Citations

Abstract Introduction There is wide variation in male fertility preservation practices. While physician preference accounts for some of this diversity, practice patterns often reflect multiple extrinsic factors including patient demographics, equipment availability, laboratory protocols, and state law. Objective We sought to characterize national trends in sperm retrieval and storage across reproductive urology practices in the United States. Methods An anonymous 34-item survey characterizing provider demographics, practice settings, fertility preservation procedures, andrology laboratory practices, and cryopreservation expenses was designed. Practicing reproductive urologists were identified using information available through professional societies. Our survey was constructed using the Qualtrics platform and distributed electronically between October 2024 and May 2025. Results 39 responses were received by urologists practicing across 21 states (response rate: 21%, n=189). A majority (74%, n=29) of survey responders practiced at academic medical centers, with others practicing at non-academic hospitals (8%, n=3) and private practices (13%, n=5). The most common indications for fertility preservation reported included oncologic care (42%), gamete storage for planned ART (31%), transgender care (18%), pre-vasectomy sperm banking (10%), and pre-deployment banking for military personnel (5%). Nearly all providers performed microsurgical sperm retrievals (97%, n=38, Figure) and oncologic testicular sperm extractions (85%, n=33) when indicated. More than half of providers offered conventional testicular sperm extractions (72%, n=28), microsurgical epididymal sperm aspirations (59%, n=23), testicular sperm aspirations (56%, n=22), penile vibratory stimulation (54%, n=21), or percutaneous epididymal sperm aspirations (52%, n=20). Fewer providers offered post-mortem sperm retrieval (49%, n=19), pre-pubertal testicular tissue cryopreservation (36%, n=14), or electroejaculation (31%, n=12). Most respondents (62%, n=24) had access to an on-site andrology laboratory. Semen analyses were evaluated using manual (53%, n=20), computer-assisted (11%, n=4), or combinatorial methods (26%, n=10). Though many (37%, n=14) providers were uncertain about institutional costs for semen specimen processing, a plurality of respondents (40%, n=15) reported fees ranging from $100-500 with the remainder (23%, n=9) reporting fees exceeding $500. Respondents most frequently reported semen storage fees ranging between $100-300 per year (39%, n=15), while approximately a third (31%, n=12) estimated these costs to range between $300-600 per year. However, 18% (n=7) of respondents reported higher costs for specimen storage and 13% (n=5) were uncertain about the expense of this service. Conclusions This multi-institutional, geographically diverse survey reveals significant variation in reproductive urology practice patterns and cost associated with semen analyses and storage. Future studies will explore differences in practice patterns to better understand the factors influencing this variation and their effect on male reproductive healthcare. In the absence of society guidelines, reproductive urologists must collaborate, share best practices, and maintain price transparency to ensure sperm retrieval remains accessible and affordable. Disclosure No

Abstract Introduction While microdeletions in the azoospermia factor (AZF) regions of the Y chromosome are a well-recognized cause of genetic male infertility, reproductive outcomes and broader health profiles among affected men remain poorly characterized. Objective We explore the distribution of AZF deletion subtypes and evaluate comorbidities and fertility management patterns in this unique population. Methods We performed a multi-institutional retrospective cohort study of men diagnosed with AZF deletions following evaluation by a reproductive urologist and genetic testing. The primary exposure variable was the AZF subtype (AZFa, AZFb, AZFc, or multilocus [e.g., AZFabc]).Clinical data were extracted to assess the presence of comorbidities, including hypertension, diabetes mellitus, hyperlipidemia, liver disease, and cardiac disease. Descriptive statistics were used to characterize the distribution of AZF subtypes, comorbidity profile, and outcomes of sperm retrieval procedures within our cohort. Results Among 40 men with confirmed AZF microdeletions across three academic centers, four patients with SRY translocations were excluded. Of the remaining 36, AZFc was the most common subtype (75%), followed by multilocus (16.6%), AZFa (5.5%), and AZFb (2.7%). The median age was 32.8 years (IQR: 29.2–33.6) and median BMI was 28.6 kg/m2 (IQR: 25.6–32.8). Comorbid conditions were identified in 8% of the cohort, with hyperlipidemia (13.9%), hypertension (11%), and diabetes (11%) most commonly reported. Sperm retrieval was attempted in 31% (n=11) of patients, exclusively among those with AZFc (n=10) andAZFb (n=1) deletions. Microscopic testicular sperm extraction (mTESE) was the predominant technique (91%). Sperm was successfully retrieved in 46% of these cases, all within the AZFc subgroup. Conclusions This study advances limited literature on AZF microdeletions by characterizing systemic health profiles and post-diagnosis infertility management. Our results support a broad phenotype associated with genetic causes of male infertility. In this cohort of men with YCMD, AZFc was the most prevalent subtype. Compared to national estimates for similarly aged men, our findings suggest that men with YCMD may have a distinct comorbidity profile compared to the general population, with an elevated prevalence of metabolic disease. Our findings reinforce male infertility as a heterogeneous condition that may serve as an early marker for broader metabolic disease. In addition, nearly all patients who underwent sperm retrieval were within the AZFc group. Fertility management trends favored mTESE, with moderate success rates in sperm retrieval, particularly among AZFc patients. Our results highlight provider preferences in surgical fertility management in patients withYCMD. Our findings underscore the need for a holistic approach to men with YCMD, addressing both surgical fertility management and systemic health risks. Clear patient counseling on sperm retrieval success rates and early identification of comorbidities may redefine outcomes for this unique population. Our results support a broad phenotype associated with genetic causes of male infertility. Disclosure No

Abstract Introduction Fertility preservation is an essential component to cancer survivorship. One third of male survivors experience infertility following gonadotoxic treatments, and expeditious preservation prior to therapy is recommended by oncology guidelines. However, this can be challenging given time constraints, lab expertise, and financial considerations. Objective We describe national practice patterns and identify barriers and facilitators regarding inpatient male fertility preservation. Methods An anonymous 34-item Qualtrics survey was sent to reproductive Urologists in the United States. Email addresses were obtained from public membership databases. Respondents were queried across several domains, including provider demographics, specific inpatient cryopreservation scenarios, and fertility preservation procedures. Results Thirty-nine (21%, n=39/189) responses were received. The majority of respondents were fellowship-trained reproductive urologists 89.7% (35). The majority (97.4%) of respondents offer microdissection testicular sperm extraction (mTESE) for fertility preservation, and many offer conventional TESE (71.8%), traditional ejaculated sperm cryopreservation (71.8%), or microsurgical epididymal sperm aspiration (59%). Only 30.8% of respondents offer electroejaculation. Respondents rate non-urology provider awareness of male cancer fertility preservation options at 5.05/10 on a Likert scale. Many (65%) respondents provide formal materials or education to nonurology providers to address this deficit. On average, respondents reported 2.6 inpatient oncofertility preservation consults per month (range 0-25, median=1). Most (60%) of respondents reported that <25% of these patients ultimately complete inpatient preservation. Financial burdens (97%), logistical hurdles (97%), limited awareness (97%), and concern for delay of oncologic care (92%) were identified as the most common barriers for patients precluding fertility preservation. In addition, 85% of respondents also listed difficulty coordinating with other specialists as a barrier. On free-text queries, respondents identified facilitators of fertility preservation as automatically triggered consults, use of an urgent cryopreservation pager, formal fertility preservation pathway within the order set, and utilization of an inpatient coordinator as facilitators that aid in achieving timely fertility preservation prior to gonadotoxic therapies. Conclusions Despite all reproductive urologists offering cryopreservation services and education regarding the urgency and priority of inpatient fertility preservation, less than a quarter of patients complete this process during hospitalization prior to initiation of treatment. This remains the consequence of numerous patient, provider, and facility level barriers, even in systems with robust referral processes. Inpatient fertility preservation remains an underutilized and often missed opportunity. Multidisciplinary interventions are needed to address ongoing barriers. Disclosure No

Abstract Introduction Chronic scrotal content pain (CSCP), defined as three or more months of scrotal pain interfering with daily life, affects approximately 100,000 men annually in the United States. Historically, the absence of standardized guidelines led to wide variability in diagnosis and treatment. At the time of our study design and data collection, no formal guidance existed for CSCP. In April 2025, after the study’s completion, the American Urological Association (AUA) published its first clinical guidelines for CSCP. Our findings now offer important context regarding real-world practice patterns before guideline publication. Objective To characterize diagnostic and treatment strategies for CSCP among U.S. reproductive urologists. Methods An anonymous 25-question Qualtrics survey was distributed to U.S.-based reproductive urologists. The survey assessed physician demographics, diagnostic evaluations, conservative and surgical treatment strategies, and perceived patient outcomes. Descriptive statistics were calculated, and comparisons were performed using Mann-Whitney U, chi-square, or Fisher’s exact tests, as appropriate. Results Of 183 invited physicians, 41 (22.4%) completed the survey in full. All respondents were fellowship-trained, practicing urologists, with most board-certified (82.9%). Respondents were nearly evenly split between ≤5 years (48.8%) and >5 years (51.2%) in practice. Among ten conservative treatment options, reassurance (41.5%) and NSAIDs (31.7%) were the most frequently selected first-line treatments, with median ranks of 2.5 and 2, respectively (Figure 1). Opioid medications were the least favored (median rank: 10), with 56.1% ranking them last. Pelvic floor physical therapy (PFPT) had a favorable median rank of 3 and was ranked higher by those with ≤5 years in practice compared to those in practice >5 years (median: 3 vs. 4, p = 0.019). GABA analogues and tricyclic antidepressants were assigned median ranks of 6 and 7.5, respectively. The most commonly performed surgical procedure for CSCP was microsurgical denervation of the spermatic cord (MDSC, 95.1%), followed by varicocelectomy (92.7%), vasectomy reversal (78.0%), epididymectomy (73.2%), and orchiectomy (51.2%). For post-vasectomy pain syndrome, MDSC was preferred by 63.4%, followed by vasectomy reversal (22.0%) and epididymectomy (9.8%). Among those performing vasectomy reversals, 80% of patients paid out-of-pocket (IQR: 50.0–93.5%). Respondents perceived surgical management as more effective than conservative treatment, with median complete symptom resolution rates of 70% (IQR: 50–80%) versus 25% (IQR: 10–40%) (p < 0.001). Only 7.3% reported using validated tools like the Chronic Orchialgia Symptom Index (COSI) to evaluate patient outcomes. Conclusions Our study offers a contemporary snapshot of CSCP management among reproductive urologists, revealing substantial variability in practice. Surgery was consistently perceived as more effective than conservative approaches. These findings underscore areas of alignment and divergence with the newly released AUA guidelines and support the need for future comparative trials and implementation studies to guide standardized, evidence-based care. Disclosure No

Abstract Introduction Oncologic testicular sperm extraction (oncoTESE) remains a poorly defined concept that is a heterogeneous and understudied fertility preservation option for cancer patients with male gonads. Given variation in practice patterns, reproductive insurance coverage, and provider availability, there is significant diversity among the accepted indications, desired evaluations, and surgical practices afforded to patients facing a cancer diagnosis. Objective This study aimed to characterize and help further define oncoTESE practice patterns across the United States. Methods A 34-item, anonymized survey assessed provider demographics and oncoTESE practice patterns, including indications, contraindications, workflows, and institutional barriers surrounding OncoTESE procedures. A survey was created and electronically distributed to reproductive urologists across the United States using email addresses obtained via society membership websites. Results Thirty-eight urologists (20%, 38/189) from 21 states responded to the survey. Most (95%, 36/38) were fellowship-trained reproductive urologists, and nearly all (87%, 33/38) reported offering oncoTESE to indicated patients. The most cited indications for oncoTESE were azoospermia (78%, 28/36), anejaculation (72%, 26/36), and severe oligozoospermia or cryptozoospermia on ejaculated specimen (53%, 19/36). Less commonly reported indications included prepubertal or peripubertal status (33%, 12/36) and elevated sperm DNA fragmentation (19%, 7/36). Relative contraindications included inability to consent (86%, 31/36), clinical instability (83%, 30/36), thrombocytopenia (61%, 22/36), and a history of remote chemotherapy (58%, 21/36). When asked how many semen analyses are obtained to confirm azoospermia before proceeding to oncoTESE in patients able to ejaculate, the majority reported two analyses (67%, 24/36), while 28% (10/36) reported one. There was stronger consensus that oncoTESE includes sperm retrieval during back-table orchiectomy (94%, 34/36) and ipsilateral microTESE during partial orchiectomy (86%, 31/36). Greater variability was noted regarding contralateral microTESE at the time of orchiectomy (64%, 23/36), procedures for non-genitourinary malignancies (61%, 22/36), and delayed procedures performed years after diagnosis (42%, 15/36). (Figure 1) Estimated patient costs for oncoTESE were most commonly reported as $2,000–$5,000 (39%, 14/36), followed by $500–$2,000 (22%, 8/36), $5,000–$10,000 (19%, 7/36), and over $10,000 (3%, 1/36); 14% (5/36) were unsure. On a 10-point Likert scale, the most significant barriers to performing oncoTESE were logistical challenges (mean 6.6, median 8), followed by patient cost (mean 5.4, median 5.5) and patient illness (mean 5.3, median 5.0). Conclusions This multi-institutional survey found strong agreement among reproductive urologists on core procedural elements, but substantial variation on oncoTESE definition, patient selection criteria, pre-procedural evaluation, and fertility preservation management. Similar institutional barriers across centers highlight opportunities to improve accessibility and standardize oncoTESE practices. Disclosure No

Abstract Rehabilitation after musculoskeletal trauma is globally acknowledged as essential for restoring function and improving quality of life; however, significant variation exists in rehabilitation frameworks and services worldwide. Although certain principles—such as early intervention, structured care pathways, and multidisciplinary approaches—are universally recognized as important determinants of outcomes in trauma patients, their implementation and effectiveness vary considerably due to differences in health care infrastructure, economic resources, policy frameworks, and cultural contexts. Drawing on comparative analyses of rehabilitation frameworks across regions, including North America, Latin America, Europe, Asia-Pacific, and Africa, this paper identifies structural variations, systemic challenges, and innovations that can inform global rehabilitation efforts. Strategic international collaboration focusing on shared learning, standardized protocols, technology integration, and targeted investments is key to creating equitable and sustainable rehabilitation models, especially in resource-limited settings and aging populations.

Objectives: An unexpectedly low word recognition (WR) score may be taken as evidence of increased risk for retrocochlear tumor. We sought to develop evidence for or against using a standardized WR (sWR) score in detecting retrocochlear tumors. The sWR is a z score expressing the difference between an observed WR score and a Speech Intelligibility Index–based predicted WR score. We retrospectively compared the sensitivity and specificity of pure-tone asymmetry-based logistic regression models that incorporated either the sWR or the raw WR scores in detecting tumor cases. Two pure-tone asymmetry calculations were used: the 4-frequency pure-tone asymmetry (AAO) calculation of the American Academy of Otolaryngology–Head and Neck Surgery and a 6-frequency pure-tone asymmetry (6-FPTA) calculation previously optimized to detect retrocochlear tumors. We hypothesized that a regression model incorporating the 6-FPTA calculation and the sWR would more accurately detect retrocochlear tumors. Design: Retrospective data from all patients seen in the audiology clinic at Mayo Clinic in Florida in 2016 were reviewed. Cases with retrocochlear tumors were compared with a reference group with noise- or age-related hearing loss or idiopathic sensorineural hearing loss. Two pure-tone–based logistic regression models were created (6-FPTA and AAO). Into these base models, WR variables (WR, sWR, WR asymmetry [WRΔ], and sWR asymmetry [sWRΔ]) were added. Tumor detection performance for each regression model was compared twice: first, using all qualifying cases (61 tumor cases; 2332 reference group cases), and second, using a data set filtered to exclude hearing asymmetries greater than would be expected from noise-related or age-related hearing loss (25 tumor cases; 2208 reference group cases). The area under the curve and the DeLong test for significant receiver operating curve differences were used as outcome measures. Results: The 6-FPTA model significantly outperformed the AAO model—with or without the addition of WR or WRΔ variables. Including sWR into the AAO base regression model significantly improved disease detection performance. Including sWR into the 6-FPTA model significantly improved disease detection performance when large hearing asymmetries were excluded. In the data set that included large pure-tone asymmetries, area under the curve values for the 6-FPTA + sWR and AAO + sWR models were not significantly better than the base 6-FPTA model. Conclusions: The results favor the superiority of the sWR computational method in identifying reduced WR scores in retrocochlear cases. The utility would be greatest where undetected tumor cases are embedded in a population heavily representing age- or noise-related hearing loss. The results also demonstrate the superiority of the 6-FPTA model in identifying tumor cases. The 2 computational methods may be combined (ie, the 6-FPTA + sWR model) into an automated tool for detecting retrocochlear disease in audiology and community otolaryngology clinics. The 4-frequency AAO-based regression model was the weakest detection method considered. Including raw WR scores into the model did not improve performance, whereas including sWR into the model did improve tumor detection performance. This further supports the contribution of the sWR computational method for recognizing low WR scores in retrocochlear disease cases.

Abstract We have studied the molecular diversity of the allogeneic TCR repertoire specific for the HLA-DR4 variant, DRB1*0404, by analyzing the V beta gene segment usage of CD4+ T cell clones from nine different donors and comparing the V beta repertoire in allospecific and unselected T cell populations. To investigate the forces shaping the repertoire of the alloreactive T cell response we compared the diversity of TCR specificities utilized in very similar and in disparate responder/stimulator combinations. Six of the responders shared the HLA-DRB1*0401 allele, which differs from the HLA-DRB1*0404 allele by only two amino acid substitutions at positions 71 and 86 of the HLA-DR beta 1 chain; three responders expressed HLA-DRB1 alleles with extensive polymorphisms compared with the stimulator HLA-DRB1 allele. In all nine responders, TCR specificities recruited to recognize HLA-DRB1*0404 were strongly biased toward the dominant usage of one to three V beta elements. Despite some degree of heterogeneity between different responders, the overall pattern was very similar with a hierarchy of TCR V beta elements expressed by HLA-DRB1*0404 specific T cells. A core group of V beta elements (V beta 6, 5, 2, 13.2, 18, and 7) was preferentially used, whereas other V beta elements including V beta 3, 4, and 8 were infrequently used or not used at all. Sequencing of the VDJ beta region from selected T cell clones showed no junctional bias associated with the preferential V beta gene segment usage. Surprisingly, the T cell diversity in focused and in complex alloreactive responses were equally biased. The finding that HLA-DR4+ and DR4- donors exhibited a similar bias supports the interpretation that the alpha-helical HLA-DR structure of the stimulator cell has a dominant contribution in shaping the alloreactive repertoire.

Abstract Tumor-infiltrating lymphocytes (TIL) were obtained from a mouse melanoma cell line (CL 62) transfected with the gene for the human melanoma Ag p97. TIL were cultured with anti-CD3 antibody and IL-2 for up to 38 days. Flow cytometry identified these TIL as Thy-1.2 + ve/CD4-ve/CD8 + ve cells. A heteroconjugated antibody 500A2 x 96.5, specific for both the CD3 Ag on TIL and the p97 Ag on CL 62 melanoma cells, was prepared using N-succinimidyl-3-(2-pyridyldithio)-propionate as a linking agent. TIL alone demonstrated low levels of cytotoxicity against autologous CL 62 tumor and also against the parental K1735 tumor and an allogeneic murine melanoma (B16). The addition of 500A2 x 96.5 heteroconjugated antibody enhanced TIL-mediated lysis of CL 62 tumor, but not of the K1735 or B16 tumors. This enhanced cytotoxicity was elicited at E:T ratios as low as 0.4:1, and in TIL cultured for 7 to 38 days. These results suggest that hetero-conjugated antibody may enhance the anti-tumor effect of TIL in vivo.

Abstract A rare D-region recombination event which gave rise to the B10.RQDB major histocompatibility complex haplotype has been examined to ascertain the nature of the crossover and to determine which class I genes are present in the new alignment of D-region genes. Serologic analysis have shown that the B10 . RQDB major histocompatibility complex recombinant mouse inherited the H-2Dd gene from the B10.T(6R) parental line and the H-2Dd gene from the B10.A(2R) parental line, representing the first example of an intra-D-region crossover resulting from an intercross. Previous molecular genetic analyses of the d and b haplotypes revealed structural diversity in the organization of their D-region gene clusters. Hence, the D region is comprised of five class I genes in the d haplotype and only one in the b haplotype. Because allelic relationships among the various D-region genes are not defined, either a homologous or nonhomologous alignment of genes has generated the RQDB crossover. Therefore, the possibility that all three D-region antigen-presenting molecules (Dd, Ld, and Db) might be encoded by the RQDB haplotype was examined. Fluorescence-activated cell sorter and cytotoxic T lymphocyte analyses revealed no detectable levels of H-2Ld cell-surface expression, confirming earlier studies with antibody-mediated cytotoxicity and immunoprecipitation. Southern blot analysis localized the recombination point to within a 1-kb region at the centromeric end of the H-2Ld gene on the B10 . T(6R) chromosome in a region of high homology to the H-2Db gene on the B10 . A(2R) chromosome. Together, these studies define the D region of the RQDB haplotype as containing the five class I genes: Dd, D2d, D3d, D4d, and Db. In addition to providing insight into rare recombination events in the D region, the B10.RQDB mouse should be a useful tool for exploring the function of D-region genes.