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Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

ABSTRACT: STUDY QUESTION:Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER:Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY:Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION:Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS:Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE:The average age of fertility preservation patients was 7.9 (SD?=?5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD?=?837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n?=?118) were the most common indication for testicular tissue freezing, followed by blood disorders (n?=?45) and other conditions (n?=?26). Thirty nine percent (n?=?74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION:This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS:Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S):Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.

SUBMITTER: Valli-Pulaski H

PROVIDER: S-EPMC6554046 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

Valli-Pulaski H H Peters K A KA Gassei K K Steimer S R SR Sukhwani M M Hermann B P BP Dwomor L L David S S Fayomi A P AP Munyoki S K SK Chu T T Chaudhry R R Cannon G M GM Fox P J PJ Jaffe T M TM Sanfilippo J S JS Menke M N MN Lunenfeld E E Abofoul-Azab M M Sender L S LS Messina J J Klimpel L M LM Gosiengfiao Y Y Rowell E E EE Hsieh M H MH Granberg C F CF Reddy P P PP Sandlow J I JI Huleihel M M Orwig K E KE

Human reproduction (Oxford, England) 20190601 6

<h4>Study question</h4>Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities?<h4>Summary answer</h4>Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice.<h4>What i ...[more]

PMID: 31111889

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Project description:Testicular tissue cryopreservation is the only option of fertility preservation in prepubertal boys. While it is considered experimental, since procedures to obtain mature spermatozoa from prepubertal testicular tissue are still under development, testicular tissue cryopreservation programs have emerged worldwide. Our aim was to study the feasibility and safety of a program of testicular tissue cryopreservation in prepubertal and adolescent boys facing gonadotoxic treatment in three University hospitals in Switzerland. Testicular tissue cryopreservation was accepted by 90% of families, with a total of 35 patients included. The average patient age was 8.5 years (range 7 months to 18.5 years). Malignancies were the most common diagnosis (31 patients, 88.6%) with 16 (45.7%) solid tumors and 15 (42.9%) hematological malignancies. Four (11.4%) patients had a benign condition. The main indication for testicular tissue cryopreservation was conditioning for hematologic stem cell transplantation (25 patients, 71.4%). Testicular tissue was cryopreserved according to the freezing protocol of Louvain Catholic University (Belgium), which includes either only immature testicular tissue freezing, or mature and immature testicular tissue freezing depending on the age of the patient and the presence or absence of haploid cells. The median number of spermatogonia per tubule cross-section was 2 (range 0-6) and spermatozoa were found in only one patient. Tumoral cells were found in one testicular biopsy of a leukemic patient. There were two minor adverse events and none of them required medical treatment or surgical revision. Five patients died during follow-up. Our data demonstrate the feasibility and safety of a program of testicular tissue cryopreservation coordinated by a multidisciplinary team of fertility preservation. Despite the experimental aspect of the procedure, the acceptation rate was high, which highlights the willingness of families and patients to participate in testicular tissue cryopreservation.

Project description:The aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries.A questionnaire was sent to 14 Nordic academic reproductive centers with established fertility preservation programs. It covered fertility preservation cases performed up to December 2014, standard procedures for ovarian tissue cryopreservation and oocyte cryopreservation and reproductive outcomes following ovarian tissue transplantation.Among the Nordic countries, Denmark and Norway practice ovarian tissue cryopreservation as a clinical treatment (822 and 164 cases, respectively) and their programs are centralized. In Sweden (457 cases), ovarian tissue cryopreservation is practiced at five of six centers and in Finland at all five centers (145 cases). Nearly all considered ovarian tissue cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow-freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue was predominantly retrieved laparoscopically by unilateral oophorectomy. Only minor complications were reported. In total, 46 women have undergone ovarian tissue transplantation aiming at recovering fertility, 17 healthy children have been born and several additional pregnancies are currently ongoing. Whenever patients' clinical condition is permissive, oocyte cryopreservation after hormonal stimulation is preferred for fertility preservation. Between 2012 and 2014, a smaller proportion of females have undergone fertility preservation in the Nordic centers, in comparison to males (1:3).Overall, ovarian tissue cryopreservation was reported to be safe. Slow freezing methods are still preferred. Promising results of recovery of fertility have been reported in Nordic countries that have initiated ovarian tissue transplantation procedures.

Project description:Cryopreservation of human testicular tissue, as a key element of anticancer therapy, includes the following stages: saturation with cryoprotectants, freezing, thawing, and removal of cryoprotectants. According to the point of view existing in "classical" cryobiology, the thawing mode is the most important consideration in the entire process of cryopreservation of any type of cells, including cells of testicular tissue. The existing postulate in cryobiology states that any frozen types of cells must be thawed as quickly as possible. The technologically maximum possible thawing temperature is 100 °C, which is used in our technology for the cryopreservation of testicular tissue. However, there are other points of view on the rate of cell thawing, according to how thawing should be carried out at physiological temperatures. In fact, there are morphological and functional differences between immature (from prepubertal patients) and mature testicular tissue. Accordingly, the question of the influence of thawing temperature on both types of tissues is relevant. The purpose of this study is to explore the transcriptomic differences of cryopreserved mature and immature testicular tissue subjected to different thawing methods by RNA sequencing. Collected and frozen testicular tissue samples were divided into four groups: quickly (in boiling water at 100 °C) thawed cryopreserved mature testicular tissue (group 1), slowly (by a physiological temperature of 37 °C) thawed mature testicular tissue (group 2), quickly thawed immature testicular tissue (group 3), and slowly thawed immature testicular tissue (group 4). Transcriptomic differences were assessed using differentially expressed genes (DEG), the Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology (GO), and protein-protein interaction (PPI) analyses. No fundamental differences in the quality of cells of mature and immature testicular tissue after cryopreservation were found. Generally, thawing of mature and immature testicular tissue was more effective at 100 °C. The greatest difference in the intensity of gene expression was observed in ribosomes of cells thawed at 100 °C in comparison with cells thawed at 37 °C. In conclusion, an elevated speed of thawing is beneficial for frozen testicular tissue.

Project description:Background and purposeSpinal dural arteriovenous fistulas are a rare entity that, if left untreated, can lead to considerable morbidity with progressive spinal cord symptoms. The aim of this study was to evaluate the clinical outcome of patients with spinal dural arteriovenous fistulas that were primarily treated with endovascular embolization.Materials and methodsA retrospective review was performed of all patients from 1997-2010 who underwent treatment at 2 academic referral centers for a spinal dural arteriovenous fistula. Follow-up was performed by clinical examination, and functional status was measured by use of the Aminoff-Logue Disability Scale, McCormick classification grading, and mRS scores. The nonparametric Wilcoxon signed rank test was used to compare pretreatment and posttreatment Aminoff-Logue Disability Scale gait and micturition scores, McCormick classification grading, and mRS scores. P values < .05 were considered significant.ResultsA total of 38 patients were included. Five patients (2 endovascular, 3 surgical) were lost to follow-up and therefore were excluded from the analysis, 29 patients were initially treated from an endovascular approach (9 Onyx, 20 cyanoacrylate), and 4 patients were treated from a standard surgical approach. Five patients in the endovascular group subsequently underwent surgery for various reasons. The clinical improvements in the Aminoff-Logue Disability Scale gait and micturition scores, McCormick classification grading, and the mRS scores were statistically significant (P < .05, Wilcoxon signed rank test).ConclusionsWe conclude that endovascular treatment of spinal dural arteriovenous fistulas can result in good clinical outcomes. Surgery remains the treatment of choice when safe embolization of the proximal radicular draining vein cannot be obtained or because the shunting artery of the spinal dural arteriovenous fistula also supplies the anterior spinal, posterior spinal, or a radiculomedullary artery.

Project description:BackgroundHospital capacity strain impacts quality of care and hospital throughput and may also impact the well being of clinical staff and teams as well as their ability to do their job. Institutions have implemented a wide array of tactics to help manage hospital capacity strain with variable success.ObjectiveThrough qualitative interviews, our study explored interventions used to address hospital capacity strain and the perceived impact of these interventions, as well as how hospital capacity strain impacts patients, the workforce, and other institutional priorities.Design, setting, and participantsQualitative study utilizing semi-structured interviews at 13 large urban academic medical centers across the USA from June 21, 2019, to August 22, 2019 (pre-COVID-19). Interviews were recorded, professionally transcribed verbatim, coded, and then analyzed using a mixed inductive and deductive method at the semantic level.Main outcome measuresThemes and subthemes of semi-structured interviews were identified.ResultsTwenty-nine hospitalist leaders and hospital leaders were interviewed. Across the 13 sites, a multitude of provider, care team, and institutional tactics were implemented with perceived variable success. While there was some agreement between hospitalist leaders and hospital leaders, there was also some disagreement about the perceived successes of the various tactics deployed. We found three main themes: (1) hospital capacity strain is complex and difficult to predict, (2) the interventions that were perceived to have worked the best when facing strain were to ensure appropriate resources; however, less costly solutions were often deployed and this may lead to unanticipated negative consequences, and (3) hospital capacity strain and the tactics deployed may negatively impact the workforce and can lead to conflict.ConclusionsWhile institutions have employed many different tactics to manage hospital capacity strain and see this as a priority, tactics seen as having the highest yield are often not the first employed.

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Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

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Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

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