Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. MATERIALS AND METHODS: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. RESULTS: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. CONCLUSIONS: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.

Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

PURPOSE: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. MATERIALS AND METHODS: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. RESULTS: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. CONCLUSIONS: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Recycling transplanted organs: An exceptional case and literature review.

BACKGROUND: Recycling transplant kidneys, in other words using an allograft which has previously been transplanted in one recipient for transplant in a second recipient, can be a source of opportunity for expanding the pool of available grafts in the United States and beyond. SUMMARY: We describe a case of renal transplantation from a donor who had undergone a kidney transplant 3 years prior and had good graft function at the time of procurement. The recipient underwent transplantation uneventfully and to date has demonstrated excellent graft function. We also include a literature review of reported cases of recycled/retransplanted kidneys. KEY MESSAGES: -Recycling transplanted kidneys is a largely untapped resource which could help decrease the transplant waitlist. -Utilizing such kidneys does need special considerations in terms of procurement technique, backtable, crossmatch, recipient selection and follow-up.

The evolution of centriole degradation in mouse sperm.

Centrioles are subcellular organelles found at the cilia base with an evolutionarily conserved structure and a shock absorber-like function. In sperm, centrioles are found at the flagellum base and are essential for embryo development in basal animals. Yet, sperm centrioles have evolved diverse forms, sometimes acting like a transmission system, as in cattle, and sometimes becoming dispensable, as in house mice. How the essential sperm centriole evolved to become dispensable in some organisms is unclear. Here, we test the hypothesis that this transition occurred through a cascade of evolutionary changes to the proteins, structure, and function of sperm centrioles and was possibly driven by sperm competition. We found that the final steps in this cascade are associated with a change in the primary structure of the centriolar inner scaffold protein FAM161A in rodents. This information provides the first insight into the molecular mechanisms and adaptive evolution underlying a major evolutionary transition within the internal structure of the mammalian sperm neck.

CP110 and CEP135 localize near the proximal and distal centrioles of cattle and human spermatozoa.

Centrosomes play an important role in the microtubule organization of a cell. The sperm's specialized centrosome consists of the canonical barrel-shaped proximal centriole, the funnel-shaped distal centriole, and the pericentriolar material known as striated columns (or segmented columns). Here, we examined the localization of the centriole proteins CEP135 and CP110 in cattle and human spermatozoa. In canonical centrioles, CP110 is a centriole tip protein that controls cilia formation, while CEP135 is a structural protein essential for constructing the centriole. In contrast, we found antibodies recognizing CEP135 and CP110 label near the proximal and distal centrioles at the expected location of the striated columns and capitulum in cattle and humans in an antibody and species-specific way. These findings provide a pathway to understanding the unique functions of spermatozoan centrosome.

Electronic Patient Portal Use After Kidney Transplant: A Single-Center Retrospective Study.

INTRODUCTION: Online patient portals have become a core component of patient-centered care. Limited research exists on such portal use in patients after kidney transplantation. The aim of this study was to examine preoperative, perioperative, and postoperative factors associated with post-transplantation portal use. METHODS: This cross-sectional study included all patients who underwent kidney transplantation from April 2016 to May 2019 at the University of Toledo Medical Center. Exclusion criteria included international travel for transplantation and those without available postoperative lab or follow-up records. Data were collected for 2 y post-transplantation. Univariable and multivariable linear regression was performed to determine associations with portal use. RESULTS: Two hundred and forty-seven kidney transplant recipients were included in the study; 35.6% (n = 88) used the portal versus 64.4% (n = 159) did not. Preoperative factors associated with increased use included income >$40,000 (odds ratio [OR], 2.95; P = 0.006) and cancer history (OR, 2.46; P = 0.007), whereas diabetes history had reduced use (OR, 0.51; P = 0.021). The Black race had the least use. Perioperatively, reduced use was associated with dialysis before transplant (OR, 0.25; P < 0.001) and hospital stay ≥4 d (OR, 0.49; P = 0.009). Postoperatively, associations with increased use included average eGFR >30 (P = 0.04) and hospital readmissions (n = 102), whereas those with ER (n = 138) visits had decreased use. Multivariable analysis revealed increased use with income >$40,000 (OR, 2.51; P = 0.033). CONCLUSIONS: There was no observed difference in clinical outcomes for portal users and nonusers undergoing kidney transplantation, although portal use may decrease the likelihood of ER visits. Socioeconomic status and ethnicity may play a role on who utilizes the patient portals.

Patient-reported disruptions to cancer care during the COVID-19 pandemic: A national cross-sectional study.

BACKGROUND: The aim of this study is to evaluate the extent and associations with patient-reported disruptions to cancer treatment and cancer-related care during the COVID-19 pandemic utilizing nationally representative data. METHODS: This analysis uses data from the 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey of US adults. Adults (age >18) who reported requiring current cancer treatment or other cancer-related medical care in the second half of 2020 were included. Estimated proportions of patients with self-reported changes, delays, or cancelations to cancer treatment or other cancer care due to the COVID-19 pandemic were calculated using sampling weights and associations with sociodemographic and other health-related variables were analyzed. RESULTS: In total, 574 (sample-weighted estimate of 2,867,326) adults reported requiring cancer treatment and/or other cancer care since the start of the COVID-19 pandemic. An estimated 32.1% reported any change, delay, or cancelation. On sample-weighted univariable analysis, patients who were younger, female, had one or fewer comorbidities, and uninsured were significantly more likely to report disruptions. On sample-weighted, multivariable analysis, patients who were younger and female remained significant predictors. Nearly 90% of patients included in the study reported virtual appointment use. Patients reporting disruptions were also significantly more likely to report feelings of anxiety. CONCLUSIONS: An estimated 1/3 of patients experienced disruptions to cancer care due to the COVID-19 pandemic. Patients experiencing disruptions in care were more likely to be female or younger which may reflect risk stratification strategies in the early stages of the pandemic, and also had higher rates of anxiety. The longitudinal impact of these disruptions on outcomes merits further study.

Tubulin posttranslational modifications modify the atypical spermatozoon centriole.

Sperm cells are transcriptionally and translationally silent. Therefore, they may use one of the remaining mechanisms to respond to stimuli in their environment, the post-translational modification of their proteins. Here we examined three post-translational modifications, acetylation, glutamylation, and glycylation of the protein tubulin in human and cattle sperm. Tubulin is the monomer that makes up microtubules, and microtubules constitute the core component of both the sperm centrioles and the axoneme. We found that the sperm of both species were labeled by antibodies against acetylated tubulin and glutamylated tubulin.

False Positive Pregnancy Test Before Kidney Transplant: Case Report and Review of Literature.

Pregnancy tests are routinely done before any surgery under general anesthesia including kidney transplantation. Positive test usually leads to more investigations to detect a possible pregnancy or malignancy and the surgery gets canceled or postponed. Because a kidney transplant from a deceased donor is not elective, it usually gets canceled in this scenario. Some groups have reported on normally elevated human chorionic gonadotrophin (hCG) levels in perimenopausal women and in patients with chronic kidney disease. This is thought to be from the pituitary. We present a highly sensitized prospective kidney transplant recipient with a positive pregnancy test with low levels of serum human chorionic gonadotrophin. She underwent additional preoperative testing after which we proceeded with the kidney transplant. Herein, we discuss the management of patients who have an unexpected positive pregnancy test before transplant.

Assessing Vasectomy-Related Information on YouTube: An Analysis of the Quality, Understandability, and Actionability of Information.

This study aims to critically appraise the quality of vasectomy-related health information currently available on YouTube to better address patient information needs moving forward. A YouTube search was performed using the keyword "vasectomy." The first 100 videos were assessed, with irrelevant and duplicate videos excluded. Two independent reviewers evaluated the remaining videos using the DISCERN instrument for evaluating the quality of information and the Patient Education Materials Assessment Tool for Audiovisual materials (PEMAT-A/V) for assessing the understandability and actionability of materials. Source characteristics and markers of bias and misinformation were also collected. Seventy-eight videos were included in the study, with a mean duration of 6.6 minutes and mean of 216,672 views. The median DISCERN score was poor at 28 (IQR 22-33) out of a possible 80 with mean PEMAT-AV Understandability and Actionability scores of 67.6% (±16.7%) and 33.8% (±36.2%), respectively. A medical doctor was present in 61 (78.2%) of the videos, of which 53 (86.9%) were urologists and 38 (62.2%) promoted their personal practice or institution. False statements regarding vasectomy were made in 14 (17.9%) videos. Notably, no significant difference was noted in quality, understandability, or actionability of videos created by those with personal promotion to those without. The quality of information regarding vasectomy on YouTube is poor and reaches a wide audience. Continued appraisal and creation of YouTube videos that contain quality, understandable and actionable information by urologists is necessary to ensure patients are well-informed.

The Sun Is Still Shining: Nature of Industry Payments to Transplant Surgeons From 2014 to 2019.

Background: Established in 2013, the Open Payments Program (OPP) mandated that medical device and pharmaceutical manufacturers submit record of any financial incentive given to physicians to the Centers for Medicare and Medicaid Services, which is in turn made publicly available. This study aims to characterize these payments to transplant surgeons over the first 6 y of OPP data. Methods: The study sample included all physicians who received at least one nonresearch payment as transplant surgeons to the OPP. To capture transplant surgeons who may be listed under their pipeline specialty, the American Society of Transplant Surgeons member directory as of January 2021 was queried. Payments were analyzed temporally, geographically, and by payment type, physician, and industry payer. Results: In total, payments totaling $15 661 536 were made to 1335 transplant surgeons over the study period. The mean payment was $436.90 (SD, $1760), and the median payment was $52.94 (interquartile range, $18.29-$159.80). The top contributing companies were Intuitive Surgical, Inc.; Gilead Sciences, Inc.; and Novartis Pharmaceuticals. Only 5.3% ($827 236) was paid toward faculty or as a speaker for a nonaccredited and noncertified continuing education program and honorarium. Educational payments came in at $1 233 141 (7.9%) over the study period. $13 750 828.60 (87.8%) of the payments were for other categories (consulting fees, food and beverages, etc). Organ transplant and procurement region 7 and 8 transplant surgeons received the highest median payments during the study period. Conclusions: This study is the first to characterize the payments made to transplant surgeons since the passage of the Sunshine Act. Further studies are needed to understand and interpret the relationship between industry and transplant surgeons, as the payments may or may not translate to influence in medical decisions or use of medical devices.

PARP inhibitors chemopotentiate and synergize with cisplatin to inhibit bladder cancer cell survival and tumor growth.

BACKGROUND: Management of bladder cancer (BLCA) has not changed significantly in the past few decades, with platinum agent chemotherapy being used in most cases. Chemotherapy reduces tumor recurrence after resection, but debilitating toxicities render a large percentage of patients ineligible. Recently approved immunotherapy can improve outcomes in only a third of metastatic BLCA patients. Therefore, more options for therapy are needed. In this study, we explored the efficacy of PARP inhibitors (PARPi) as single agents or as combinations with platinum therapy. METHODS: We treated BLCA cells with PARPi (olaparib, niraparib, rucaparib, veliparib, or talazoparib) alone or as the combination of cisplatin with PARPi. We then measured their survival, proliferation, apoptosis, as well as their ability to form colonies. BLCA xenografts in male SCID mice were treated similarly, followed by the assessment of their growth, proliferation, and apoptosis. RESULTS: PARPi niraparib and talazoparib were effective in reducing BLCA cell survival as single agents. Combinations of Cisplatin with talazoparib and niraparib effectively reduced the survival of BLCA cells, while veliparib was not effective even at high concentrations. In vivo, the combinations of cisplatin with niraparib, rucaparib, or talazoparib reduced BLCA xenograft growth significantly. CONCLUSIONS: We provide evidence that PARPi can be effective against BLCA as single agents or as combinatorial therapy with cisplatin.

Serum bilirubin as a predictor of graft outcomes after renal transplant.

Bilirubin is a signaling molecule that alters the immune response and metabolism. While bilirubin has been employed as a marker of renal and cardiovascular health, its role in renal transplant recipients is not known. In this study, we sought to determine the impact of bilirubin (total, direct and indirect) on the estimated glomerular filtration rate (eGFR) after renal transplantation. We conducted a retrospective review of pre- and postoperative bilirubin levels in 457 renal transplant recipients at a single center. Pre- and post-rejection bilirubin levels were also assessed in those patients who experienced a rejection episode. No statistically significant differences were found in bilirubin levels during the pre-transplant to post-rejection period among patients who experienced rejection with kidney allograft survival. No statistically significant associations were observed between baseline bilirubin and post-transplant eGFR in the full patient group or within the gender- or race-stratified groups. Baseline bilirubin was not correlated with time to rejection. Our results suggest that bilirubin may not offer renoprotection in renal transplant recipients.

Optimal Timing of COVID-19 Vaccination in the Peri-Transplant Period: A Single Institution Case Series.

The outcomes of vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 in organ transplant recipients are unclear. Recent studies have investigated outcomes for patients who are several years post transplant. There has not been much data in peri-transplant patients. This is important because patients are highly immunosuppressed during this period owing to induction immunosuppression and are thus susceptible to infection. We looked at 6 patients who were transplanted at our center after receiving their first dose of mRNA vaccines. We assessed their antibody response after 1, 2, and in two patients, 3 doses of the vaccine. Out of the two patients who received their third booster dose, one had a detectable antibody level after the third dose. We report that the overall antibody response to vaccination was weaker in transplant patients compared with the general population, with a rapid attrition of antibody response over time. There is a need for more studies that follow-up antibody levels in transplant patients over time, especially those in the peri-transplant period to help guide the vaccination plan for immunosuppressed transplant patients.

Global Trends in Incidence and Burden of Urolithiasis from 1990 to 2019: An Analysis of Global Burden of Disease Study Data.

BACKGROUND: Urolithiasis is among the most common urologic diagnoses globally, with substantial burden and cost on healthcare systems worldwide. Increasing evidence links urolithiasis with an array of risk factors, including diet and lifestyle trends, noncommunicable diseases such as diabetes and obesity, and global warming. OBJECTIVE: To examine geographic, temporal, and sociodemographic patterns to better understand global disease burden of urolithiasis. DESIGN SETTING AND PARTICIPANTS: We extracted data on age-standardized incidence rate (ASIR), deaths, and disability-adjusted life years (DALYs) attributed to urolithiasis for 21 regions, including 204 countries, for 1990-2019 from the Global Burden of Disease (GBD) study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data were analyzed at the global, regional, and country levels, as well as stratified by the Socio-Demographic Index. The average annual percentage change (AAPC) was calculated to measure temporal trends across groups. RESULTS AND LIMITATIONS: Globally, total cases, DALYs, and deaths attributed to urolithiasis increased over the study period, while the age-standardized rates of these measures decreased. The age-standardized incidence of urolithiasis decreased from 1696.2 (95% confidence interval [CI] 1358.1-2078.1) cases per 100 000 population in 1990 to 1394.0 (95% CI, 1126.4-1688.2) cases per 100 000 population in 2019, with an AAPC of -0.7 (95% CI [-0.8, -0.6]). Of the GBD regions, Eastern Europe demonstrated a consistently higher ASIR of urolithiasis than all other regions, while the Caribbean had the highest AAPC. This study is limited by the available national and regional data, as described in the original GBD study. CONCLUSIONS: Worldwide, total cases, DALYs, and deaths attributed to urolithiasis have increased since 1990, while age-standardized rates have decreased, with demonstrated regional and sociodemographic variation. Multifaceted strategies to address urolithiasis prevention and treatment are necessary. PATIENT SUMMARY: In this study, we looked at trends in the global burden of stone disease using data from 204 countries from 1990 to 2019. We found that the overall burden has increased, but it varies by age, sociodemographic variables, and geographic region. We conclude that we need adaptable policies that suit the specific needs of the country to address this burden.

Renal Displacement with Supine to Prone Positional Change: Effect of Sex and Body Mass Index.

Objective: To determine patterns of kidney and retroperitoneal organ movement during positional change between the supine and prone positions as seen on CT scans. Methods: Axial CT scans of 75 subjects who underwent supine and prone positions were retrospectively analyzed. A total of 1650 measurements were taken for anterior/posterior, medial/lateral, cranial/caudal, skin-to-calix distance, kidney-to-liver distance, and kidney-to-colon distance in both positions. Results: Pronation shortens the distance from the skin to renal calix for both the right (99.62 mm vs 85.14 mm; p < 0.00001) and left (96.67 mm vs 90.80 mm; p < 0.00001) sides. The reduction in left-side tract length for obese patients is significantly greater than that of normal weight patients (11.88 mm vs -5.02 mm; p = 0.001). The left kidney displaces ventrally (11.12 mm vs 18.59 mm; p < 0.00001), while the right kidney does not (14.26 mm vs 15.30 mm; p = 0.30). The right kidney displaces cranially (62.76 mm vs 79.51 mm; p < 0.00001), while the left kidney does not (64.35 mm vs 66.52 mm; p = 0.14). The left kidney in females moves medially, while no change is seen in males (4.22 mm vs -0.48 mm; p = 0.0004). The left kidney in females displaces toward the descending colon, while it moves farther away in males (2.73 mm vs -2.01 mm; p = 0.011). Conclusions: Both sex and body mass index had effects on the movement of the kidneys upon pronation. The differences can be clinically useful to help pre- and intraoperative planning.

Assessing information on YouTube™ as a quality source for the treatment of varicoceles.

INTRODUCTION: YouTube™ has grown into one of the largest disseminators of health care information. We assessed the quality of information on varicoceles and their treatment, available on YouTube™. METHODS: Using a YouTube™ search query with the keyword "varicocele," the quality of the first 50, nonrepeat videos in English were assessed as a representative group for the topic. DISCERN and Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-AV) standardized tools were utilized by three independent reviewers to grade the quality of these videos based on content, understandability, and actionability. RESULTS: The average and median DISCERN score was 31.34 (±9.37) and 31 (interquartile range 25-35), respectively, indicating poor quality. The interrater reliability (IRR) scores ranged from 0.51 to 0.93, indicating fair to excellent reliability. The average PEMAT-AV understandability and actionability scores were 69.8% ±15.4% and 11.0% ±24.6%, respectively, indicating mostly understandable but poor actionability. The t-test results showed that international videos scored higher without statistical significance in the DISCERN or PEMAT-AV scores (P = 0.18, 0.59, and 0.20). CONCLUSIONS: The current quality of videos on YouTube™ on the topic of varicoceles is of poor quality due to a lack of a holistic approach in explaining the wide range of treatment options available. With the ease of access to produce and disseminate health information, there is a need to create high-quality videos on varicoceles that empower a patient to make an informed decision.

The Emerging Role of Poly (ADP-Ribose) Polymerase Inhibitors as Effective Therapeutic Agents in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is the sixth most common cancer in the US. However, no significant changes in management have occurred since the tyrosine kinase era until the recent breakthrough with checkpoint inhibitors. Therefore, the need for more therapeutic options is paramount. Our objective was to determine whether PARP inhibition represents a novel therapeutic option for RCC. We used publicly available COSMIC, GDC Data Portal, and cBioPortal databases to explore mutations in DNA repair genes in RCC tissues from the TCGA cohort. We treated a human normal renal epithelial cell line RPTEC/TERT1 and two human renal cancer cell lines ACHN and CAKI-2 with PARPi niraparib, olaparib, rucaparib, veliparib, and talazoparib. Cell survival, cell proliferation, clonogenic ability, and apoptosis were assessed. RCC xenografts in SCID mice were treated with PARPi to evaluate their efficacy in vivo. Data mining revealed that ~27-32% of RCC tissues contain mutations in homologous recombination genes. Niraparib and talazoparib were the most effective at reducing cell survival, proliferation, and clonogenic ability in vitro. Niraparib, talazoparib, and rucaparib were the most effective in reducing RCC xenograft growth in vivo. Agents such as PARPi that exploit mutations in DNA damage repair genes may be effective therapeutic options for RCC.

Urine versus stent cultures and clinical UTIs.

PURPOSE: Current American Urological Association guidelines recommend pre-operative antimicrobial therapy based on prior urine cultures (UC); however, the role of stent culture (SC) in urologic practice is unclear. We examined whether UC and SC differed at the time of stent removal, as well as the association, microbiology, and timing of subsequent UTIs as related to SC. METHODS: This was a retrospective review of 159 patients with ureteral stents for indications of urolithiasis, benign stricture, malignant obstruction, and kidney transplant. UC and SC were analyzed at the time of stent removal. Patients were followed for 12 months after stent removal for development, concordance, and timing of clinical UTIs. RESULTS: In 159 patients, 15% had positive UC and 45% had positive SC. Of patients who had positive SC, 66% had negative UC. All patients with positive UC had identical micro-organisms on SC; however, 33% of these had SC with additional micro-organisms. Relative to those with both negative UC and SC, patients with negative UC and positive SC had a 5.7 odds, and those with both positive UC and SC had a 13.6 odds of developing a clinical UTI within 12 months. Concordance of SC and future UTI was highest in those with post-operative sepsis, and those with Candida species on SC. CONCLUSIONS: SC was a unique risk factor for development of UTI within 12 months of stent removal. Clinicians should consider SC results when empirically treating those with post-operative sepsis or those with UTI after Candida on SC.

Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) Finds Patient Age and Sperm Morphology Are Associated With Centriole Quality.

A large proportion of infertility and miscarriage causes are unknown. One potential cause is a defective sperm centriole, a subcellular structure essential for sperm motility and embryonic development. Yet, the extent to which centriolar maladies contribute to male infertility is unknown due to the lack of a convenient way to assess centriole quality. We developed a robust, location-based, ratiometric assay to overcome this roadblock, the Fluorescence-based Ratiometric Assessment of Centrioles (FRAC). We performed a case series study with semen samples from 33 patients, separated using differential gradient centrifugation into higher-grade (pellet) and lower-grade (interface) sperm fractions. Using a reference population of higher-grade sperm from infertile men with morphologically standard sperm, we found that 79% of higher-grade sperm of infertile men with substandard sperm morphology have suboptimal centrioles (P = 0.0005). Moreover, tubulin labeling of the sperm distal centriole correlates negatively with age (P = 0.004, R = -0.66). These findings suggest that FRAC is a sensitive method and that patient age and sperm morphology are associated with centriole quality.