Reproductive Medicine Network Biorepository: A Road Map to the Future

The phrase ‘the future is now’ can be readily applied to reproductive biology as the last 50 years have seen tremendous advances. Sequencing of the human genome stands out as the landmark event of this generation, with an ever expanding arsenal of molecular techniques providing invaluable insight into genetic determinants of disease. Likewise, assisted reproductive technologies, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and pre-implantation genetic diagnosis (PGD) have revolutionized the practice of reproductive medicine. These accomplishments have been made possible by close partnerships between basic researchers and clinicians through translational research. Multicenter or network trials with large numbers of study subjects and heterogeneous populations have contributed greatly to these endeavors. However, declining resources have demanded further refinements in recent years. A dynamic regulatory climate and well publicized concern for patient privacy and protection of data have led to improvements in many research practices. Every step from patient recruitment, consent, and enrollment to maintenance of records and storage of data and specimens has come under scrutiny. Biorepositories embody the latest advances, dynamic complexities, and inherent concerns of modern research systems.

This issue of Systems Biology in Reproductive Medicine contains two submissions from the NIH/NIHCD Cooperative Reproductive Medicine Network (RMN) that highlight a proactive, systematic approach to establishing a reproductive biorepository. Dr. Casson and his colleagues [Casson et al. 2011; Krawetz et al. 2011] outline a cogent argument for biorepositories and provide the reader with considerable insight into the practical aspects of establishing one. The authors suggest that a repository amplifies the value of the parent trial by making available specimens to answer hypotheses that may arise only after the primary trial was complete. They also clearly address the well recognized challenges encountered in the long term storage of biologic specimens including informed consent, privacy and confidentiality, disclosure of research results, intellectual property, and biobank governance.

The RMN repository is built on a strong foundation of prospectively established policies and procedures to protect patient confidentiality and allow for responsible use of the samples while maintaining the tenets of informed consent. The goal of full informed consent that will endure ethical and legal scrutiny well into the future is both admirable and lofty. However, the difficulty of predicting future research endeavors or the cultural climate in which they may be conducted does not relieve one of the responsibility to establish systems today that will be useful in the future. The RMN's well defined approach for access and utilization of the reproductive samples encourages transparency and allows for the future pursuit of answers to questions not yet formulated.

Large network trials have demonstrated widespread acceptance for storage of DNA for future research use [Levy et al. 2010] but clear ethnic and gender differences have been noted in some cohorts[McQuillan et al. 2003]. Of importance to reproductive tissue repositories, women were less likely to agree to store samples for future studies. The authors acknowledge that society has become increasingly sensitized to the ramifications of unregulated storage of data, genetic or biological material resulting from patient care or research endeavors. The Health Information Portability and Accountability Act (HIPAA) is a direct result of past abuses. The wariness is warranted as protection of individual rights and privacy are an absolute requirement of research involving human subjects.

The sacred principle of human subject protection also takes center stage in any discussion of storage of reproductive specimens, with local Institutional Review Boards (IRBs) historically serving as its guardian. However, network trials in general and specifically, biorepositories, challenge the perceived sovereignty of local IRBs. Some authors have suggested that the local IRBs are remnants of the research past, may provide an obstacle to network trials and do not enhance patient safety or improve the ethical conduct of research.[Menikoff 2010] A wide array of organizations including the Endocrine Society and The National Cancer Institute have called for a shift away from local oversight to central IRBs. The RMN has also reported a significant increase in the size and requirements of local IRB submissions as well as significant variability of IRB performance among its member institutions [Schlaff. et al. 2011].

While the arguments in favor of biorepositories are important, the practical aspects of their execution are equally crucial to success. Sample integrity and uniformity relies on proactive policies for certified shipping, proper entry, maintenance, and disposition. Disposition of sample material can be a daunting and complex task as patients may request return or destruction of their sample. Especially germane in this era of budget cuts is that a repository may close due to a lack of funds. In an ideal world, repositories would only cease to exist when their contents had been exhausted in the pursuit of productive research. The deposition of samples may be at odds with the complete subject de-identification and absolute accuracy of the link with the clinical data. For example, the RMN group noted that complete de-identification may preclude the ability of a study subject to request destruction or return of their individual specimens. They chose to prevent access to samples by the study subjects once the material has been moved to the repository. Another unanticipated result of complete de-identification is the real potential that an abnormal result cannot be communicated with the individual subject. Although unanticipated issues may arise, every effort should be made to address likely scenarios prior to storage of samples.

The RMN has provided us with a biorepository road map for future investigators to follow. While they may not have identified every pot hole along the way, their insight and guidance should assure a safe arrival for all who travel this way.

G. Wright Bates, M.D.

Director, Reproductive Endocrinology and Infertility

Department of Obstetrics and Gynecology University of Alabama at Birmingham

Birmingham, Alabama, United States