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Recent advances surrounding in vitro spermatogenesis (IVS) have shown potential in creating a new paradigm of regenerative medicine in the future of fertility treatments for males experiencing non-obstructive azoospermia (NOA). Male infertility is a common condition affecting approximately 15% of couples, with azoospermia being present in 15% of infertile males (Cocuzza et al., 2013; Esteves et al., 2011a). Treatment for patients with NOA has primarily been limited to surgical sperm retrieval combined with in vitro fertilization intracytoplasmic sperm injection (IVF-ICSI); however, sperm retrieval is successful in only half of these patients, and live birth rates typically range between 10 and 25% (Aljubran et al., 2022). Therefore, a significant need exists for regenerative therapies in this patient population. IVS has been considered as a model for further understanding the molecular and cellular processes of spermatogenesis and as a potential regenerative therapeutic approach. While 2D cell cultures using human testicular cells have been attempted in previous research, lack of proper spatial arrangement limits germ cell differentiation and maturation, posing challenges for clinical application. Recent research suggests that 3D technology may have advantages for IVS due to mimicry of the native cytoarchitecture of human testicular tissue along with cell-cell communication directly or indirectly. 3D organotypic cultures, scaffolds, organoids, microfluidics, testis-on-a-chip, and bioprinting techniques have all shown potential to contribute to the technology of regenerative treatment strategies, including in vitro fertilization (IVF). Although promising, further work is needed to develop technology for successful, replicable, and safe IVS for humans. The intersection between tissue engineering, molecular biology, and reproductive medicine in IVS development allows for multidisciplinary involvement, where challenges can be overcome to realize regenerative therapies as a viable option., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Tension and malalignment of vasectomy reversal (VR) anastomoses are hypothesized to contribute to failure. We report VR outcomes using a novel technique introducing a tension-reliving hitch in the multi-layer microdot vasovasostomy (VV) and longitudinal intussuscepted vasoepididymostomy (LIVE; VE)., Methods: All vasectomy reversal patients between May 2019 and September 2023 from a single surgeon were reviewed. Patients were included if they underwent a VR, with at least one semen analysis within six months of surgery and a minimum of six months of followup after the surgery to deem a failure. The primary outcome was patency, which was defined as 1) any sperm in the ejaculate; and B) functionally as at least two million motile sperm. Late failure was defined as an azoospermic semen analysis result after previously documented presence of sperm., Results: A total of 159 patients were evaluated, of which 136 patients met the inclusion criteria. The patency rate among all VRs was 97.7 %, with an overall functional patency rate of 93.1%. One hundred and one patients underwent bilateral VVs, with a 99% patency rate and 95.5% functional patency rate. Twenty-three patients underwent a mixed VV/VE with a patency rate of 100% and a functional patency rate of 88.8%. Finally, 12 patients underwent bilateral VE, with a patency rate of 83.3% and a functional patency rate of 77.7%. Among these patients, four VV patients were identified to have a late failure., Conclusions: The combination of tension-relieving stitches for VVs and VEs, along with attention to symmetrical and precise stitch placement, results in high patency rates.

Collagenase Clostridium histolyticum (CCh), the first approved non-surgical treatment for Peyronie's disease (PD), was withdrawn from the European, Canadian, and Asian markets due to poor demand and lack of government reimbursement options. We sought to assess insurance approval rates and usage of CCh across Canada to understand the factors that led to its withdrawal. Data on patients prescribed CCh for PD or Dupuytren's contracture was obtained through collaboration with BioScript Solutions to assess the association of variables with insurance approval and prescription filling. We identified 3297 insurance coverage applications for Xiaflex® from April 2018 to June 2020. Of all applications for PD, 92.9% applications were approved while 7.1% were rejected. Despite the withdrawal of CCh from Canadian markets, coverage application approval rates for 2018, 2019, and 2020 were 86.5%, 90.1%, and 89.1%, respectively. Of 2921 approved applications, 88.8% prescriptions were filled. For the 376 rejected applications, 66.4% of prescriptions were filled. Overall, 90% of the cost of Xiaflex® was covered in Canada among those with extended health benefits, with an out-of-pocket expense of $210.4. Insurance coverage requests for Xiaflex® were approved at a high rate in Canada with approved patients being very likely to proceed with therapy, despite interprovincial variation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Deep dyspareunia affects 50% of people with endometriosis. The Ohnut is a set of interlocking rings that fit over the penis/insertive object. One or more rings can be used to limit insertion depth and reduce deep dyspareunia., Aim: We conducted a pilot, parallel, open-label randomized controlled trial (RCT) to investigate the feasibility of the study design and the acceptability and preliminary efficacy of the Ohnut., Method: Participants were recruited from a tertiary center for endometriosis. Eligibility criteria were surgically confirmed endometriosis, age 19-49 years, monogamous sexual relationship with a partner willing to participate in the study, and no comorbid superficial dyspareunia, anxiety, or depression. Couples were randomized into an intervention group or a waitlist control group using a 1:1 allocation ratio. All couples had sex as normal during weeks 1 to 4 (baseline period), and couples in the intervention group used the Ohnut with sex during weeks 5 to 10 (intervention period) while controls had sex as normal. Patient participants used daily diaries to record sexual activity and deep dyspareunia score (0-10) for the 10-week study. Intervention group participants completed an acceptability questionnaire at the end of the study., Outcomes: The primary outcomes were feasibility of the study and acceptability of the Ohnut. We also assessed differences in deep dyspareunia scores in the participants who used the Ohnut compared to the control participants who did not., Results: We recruited approximately 5 couples per month of active recruitment. Of 864 potentially eligible participants, we successfully contacted 44.7% (n = 386), of whom 8.0% (n = 31) consented, 64.8% (n = 250) were ineligible, and 27.2% (n = 105) declined. Thirty-one couples were randomly assigned to the intervention or control group, and 17 couples completed the study. Intervention group couples used the Ohnut for an average of 72.4% (32.7%) of sexual encounters during the intervention period. The mean acceptability index score for the Ohnut was 0.83 (0.078) among patients and 0.83 (0.049) among partners (index between 0 and 1). After controlling for baseline deep dyspareunia, there was a significant difference in the intervention period mean deep dyspareunia scores between the control and intervention group (4.69 (2.44) vs 2.46 (1.82), P = .012)., Clinical Implications: We identified preliminary evidence for the acceptability and efficacy of the Ohnut among both patients and partners, suggesting that the Ohnut may be a useful stand-alone or adjuvant management tool for endometriosis-associated deep dyspareunia., Strengths and Limitations: Strengths of this study were the "real-world" use of the Ohnut and data collection from both patients and partners. Limitations of the study design included the strict eligibility criteria that affected feasibility and generalizability., Conclusion: This pilot RCT indicated that the Ohnut may be an acceptable and effective intervention to reduce endometriosis-associated deep dyspareunia. We identified opportunities to improve design for a larger RCT., Clinical Trial Registration: This clinical trial was registered with clinicaltrials.gov (#NCT04370444)., Competing Interests: R.F. is co-owner of Teumo Health Technologies Inc, a digital health company in sexual medicine., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine.)

Objective: To determine if early spermatocytes can be enriched from a human testis biopsy using fluorescence-activated cell sorting (FACS)., Design: Potential surface markers for early spermatocytes were identified using bioinformatics analysis of single-cell RNA-sequenced human testis tissue. Testicular sperm extraction samples from three participants with normal spermatogenesis were digested into single-cell suspensions and cryopreserved. Two to four million cells were obtained from each and sorted by FACS as separate biologic replicates using antibodies for the identified surface markers. A portion from each biopsy remained unsorted to serve as controls. The sorted cells were then characterized for enrichment of early spermatocytes., Setting: A laboratory study., Patients: Three men with a diagnosis of obstructive azoospermia (age range, 30-40 years)., Intervention: None., Main Outcome Measures: Sorted cells were characterized for RNA expression of markers encompassing the stages of spermatogenesis. Sorting markers were validated by their reactivity on human testis formalin-fixed paraffin-embedded tissue., Results: Serine protease 50 (TSP50) and SWI5-dependent homologous recombination repair protein 1 were identified as potential surface proteins specific for early spermatocytes. After FACS sorting, the TSP50-sorted populations accounted for 1.6%-8.9% of total populations and exhibited the greatest average-fold increases in RNA expression for the premeiotic marker stimulated by retinoic acid (STRA8), by 23-fold. Immunohistochemistry showed the staining pattern for TSP50 to be strong in premeiotic undifferentiated embryonic cell transcription factor 1 - /doublesex and Mab-3 related transcription factor 1 - /STRA8 + spermatogonia as well as SYCP3 + /protamine 2 - spermatocytes., Conclusion: This work shows that TSP50 can be used to enrich early STRA8-expressing spermatocytes from human testicular biopsies, providing a means for targeted single-cell RNA sequencing analysis and in vitro functional interrogation of germ cells during the onset of meiosis. This could enable investigation into details of the regulatory pathways underlying this critical stage of spermatogenesis, previously difficult to enrich from whole tissue samples., Competing Interests: Declaration of Interests M.R. has nothing to disclose. K.Z. has nothing to disclose. S.H.Y.K. has nothing to disclose. F.K. has nothing to disclose. A.G. has nothing to disclose. A.S. has nothing to disclose. C.C. has nothing to disclose. L.W. has nothing to disclose. F.H. has nothing to disclose. R.F. has received competitive research funding from the Canadian Institute for Health Research, New Frontiers Research Fund, American Society of Reproductive Medicine, Vancouver Coastal Health Research Institute, Canadian Urologic Association Scholarship Foundation, Michael Smith Foundation for Health Research, and Boston Scientific. R.F. has consulted with Boston Scientific and Coloplast., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Sexual dysfunction is highly prevalent in males with spinal cord injury (SCI) and has been recognized to be a key recovery priority., Objectives: This cross-sectional, mixed-methods study aimed to investigate the major themes linked to sexual functioning in males with chronic (>1 year) SCI., Methods: Twenty male participants with SCI, aged 25 to 59 years, completed validated questionnaires exploring sexual function/satisfaction and health-related quality of life and a semi-structured interview with an experienced sexual medicine physician. Sex hormone concentrations and metabolic biomarkers, along with body composition and habitual physical activity levels, were assessed. Interview recordings were transcribed and thematic analysis performed using combined COM-B (Capability, Opportunity, Motivation, and Behavior) and biopsychosocial models to identify and organize major contributors and barriers to sexual functioning., Results: Metabolic and hormonal biomarkers largely fell within normal physiological ranges despite reduced sexual functioning reported in our cohort (19/20 participants reported some degree of erectile dysfunction). Qualitative analysis of interview transcripts revealed 24 themes. Adaptability was important for improving sexual satisfaction. Attraction and attentiveness to sex and partners remained stable over time, while the desire for intimacy increased post injury. Sexual social norms, and comparisons to the able-bodied population, provided challenges for sexual activity and partnership. Environmental concerns regarding access to sexual health resources and accessible physical spaces during intimacy were relevant. Mood disorders and general life stressors negatively impacted sexual desire, while physical activity encouraged sexual activity., Conclusion: By considering a holistic view of sexuality in males with SCI, we identified key contributors and barriers to sexual functioning for the cohort studied., (© 2024 American Spinal Injury Association.)

As the number of cancer survivors increases, so does the demand for preserving male fertility after radiation. It is important for healthcare providers to understand the pathophysiology of radiation-induced testicular injury, the techniques of fertility preservation both before and during radiation, and their role in counseling patients on the risks to their fertility and the means of mitigating these risks. Impaired spermatogenesis is a known testicular toxicity of radiation in both the acute and the late settings, as rapidly dividing spermatogonial germ cells are exquisitely sensitive to irradiation. The threshold for spermatogonial injury and subsequent impairment in spermatogenesis is ~ 0.1 Gy and the severity of gonadal injury is highly dose-dependent. Total doses < 4 Gy may allow for recovery of spermatogenesis and fertility potential, but with larger doses, recovery may be protracted or impossible. All patients undergoing gonadotoxic radiation therapy should be counseled on the possibility of future infertility, offered the opportunity for semen cryopreservation, and offered referral to a fertility specialist. In addition to this, every effort should be made to shield the testes (if not expected to contain tumor) during therapy., Competing Interests: Competing interests: N/A. Conflict of interest: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors declare no potential conflicts of interest, including financial interests, activities, relationships and affiliations., (© 2023 Greater Poland Cancer Centre.)

Motivation: Transcriptomic long-read (LR) sequencing is an increasingly cost-effective technology for probing various RNA features. Numerous tools have been developed to tackle various transcriptomic sequencing tasks (e.g. isoform and gene fusion detection). However, the lack of abundant gold-standard datasets hinders the benchmarking of such tools. Therefore, the simulation of LR sequencing is an important and practical alternative. While the existing LR simulators aim to imitate the sequencing machine noise and to target specific library protocols, they lack some important library preparation steps (e.g. PCR) and are difficult to modify to new and changing library preparation techniques (e.g. single-cell LRs)., Results: We present TKSM, a modular and scalable LR simulator, designed so that each RNA modification step is targeted explicitly by a specific module. This allows the user to assemble a simulation pipeline as a combination of TKSM modules to emulate a specific sequencing design. Additionally, the input/output of all the core modules of TKSM follows the same simple format (Molecule Description Format) allowing the user to easily extend TKSM with new modules targeting new library preparation steps., Availability and Implementation: TKSM is available as an open source software at https://github.com/vpc-ccg/tksm., (© The Author(s) 2024. Published by Oxford University Press.)

Male factor infertility affects 50% of infertile couples worldwide; the most severe form, non-obstructive azoospermia (NOA), affects 10-15% of infertile males. Treatment for individuals with NOA is limited to microsurgical sperm extraction paired with in vitro fertilization intracytoplasmic sperm injection. Unfortunately, spermatozoa are only retrieved in ~50% of patients, resulting in live birth rates of 21-46%. Regenerative therapies could provide a solution; however, understanding the cell-type-specific mechanisms of cellular dysfunction is a fundamental necessity to develop precision medicine strategies that could overcome these abnormalities and promote regeneration of spermatogenesis. A number of mechanisms of cellular dysfunction have been elucidated in NOA testicular cells. These mechanisms include abnormalities in both somatic cells and germ cells in NOA testes, such as somatic cell immaturity, aberrant growth factor signalling, increased inflammation, increased apoptosis and abnormal extracellular matrix regulation. Future cell-type-specific investigations in identifying modulators of cellular transcription and translation will be key to understanding upstream dysregulation, and these studies will require development of in vitro models to functionally interrogate spermatogenic niche dysfunction in both somatic and germ cells., (© 2023. Springer Nature Limited.)

Background: Approximately half of people with endometriosis experience deep dyspareunia; however, there is no means of objective self-testing of endometriosis-associated deep dyspareunia., Aim: The aim of this study was to assess the acceptability, test-retest reliability, and validity of a vaginal insert for a self-assessment of endometriosis-associated deep dyspareunia., Methods: Participants were recruited from a tertiary endometriosis center. Inclusion criteria were: 19 to 49 years of age, self-reported deep dyspareunia of ≥4 of 10, and surgically confirmed endometriosis. Participants completed 2 self-assessments using the vaginal insert to self-assess tenderness at the right and left pelvic floor, bladder, cervix-uterus, and posterior cul-de-sac (vaginal fornix). The participants recorded tenderness at each pelvic site and completed a questionnaire regarding the acceptability of the vaginal insert to assess deep dyspareunia. Test-retest reliability was assessed by correlating the tenderness scores between the 2 assessment dates. Over a 4-week period, the participants also recorded deep dyspareunia severity at each penetrative vaginal sex encounter. Validity was assessed by correlating vaginal insert tenderness to deep dyspareunia severity, and also to tenderness reported on a prior gynecologic pelvic examination., Outcomes: The main outcome measures were the acceptability index score, tenderness (0-10) at each pelvic site, and prospective deep dyspareunia scores (0-10) over 4 weeks., Results: There were 19 participants (mean age 34 ± 7 years) who completed the study. The majority identified as female (94.7%), heterosexual (89.5%), and white (89.5%). The median acceptability index score was 0.72 (interquartile range, 0.66-0.81). For test-retest reliability, the intraclass correlation coefficients were 0.79 (P = .001) for the left pelvic floor, 0.82 (P < .001) for the right pelvic floor, 0.54 (P = .07) for the bladder, 0.89 (P < .001) for the cervix-uterus, and 0.77 (P = .003) for the cul-de-sac. The correlation between the highest self-assessed mean tenderness in each participant and self-reported deep dyspareunia over 4 weeks was r = 0.32, but correlations for each pelvic site varied significantly. Tenderness at each site on prior gynecologist pelvic exam was associated with higher self-assessed mean tenderness with the vaginal insert in each participant (effect sizes = 0.42-0.88)., Clinical Implications: The vaginal insert is acceptable and reliable for the objective self-assessment of endometriosis-associated deep dyspareunia, with initial evidence of validity., Strengths and Limitations: A strength was the inclusion of participants who were avoiding sexual activity and a limitation was the small sample size., Conclusion: Future studies with larger sample sizes are required to further establish the validity of the vaginal insert for the self-assessment of endometriosis-associated deep dyspareunia., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Some medications used to treat comorbidities and conditions in reproductive-aged individuals could have a negative impact on fertility. This may occur through hormonal disruption, toxicity to germ cells and spermatozoa, functional impact on the sperm, teratogenicity potential, or ejaculatory abnormalities. Having knowledge of these potential interactions between medications and reproductive potential is important for clinicians to be aware of and guide the patient, along with their treating clinicians, to reproductively favorable alternatives when available. This review aims to summarize the state of the literature regarding medication interactions with human male reproduction using the Anatomical Therapeutic Chemical Classification System of medications., Competing Interests: Declaration of interests A.A. has nothing to disclose. L.R.G. has nothing to disclose. S.J. has nothing to disclose. R.F. has reported funding from the Canadian Institute of Health Research, the American Society for Reproductive Medicine, the Vancouver Coastal Health Research Institute, the Sexual Medicine Society of North America, and the New Frontiers Research Fund; honoraria from Boston Scientific and Coloplast; provisional patents (US 63,313470 and US 63,418714); and research infrastructure support from the Woodward Foundation and the Canadian Foundation for Innovation outside the submitted work., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Spermatogenesis involves precise temporal and spatial gene expression and cell signalling to reach a coordinated balance between self-renewal and differentiation of spermatogonial stem cells through various germ cell states including mitosis, and meiosis I and II, which result in the generation of haploid cells with a unique genetic identity. Subsequently, these round spermatids undergo a series of morphological changes to shed excess cytoplast, develop a midpiece and tail, and undergo DNA repackaging to eventually form millions of spermatozoa. The goal of recreating this process in vitro has been pursued since the 1920s as a tool to treat male factor infertility in patients with azoospermia. Continued advances in reproductive bioengineering led to successful generation of mature, functional sperm in mice and, in the past 3 years, in humans. Multiple approaches to study human in vitro spermatogenesis have been proposed, but technical and ethical obstacles have limited the ability to complete spermiogenesis, and further work is needed to establish a robust culture system for clinical application., (© 2023. Springer Nature Limited.)

Introduction: 3D printing, a versatile additive manufacturing technique, has diverse applications ranging from transportation, rapid prototyping, clean energy, and medical devices., Areas Covered: The authors focus on how 3D printing technology can enhance the drug discovery process through automating tissue production that enables high-throughput screening of potential drug candidates. They also discuss how the 3D bioprinting process works and what considerations to address when using this technology to generate cell laden constructs for drug screening as well as the outputs from such assays necessary for determining the efficacy of potential drug candidates. They focus on how bioprinting how has been used to generate cardiac, neural, and testis tissue models, focusing on bio-printed 3D organoids., Expert Opinion: The next generation of 3D bioprinted organ model holds great promises for the field of medicine. In terms of drug discovery, the incorporation of smart cell culture systems and biosensors into 3D bioprinted models could provide highly detailed and functional organ models for drug screening. By addressing current challenges of vascularization, electrophysiological control, and scalability, researchers can obtain more reliable and accurate data for drug development, reducing the risk of drug failures during clinical trials.

Infertility affects 10-15% of couples, with half attributed to male factors. An improved understanding of the cell-type-specific dysfunction contributing to male infertility is needed to improve available therapies; however, human testicular tissues are difficult to obtain for research purposes. To overcome this, researchers have begun to use human induced pluripotent stem cells (hiPSCs) to generate various testis-specific cell types in vitro. Peritubular myoid cells (PTMs) are one such testicular cell type that serves a critical role in the human testis niche but, to date, have not been derived from hiPSCs. This study set forth to generate a molecular-based differentiation method for deriving PTMs from hiPSCs, mirroring in vivo patterning factors. Whole transcriptome profiling and quantitative polymerase chain reaction (qPCR) show that this differentiation method is sufficient to derive cells with PTM-like transcriptomes, including upregulation of hallmark PTM functional genes, secreted growth and matrix factors, smooth muscle, integrins, receptors, and antioxidants. Hierarchical clustering shows that they acquire transcriptomes similar to primary isolated PTMs, and immunostaining shows the acquisition of a smooth muscle phenotype. Overall, these hiPSC-PTMs will allow in vitro study of patient-specific PTM development and function in spermatogenesis and infertility., (© 2023 Wiley-VCH GmbH.)

Introduction: Patients with chronic scrotal content pain (CSCP) lack effective, non-invasive treatment options. We aimed to determine the local and systemic safety, tolerability, pharmacokinetics (PK), and efficacy of a long-lasting local anesthetic in patients with CSCP., Methods: This was a prospective, single-center, open-label, single-arm, phase 1, dose-escalating trial completed between October 2019 and March 2021. Twelve patients ≥19 years old with unilateral scrotal pain lasting ≥3 months reporting an average maximum pain score over seven days of ≥4 on a 0-10 numerical rating scale (NRS) were included. Patients underwent a test spermatic cord block and those reporting a decrease of ≥2 points were included. The investigational drug, ST-01 (sustained-release lidocaine polymer solution), is a long-acting injection of lidocaine around the spermatic cord. Subjects were provided a NRS dairy and recorded their NRS score until day 28. The Chronic Epididymitis Symptom Index (CESI) was completed on days 0, 7, 14, and 28. All patients underwent an examination and assessment for adverse events (AE) on days 0, 1, 7, 14, and 28. Exploratory statistical hypothesis testing was planned for this study due to its investigative nature., Results: There were no serious adverse events (SAEs) reported. All subjects reported at least one treatment-emergent adverse event (TEAE); 83% of related AEs were injection-site reactions consisting of swelling and bruising. NRS was reduced across all cohorts between baseline and end of study., Conclusions: This study provides evidence that the novel ST-01 treatment is safe and well-tolerated.

The present work provides a comprehensive review of the literature on the mechanical properties and existing human tunica albuginea tissue testing methods. Assessments were completed on papers reporting experimental values of Young's modulus, tensile strength, puncture strength, stiffness, toughness, and strain at the ultimate tensile strength (UTS). A high degree of variability in the reported experimental values was found; Young's modulus ranged from 5 MPa to 118 MPa, and tensile strength went from 1.1 MPa to 6.1 MPa. A comparison of the variability of the reported experimental values for puncture strength, stiffness, toughness, and strain at the UTS could not be completed due to a lack of experimental results. This review discusses the pathophysiology and surgical treatment of erectile dysfunction and Peyronie's disease, variability in the existing reported mechanical properties, the impact of the variability of mechanical properties on in silico models and explores the absence of a standardised testing method as a possible reason for the variable in results. Finally, this work attempts to provide suggestions for standardising future mechanical testing of the tunica albuginea through minimising and reporting freeze/thaw cycling, noting the proximal/distal region of the cadaver tunica sample, reporting the orientation (o'clock position) of the cadaver tunica sample, and testing the cadaver tunica samples in bi-axial tension. Ultimately, standardising the testing methodologies of the tunica albuginea will provide higher confidence in reported mechanical property values.

Background: Endometriosis-associated deep dyspareunia is associated with reduced sexual quality of life, lower self-esteem, and impaired sexual function., Objective: The primary objective is to assess the acceptability of a phallus length reducer (brand name: Ohnut [OhnutCo]), which is a buffer worn over the penis or a penetrating object to reduce endometriosis-associated deep dyspareunia, and the feasibility of a definitive randomized controlled trial (RCT). The secondary objective is to obtain estimates of the effectiveness of the buffer. An embedded substudy will explore the acceptability and the preliminary validity and reliability of a vaginal insert for the self-assessment of deep dyspareunia., Methods: Ours is an investigator-initiated, 2-arm RCT. We will recruit 40 patient participants with diagnosed endometriosis between the ages of 19 and 49 years, as well as their sexual partners. The participating couples will be randomized in a 1:1 ratio into the experimental arm or the waitlist control arm. The length of the study period will be 10 weeks, during which time all participants will record deep dyspareunia severity following each episode of sexual intercourse. In weeks 1 to 4, all patient participants will record deep dyspareunia severity at each sexual encounter. In weeks 5 to 10, participants in the experimental arm will use the buffer during vaginal penetration; participants in the waitlist control arm will continue engaging in vaginal penetration as usual. Participants will complete questionnaires for assessing measures of anxiety, depression, and sexual function at baseline, at 4 weeks, and at 10 weeks. In the substudy, patient participants will self-assess dyspareunia by using a vaginal insert on 2 occasions, at least 1 week apart. The primary outcomes-the acceptability and feasibility of the buffer-will be assessed with descriptive statistics, and the secondary outcome-phallus length reducer effectiveness-will be assessed by using an analysis of covariance-based approach. For the vaginal insert, we will assess acceptability, test-retest reliability, and convergent validity via correlation analyses comparing the use of the insert to clinical examination in terms of dyspareunia assessment outcomes., Results: Our pilot will provide initial data on the acceptability and effectiveness of the buffer and the feasibility of the study methodology. The results from our study are expected to be submitted for publication by the spring of 2023. As of September 2021, we have consented 31 couples into the study., Conclusions: Our study will provide preliminary evidence for the self-assessment and management of endometriosis-associated deep dyspareunia. The findings will inform the decision to proceed to a definitive RCT., Trial Registration: ClinicalTrials.gov NCT04370444; https://clinicaltrials.gov/ct2/show/NCT04370444., International Registered Report Identifier (irrid): DERR1-10.2196/39834., (©Sandy X J Zhang, Rebecca G K MacLeod, Gurkiran Parmar, Natasha L Orr, Kate J Wahl, Heather Noga, Arianne Albert, Ryan Flannigan, Lori A Brotto, Paul J Yong. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 27.03.2023.)

Introduction: Postorgasmic illness syndrome (POIS) is a rare condition in which individuals develop generalized and flu-like symptoms after ejaculation. Several mechanisms and treatments for this disorder have been proposed but many questions remain., Aims: We sought to present a summary of literature to date and highlight common symptoms, associated features, comorbidities, and laboratory findings in a clinical sample of patients with POIS., Methods: We conducted a retrospective chart review of 6 patients with POIS in our clinic and presented compiled results., Results: We identified newly described non-flu-like presentations, onset of symptoms with high states of arousal without ejaculation, and presence of psychiatric comorbidity in a majority of patients. We did not identify a postorgasm allergic response with bloodwork available., Conclusion: POIS remains a poorly understood condition that likely comprises a number of different clinical entities. Further research on a larger clinical sample is necessary to better characterize POIS and understand its biological and psychological basis., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Background: Sexual dysfunction is the most common and most distressing consequence of prostate cancer (PCa) treatment and has been shown to directly affect the sexual function and quality of life of survivors' partners. There are currently no established therapies to treat the emotional and psychological burden that sexual issues impose on the couple after PCa., Aim: Our study examined the impact of 2 therapies-cognitive behavioral therapy (CBT) and mindfulness therapy-on sexual, relational, and psychological outcomes of PCa survivor and partner couples., Methods: PCa survivors (n = 68) who self-reported current sexual problems after PCa treatments and their partners were randomized to 4 consecutive weeks of couples' mindfulness therapy, couples' CBT, or no treatment (control)., Outcomes: Couples' sexual distress, survivors' sexual satisfaction, and couples' relationship satisfaction, quality of life, psychological symptoms (anxiety and depression), and trait mindfulness were measured at baseline, 6 weeks after treatment, and 6 months after treatment., Results: Sexual distress and sexual satisfaction were significantly improved 6 weeks after the CBT and mindfulness interventions as compared with the control group, but only sexual distress remained significantly improved at 6 months. Relationship satisfaction decreased and more so for partners than survivors. There were increases in domains of quality of life for survivors vs their partners 6 months after treatments and an overall increase in general quality of life for couples 6 weeks after mindfulness. There were no significant changes in psychological symptoms and trait mindfulness. Qualitative analysis showed that the mindfulness intervention led to greater personal impact on couple intimacy after the study had ended., Clinical Implications: CBT and mindfulness can be effective treatments for helping couples adapt to and cope with changes to their sexual function after PCa treatments and could help improve the most common concern for PCa survivors-that is, couples' sexual intimacy-after cancer, if added to routine clinical care., Strengths and Limitations: We used established standardized treatment manuals and highly sensitive statistical methodology and accounted for covariable factors and moderators of primary outcomes. Due to difficulty in recruitment, we had a smaller control group than treatment, reducing our power to detect between-group differences. Our sample was mostly White, heterosexual, and affluent, thereby limiting the generalizability., Conclusion: This is the first randomized clinical trial to test and demonstrate benefits among PCa survivors and partners' sexual outcomes after CBT and mindfulness as compared with a nontreatment control group., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

An in vitro testis model will provide a superior platform for studying the testis microenvironment and molecular mechanisms that affect male fertility. The ultimate aim is to provide reproductive hope for children diagnosed with cancer who were sterilized by aggressive gonadotoxic therapies., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Intralesional Collagenase Clostridium histolyticum (CCh) was the first non-surgical therapy approved for Peyronie's disease (PD). However, CCh's cost and poor market uptake has led to its discontinuation in Europe and Canada. In Canada, Xiaflex® is the trade name for CCh and it is produced by Paladin Labs Inc, an operating company of Endo International. The paper aims to better understand Canadian CCh providers' perspectives regarding its treatment efficacy and the potential impact of its discontinuation. All Xiaflex®-approved Canadian providers were asked to complete an anonymous 21-question survey using an online platform. Analysis consisted of descriptive statistics. Outcomes of interest included previous experience with CCh, protocols utilized, experience with insurance coverage, clinical and patient-reported outcomes, and provider perspectives on the discontinuation of CCh. Overall response rate was 48.3% (29/60). A total of 89% of respondents were male, 61% were in practice more than 10 years, 32% were in an academic practice, and 46% had completed an Andrology/Sexual Medicine fellowship. A total of 93% of respondents felt that CCh was superior to other intralesional therapies for PD. In all, 86% reported a patient satisfaction rate of at least 50%, and the majority (75%) saw a clinically meaningful response. Only 7% expressed difficulty obtaining insurance coverage, with many providers (71%) achieving an insurance approval rate between 75 and 100%. Only 54% of respondents reported that they would continue treating PD in light of CCh's discontinuation, and 96% felt that CCh's discontinuation represents a loss to Canadian patients. In light of CCh's discontinuation, most (79%) are now more likely to offer surgical treatment. In conclusion, most CCh providers found CCh to be effective and were dismayed by its discontinuation. The survey demonstrated that due to the withdrawal of CCh from Canada, physicians' abilities to offer effective medical therapy may become limited, with more providers offering surgical options for PD., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To develop a machine learning algorithm to detect rare human sperm in semen and microsurgical testicular sperm extraction (microTESE) samples using bright-field (BF) microscopy for nonobstructive azoospermia patients., Design: Spermatozoa were collected from fertile men. Testis biopsies were collected from microTESE samples determined to be clinically negative for sperm. A convolutional neural network based on the U-Net architecture was trained using 35,761 BF image patches with fluorescent ground truth image pairs to segment sperm. The algorithm was validated using 7,663 image patches. The algorithm was tested using 7,663 image patches containing abundant sperm, as well as 7,985 image patches containing rare sperm., Setting: In vitro fertilization center and university laboratories., Patient(s): Normospermic and nonobstructive azoospermia patients., Intervention(s): None., Main Outcome Measure(s): Precision (positive predictive value [PPV]), recall (sensitivity), and F1-score of detected sperm locations., Result(s): For sperm-only samples, our algorithm achieved 91% PPV, 95.8% sensitivity, and 93.3% F1-score at ×10 magnification. For dissociated microTESE samples doped with an abundant quantity of sperm, our algorithm achieved 84.0% PPV, 72.7% sensitivity, and 77.9% F1-score. For dissociated microTESE samples doped with rare sperm, our algorithm achieved 84.4% PPV, 86.1% sensitivity, and 85.2% F1-score., Conclusion(s): Rare sperm can be detected in patients' testis biopsy samples for potential subsequent use in in vitro fertilization-intracytoplasmic sperm injection. A machine learning algorithm can use BF images at ×10 magnification to accurately detect sperm locations using automated imaging., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Single-cell RNA sequencing allows for characterizing the gene expression landscape at the cell type level. However, because of its use of short-reads, it is severely limited at detecting full-length features of transcripts such as alternative splicing. New library preparation techniques attempt to extend single-cell sequencing by utilizing both long-reads and short-reads. These techniques split the library material, after it is tagged with cellular barcodes, into two pools: one for short-read sequencing and one for long-read sequencing. However, the challenge of utilizing these techniques is that they require matching the cellular barcodes sequenced by the erroneous long-reads to the cellular barcodes detected by the short-reads. To overcome this challenge, we introduce scTagger, a computational method to match cellular barcodes data from long-reads and short-reads. We tested scTagger against another state-of-the-art tool on both real and simulated datasets, and we demonstrate that scTagger has both significantly better accuracy and time efficiency., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Background: Increased physical activity (PA) levels are associated with improved prostate cancer (PCa) outcomes. Sustainable PA has been linked to improved health-related quality of life (QoL) in cancer patients. The time of diagnosis of PCa may offer a critical time point when patients might be more likely to consider lifestyle changes. This, in turn, may contribute to sustainable PA and its likely benefits., Objective: The aims of this study were to determine if a structured PA intervention introduced at the time of diagnosis can (1) lead to sustainable PA and (2) help improve psychosocial and QoL outcomes as compared with usual PA., Interventions/methods: This was a pilot randomized controlled trial enrolling patients with intermediate-risk PCa into either arm A (supervised 8- to 12-week physical exercise program; n = 10) or control arm B (usual PA; n = 10). Primary outcome was PA at 6 months. Secondary outcomes were QoL, psychological well-being, physical fitness, and functional outcomes postintervention. Change over time was compared using a nonparametric Wilcoxon test., Results: Demographic variables were the same between arms. Comparing parameters at the start and 6 months post-radical prostatectomy, PA significantly improved in arm A (self-reported Godin score 24.7 vs 42.8 units, P < .01, objective number of chair stands [14-19, P < .01]), but not in arm B. There were no significant differences between arms in QoL and psychosocial outcomes., Conclusions: A preoperative supervised exercise training program increases long-term PA., Implications for Practice: Future trials should evaluate PA sustainability beyond 6 months and if this leads to improved psychosocial and QoL outcomes., Competing Interests: G.B.S. was financially supported by a fellowship (SCHU 3406/1-1) from the Deutsche Forschungsgemeinschaft (DFG). The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To study the feasibility and spermatogenic potential of 3-dimensional (3D) bioprinting personalized human testicular cells derived from a patient with nonobstructive azoospermia (NOA)., Design: A human testicular biopsy from a single donor with NOA was dissociated into single cells, expanded in vitro, and 3D bioprinted into tubular structures akin to the seminiferous tubule using AGC-10 bioink and an RX1 bioprinter with a CENTRA coaxial microfluidic printhead from Aspect Biosystems. Three-dimensional organoid cultures were used as a nonbioprinted in vitro control., Setting: Academic medical center., Patient(s): A 31-year-old man with NOA with testis biopsy demonstrating Sertoli cell-only syndrome., Intervention(s): Three-dimensional bioprinting and in vitro culturing of patient-derived testis cells., Main Outcome Measure(s): Cellular viability after printing was determined, along with the expression of phenotypic and spermatogenic functional genetic markers after 12 days of in vitro culture., Result(s): Testicular cultures were expandable in vitro and generated sufficiently large numbers for 3D bioprinting at 35 million cells per mL of bioink. Viability 24 hours after printing was determined to be 93.4% ± 2.4%. Immunofluorescence staining for the phenotype markers SRY-Box transcription factor 9, insulin-like 3, actin alpha 2 smooth muscle, and synaptonemal complex protein 3 after 12 days was positive, confirming the presence of Sertoli, Leydig, peritubular myoid, and meiotic germ cells. Reverse transcription qualitative polymerase chain reaction analysis showed that after 12 days in spermatogenic media, the bioprints substantially up-regulated spermatogenic gene expression on par with nonbioprinted controls and showed a particularly significant improvement in genes involved in spermatogonial stem cell maintenance: inhibitor of deoxyribonucleic acid binding 4 by 365-fold; fibroblast growth factor 3 by 94,152-fold; stem cell growth factor receptor KIT by twofold; stimulated by retinoic acid 8 by 125-fold; deleted in azoospermia-like by 114-fold; synaptonemal complex protein 3 by sevenfold; zona pellucida binding protein by twofold; transition protein 1 by 2,908-fold; and protamine 2 by 11-fold., Conclusion(s): This study demonstrates for the first time the feasibility of 3D bioprinting adult human testicular cells. We show that the bioprinting process is compatible with high testicular cell viability and without loss of the main somatic phenotypes within the testis tissue. We demonstrate an increase in germ cell markers in the 3D bioprinted tubules after 12 days of in vitro culture. This platform may carry future potential for disease modeling and regenerative opportunities in a personalized medicine framework., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to highlight the biopsychosocial recommendations provided to prostate cancer survivors and their partners during sexual rehabilitation., Methods: Retrospective analysis of a prospectively maintained patient database was conducted for visits between 2013 and 2019. The sexual health rehabilitation action plan (SHRAP) is a standardized 29-item list of biopsychosocial recommendations. The frequency of biopsychosocial recommendations provided to patients via their SHRAPs was assessed., Results: Among 913 patients, across 2671 appointments, nearly 74% of patients underwent radical prostatectomy. Other treatments included combination therapy (surgery, radiation, and/or androgen deprivation therapy (ADT)) (13%), radiation (external beam radiation or brachytherapy) (5%), and active surveillance (2%). Each patient had a median of 2 (SD 2.06) appointments and received a mean of 10.0 (SD 3.9) recommendations at each visit. Educational recommendations (penile rehabilitation, orgasmic guidelines, and climacturia management) were provided in 84% of visits followed by psychosexual recommendations (pleasure-focused, dedicated time, simmering, sexual aids, and sensate focus) in 71% of all appointments. The top recommendations (total n, frequency of recommendation) were penile rehabilitation (2253, 84%), pleasure-focus (1887, 71%), phosphodiesterase inhibitors (1655, 62%), clinical counselor (1603, 60%), vacuum erectile device (1418, 53%) and intracavernosal injections (1383, 52%)., Conclusions: Biopsychosocial programs are evolving to be a key part of prostate cancer survivorship. This study's insight suggests that prostate cancer survivors require education around their sexual consequences and psychosexual counseling alongside proven biomedical strategies for erectile dysfunction., Implications for Cancer Survivors: Cancer survivorship programs should integrate educational and psychosocial strategies alongside biological strategies for prostate cancer survivors and their partners., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)