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.

Cristina Thomas (top) with her mentors in the Woodruff Lab, Candace Tingen, PhD, and Min Xu, PhD.

Cristina Thomas is like many young students at Northwestern University. She spends her time studying, participating in school activities, and having fun with her friends. In addition to all this, over the past four years she has worked in the laboratory of Teresa K. Woodruff, PhD, on a variety of projects dealing with ovarian follicle development. A few weeks ago, all the hard work paid off when Cristina was awarded the Constance L. Campbell Award, one of just a few prestigious awards given to graduating biology students at Northwestern.

In her research, Cristina investigated some factors that may aid in the development of future fertility techniques for cancer patients, such as in vitro follicle growth. Specifically she examined how different oxygen concentrations and the presence of theca cells or macrophages (white blood cells) may increase the growth and survival of follicles. Some of this work was recently published in the journal Reproduction in a paper titled, “A macrophage and theca cell-enriched stromal cell population influences growth and survival of immature murine follicles in vitro,” by Tingen et al.

In addition to investigating new techniques, Cristina also worked with researchers to determine whether existing fertility preservation techniques are appropriate for specific cancer patients. She and a medical fellow examined the number of antral (more mature) follicles in ovaries from 140 patients with ovarian cancer and correlated those follicle numbers with the severity of the ovarian masses. These results may affect the fertility preservation treatments offered to ovarian cancer patients in the future and can guide development of additional oncofertility techniques.

A gender studies minor, Cristina also enthusiastically participated in the Oncofertility Saturday Academy, where she organized fellow undergraduate students to mentor younger girls in the Chicago program. These undergraduates provided advice on the college application process and gave the high school students a tour of Northwestern’s campus.

Cristina will continue to employ her research and oncofertility expertise as she enters the next phase of her life, as a medical student at Northwestern’s Feinberg School of Medicine. She is only one example of how the Oncofertility Consortium is training the next generation of medical specialists in the principles of oncofertility.

Today the National Institutes of Health published a news released based on an article about Oncofertility research from the journal Human Reproduction “In vitro grown human ovarian follicles from cancer patients support oocyte growth” by Min Xu, Susan Barrett, Erin West-Farrell, Laxmi Kondapalli, Sarah Kiesewetter, Lonnie Shea and Teresa Woodruff.

The researchers were trying to develop a way for the in vitro (in a controlled environment outside of the body) growth of undeveloped follicles (a fluid-filled sac containing an immature egg) as a way to restore fertility in women who have undergone radiation or chemotherapy to fight cancer. For the investigation, the researchers took out secondary follicles from human ovarian tissue donated by 14 different cancer patients ranging from 16 to 39 years old. The follicles were then grown in a specially-designed bio-engineered culture for 30 days.

The researchers found that the follicles developed from the secondary stage to the antral stage (the final stage of growth of an oocyte which then develops into an egg). Therefore, the results of the study indicated that it was possible for follicles to continue development even when not in the human body. This is encouraging but more research needs to be done to see whether these oocytes can eventually be fertilized.

(To see an animation of normal female fertility, click here.)

To read the study online on the Human Reproduction Web site, click here.

To read the NIH news release, click here.

Look out for more news coverage of the Oncofertility Consortium‘s study!

Marina Peluffo and Teresa Woodruff stand in front of the abstract poster Peluffo won an award for at the 15th World Congress on IVF in Geneva, Switzerland in April 2009.

Marina Peluffo, an Oncofertility Consortium member from Portland, Oregon, won an award for her poster abstract “Cumulus Oocyte Complexes from Small Antral Follicles during the Early Follicular Phase of Spontaneous Cycles in Rhesus Monkeys Can Expand and Yield Oocytes Capable of Maturation In Vitro”.

Her poster was presented at the 15th World Congress on IVF in Geneva, Switzerland earlier this year. Teresa Woodruff also attended the Congress in April and was one of the 100 plenary speakers to address close to 750 participants from 67 different countries. For more information about the Congress go to the ISIVF Web site.

To view our previous entry on the World Congress, click here: Oncofertility at the 15th World Congress on IVF.

Cancer is now a disease with a variety of treatment options, which are leading to longer and more productive lives by survivors. Globally, there are 10 million people diagnosed with cancer.  10% of these newly diagnosed men and women are under the age of 45 years old. Infertility can be a consequence of many of the more aggressive chemo- and radiation therapies that prolong and save lives.  The ability to easily preserve sperm prior to cancer treatment provides hope at the time of diagnosis and families later in life for male survivors.  A notable example is Tour de France winner Lance Armstrong who has three children conceived using sperm frozen days before he underwent the massive chemo- and radiation therapy that saved his life. Unlike sperm, the female germ cell, the oocyte or egg must be retrieved surgically.  Moreover, the vast majority of collected oocytes will be immature and cannot be used immediately by a woman who is ready to start a family.  The overall hypothesis  of the program is that effective fertility-extending options can be provided to young women undergoing life-preserving cancer treatment. The purpose of our work is to bring physicians, medical ethicists, social scientists and basic scientists together to develop new strategies for fertility preservation for female cancer survivors under the new discipline of oncofertility.  And even as the lexicon is being established, complex bioethical issues face both providers and parents.  At the basic science level, complex issues of ovarian function and preservation must be addressed including the problem of follicle growth and development in vitro. Our investigative group has pioneered the development of a 3-dimensional system that supports follicle development, largely, we believe, because the links between the egg and its surrounding cells are maintained.  Using a tissue-engineered approach, we have developed an in vitro follicle growth system that supports the maturation of the enclosed oocyte, which can be fertilized and results in live, healthy and reproductively competent mice.  The goal of our program and the broader Oncofertility Consortium is to explore and expand the reproductive options available to young people facing a fertility-threatening but life-preserving cancer treatment.