0.25% and 0.5% SDS solution and preservation in 10% formalin) was determined as the optimized method with efficient removal of the cellular components while preserving the extracellular matrix. Also, the bioscaffolds demonstrated native-like biomechanical, structural, and vascular properties. Histological and immunohistochemical evaluations of the harvested grafts confirmed the biocompatibility and recellularization potential of bioscaffolds. Also, the grafts demonstrated higher positive reaction for CD31 and Ki67 markers compared with the control samples which indicated eminent angiogenesis properties and proliferative capacity of the implanted tissues. CONCLUSIONS: This investigation introduces an optimized protocol for whole-organ decellularization of the human-sized uterus with native-like characteristics and a prominent potential for regeneration and angiogenesis which could be employed in in vitro and in vivo studies. To the best of our knowledge, this is the first study to report biomechanical properties and angiographic evaluations of a large animal uterine scaffold.

Correction to: Development of an efficient perfusion-based protocol for whole-organ decellularization of the ovine uterus as a human-sized model and in vivo application of the bioscaffolds.

The original version of this article unfortunately contained a mistake. The affiliation of Fariba Ghorbani should be Tracheal Diseases Research Center (TDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

Application of a novel bioreactor for in vivo engineering of pancreas tissue.

Type 1 diabetes is characterized by autoimmune destruction of pancreatic cells. Organ transplantation is an acceptable treatment for native organ failure. However, it is associated with several problems due to a number of reasons, such as the lack of appropriate donors and immunosuppression. In our present study, a novel model is presented for in vivo recellularization of acellular pancreas by implanting between the host pancreas and the adjacent omental flap. In this study, the pancreases were harvested and cannulated via the common bile duct and then, the scaffolds were acellularized by a detergent-based protocol. After that, the abdomens of 35 rats were opened and the spleen was extracted with the adjacent omentum, and placed outside the abdomen. The acellularized scaffold was stretched over the host pancreas and the omentum was wrapped around it to make a sandwich-like structure, which was then fixed with Chromic Sutures 6-0 and marked with Prolene 4-0 on four sides. All samples were biopsied at 14, 30, 60, 90, and 120 days post-transplantation. The result showed marked recellularization of acellularized pancreas with visible neovascularization and neoß-cells with minimal inflammatory response. This study provides a new approach to produces a normal-like pancreas by allograft transplantation for pancreas tissue engineering. We observed that in vivo transplantation of acellularized pancreas can promote recellularization, proliferation, and differentiation by blood circulation. These findings support that in vivo studies can contribute to finding faster solutions for the treatment of diabetes.

Sperm telomere length in male-factor infertility and reproduction.

The underlying reasons for male-factor infertility are often unknown. 30% of all men have unexplained semen analysis abnormalities. Moreover, 15%-40% of infertile men have normal semen analyses. There have been increasing efforts to identify causes and associations that may explain idiopathic male-factor infertility. Telomeres have become an area of considerable interest in the field because of the essential roles they have in cellular division and genome integrity. Research to date most consistently supports that men with infertility have shorter sperm telomere length (STL); however, associations between shorter STL and meaningful reproductive health outcomes are less consistent. There is a major need for additional studies to better identify the role of STL in male reproductive health and use the information to improve the counseling and treatment of couples with idiopathic male-factor infertility.

Comparison of Urinary Diversion in Patients With Prostatic Fistula to Those with Localized Radiation Injury After Radiotherapy for the Treatment of Prostate Cancer.

OBJECTIVE: To compare characteristics and outcomes in patients who had radiotherapy (RT) for prostate cancer (PCa) and underwent urinary diversion (UD) due to prostatic fistula (Fistula) vs localized radiation injury (Localized). METHODS: This study was a retrospective single-institution study. Exclusion criteria included follow-up <3 months, large pelvic tumor, and surgery for cancer control. The Fistula group included fistulization outside of the urinary tract (rectal, soft tissue, thigh, pubic symphysis, and extensive necrosis surrounding the prostate). The group Localized had a multitude of problems; however, all were confined to the urinary tract. Patient characteristics, perioperative variables, and outcomes were compared between groups. RESULTS: Sixty-nine patients were included and had UD from 2009-2022. Median age and time from RT to UD were 73 (interquartile range (IQR) 67.9, 78.1) and 7.3 (IQR 3.2, 12.5) years. There were 29 (42%) and 40 (58%) patients in the Fistula and Localized groups. The Fistula group had a higher rate of abdominal/perineal approach (62.1% vs 12.5%, P <.001), a lower rate of right colon pouch (17.2% vs 40%, P = .043), and a longer operative time (515.7 vs 414.2 minutes, P = .017). Clavien-Dindo complications ≥3 were higher in the Fistula group (44.8% vs 20%, P = .027), including a higher rate of re-operation for recurrent pelvic abscess (37.9% vs 5%, P <.001). Survival for the cohort was 85.5% and did not differ between groups. CONCLUSION: Patients with prostate fistula after RT for PCa undergoing UD had longer, more complex operations, and higher rates of complications, notably post-operative pelvic abscesses, compared to men with localized RT injury. Long-term survival was comparable in both groups.

Transgenerational effects of paternal exposures: the role of germline de novo mutations.

Germline de novo mutations (DNMs) refer to spontaneous mutations arising during gametogenesis, resulting in genetic changes within germ cells that are subsequently transmitted to the next generation. While the impact of maternal exposures on germline DNMs has been extensively studied, more recent studies have begun to highlight the increasing importance of the effects of paternal factors. In this review, we have summarized the existing literature on how various exposures experienced by fathers affect the germline DNM burden in their spermatozoa, as well as their consequences for semen analysis parameters, pregnancy outcomes, and offspring health. A growing body of literature supports the conclusion that advanced paternal age (APA) correlates with a higher germline DNM rate in offspring. Furthermore, lifestyle choices, environmental toxins, assisted reproductive techniques (ART), and chemotherapy are associated with the accumulation of paternal DNMs in spermatozoa, with deleterious consequences for pregnancy outcomes and offspring health. Ultimately, our review highlights the clear importance of the germline DNM mode of inheritance, and the current understanding of how this is affected by various paternal factors. In addition, we explore conflicting reports or gaps of knowledge that should be addressed in future research.

Hispanic Ethnicity and Fertility Outcomes.

OBJECTIVE: To assess the association between ethnicity and fertility outcomes for men in a statewide cohort. METHODS: We linked data from the Utah Population Database and Subfertility Health Assisted Reproduction and Environment database, to comprise a cohort of sub-fertile men who underwent semen analysis between 1998 and 2017 in Utah. A multivariable Cox proportional hazard model was constructed to understand the impact of ethnicity on fertility outcomes in our cohort. RESULTS: A total of 11,363 men were included. 1039 (9.1%) were Hispanic. 39.7% of men in the lowest socioeconomic status group were Hispanic (P <.001). When controlling for demographic and clinical factors, the number of live births was reduced for Hispanic men (hazard ratios [HR] = 0.62 [0.57-0.67], P <.001). Though fertility treatment had a positive effect (HR 1.242 [1.085-1.421], P <.001), in competing risks models, Hispanic men were less likely to use fertility treatment (HR = 0.633 [0.526-0.762], P <.001). CONCLUSION: Hispanic ethnicity is significantly associated with a lower likelihood of successful fertility outcomes in Utah. Hispanic men had nearly a 40% reduced likelihood of live births when controlling for sociodemographic factors. Our results indicate that, depending on age, Hispanic men have up to approximately 14 fewer live births per 100 men per year, pointing to a significant disparity in fertility outcomes in the state of Utah. Given 15.1% of Utah's population identifies as Hispanic and 18.7% of the United States population identifies as Hispanic on the 2020 Census, a better understanding of the association of ethnicity and fertility outcomes is imperative.

Stripping versus ligation of vas deferens in microscopic denervation of spermatic cord in men with chronic orchialgia: A multicenter study.

BACKGROUND: Microdenervation of the spermatic cord (MSCD) is an effective treatment modality for men with intractable scrotal content pain. For patients not interested in preserving fertility, some centers advocate ligation of the vas during denervation, while others prefer stripping of the vas deferens to preserve the vasal artery, hence preserving vasculature to the testis and possibly decreasing post-operative congestion pain. OBJECTIVE: To compare outcomes of patients with chronic orchialgia, who underwent MSCD by either stripping or ligating the vas deferens. MATERIALS AND METHODS: A retrospective chart review of 85 patients who underwent MSCD from 2017-2023 was performed. Patients' demographics including history of prior surgical procedures were recorded. Response to surgery was evaluated as either complete resolution of pain, partial resolution of pain, or no improvement in pain. RESULTS: Eighty-five patients underwent MSCD with a median (interquartile range, IQR) age of 36 (25.5-46.5) years and median duration of pain of 16 (6-31) months. Thirty-seven patients underwent stripping of vas, while 48 underwent ligation of vas during MSCD. Median follow up was 12 months. Twenty-one (43.5%) patients had prior inguinal scrotal surgery in the ligation group compared to 5 (13.5%) in the stripping group, p = 0.003. The etiology of pain was similar between the groups. The response to MSCD between the two groups was similar, 67.6% of patients who underwent stripping had complete resolution of pain versus 66.7% of those who had ligation (p = 0.968), with similar rates of post-operative complications (p-value = 0.132). CONCLUSIONS: In men with intractable chronic scrotal content pain with no interest in preserving fertility, ligation, or stripping of the vas deferens yields similar outcomes with regard to pain resolution. Both techniques are safe with no reports of any testicular atrophy.

Variation in Provider Practice Patterns and the Perceived Need for a Shared Decision-making Tool for Neurogenic Lower Urinary Tract Dysfunction.

OBJECTIVE: To evaluate neurogenic lower urinary tract dysfunction (NLUTD) care providers' current practice patterns, their perceived need for a shared decision-making tool for NLUTD management. METHODS: We developed an electronic survey to assess multiple factors surrounding NLUTD management including practice patterns, perceived need for a decision aid and willingness to use it. Prior to survey dissemination, a panel of expert NLUTD care providers reviewed and provided a critique of the survey. It was delivered via email to the members of the Genitourinary Reconstructive Surgeons, and the Society of Urodynamics, female pelvic medicine and urogenital reconstruction between March and May 2022. RESULTS: A total of 117 NLUTD care providers from 11 countries participated in this survey. Most participants were urologists (n: 109, 93%) working at academic teaching hospitals (n: 82, 70%). The most common treatments the providers had provided for stress urinary incontinence and detrusor overactivity were sling procedures (n: 76, 65%) and anticholinergics (n: 111, 95%). Participants believed that NLUTD management can be highly patient-specific and extensively vary from one individual to another. Most participants believed that patients performing clean intermittent catheterization have better QoL compared to those utilizing indwelling urinary catheters (n: 81, 69%). Participants believed there is a need for a NLUTD decision aid, and they expressed their willingness to use one if available. CONCLUSION: We found discordances between guideline recommendations, provider practice patterns, and patient-reported outcome measures and essential attributes that indicated the need for a decision aid to improve patient-provider communication and shared decision-making in NLUTD management.

The impact of socioeconomic status on bulk semen parameters, fertility treatment, and fertility outcomes in a cohort of subfertile men.

OBJECTIVE: To study the effect of socioeconomic status on the use of fertility treatment and the rate of live birth in men with subfertility. DESIGN: A retrospective, time-to-event analysis of men with subfertility in Utah stratified by socioeconomic status. SETTING: Patients seen in fertility clinics throughout Utah. PATIENT(S): All men in Utah undergoing semen analysis between 1998 and 2017 at the state's 2 largest health care networks. INTERVENTION(S): Socioeconomic status (defined as area deprivation index of patients' residential location). MAIN OUTCOME MEASURE(S): Categorical use of fertility treatment, the count of fertility treatments (in patients with ≥1 treatment), and live birth after semen analysis. RESULT(S): When controlling for age, ethnicity, and semen parameters (count and concentration), men from low socioeconomic areas were only 60%-70% as likely to use fertility treatment depending on type compared with men from high socioeconomic areas (intrauterine insemination [IUI] hazards ratio [HR] = 0.691 (0.581-0.821), P<.001; in vitro fertilization [IVF] HR = 0.602 (0.466-0.778), P<.001). Of men undergoing fertility treatment, those from low socioeconomic areas had 75%-80% the number of treatments as men from high socioeconomic areas depending on type (IUI incident rate ratio = 0.740 (0.645-0.847), P<.001; IVF incident rate ratios = 0.803 (0.585-1.094), P=.170). When controlling for age, ethnicity, semen parameters, and use of fertility treatment, men from low socioeconomic areas were only 87% as likely to experience a live birth as men from high socioeconomic areas (HR = 0.871 (0.820-0.925), P<.001). Given the overall higher likelihood of live birth in men from high socioeconomic areas, as well as their greater chance of using fertility treatment, we predicted an annual disparity of 5 additional live births in high socioeconomic men compared with low for every 100 men. CONCLUSION(S): Men from low socioeconomic areas undergoing semen analyses are significantly less likely to use fertility treatment and experience a live birth than their counterparts from high socioeconomic areas. Mitigation programs to increase access to fertility treatment may help to reduce this bias; however, our results suggest that additional discrepancies beyond fertility treatment require addressing.

Environmental exposure to industrial air pollution is associated with decreased male fertility.

OBJECTIVE: To understand how chronic exposure to industrial air pollution is associated with male fertility through semen parameters. DESIGN: Retrospective cohort study. PATIENTS: Men in the Subfertility, Health, and Assisted Reproduction cohort who underwent a semen analysis in the two largest healthcare systems in Utah from 2005-2017 with ≥1 measured semen parameter (N = 21,563). INTERVENTION(S): Residential histories for each man were constructed using locations from administrative records linked through the Utah Population Database. Industrial facilities with air emissions of nine endocrine-disrupting compound chemical classes were identified from the Environmental Protection Agency Risk-Screening Environmental Indicators microdata. Chemical levels were linked with residential histories for the 5 years before each semen analysis. MAIN OUTCOME MEASURES: Semen analyses were classified as azoospermic or oligozoospermic (< 15 M/mL) using World Health Organization cutoffs for concentration. Bulk semen parameters such as concentration, total count, ejaculate volume, total motility, total motile count, and total progressive motile count were also measured. Multivariable regression models with robust standard errors were used to associate exposure quartiles for each of the nine chemical classes with each semen parameter, adjusting for age, race, and ethnicity, as well as neighborhood socioeconomic disadvantage. RESULTS: After adjustment for demographic covariates, several chemical classes were associated with azoospermia and decreased total motility and volume. For exposure in the 4th relative to 1st quartile, significant associations were observed for acrylonitrile (ßtotal motility = -0.87 pp), aromatic hydrocarbons (odds ratio [OR]azoospermia = 1.53; ßvolume = -0.14 mL), dioxins (ORazoospermia = 1.31; ßvolume = -0.09 mL; ßtotal motility = -2.65 pp), heavy metals (ßtotal motility = -2.78pp), organic solvents (ORazoospermia = 1.75; ßvolume = -0.10 mL), organochlorines (ORazoospermia = 2.09; ßvolume = -0.12 mL), phthalates (ORazoospermia = 1.44; ßvolume = -0.09 mL; ßtotal motility = -1.21 pp), and silver particles (ORazoospermia = 1.64; ßvolume = -0.11 mL). All semen parameters significantly decreased with increasing socioeconomic disadvantage. Men who lived in the most disadvantaged areas had concentration, volume, and total motility of 6.70 M/mL, 0.13 mL, and 1.79 pp lower, respectively. Count, motile count, and total progressive motile count all decreased by 30-34 M. CONCLUSION(S): Several significant associations between chronic low-level environmental exposure to endocrine-disrupting compound air pollution from industrial sources and semen parameters were observed. The strongest associations were seen for increased odds of azoospermia and declines in total motility and volume. More research is needed to further explore additional social and exposure factors as well as expand on the risk posed to male reproductive health by the studied chemicals.

Genitourinary Radiation Injury Following Prostate Cancer Treatment: Assessment of Cost and Health Care System Burden.

OBJECTIVE: To evaluate the healthcare resource impact of radiation injury following prostate cancer treatment. METHODS: Using IBM MarketScan, we performed a retrospective study of men with prostate cancer who were treated with radiotherapy and subsequently developed low-grade (LGRI) and high-grade radiation injury (HGRI). Radiation injury diagnoses included bladder neck stenosis, hematuria/cystitis, fistula, ureteral stricture, and incontinence. LGRI and HGRI included injury diagnosis without intervention and with intervention, respectively. Health care visits and costs were measured over 5 time periods including 2 years before radiation, 1 year before radiation, radiation to injury diagnosis, injury diagnosis to first intervention (LGRI), and following first intervention (HGRI). Negative binomial regression modeling was used to assess the effect of radiation injury on average cost adjusting for demographics and comorbidities. RESULTS: Between 2008 and 2017, we identified 121,027 men who received radiotherapy following prostate cancer diagnosis of which 10,057 (8.3%) experienced a HGRI. The frequency of urologic visits and average costs were similar in those without injury and LGRI. However, men with HGRI experienced higher visit frequency and monthly costs. Amongst high-grade injuries, urinary fistula had the highest frequency of visit utilization at 378 visits before first intervention and 245 visits after first intervention. Following radiation injury diagnosis, the average monthly cost was twice as high in those with HGRI ($85.78) compared to LGRI ($38.66). CONCLUSIONS: HGRI was associated with increased urologic health care use and average monthly cost when compared to those who experienced LGRI or no injury. Urinary fistula was associated with the largest resource burden.

Hypogonadism and urologic surgeries: a narrative review.

Background and Objective: Previous studies indicated that the treatment of male hypogonadism can be beneficial for intraoperative and postsurgical outcomes. In this study, we aimed to determine the impact of male hypogonadism on urologic surgeries. We provided an overview of the key studies in the field with the focus on the outcomes of urologic surgeries in hypogonadal men with/without testosterone replacement therapy (TRT). Methods: We performed a literature review in PubMed and Google Scholar databases for the most relevant articles pertaining to the outlined topics without placing any limitations on publication years or study designs. We included full-text English articles published in peer reviewed journals between January 1970 and March 2022. Key Content and Findings: Androgen deficiency is a common finding after major urologic surgeries. Although guidelines recommend against TRT in men with prostate carcinoma, recent investigations showed no association between TRT and disease progression and recurrence. Indeed, recent evidence suggested that low androgen levels could be related to high grade prostate carcinoma and increased risk of upgrading from low to high grade disease. Investigations on the application of TRT in benign prostatic hyperplasia (BPH) patients also revealed contrasting results. While some studies suggested higher rates of prostate-related events in men who received TRT, others showed that TRT could alleviate urinary symptoms in hypogonadal men with BPH. Decreased testosterone level is commonly seen in bladder cancer patients. The treatment of perioperative androgen deficiency can reduce postoperative morbidities and lower the risk of recurrence in these patients. Low testosterone levels are observed in approximately half of the men who undergo artificial urinary sphincter (AUS) placement and can increase the risk of complications. Conclusions: The role of testosterone treatment in patients with urologic diseases such as prostate carcinoma and BPH is controversial. Further investigations are needed to determine the impact of hypogonadism and TRT on the outcomes of urologic surgeries in patients with androgen deficiency.