Financial decision analysis based on "willingness to pay" for surgical sperm retrieval approaches among men with non-obstructive azoospermia in the United States.

OBJECTIVE: To determine the most financially optimal surgical approach for testicular sperm retrieval for men with non-obstructive azoospermia. DESIGN: A decision tree was created examining five potential surgical approaches for men with non-obstructive azoospermia pursuing one cycle of intracytoplasmic sperm injection. An expected financial net loss was determined for each surgical option based on couples' willingness to pay for one cycle of intracytoplasmic sperm injection resulting in pregnancy. The branch with the lowest expected net loss was defined as the most optimal financial decision (minimizing loss to a couple). Fresh testicular sperm extraction implied testicular sperm extraction was performed in conjunction with programmed ovulation induction. Frozen testicular sperm extraction implied testicular sperm extraction was performed initially, and ovulation induction/intracytoplasmic sperm injection was canceled if sperm retrieval failed.  The surgical options included fresh conventional testicular sperm extraction, with and without "back-up" sperm cryopreservation, fresh microsurgical testicular sperm extraction, with and without "back-up" sperm cryopreservation, and frozen microsurgical testicular sperm extraction. Success was defined as pregnancy after one intracytoplasmic sperm injection cycle. MATERIALS AND METHODS: Probabilities of successful sperm retrieval with conventional testicular sperm extraction/microsurgical testicular sperm extraction, post-thaw sperm cellular loss following frozen microsurgical testicular sperm extraction, ovulation induction/intracytoplasmic sperm injection cycle out-of-pocket costs, intracytoplasmic sperm injection pregnancy rates for men with non-obstructive azoospermia, standard conventional testicular sperm extraction cost and average willingness to pay for intracytoplasmic sperm injection cycle were gathered from the systematic literature review. Costs were in USD and adjusted to inflation (as of April 2020). Two-way sensitivity analysis was performed on varying couples' willingness to pay for one cycle of intracytoplasmic sperm injection and varying microsurgical testicular sperm extraction out-of-pocket costs. RESULTS: According to our decision tree analysis (assuming minimum microsurgical testicular sperm extraction cost of $1,000 and willingness to pay of $8,000), the expected net loss for each branch was as follows: -$17,545 for fresh conventional testicular sperm extraction, -$17,523 for fresh microsurgical testicular sperm extraction, -$9,624 for frozen microsurgical testicular sperm extraction, -$17,991 for fresh conventional testicular sperm extraction with "backup", and -$18,210 for fresh microsurgical testicular sperm extraction with "backup". Two-way sensitivity analysis with a variable willingness to pay values and microsurgical testicular sperm extraction and in-vitro fertilization costs confirmed that frozen microsurgical testicular sperm extraction consistently presented the lowest net loss compared to other options. Interestingly, when directly comparing fresh microsurgical testicular sperm extraction and conventional testicular sperm extraction with "back-up", scenarios with decreasing willingness to pay and lower microsurgical testicular sperm extraction costs demonstrated fresh conventional testicular sperm extraction with "back-up" as more optimal than fresh microsurgical testicular sperm extraction with "back-up". CONCLUSIONS: For those couples who must pay out of pocket, our study suggests that frozen microsurgical testicular sperm extraction is the most financially optimal decision for the surgical management of non-obstructive azoospermia, regardless of microsurgical testicular sperm extraction cost and the couple's willingness to pay.

Evidence-Based Analysis of the Critical Steps of Radical Cystectomy for Bladder Cancer.

Radical cystectomy (RC) is an integral part of the management of patients with advanced-stage bladder cancer. This major oncologic operation is prone to complications resulting in morbidity and mortality. We analyzed the critical steps of open RC, performed an evidence-based review of these steps, and discussed our experience and approach. We conducted a literature review of the open RC technique, identified the critical steps that consistently appeared across different sources, and organized these steps into a framework. PubMed was queried with the critical steps as keywords for relevant articles published from 1 January 2013 to 1 August 2023. We utilized this query to conduct a systematic review of the literature using the outcomes of overall survival and 90-day complication rate. We developed the "Summary for the 10 Critical Operative Steps of Radical Cystectomy", a concise guide to the approach to open RC. When available, an evidence-based analysis of each critical step was performed. We also included additional components of cystectomy optimization such as pre-habilitation in the preoperative phase, standard versus extended lymphadenectomy, the vaginal-sparing approach to female radical cystectomy, patient-reported outcomes following urinary diversion, the use of a mesh for stoma formation, and the use of the ERAS protocol for postoperative care. An evidence-based assessment of RC may help provide valuable information to optimize surgical techniques and patient outcomes.

The effects of male anxiety and depression on IVF outcomes.

STUDY QUESTION: What are the effects of male anxiety and depression on IVF outcomes? SUMMARY ANSWER: Men with anxiety had lower final total motile sperm counts (fTMSC) during IVF compared to men without anxiety; however, there were no differences in live birth rates (LBRs). WHAT IS KNOWN ALREADY: Studies have shown that male anxiety causes low sperm motility, worse sperm morphology, and increased DNA fragmentation, which are known to be influential factors on fertilization rates and embryo quality during IVF. However, data are lacking on whether there is a direct association between male anxiety and/or depression and IVF outcomes. STUDY DESIGN, SIZE, DURATION: This was a survey-based, retrospective cohort study completed at a single, large hospital-affiliated fertility center with 222 respondents who underwent IVF with or without ICSI. The study was conducted between 6 September 2018 and 27 December 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Male partners of couples who underwent IVF or IVF/ICSI completed a Hospital Anxiety and Depression Scale (HADS) questionnaire. They were separated into two groups for both anxiety (HADS-A ≥ 8 or HADS-A < 8) and depression (HADS-D ≥ 8 or HADS-D < 8). Men with an elevated HADS-A or HADS-D score ≥8 were considered to have anxiety or depression, respectively. The primary outcome was LBR. Secondary outcomes included semen parameters at the time of IVF, cycle outcomes, pregnancy outcomes, and prevalence of erectile dysfunction and low libido. MAIN RESULTS AND THE ROLE OF CHANCE: There were a total of 222 respondents, of whom 22.5% had a HADS-A ≥ 8 and 6.5% had a HADS-D ≥ 8. The average age of respondents was 37.38 ± 4.90 years old. Antidepressant use was higher in the respondents with a HADS-A or HADS-D ≥ 8 (P < 0.05). Smoking use was similar between groups for both HADS-A and HADS-D (P > 0.05). When adjusted for male BMI, antidepressant use and smoking, men with a HADS-A or HADS-D ≥ 8 had similar rates of erectile dysfunction (adjusted relative risk (aRR) = 1.12 (95% CI 0.60, 2.06)) and low libido (aRR = 1.70 (95% CI 0.91, 3.15)) compared to those with a HADS-A or HADS-D ≤ 8. Men with a HADS-A ≥ 8 were more likely to have a lower fTMSC on the day of oocyte retrieval (11.8 ≥ 8 vs 20.1 < 8, adjusted ß = -0.66 (95% CI -1.22, -0.10)). However, the LBR per embryo transfer (ET) was similar between the HADS-A groups (43.2% ≥8 vs 45.1% <8, adjusted relative risk = 0.90 (95% CI 0.65, 1.06)). Although depression was uncommon in the entire cohort, the HADS-D groups were clinically similar for fTMSC (18.7 ≥ 8 vs 16.0 < 8) and LBR per ET (46.7% ≥8 vs 45.4% <8). LIMITATIONS, REASONS FOR CAUTION: Limitations of our study are the survey-based design, the lack of sperm morphology assessment at the time of IVF, our inability to fully assess the HADS-D ≥ 8 cohort due to the small sample size and the large Caucasian demographic. WIDER IMPLICATIONS OF THE FINDINGS: Couples undergoing IVF have an increased likelihood of suffering from anxiety and/or depression. There is currently a debate on whether or not men should be treated with antidepressants while attempting to conceive due to potential detrimental effects on sperm quality. Our study shows that, regardless of antidepressant use, couples with men who did or did not report anxiety and/or depression have similar LBRs when undergoing IVF. Therefore, it is important to assess both partners for mental health and to not withhold treatment due to a concern about a potential impact of antidepressants or anxiety/depression on sperm quality. STUDY FUNDING/COMPETING INTEREST(S): There was no funding to report for this study. Z.W. is a contributing author for UptoDate. S.S.S. is on the advisory board for Ferring Pharmaceuticals. E.G. was a medical consultant for Hall-Matson Esq, Teladoc, and CRICO and is a contributing author for UptoDate. The remaining authors have nothing to report. TRIAL REGISTRATION NUMBER: N/A.

Does benign prostate hyperplasia histopathological variation impact disease-specific clinical outcomes after transurethral resection?

The impact of histopathological variants in stromal and glandular tissue on clinical outcomes following transurethral resection of prostate (TURP) is unexplored. We sought to evaluate the relationship between histopathological variations in TURP specimen and postoperative clinical outcomes. We performed a retrospective analysis of men undergoing initial TURP at our institution from 2017 to 2019. All pathology slides were re-reviewed by one specialized genitourinary pathologist who was blinded to all clinical data. Types of BPH were defined as: glandular-predominant (gland:stroma ratio >50%), mixed (gland:stroma ratio 25%-50%), and stromal-predominant (gland:stromal ratio <25%). Primary clinical outcomes were ∆ post-void residual and ∆ American Urological Society Symptom Score (AUASS) at 3, 6, and 12 months post-operatively. We also evaluated for a temporal relationship between time since surgery and ∆AUASS amongst different histopathological subgroups. One hundred and five patients were included in the final analysis. 61/105 (58.1%) had glandular-predominant histopathology, 21/105 (20%) had stromal-predominant histopathology, and 23/105 (21.9%) were classified as mixed histopathology. On univariate and multivariate analysis, histopathological subtype was not a significant predictor of any of the clinical post-operative endpoints of interest at any time points. Disease-specific outcomes after TURP appear to be consistent across these different histopathologic subtypes.

Awareness and reporting of globozoospermia among in vitro fertilization and andrology laboratories: A national survey.

Globozoospermia (GZ) is a rare disorder found in less than 0.1% of infertile men in which spermatozoa lack acrosomes necessary for penetration of an oocyte. While methods have been demonstrated to allow globozoospermic men to achieve a viable pregnancy with their partner, the Wold Health Organization considers identifying and reporting GZ on semen analysis to be 'important'. Our study aims to determine if and to what extent in vitro fertilization (IVF) laboratories nationwide recognize and report GZ on semen analysis reports. We constructed an IRB-approved survey sent nationwide to IVF and andrology clinic laboratory directors listed by the Society for Assisted Reproductive Technology and/or the American Society for Reproductive Medicine. Results from the survey were de-identified for analysis. A total of 490 surveys were sent with a response rate of 10% (n = 51). Most respondents (66%) practiced in a private, rather than academic, setting. A majority of respondents were confident in their technicians' knowledge of GZ (86%) and ability to identify it on a sample (94%). However, only half of respondents noted a space to report the concern for GZ to the ordering physician, and 25% of respondents did not feel their clinic was able to identify patients where there is a concern for GZ. Similarly, 84% of respondents did not report a percent of acrosome-deficient sperm. Less than half of respondents reported that their clinic has previously diagnosed GZ. Though the majority of respondents felt that their laboratory technicians would be able to identify GZ, a significant minority felt that their clinic did not have means to be able to report concern for GZ. This may be due to the absence of a proper channel to report a concern for GZ, a lack of knowledge about the condition, or failure to distinguish GZ from a broader reported percentage of morphologically abnormal sperm. Given evidence that the diagnosis of GZ may be under-reported in the United States, there should be a national standard for laboratory technicians to be trained to recognize GZ and be able to report their suspicion to the ordering clinician.

Adjuvant Chemotherapy Plus Radiotherapy versus Chemotherapy Alone for Locally Advanced Bladder Cancer after Radical Cystectomy.

BACKGROUND: Survival with locally advanced bladder cancer (LABC) following radical cystectomy (RC) remains poor. Although adjuvant chemotherapy (AC) is standard of care, one small, randomized trial has suggested a potential survival benefit when combined with post-operative radiotherapy (PORT). OBJECTIVE: We examined the association of AC + PORT with overall survival (OS) in patients with LABC after RC. METHODS: Using a prior phase 2 trial to inform design, we conducted observational analyses to emulate a hypothetical target trial of patients aged 18-79 years with pT3-4 Nany M0 or pTany N1-3 M0 urothelial bladder carcinoma following RC who were treated with AC (multiagent chemotherapy within 3 months of RC) with or without PORT (≥45 Gy to the pelvis) from 2006-2015 in the NCDB. Patients who received preoperative chemotherapy or radiotherapy were excluded. The associations of treatment with OS were evaluated using multivariable Cox regression. RESULTS: 1,684 patients were included, with 66 receiving AC + PORT and 1,618 AC alone. Compared to patients treated with AC alone, those treated with AC + PORT were more likely to have pT4 disease (52% vs 26%; p < 0.01), positive surgical margins (44% vs 17%; p < 0.01), and be treated at a non-academic facility (75% vs 53%; p < 0.01). Crude 5-year OS was 19% for AC + PORT versus 36% for AC alone (p = 0.01). Adjusted 5-year OS was 33% for AC + PORT versus 36% for AC alone (p = 0.49). After adjusting for baseline characteristics including pathologic features, AC + PORT was not associated with improved OS compared to AC alone (HR 1.11; 95% CI 0.82-1.51). CONCLUSIONS: Although infrequently utilized, the addition of radiotherapy to AC is not associated with improved OS in LABC. These results highlight the need for prospective trials to better define the potential benefits from PORT with regard to symptomatic progression and oncologic outcomes.

Evaluating the quality of reported outcomes for microsurgical TESE in men with non-obstructive azoospermia: A methodological analysis.

BACKGROUND: Publications of microsurgical testicular sperm extraction (mTESE) techniques and outcomes are heterogeneous, which may limit creation of best surgical practices. OBJECTIVE: To study the quality and heterogeneity of published mTESE outcomes via a methodological analysis. MATERIALS/METHODS: A systematic methodological analysis of all published literature on the use of mTESE in men with non-obstructive azoospermia from 1999 to the July 2020 was performed. PubMed and MEDLINE searches were performed using the search terms "microdissection TESE OR microsurgical TESE." Publications were evaluated on their reporting of pre-operative factors, intraoperative techniques, surgical and clinical outcomes, and adverse events. RESULTS: Fifty-five studies met inclusion criteria. Surgical technique and sperm retrieval rates were the most reported criteria. Reporting on the presence of an embryologist intraoperatively was observed in approximately 30% of articles, while other procedural details including method of sperm quantification, quantity retrieved, and number of cryopreserved vials were observed in fewer than 10% of articles. Clinical outcomes, including pregnancy rates and live birth rates, were reported in fewer than 40% of the articles. Fetal outcomes including fetal and neonatal anomalies were rarely reported. Fetal growth restriction, preterm delivery, small or large for gestational age, and NICU admissions were never reported. CONCLUSION: There are inconsistencies in reporting quality of mTESE outcomes, specifically a lack of information on the quantity and quality of sperm retrieved, the role of embryology intraoperatively, and clinical outcomes, such as live birth rate and fetal anomalies. These gaps may guide development of standardized reporting guidelines to better assess and compare clinical outcomes across institutions and maintain focus on couples-centric fertility outcomes in future mTESE studies.