Factors predicting clinical outcomes from 494 vitrified oocyte donation cycles at a UK-regulated egg bank.

RESEARCH QUESTION: Do donor age, AMH, AFC, BMI and reproductive history predict response to ovarian stimulation? Do donor and recipient clinical markers and embryology parameters predict recipient pregnancy and live birth? DESIGN: Retrospective cohort study of 494 altruistic oocyte donors aged 18-35 years; 340 were matched to 559 recipients. Predictors of donor total oocyte yield and total mature oocyte yield were identified. Total and mature oocyte number were compared according to stratified donor AMH and age. Donor, recipient and embryology parameters predictive of recipient primary outcomes (clinical pregnancy and live birth) were identified. RESULTS: Donor age and AMH predicted total oocyte yield (P = 0.030 and P < 0.001)) and total mature oocyte yield (P = 0.011 and P < 0.001). Donors aged 30-35 years with AMH 15-29.9 pmol/l had lower total oocyte yield (P = 0.004) and mature oocyte yield (P < 0.001) than donors aged 18-24 years. Up to an AMH threshold of 39.9 pmol/l, increasing AMH levels predicted higher total oocyte yield (<15 pmol/l versus 15-29.9 pmol/l, P = 0.001; 15-29.9 pmol/l versus 30-39.9 pmol/l, P < 0.001; 30-39.9pmol/l versus ≥ 40 pmol/l, P = 1.0) and mature oocyte yield (<15 pmol/l versus 15-29.9 pmol/l, P = 0.005; 15-29.9 pmol/l versus 30-39.9 pmol/l, P = 0.006; 30-39.9 pmol/l versus ≥40 pmol/l, P = 1.0). In recipients, the rate of transferrable embryos per oocytes received, fertilized and number of embryo transfers needed to achieve the primary outcome were predictors of cumulative clinical pregnancy (P = 0.011, P = 0.017 and P < 0.001) and live birth (P = 0.008, P = 0.012 and P < 0.001) rates. Recipient BMI (P = 0.024) and previous miscarriages (P = 0.045) were predictors of cumulative live birth rate. Donor age 18-22 years was associated with a lower incidence of recipient clinical pregnancy (P = 0.004) and live birth (P = 0.001) after the first embryo transfer versus donor age 23-29 years. CONCLUSIONS: Donor age and AMH are independent predictors of oocyte yield. Raised recipient BMI and history of miscarriages reduce cumulative live birth rates, which may be increased by selecting donors aged 23-29 years, instead of younger donors.

Establishing a reproductive biorepository for basic and translational research: experience developing the reproductive subjects registry and sample repository.

PURPOSE: To report experience designing and establishing a reproductive registry and sample biorepository and to describe initial subject characteristics and biospecimens. METHODS: Beginning in December 2017, patients presenting for reproductive care at the University of Michigan were approached for study enrollment. Following consent, subjects completed detailed reproductive and health questionnaires. A variety of reproductive specimens and tissues were collected and processed for multiple downstream applications. RESULTS: Subject enrollment began in December of 2017. There are currently 1798 subjects enrolled. Female participants report a variety of reproductive disorders. Available samples include semen, sperm, follicular fluid, granulosa cells, immature oocytes, ovarian and uterine tissue, and blood samples. CONCLUSION: We report the successful establishment of a reproductive registry and sample biorepository. Furthermore, we describe methods for collection and storage of a variety of reproductive tissue processed for multiple downstream translational applications.

Loss-of-Function Variants in the Tumor-Suppressor Gene PTPN14 Confer Increased Cancer Risk.

The success of genome-wide association studies (GWAS) in identifying common, low-penetrance variant-cancer associations for the past decade is undisputed. However, discovering additional high-penetrance cancer mutations in unknown cancer predisposing genes requires detection of variant-cancer association of ultra-rare coding variants. Consequently, large-scale next-generation sequence data with associated phenotype information are needed. Here, we used genotype data on 166,281 Icelanders, of which, 49,708 were whole-genome sequenced and 408,595 individuals from the UK Biobank, of which, 41,147 were whole-exome sequenced, to test for association between loss-of-function burden in autosomal genes and basal cell carcinoma (BCC), the most common cancer in Caucasians. A total of 25,205 BCC cases and 683,058 controls were tested. Rare germline loss-of-function variants in PTPN14 conferred substantial risks of BCC (OR, 8.0; P = 1.9 × 10-12), with a quarter of carriers getting BCC before age 70 and over half in their lifetime. Furthermore, common variants at the PTPN14 locus were associated with BCC, suggesting PTPN14 as a new, high-impact BCC predisposition gene. A follow-up investigation of 24 cancers and three benign tumor types showed that PTPN14 loss-of-function variants are associated with high risk of cervical cancer (OR, 12.7, P = 1.6 × 10-4) and low age at diagnosis. Our findings, using power-increasing methods with high-quality rare variant genotypes, highlight future prospects for new discoveries on carcinogenesis. SIGNIFICANCE: This study identifies the tumor-suppressor gene PTPN14 as a high-impact BCC predisposition gene and indicates that inactivation of PTPN14 by germline sequence variants may also lead to increased risk of cervical cancer.

Brain donation in the era of COVID 19: challenges to the harvest in the face of a pandemic.

We have experienced numerous new challenges during the process of brain harvesting in the period of COVID-19. Although brain harvests have continued successfully during this time period, the numerous uncertainties and challenges described in this paper have nearly derailed the process several times. While the interface of the medical profession with patients in the context of a pandemic has been well-documented on several fronts, and particularly for those health care workers on the front lines, we are not aware of any documentary accounts of the challenges facing research and tissue donation programs. With this paper, we contribute an additional perspective and describe the lessons we have learned in addressing these novel issues.

Analysis of impact on tissue activity during COVID-19 outbreak: a survey of 8 banks in Spain.

On March 19 World Health Organization declare the pandemic situation by outbreak coronavirus disease 2019 in the world. The pressure on the health care system has been very high in several countries. Spanish National Transplant Organization (ONT) have made many efforts in maintaining transplantation activity. Although the impact of the pandemic on organ activity has been analysed, to date, less data exist regarding the impact on tissue activity. The aim of this study has been the evaluation of the possible impact on the procurement, processing and distribution of tissues during the peak period of the pandemic COVID-19 in Spain. For this study, a multicentre analysis has been made with a survey of the tissue banks in Spain, during the period March 1 to April 30, 2020. Our data suggest that the impact of coronavirus in Spain has affected dramatically tissue donation but with a moderate effect on stored tissues such as bone, valves, vessels or skin. Tissue banks should prepare if future next pandemic waves surges so that tissue provision is guaranteed both in urgent and elective surgeries.

Canadian Tissue Repository Network Biobank Certification Program: Update and Review of the Program from 2011 to 2018.

The Canadian Tissue Repository Network (CTRNet) Biobank Certification Program was first launched in 2011 to foster translational research through improved access to high quality biospecimens. This was accomplished by creating and providing biobank education and through the establishment and deployment of common standards to harmonize biospecimen quality and approaches to governance. The CTRNet program comprises registration and certification steps as two linked phases. In the two-step registration phase, the biobank is registered into the system, and an individual completes an overview educational module. In the subsequent certification phase, biobanks undergo a seven-step process, including inviting team members, assigning and completing relevant education modules, uploading documents, and undergoing a documentation audit. As of June 2018, there were 251 biobanks engaged in the CTRNet program, 193 had completed registration, and 40 were fully certified. Over 3/4 of these biobanks completed registration within a week and over 1/3 completed certification within a month. Among registered biobanks, 163 were associated with North American institutions, while 30 were from other international locations, including Australia, Europe, and Asia. The CTRNet program enables biobanks to adopt standards with a flexible approach to accommodate different types of biobanks and a measured investment of effort, creating the foundation for increased access to high quality biospecimens.

Fresh osteochondral grafting in the United States: the current status of tissue banking processing.

The use of musculoskeletal allografts has become increasingly popular among surgeons. The purpose of this review is to highlight the procurment and delievery process of fresh osteochondral allografts in the United States. The four distributors of fresh osteochondral allografts in the United States were contacted. Surveys containing quantitative and qualitative sections concerning the procurement and processing of osteochondral allograft tissue were obtained. Our results showed an average of 13 ± 4.24 years of experience with osteochondral allografts. The average donor age ranged from 13.5 ± 3 to 37.5 ± 5 years, with an average age of 27 ± 2.83 years. All donors were between ages 12 and 45 years old. The percentage of screened donors that were accepted for allograft transplant was consistent at 70-75% for 3 out of the 4 tissue banks. The percentage of grafts that expire without implantation ranged from 20% to 29%. Maximum shipping time varied between 24 and 96 hours. Each tissue bank used its own proprietary storage medium. The time from donor death to the harvest of allograft tissue was < 24 hours. The most commonly requested osteochondral allograft tissue for all banks was the medial femoral condyle. The market share of fresh allografts is as follows: Joint Restoration Foundation (JRF) 59.9%, Muskuloskeletal Transplant Foundation (MTF) 15.3%, LifeNet Health (LN) 14.5%, and Regeneration Technology Incorporated (RTI) 10.2%, with approximately 4700 fresh allografts distributed in 2018. This compiled data from the four tissue banks that supply fresh osteochondral allograft in the United States  provides important background information for patients and orthopaedic surgeons.

Gender differential in inclination to donate brain for research among Nigerians: the IBADAN Brain Bank Project.

BACKGROUND: Laboratory-based studies of neurological disease patterns and mechanisms are sparse in sub-Saharan Africa. However, availability of human brain tissue resource depends on willingness towards brain donation. This study evaluated the level of willingness among outpatient clinic attendees in a Nigerian teaching hospital. METHODS: Under the auspices of the IBADAN Brain Bank Project, a 43-item semi-structured interviewer-administered questionnaire was designed to evaluate knowledge, attitude, and beliefs of individuals attending Neurology, Psychiatry and Geriatrics Outpatient clinics regarding willingness to donate brain for research. Association between participants characteristics and willingness towards brain donation was investigated using logistic regression models. Analysis was conducted using Stata SE version 12.0. RESULTS: A total of 412 participants were interviewed. Their mean age was 46.3 (16.1) years. 229 (55.6%) were females and 92.5% had at least 6 years of formal education. Overall, 109 (26.7%) were willing to donate brains for research. In analyses adjusting for educational status, religion, ethnicity, marital status and family setting, male sex showed independent association with willingness towards brain donation OR (95% CI) 1.7 (1.08-2.69), p = 0.023. Participants suggested public engagement and education through mass media (including social media) and involvement of religious and community leaders as important interventions to improve awareness and willingness towards brain donation. CONCLUSION: The survey revealed low willingness among outpatient clinic attendees to donate brain for research, although men were more inclined to donate. It is imperative to institute public engagement and educational interventions in order to improve consent for brain donation for research.

Genetic databases and the future of donor anonymity.

Anonymity is a multifaceted term. Anonymity is rarely eternal or absolute. The use of genetic databases increases the risk of identification of previously anonymous donors. Searches through genetic databases jeopardize the privacy of people who did and did not register on them. Three types of searches can be distinguished in the context of gamete donation: offspring looking for their donor, offspring looking for donor siblings and donors looking for their donor offspring. All three types of searches violate the rights of recipients and donors. It is argued that despite the existence of genetic databases, anonymity maintains the same function as it had before: it expresses a wish for distance and privacy by both donors and recipients and, even if not enforceable, should be respected by all parties in good faith.

Microbial contamination and tissue procurement location: A conventional operating room is not mandatory. An observational study.

BACKGROUND: Standard operating rooms (SOR) are assumed to be the best place to prevent microbial contamination when performing tissue procurement. However, mobilizing an operating room is time and cost consuming if no organ retrieval is performed. In such case, non-operating dedicated rooms (NODR) are usually recommended by European guidelines for tissue harvesting. Performing the tissue retrieval in the Intensive care unit (ICU) when possible might be considered as it allows a faster and simpler procedure. OBJECTIVE: Our primary objective was to study the relationship between the risk of microbial contamination and the location (ICU, SOR or NODR) of the tissue retrieval in heart-beating and non-heart-beating deceased donors. MATERIALS AND METHOD: We retrospectively reviewed all deceased donors' files of the local tissue banks of Montpellier and Marseille from January 2007 to December 2014. The primary endpoint was the microbial contamination of the grafts. We built a multivariate regression model and used a GEE (generalized estimating equations) allowing us to take into account the clustered structure of our data. RESULTS: 2535 cases were analyzed involving 1027 donors. The retrieval took place for 1189 in a SOR, for 996 in a hospital mortuary (NODR) and for 350 in an ICU. 285 (11%) microbial contaminations were revealed. The multivariate analysis found that the location in a hospital mortuary was associated with a lower risk of contamination (OR 0.43, 95% CI [0.2-0.91], p = 0.03). A procurement performed in the ICU was not associated with a significant increased risk (OR 0.62, 95% CI [0.26-1.48], p = 0.4). CONCLUSION: According to our results, performing tissue procurement in dedicated non-sterile rooms could decrease the rate of allograft tissue contamination. This study also suggests that in daily clinical practice, transferring patients from ICU to SOR for tissue procurement could be avoided as it does not lead to less microbial contamination.

Bacterial contamination of human skin allografts and antimicrobial resistance: a skin bank problem.

BACKGROUND: Bacterial contamination remains the major problem in skin banks, even after antimicrobial treatment, and results in high rates of tissue discarding. This study aimed to analyze bacterial contamination in 32 human skin allografts from the skin bank of Dr. Roberto Corrêa Chem from the Hospital Complex Santa Casa de Misericórdia de Porto Alegre. These samples were already discarded due to microbial contamination. The identification of the bacteria isolated from skin allografts was performed by matrix assisted laser desorption ionization-time of flight. The antimicrobial susceptibility of the isolates to six different classes of antimicrobials was determined using the disk-diffusion agar method, and the evaluation of the inhibitory potential was determined by the minimal inhibitory concentration (50/90) of antimicrobials already used in the skin bank and those that most isolates were susceptible to. RESULTS: A total of 21 (65.6%) skin samples were contaminated with Gram-positive bacteria: 1 (4.7%) with Paenibacillus sp., 12 (61.9%) with Bacillus sp., 6 (28.5%) with Staphylococcus sp., and 2 (9.5%) with Bacillus sp. and Staphylococcus sp. Several resistance profiles, including multiresistance, were found among the isolates. Most of the isolates were susceptible to at least one of the antimicrobials used in the skin bank. All isolates were susceptible to amikacin, gentamicin, and tetracycline, which demonstrated the best inhibitory activities against the isolates and were considered as potential candidates for new antimicrobial treatments. CONCLUSIONS: Bacillus, Paenibacillus, and Staphylococcus were isolated from the skin allografts, thus demonstrating the predominance of Gram-positive bacteria contamination. Other factors not related to the resistance phenotype may also be involved in the persistence of bacterial isolates in the skin allografts after antibiotic treatment. Gentamicin, amikacin, and tetracycline can be considered as an option for a more effective treatment cocktail.

Experience in Using Fetal Membranes: The Present and New Perspectives.

INTRODUCTION: The placenta is an accessible source of tissues for transplantation. Placental transplants have been used in wound treatment because of the basic function of the placenta and its nutritious properties and structure. PATIENTS AND METHODS: The aim of this work is to present the clinical usage of fetal membranes, including human amnion, on the basis of the burn treatment center's experience. The clinical use of amnion and different types of placental transplants are described. The initial results of research work within the MEDPIG project are presented regarding the application of placenta from transgenic pigs as a source of tissues for transplantation. RESULTS: From August 2011 to March 2017, 252,592 cm2 of biostatic human amnion transplants were prepared in our tissue bank. During this period they were transplanted to 528 patients, including 10 patients with Lyell syndrome. Initial studies were conducted in which placentas were collected from 5 transgenic pigs and 27,426 cm2 of amniotic grafts were prepared from them. DISCUSSION: The authors' own experience as well as the literature confirm the extraordinary efficiency of transplants prepared from placental tissues, especially from the amniotic membrane. CONCLUSIONS: The clinical effects confirm the effectiveness of using human amnion in wound treatment. Amniotic transplant is a new treatment standard in toxic epidermal necrolysis TEN (Lyell's syndrome), which has found confirmation in very good clinical outcomes. The collected placentas from transgenic animals enabled the preparation of significantly more grafts than in the case of human material, which is a great advantage of this source of placenta over human tissues.

Analysis of the order-implantation relationship for musculoskeletal tissue transplantation. / Análisis de la relación solicitud-implante de injerto para trasplante osteomuscular.

OBJECTIVE: To analyze orders requested from a musculoskeletal tissue bank and to evaluate the percentage of tissue implantation. MATERIAL AND METHODS: Two hundred and sixty-five orders for musculoskeletal tissue were analyzed over the course of a year. EXCLUSIONS: 5 duplications and 5 orders for which there was no availability to cover the need. We analyzed the number of surgeries in which the graft was finally used. RESULTS: Of a total of 255 orders, the graft was used in 178 (70%), and the graft was not used in 77 (30%). Of the 178 used, there was a partial refund in 23 (10%). Of the 77 orders not used, surgery was performed in 32 (13%) without the use of bank tissue, while surgery was discontinued in the remaining 45 (17%). DISCUSSION: A non-utilization rate of 30% was identified, of which 17% was from surgery that was not performed and 13% from surgery that was performed, but the tissue was returned to the tissue bank, because it was not required. In a further 10% there was partial return of the tissue. Based on this analysis, we consider that it is important to have direct confirmation of the surgery to avoid sending tissue for discontinued surgeries, since in addition to the economic impact, the bank must ensure adequate temperature maintenance during transportation and storage in the transplantation centre, to avoid discarding said tissue if it is returned.

The NIH NeuroBioBank: creating opportunities for human brain research.

The National Institutes of Health (NIH) NeuroBioBank is a federally funded research resource for human neurologic diseases and disorders. This chapter will discuss the principles that guided the creation of the NIH NeuroBioBank and the rationale for the resource model selected. In addition, we will describe some performance metrics in the first 2 years and highlight recent advances in biomedical neuroscience that could only have been achieved using postmortem human tissues. The NIH NeuroBioBank was created in order to increase availability of high-quality postmortem human brain tissues to the research community across a broad spectrum of neurologic diseases and disorders, and to achieve economies of scale over previous funding and organizational models. In addition, we aim to increase public awareness about the value of human tissue donation for research by providing web-based information to the public and through active outreach to disease advocacy communities. Studies with human brain tissue have led to a rapid increase in our knowledge of the biologic differences between humans and are bridging the divide between humans and model organisms. Studies of human brain are beginning to give us a glimpse not only into what makes us uniquely human as well as how individual biology may be connected to health and disease.

Design of a European code of conduct for brain banking.

The BrainNet Europe consortium, which is a consortium of 19 European brain banks, took the initiative to draft a series of documents to provide an ethical framework for brain banks to follow. The framework includes an ethical code of conduct, a model for brain bank regulations, and a toolkit containing several documents. The sources for the information included came from the laws, regulations, and guidelines (declarations, conventions, recommendations, guidelines, and directives) that had been issued by international key organizations, such as the Council of Europe, European Commission, World Medical Association, and World Health Organization. The code of conduct addresses fundamental topics such as the rights of the persons donating their tissue, the obligations of the brain bank with regard to respect and observance of such rights, informed consent, confidentiality, protection of personal data, collections of human biologic material and their management, and transparency and accountability within the organization of a brain bank. The code of conduct was ratified by all European brain banks in 2009. This chapter describes the process of establishing the code of conduct within the BrainNet Europe consortium and elaborates on three key aspects of the code of conduct, namely informed consent, genetics, and financial aspects in brain banking.

A review of brain biorepository management and operations.

Brain biospecimen banking requires centralized resources, national networks for referral of donors, trained personnel to interact with grieving families, and scientific staff to process the biospecimens. Process development of quality control standards is needed to meet the specific requirements of emerging genomic and proteomic technologies. Attention has to be paid to agonal factors and postmortem interval, tissue processing, neuropathology review, and long-term storage. Samples of both diseased and unaffected normal tissues are required with age- and gender-matched control tissues. Data management is vital to store and retrieve quality control measures, clinical and pathologic data linked to the biospecimens. Customized solutions for managing the acquisition and long-term storage of high-quality brain and tissue biospecimens is necessary to support neuroscience research programs, biomarker discovery and genome scale technologies. Biorepositories that operate according to best-practice policies and procedures guarantee the final wish of the families who donate tissue to support neuroscience research and discovery science.

A new viewpoint: running a nonprofit brain bank as a business.

It has become clear over the past decades that studying postmortem human brain tissue is one of the most effective ways to increase our knowledge of the pathogenesis and etiology of neuropathologic and psychiatric diseases. Many breakthroughs in neuroscience have depended on the availability of human brain tissue. However, the process of brain banking presents many different challenges, including the high cost that is associated with collecting the samples and with providing the diagnostics, storage, and distribution. Funding is generally from research and facility grants and donations but all are irregular, uncertain, and only cover the costs for a determined period of time. For professional brain banks with extensive prospective donor programs and that are open-access it can be very beneficial to draft a business plan to achieve long-term sustainability. Such a business plan should identify the interests of the stakeholders and address the implementation of cost efficiency and cost recovery systems.

A brain worth keeping? Waste, value and time in contemporary brain banking.

If a temporal rather than spatial concept of waste is adopted, novel categories emerge which are useful for identifying and understanding logics of temporality at play in determining what is kept in contemporary brain banks, and reveal that brain banks are constituted by more than stored materials. First, I apply the categories analytically on a recent UK brain banking discussion among professionals. This analysis highlights the importance of data in brain banks, as well as the centrality of ideas about pasts and futures in the discussions. Secondly, I investigate the case of a seven decades old, Danish brain bank which had been reduced to its physically stored material for 24 years, before being reinstituted in 2006. This case demonstrates the importance of material and conceptual infrastructures that co-constitute a collection, as they make up an experimental system that is crucial to maintaining the collection's continued relevance and usefulness as a scientific institution.

[Required Framework for the Collection of Real-life Data: An Example from University Eye Hospital Munich]. / Rahmenbedingungen zur Sammlung von "Real-Life"-Daten am Beispiel der Augenklinik der Universität München.

Background The importance of evaluating real-life data is constantly increasing. Currently available computer systems better allow for analyses of data, as more and more data is available in a digital form. Before a project for real-life data analyses is started, technical considerations and staff, legal, and data protection procedures need to be addressed. In this manuscript, experiences made at the University Eye Hospital in Munich will be shared. Materials and Methods Legal requirements, as found in laws and guidelines governing documentation and data privacy, are highlighted. Technical requirements for information technology infrastructure and software are defined. A survey conducted by the German Ophthalmological Society, among German eye hospitals investigating the current state of digitalization, was conducted. Also, staff requirements are outlined. Results A database comprising results of 330,801 patients was set up. It includes all diagnoses, procedures, clinical findings and results from diagnostic devices. This database was approved by the local data protection officer. In less than half of German eye hospitals (n = 21) that participated in the survey (n = 54), a complete electronic documentation is done. Fourteen institutions are completely paper-based, and the remainder of the hospitals used a mixed system. Conclusion In this work, we examined the framework that is required to develop a comprehensive database containing real-life data from clinics. In future, these databases will become increasingly important as more and more innovation are made in decision support systems. The base for this is comprehensive and well-curated databases.

Development of national system performance metrics for tissue donation, production, and distribution activity.

Canada's federal, provincial, and territorial governments gave Canadian Blood Services a mandate for organ and tissue donation and transplantation, including system performance, data and analytics. In 2012 Canadian Blood Services facilitated an eye and tissue banking workshop focused on standardized specifications and practices. At the workshop, the Canadian tissue community directed Canadian Blood Services to facilitate the development and implementation of a national data stream and analytics. Prior to this no national data was prospectively collected or collated on tissue donation, production or distribution activity. An eye and tissue data committee was formed with representation from eye and tissue banks in all Canadian jurisdictions. A minimum data set, standardized definitions, a data submission form and a quality assurance process was developed. Training was provided to data personal identified by each eye and tissue bank. Data collection was initiated January 1, 2013; with quarterly data submitted to Canadian Blood Services via excel spreadsheet. Data was submitted by sixteen Canadian eye and tissue banks, located in eight of Canada's thirteen provinces and territories, representing a census of activity. Annual data reports, with trend analysis, are generated and distributed to the tissue community to inform operational strategy and system performance improvement. This report provides an overview of the data process and provides visibility to the Canadian tissue donation, production and distribution activities for 3 years; January 1, 2013 to December 31, 2015.