By Francesca Duncan

Most cancer therapies, while life-preserving, can threaten the future fertility of both males and females.  Fortunately, the menu of fertility preservation options is broad, and due to ongoing research efforts through the Oncofertility Consortium and around the globe, these options are ever-expanding.  Hydrogel-based in vitro follicle growth is one such investigational technology developed by Oncofertility Consortium researchers in which immature follicles are isolated directly from ovarian tissue and grown in alginate, a natural biomaterial derived from algae.  This system supports follicular architecture through terminal stages of follicle development and has been shown in the mouse to produce eggs that give rise to healthy offspring.  Research is now focused on optimizing this system to produce live offspring in primate species.

As interest in learning and applying such technologies to the field of fertility preservation has increased, the Oncofertility Consortium launched a new course entitled: Oncofertility 101: a training course in in vitro follicle growth using alginate hydrogels.”  This is an intense one-day course in which participants experience  hands-on laboratory exercises aimed at learning the fundamentals of follicle micromanipulation, encapsulation, culture, and quality analysis.  This course “ensures that the transmission of technical skills needed to successfully grow healthy follicles in three dimensions are acquired quickly in order to advance the pace of reproductive research” emphasizes Teresa Woodruff, PhD, Director of the Oncofertility Consortium.  In addition to the laboratory exercises, Lonnie Shea, PhD and Min Xu, MD, PhD, both pioneers of this technology, present crucial insight into the evolution of follicle culture biomaterials and the ins and outs of setting up a follicle culture laboratory, respectively.  The course is led by Francesca Duncan, PhD, a Research Associate in the Woodruff Laboratory.

The first Oncofertility 101 course, held in September 2011, was very successful.  Participants came from diverse scientific backgrounds, including basic science, embryology, endocrinology, and biotech.  Participants found the course to be “excellent” and “a great opportunity.”  One person commented: “To really understand a technology I think you need to know how it is done so while I had read considerably about the technique, until yesterday, I did not have that important insight that goes with actually doing the technology… thank you for your time and effort and especially for your patience. It’s been twenty years since I actually sat at the bench and manipulated gametes!”

Oncofertility 101 is held twice a year, and the next course is right around the corner on Monday, March 12^th.  This course is free of charge but registration is limited to five participants.  If you are interested in registering or would like more information, please click here.  The second 2012 Oncofertility 101 course will take place on Wednesday, September 26^th, to coincide with the 2012 Oncofertility Consortium Conference.

Francesca Duncan, PhD

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I was recently introduced to the formal concept of Team Science when I was fortunate enough to attend the First Annual International Science of Team Science Conference hosted by the Northwestern University Clinical and Translational Sciences Institute (NUCATS) on April 22-24, 2010.  To understand Team Science, it is important to know the definition of a team.  As Dr. Stephen Fiore (Faculty at University of Central Florida) defined it: a team consists of two or more people or groups who interact dynamically, interdependently, and adaptively towards a shared goal.  They do so while maintaining only partially overlapping knowledge and come together to solve intractable problems.

This meeting highlighted three key points about Team Science as it relates to Basic Research.

1) There is an increasing need for Team Science in Basic Research. As Dr. Benjamin Jones (Associate Professor at the Kellogg School of Management) explained, nowadays there is an ever-growing pool of knowledge.  For a scientist to succeed, he or she must either spend more time in training or choose a narrower expertise.  Many scientists are choosing to specialize in a narrower field, which means the individual capacity decreases.  As Dr. Jones so eloquently put it: “With the burden of knowledge comes the death of the Renaissance [person].”  If the scientist wants to have a broad impact, he or she must join a team or collaborate.  In fact, teams are becoming ubiquitous, and research has shown that teams, especially those that span institutional boundaries, produce higher impact papers.

2) To succeed in Team Science is difficult – especially under the framework of Basic Research. Although there are many benefits and rewards to working as part of a team, there are many inherent challenges.  As Dr. Daniel Stokols (Professor at University of California, Irvine) highlighted, when scientists work as a team there are risks, including conflicts and strains, information overload, and fragmentation of research activities.  Furthermore, scientific teamwork requires a complex research infrastructure, and can potentially have detrimental societal ramification if it fails.

Establishing cohesive and productive teams in basic research is particularly challenging compared to other disciplines for multiple reasons that Dr. Joann Keyton (Professor of Communication at North Carolina University) brought to light.   First, for example, basic research is propelled by grants that span several years.  Technicians, students, or post-doctoral researchers, whose tenure in a particular laboratory varies, perform the funded research.  Thus, the team that begins a project is unlikely to be the team who follows it through to the end.   Second, collaborations are difficult to establish when researchers work nonstandard hours and may be separated by time and geography.  Third, research tends to be composed of distributed teams with researchers working on multiple similar yet different projects.  For example, each graduate student must have his or her own unique project to graduate.  As a result, potential team members form weak relationships with each other and identify more with the Principal Investigator (PIs) than with an overarching task or goal.

3) Tools are being developed to make Team Science work for Basic Research.  “Everyone knows that there is a magnetic pleasure of working with a successful team” states Dr. Howard Gadlin (Ombudsman, National Institutes of Health).   However, Dr. Gadlin affirms that teamwork tends to fail in research because scientists fail to be explicit about expectations.  Dr. Gadlin’s recipe for success is to sign a “prenuptial” agreement prior to entering a collaborative union.  This agreement should cover the following: overall goals and priorities, a definitive timeline, responsibilities, authorship and credit, methods of communication, and conflicts of interest.   Periodically the team should meet to evaluate the collaboration and refine the infrastructure as necessary.  Dr. Keyton also believes that teamwork can be improved if the entire team is integrated.   For example, PIs should include the students and postdoctoral researchers in decision-making processes and idea-generating meetings.  Furthermore, all the students and postdocs on a given grant should know each other and understand the entire scope of the grant on which they are working.

In addition to these tips, tools are also being developed to help researchers grasp the notion of Team Science and put it to work.   Dr. Kara Hall and her group at the National Cancer Institute will be launching the Team Science Toolkit in the coming months.  This online resource will not only aid in the study of the science of Team Science, but it will also support and facilitate team-based research activities and projects.   In July 2010, Dr. Bonnie Spring and her group at Northwestern University will be launching the Team Science Gallery – a series of online, interactive, learning modules geared towards demonstrating how team-based collaborations function in multiple disciplines.

The Oncofertility Consortium, which was highlighted at this meeting, is truly at the forefront of a new era in scientific investigation.  Basic researchers and clinicians from institutions around the country meet together in Virtual Space once a month to discuss research progress, convene in Chicago annually to summarize key findings, and are united with the common goal of exploring and expanding fertility preservation options.  The Oncofertility Consortium, however, is much more than a team of basic researchers and clinicians; it is an all-encompassing team comprised also of nurses, social workers, patient navigators, humanists, social scientists, bioethicists, religious scholars, economists, lawyers, and more.   With this union progress, change, and discovery are inevitable.

Francesca Duncan, PhD

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Applying emerging Assisted Reproductive Techonology (ART) procedures in an Oncology setting may help cancer survivors attain their desire to have a child spared of the very cancer that they themselves battled.  Preimplantation Genetic Testing (PGT) is a prenatal screen performed prior to the initiation of pregnancy.  In this procedure, cell(s) from embryos derived from ART procedures (either in vitro fertilization or intracytoplasmic sperm injection) are biopsied and used for genetic testing so that only unaffected embryos are transferred to the recipient uterus.  Since its inception in the 1990s to screen for sex-linked disorders, PGT has been used to screen embryos for a wide range of abnormalities including single gene disorders, chromosomal abnormalities, and aneuploidies.  More controversial uses of PGT include HLA-typing, sex selection for family balancing, and screening for non-medical genetic traits.  PGT has a 2% misdiagnosis rate and is generally considered to be successful.  Approximately 7,000 cycles of PGT have been reported worldwide, resulting in more than 1,000 live births.

Image: Process of PGD resulting in a healthy, hatched embryo Francesca Duncan

In the past few years there has been an increasing use of PGT to screen for cancer syndromes because the five-year survival rate for most cancers is improving for reproductive-aged men and women.  Thus, starting a family post-cancer is becoming a reality for many.  Furthermore, strides in basic research have uncovered the genetic links to many cancers, therefore allowing a technology such as PGT to be applied to this disease.  According to a 2006 paper published by Dr. Kenneth Offit and colleagues in the Journal of the American Medical Association, there are 55 published reports of using PGT to screen for 22 common cancer predisposition syndromes including hereditary breast, ovarian, and colon cancers (1).    Of the thirteen PGT centers that provide clinical or research services, nine perform cancer-related screening.

Although using PGT to screen for cancer predisposition syndromes could be a promising option for Oncofertility patients seeking to start a healthy family, caution needs to be exercised before making it standard for several reasons.  First, although the embryos selected for implantation may not harbor specific genetic mutations that will predispose the children to cancer, the embryos may have other genetic defects that were not screened for.  Second, it is important to realize that many cancers are sporadic, so PGT will not offer a protective benefit against these forms.   Finally, PGT has only been in existence for about twenty years, so we do not know the effects of this procedure on the long-term health and well-being of the offspring.  Studies in mice have demonstrated that simply culturing embryos in vitro can have subtle but statistically significant consequences on the gene expression profiles, imprinting, and long-term behavior in the resulting animals (2-4).   In contrast, my work using a mouse model of PGT demonstrates that removing a single cell from an 8-cell embryo does not affect the global patterns of gene expression in the resulting blastocyst (5).  Although these results are encouraging for demonstrating the safety of PGT, they are still preliminary and more research needs to be done.

(1) K Offit et al. JAMA (2006); 296: 2727-2730.

(2) P Rinaudo et al. Reproduction (2004); 128: 301-311.

(3) AS Doherty et al. Biology of Reproduction (2000); 62: 1526-1535.

(4) DJ Ecker et al. PNAS (2004); 101: 1595-1600.

(5) FE Duncan et al. Fertility Sterility (2009); 91: 1462-1465.