Outcomes of a Standardized Pain Pathway for Transgender Patients Undergoing Vaginoplasty and Vulvoplasty.

OBJECTIVE: To establish and evaluate a multimodal, opioid-minimizing pathway for gender-affirming vaginoplasty (GAVa) and vulvoplasty (GAVu) in treating postoperative pain. METHODS: A standardized pain pathway including opioids, non-opioid analgesics, and patient counseling was implemented at a single academic institution with a center for transgender care. Postoperative pain levels, analgesia methods, and opioid use for 84 GAVa and 64 GAVu patients were prospectively gathered during inpatient postoperative days 2-4 and outpatient follow-up at 2 weeks. Pertinent patient, operative, and medication administration data were extracted from patient charts and outpatient pain was measured with the Brief Pain Inventory short form (BPI-sf). RESULTS: On average, GAVa patients used 89.3 MME and GAVu patients used 41.8 MME during inpatient stay. MME decreased daily for both groups. There was no difference in MME between open and robotic GAVa. Forty-nine percent of GAVa patients and 54% of GAVu patients used ketorolac with decreasing daily inpatient use. Postoperative pain levels were similar between GAVa and GAVu patients. Fifty percent of respondents denied postoperative pain in the 24 hours preceding the survey. Forty-four percent of GAVa and of GAVu patients did not use any opioid medications in the outpatient setting, while 81% of GAVa and 83% of GAVu patients used fewer than 20 of 30 prescribed opioid tablets. Ibuprofen and acetaminophen were rated the most effective outpatient analgesics among GAVa and GAVu patients, respectively. CONCLUSION: The multimodal pathway demonstrated effective postoperative pain control for GAVa and GAVu patients while minimizing opioid use and has changed institutional prescribing practice.

Cessation of chronic delta-9-tetrahydrocannabinol use partially reverses impacts on male fertility and the sperm epigenome in rhesus macaques.

OBJECTIVE: To determine whether discontinuation of delta-9-tetrahydrocannabinol (THC) use mitigates THC-associated changes in male reproductive health using a rhesus macaque model of daily THC edible consumption. DESIGN: Research animal study. SETTING: Research institute environment. PATIENT(S): Adult male rhesus macaques (age, 8-10 years; n = 6). INTERVENTION(S): Chronic daily THC edible administration at medically and recreationally relevant contemporary doses followed by cessation of THC use. MAIN OUTCOME MEASURE(S): Testicular volume, serum male hormones, semen parameters, sperm deoxyribonucleic acid (DNA) fragmentation, seminal fluid proteomics, and whole genome bisulfite sequencing of sperm DNA. RESULT(S): Chronic THC use resulted in significant testicular atrophy, increased gonadotropin levels, decreased serum sex steroid levels, changes in seminal fluid proteome, and increased DNA fragmentation with partial recovery after discontinuation of THC use. For every increase of 1 mg/7 kg/day in THC dosing, there was a significant decrease in the total testicular volume bilaterally by 12.6 cm3 (95% confidence interval [CI], 10.6-14.5), resulting in a 59% decrease in volume. With THC abstinence, the total testicular volume increased to 73% of its original volume. Similarly, with THC exposure, there were significant decreases in the mean total testosterone and estradiol levels and a significant increase in the follicle-stimulating hormone level. With increasing THC dose, there was a significant decrease in the liquid semen ejaculate volume and weight of coagulum; however, no other significant changes in the other semen parameters were noted. After discontinuing THC use, there was a significant increase in the total serum testosterone level by 1.3 ng/mL (95% CI, 0.1-2.4) and estradiol level by 2.9 pg/mL (95% CI, 0.4-5.4), and the follicle-stimulating hormone level significantly decreased by 0.06 ng/mL (95% CI, 0.01-0.11). Seminal fluid proteome analysis revealed differential expression of proteins enriched for processes related to cellular secretion, immune response, and fibrinolysis. Whole genome bisulfite sequencing identified 23,558 CpGs differentially methylated in heavy-THC vs. pre-THC sperm, with partial restoration of methylation after discontinuation of THC use. Genes associated with altered differentially methylated regions were enriched for those involved in the development and function of the nervous system. CONCLUSION(S): This is the first study demonstrating that discontinuation of chronic THC use in rhesus macaques partially restores adverse impacts to male reproductive health, THC-associated sperm differentially methylated regions in genes important for development, and expression of proteins important for male fertility.

Vasectomy reversal outcomes in men after testosterone therapy.

The prevalence of males on testosterone therapy (TT) seeking vasectomy reversal (VR) is rising. As medical therapy (MT) to recover spermatogenesis after TT has been previously described, our study's objective is to present our institution's management and outcomes of VR in men previously on TT. We performed a retrospective case series of vasectomy patients on TT with subsequent VR by a single microsurgeon between March, 2010 and March, 2022. 14 men undergoing VR during the study period met inclusion criteria. The median age at VR was 43 years with a median obstructive interval of 11 years. Median time from MT to VR was 5 months. Post-operative semen analysis was performed in 10 men and all demonstrated patency. 2 patients had very low sperm counts secondary to continuing TT following VR contrary to medical advice and 5 men with patency achieved pregnancy. Our study noted a high rate of vasovasostomy (VV) (96%) and sustained patency despite a 12-year median obstructive interval. Our findings support favorable outcomes with less stringent VV indications after MT in patients previously on TT that desire VR. The use of MT reduces the recommended wait times for VR after TT discontinuation by more than half.

Chronic exposure to delta-9-tetrahydrocannabinol impacts testicular volume and male reproductive health in rhesus macaques.

OBJECTIVE: To determine the dose-dependent effect of delta-9-tetrahydrocannabinol (THC) exposure on male testes and reproductive health in a nonhuman primate model. DESIGN: Research animal study. SETTING: Research institute. ANIMAL(S): Adult male rhesus macaques 8-10 years of age (n = 6). INTERVENTION(S): Daily edible THC at medically and recreationally relevant doses. MAIN OUTCOME MEASURE(S): Testicular volume and epididymal head width, serum levels of inhibin B, albumin, total testosterone, prolactin, follicle-stimulating hormone, estradiol, and luteinizing hormone; semen volume; and sperm motility, morphology, and concentration. RESULT(S): For each 1 mg/7 kg/day increase in THC dosing, there was a marked loss in total bilateral testicular volume of 11.8 cm3 (95% confidence interval [CI]: 8.3-15.4). In total, average bilateral testicular volume decreased by 58%. Significant dose-response decreases in mean total testosterone level by 1.49 ng/mL (95% CI: 0.83-2.15) and in estradiol level by 3.8 pg/mL (95% CI: 2.2-5.4) were observed, but significant increases in the levels of follicle-stimulating hormone by 0.06 ng/mL (95% CI: 0.02-0.10), luteinizing hormone by 0.16 ng/mL (95% CI: 0.08-0.25), and prolactin by 7.4 ng/mL (95% CI: 3.4-11.3) were observed. There were no statistically significant changes in semen parameters. CONCLUSION(S): In rhesus macaques, chronic exposure to THC resulted in significant dose-response testicular atrophy, increased serum gonadotropin levels, and decreased serum sex steroids, suggestive of primary testicular failure. Further studies are needed to determine if reversal of these observed adverse effects would occur if THC was discontinued and for validation of thefindings in a human cohort.

Effects of marijuana on reproductive health: preconception and gestational effects.

PURPOSE OF REVIEW: Recent widespread legalization changes have promoted the availability of marijuana and its increased potency and perceived safety. The limited evidence on reproductive and perinatal outcomes from marijuana exposure is enough to warrant concern and action. The objective of this review is to provide a current and relevant summary of the recent literature surrounding this topic. RECENT FINDINGS: The available published studies on the effect of marijuana exposure on reproductive health and pregnancy outcomes are conflicting. Human studies are often observational or retrospective and confounded by self-report and polysubstance use. However, the current, limited evidence suggests that marijuana use adversely affects male and female reproductive health. Additionally, prenatal marijuana exposure has been reported to be associated with an increased risk of preterm birth and small for gestational age infants. SUMMARY: With the increasing prevalence of marijuana use, there is an urgent need for evidence-driven recommendations and guidelines for couples interested in conception, affected by infertility or who are expecting. At this time, no amount of marijuana use during conception or pregnancy is known to be well tolerated and the limited available evidence suggests that the safest choice is to abstain.

Hypertonic saline-induced urolithiasis presenting as acute renal failure in a child with traumatic brain injury: A case report.

We report the case of a 4 year old female with severe traumatic brain injury who developed bilateral obstructing ureteral stones after hypertonic saline treatment. She developed calcium phosphate stones after two weeks of hypertonic saline therapy, and was successfully treated with ureteral stents and ureteroscopy. She has remained stone-free since that time. We postulate that an incomplete type 1 renal tubular acidosis made her intolerant to the acid and sodium load of the saline, and discuss other lithogenic factors of her presentation.

The vasal fluid proteomic profile and microscopic sperm presence at time of vasectomy reversal.

BACKGROUND: The microscopic characteristics of vasal fluid at time of vasectomy reversal (VR) guide operative decision making and predict fertility outcomes. The proteomic profile of this vasal fluid has not been described or correlated with the microscopic fluid appearance. To characterize the vasal fluid proteome at time of VR and evaluate the variation of the vasal fluid proteome with respect to microscopic presence of sperm. METHODS: A prospective cohort study was conducted enrolling twenty-five men undergoing VR for infertility and/or pain at a University-affiliated hospital. Vasal fluid samples obtained at time of VR were grouped based on presence of sperm on light microscopy at time of VR. Proteomic profiles were generated using liquid chromatography/ tandem mass spectrometry, and MS/MS protein spectral counts compared between individuals and treatment groups, controlling for less than 5% protein false discovery rate (FDR). Proteins were matched with the human swissprot database using the Comet search engine, and categorized by Gene Ontology (GO) terms. RESULTS: There was large variability between the 46 vasal fluid samples collected, with 1,692 unique proteins detected. The three most abundant proteins were Lactotransferrin, Cysteine-rich secretory protein 1, A-kinase anchor protein 4. There was no correlation between the proteome and microscopic sperm presence. Prevalent GO terms included viral process, signal transduction, innate immune response, protein folding and spermatogenesis. CONCLUSIONS: We describe the proteome and the most common proteins in vasal fluid at time of VR. Numerable sperm, testis and epididymis specific proteins were present even in the absence of sperm on microscopy. Further evaluation is needed to determine if a protein biomarker may better guide operative decision making and predict VR fertility outcomes.

An institutional assessment of sperm cryospreservation and fertility counselling in pubertal male cancer survivors.

INTRODUCTION: Improved survivorship after treatment of pediatric malignancies has dramatically increased, while pre-treatment fertility preservation in this population has not kept pace. New guidelines emphasize fertility preservation in young adolescents, but the impact of these guidelines is unknown. OBJECTIVES: We sought to evaluate the rate of fertility preservation among at-risk adolescents diagnosed with cancer at our institution, as well as evaluate barriers to fertility preservation. DESIGN: We performed an IRB-approved historical cohort study of adolescent males 13 years and older evaluated in the Pediatric Hematology-Oncology clinic at Doernbecher Children's Hospital from 2010 to 2018. Electronic chart review was used assess discussion of fertility preservation and barrier to successful preservation in boys with a new diagnosis of cancer who received systemic chemotherapy and/or gonadal or pelvic irradiation. RESULTS: 82 boys were included in the study. Forty-two (51%) received counselling about fertility preservation, and of those 29 (70%) successfully banked sperm. Neither counseling for fertility preservation nor success at sperm banking differed by patient age, but both differed by malignancy. Patients with Hodgkin's lymphoma had the highest rate of counselling, while those with leukemia had the lowest. Acute illness as a barrier to preservation was found in 40% of those who did not receive counselling. DISCUSSION: Our study demonstrates a stagnant rate of fertility counseling and preservation despite increased advocacy. The retrospective nature of our study limited our ability to assess the counselling that occurred, and the lack of granular race data limited study of the implicit selection bias that may be involved in such counseling. As more institutions move toward a multi-disciplinary care model, we believe that pediatric urologists or fertility specialists must play a vocal role in the care of these at-risk adolescents. CONCLUSION: Despite increasing advocacy for fertility preservation, our data shows no significant change in previously reported trends. Patients with Hodgkin's lymphoma have a higher rate of counseling and cryopreservation in comparison to those with other malignancies.

Open versus robot-assisted radical cystectomy: 30-day perioperative comparison and predictors for cost-to-patient, complication, and readmission.

The objectives of this study are to evaluate if robotic cystectomy demonstrates reduced complications, readmissions, and cost-to-patient compared to open approach 30-day post-operatively, and to identify predictors of complication, readmission, and cost-to-patient. This retrospective cohort study analyzed 249 patients who underwent open (n = 149) or robotic (n = 100) cystectomy from 2009 to 2015 at our institution. Outcomes included 30-day post-operative complication, readmission, and cost-to-patient charges. We used modified Clavien-Dindo/MSKCC classifications. Multivariable logistic and linear regression models were used to evaluate associations to outcomes and to build predictive models. Patient, clinical, and surgical characteristics differed by open and robotic groups, respectively, only for estimated blood loss (median: 600 versus 150 cc, p < 0.01), operative time (mean: 6.19 versus 6.85 h, p < 0.01), and length of stay (median: 7 versus 5 days, p < 0.01). Complication: frequency of patients with at least one 30-day complication was 85% compared to 66% (p < 0.01). Minor gastrointestinal and bleeding complications were increased in the open group (50% versus 41%, p = 0.01; 52% versus 11%, p < 0.01, respectively). Fifty percent of patients required blood transfusion in open compared to 11% (p < 0.01). Patients in the open group experienced more major complications (19% versus 10%, p = 0.04). Robotic approach was a predictor for fewer complications (OR 0.44, 95% CI 0.20-0.99, p = 0.049). Readmission: no significant difference in number of patients readmitted was found. Cost-to-patient: Robotic approach predicted an 18% reduction in total cost-to-patient compared to open approach (p < 0.01). Robotic cystectomy demonstrated reduced total cost-to-patient when taking into account all 30-day post-operative services with fewer complications compared to open cystectomy.