by Megan Carlson, Guest Blogger for the Oncofertility Consortium

My name is Megan, and I will be your guest blogger for today.

I’m a journalism graduate student who had the great pleasure of shadowing Dr. Teresa Woodruff Tuesday as part of my health and science reporting practicum.

As soon as I arrived at 8 AM, Dr. Woodruff and I hit the ground running– greeting and checking in with the entire staff, from the program managers to the researchers already diligently at work in the lab.  This daily process is part of Dr. Woodruff’s efforts to maintain open communication with the entire lab.

We next traipsed over to a large conference room, where a group of 15 mostly-female scientists were already gathered with coffee and notepads ready for the weekly staff meeting, called the “R3 Data Club.”  Dr. Woodruff insists the entire team (who are located in several different locations) meet via web conference each week to discuss developments in the lab and present their research.  This is another explicit effort by Dr. Woodruff to ensure her team acts on the same page and immerses younger team members in the mission and work of the lab.

While some of the nitty-gritty details flew over my head (my knowledge of science could probably fill a thimble), I was impressed by the engagement of the staff as they listened to and questioned postdoctoral fellow, Pam Monahan, PhD’s, presentation on interactions among signaling pathways leading to potential disruptions in follicle development (itself, a possible contributing factor topolycystic ovary syndrome).

After the meeting, we rushed off to a government relations teleconference where a group, including Sharon Green, executive director of the Women’s Health Research Institute (WHRI) and Nadia Johnson, a program manager, planned the Chicago and Springfield Women’s Health Week celebrations.  Dr. Woodruff quickly switched her hat from hard-nosed scientist, asking pointed questions to her researchers about gene signaling pathways, to politically-savvy division chief, strategizing about how to best promote gender-specific scientific research to legislators, scientists and other interest groups.

I spent the remainder of the day shadowing Dr. Woodruff as she discussed efforts to increase enrollment in the Illinois Women’s Health Registry–an initiative that seeks to overcome the lack of sex-specific scientific research by connecting female research participants and researchers— and then following program managers and researchers who introduced me to the work of the Oncofertility Consortium.

The day was an educational whirlwind.  I absorbed a flood of scientific information about infertility, fertility preservation, and the reproductive system (augmented by time I spent Monday in the reproductive fertility clinic of Dr. Mary Ellen Pavone, who works closely with Dr. Woodruff).  I also witnessed the behind-the-scenes political work, research, and coordination that function to produce the newest innovations in fertility treatment and women’s health.  It was fascinating to see all the cogs in the machine interact together to create these beneficial and progressive outcomes.

Many of you may already know about the widely popular organization, Stupid Cancer, but for those of you who are new to our blog, Stupid Cancer is the nation’s largest support community for young adult survivors of cancer. They support a global network of survivors, caregivers, providers and advocates to ensure that no young adult is unaware of the age-appropriate resources available to them. Stupid Cancer empowers young adults affected by cancer through innovative and award-winning programs and services, including Stupid Cancer Happy Hours, the Stupid Cancer Show, and the annual OMG! Cancer Summit for Young Adults.

The annual OMG! Cancer Summit for Young Adults is the premier oncology conference and social networking event for the young adult cancer movement. A pivotal healthcare event, OMG! is one of the largest gatherings of young adult patients, survivors, caregivers, professionals and advocates in the world. The event inspires thousands to get organized, build community and unite as one to drive change. In April, Stupid Cancer hosted its sixth OMG! Cancer Summit in Las Vegas, NV, and attracted over 600 attendees. As one would expect, Stupid Cancer makes the weekend-long event not only informative but also FUN, with events such as an ice cream social, and Stupid Cancer pub trivia.

Over the last few years, members of the Oncofertility Consortium have attended OMG! to help young survivors understand their fertility options and provide resources and pertinent information to young adults whose fertility may have been affected by their cancer treatment. This year, Consortium member, Laxmi Kondapalli, MD, MSCE, moderated two breakout sessions entitled, “Fertility: Rights & Options With, Through, And Beyond Care.” Dr. Kondapalli served as the clinical expert and reproductive health specialist alongside Alice Crisci, advocate and Founder of Fertile Action, and Jennifer Rockman, ovarian cancer survivor.

The framework of their session revolved around all the different routes to parenthood available to young cancer survivors, including banking eggs, embryos, ovarian tissue, and semen; using a gestational carrier; and pursuing adoption. Dr. Kondapalli stated that the overwhelming theme that evolved from the sessions was the lack of information presented to newly diagnosed cancer patients regarding the potential impact on their fertility. Attendees were eager to learn about the different tests available to gauge fertility, such as ovarian reserve testing for women and semen analysis for men. They also wanted to learn more about their fertility options following cancer treatment and, specifically, how their treatment may have impacted their fertility. Participants left armed with information and resources, and even Dr. Kondapalli’s personal email address, should they need her clinical expertise at any point in their fertility journey.

To learn more about your fertility options, visit SaveMyFertility.org, or contact us at 1.866.708.FERT (3378).

There are an estimated 13 million cancer survivors living in the US today, with projected growth to 18 million by 2020. As a result, many healthcare groups and cancer centers are not equipped to address their growing survivor populations. Stemming from this need for quality after care, researchers from the University of Kansas (KU) developed Cancer Survivorship Training (CST), an eLearning solutions provider, to help improve the lives and well-being of cancer survivors by educating and training the healthcare professionals that care for them.

CST online and community courses are designed to increase education, knowledge and skills about survivorship care through theory-based and practical continuing education online curriculum and mobile based learning. The training also provides essential tools for developing and sustaining formal survivorship programs, including oncofertility resources. The Oncofertility Consortium partnered with researchers at KU to help develop CST’s oncofertility course, providing fertility preservation education and options. As studies have shown, fertility is an important factor in many young cancer survivors quality of life following treatment, thus educating patients about their reproductive options is a critical component of comprehensive cancer and survivorship care.

Lead developer of CST, Jennifer Klemp, PhD, MPH, is an Assistant Professor in the Department of Internal Medicine at the KU. Dr. Klemp has a strong interest in patients’ quality of life issues following cancer treatment and is the Director of Cancer Survivorship at KU Cancer Center. She designed CST to deliver continuing education to health care providers actively involved in the care of cancer survivors, including; physicians, oncology nurses, mid-level practitioners, allied health professionals, and practice administrators.

CST emphasizes the importance of post-treatment survivorship care as well as the opportunity for education and prevention of late and long-term effects, including infertility, from the time of diagnosis.  The multi-disciplinary approach provides the healthcare provider with information to care for the needs of cancer survivors from the time of diagnosis and develop skills focusing on essential elements to the delivery of survivorship. To learn more about Cancer Survivorship Training, please visit www.cancersurvivorshiptraining.com or click here.

By Danielle Alyce Fanslow, Francesca Duncan, and Kate Timmerman

There are several methods of fertility preservation open to female cancer patients who wish to start a family after treatment including cryopreservation of oocytes, embryos and ovarian tissue. Cryopreservation is a method of preserving biological material by storing it at extremely low temperatures. Choosing a  fertility preservation method is highly patient-specific and depends on factors such as patient age, the availability of a partner, and/or the sensitivity of the tumor to hormones.  A good option for pre-pubertal patients and patients who must undergo treatment as soon as possible after diagnosis may be cryopreservation of ovarian tissue.  However, current techniques for tissue cryopreservation may be improved as only 22 successful pregnancies have resulted from this method [1].

A group of Oncofertility researchers at the Oregon National Primate Research Center (Ting, Yeoman, Campos, Lawson, and Zelinksi) together with cryopreservation experts (Mullen and Fahy) have been developing new methods for cryopreserving ovarian tissue with the focus on preserving follicle health and quality.  Findings from their most recent work was published in the journal Human Reproduction in an article entitled “Morphological and functional preservation of pre-antral follicles after vitrification of macaque ovarian tissue in a closed system.”  This work provides insight that may lead to improved clinical protocols for ovarian tissue cryopreservation.

The goal of cryopreservation is to minimize injury to cells from the freezing process while limiting the toxicity of cryoprotective agents [2]. The current protocol for ovarian tissue cryopreservation involves slowly freezing the tissue with low concentrations of cryoprotective agents to avoid ice crystal formation inside the cell but to allow ice formation outside the cell [1]. However, ovarian tissue has an abundance of cell types and important extracellular material making it more complex to freeze compared to isolated cells. Vitrification is a method of cryopreservation that can avoid ice crystal formation inside and outside of the cell by quickly freezing the tissue with a high concentration of cryoprotective agent [3].   This method holds tremendous promise in the setting of fertility preservation and has already been applied successfully and routinely to egg and embryo freezing. However, researchers must optimize ovarian tissue vitrificaiton before it can be used in a clinical setting.

As the amount of human ovarian tissue available for research is limited, the Zelinski group used a non-human primate model to study several variables in the vitrification process including the type and concentration of cryoprotective agent used, the cooling rate, and the warming rate.  As a means to assess the quality of the tissue in each experimental condition, the researchers isolated ovarian follicles from the tissue and used them for encapsulated in vitro follicle growth (eIVFG) – a technique that this group had previously applied successfully to the non-human primate.  The researchers then monitored follicle health, diameter, and hormone production.   Using these techniques and assays,  the Zelinski group was able to determine a set of variables that resulted in the healthiest ovarian tissue. Through the findings by the Zelinski group, the field is one step closer to developing a standard protocol for ovarian tissue vitrification that can potentially result in a high rate of successful pregnancies.

References:

1. Ting AY, Yeoman RR, Campos JR, Lawson MS, Mullen SF, Fahy GM, Zelinski MB. Morphological and functional preservation of pre-antral follicles after vitrification of macaque ovarian tissue in a closed system. Hum Repro. 2013. Feb 20^th Ahead of Print.
2. Pegg DE. The history and principles of cryopreservation. Semin Reprod Med. 2002 Feb;20(1):5-13.
3. Pegg DE. The role of vitrification techniques of cryopreservation in reproductive medicine. Hum Fertil (Camb). 2005. Dec;8(4):231-9.

Fertility preservation in young cancer patients has come a long way in the last decade, as both patients and the medical community have galvanized to improve the information and reproductive technologies available surrounding oncofertility. In response to the increased likelihood of young men and women losing their fertility due to cancer and its treatment, the American Society of Clinical Oncology (ASCO) published fertility preservation guidelines for clinicians to follow when treating young cancer patients.  In recent news, the American Society for Reproductive Medicine (ASRM) announced that egg freezing would no longer be considered an “experimental” fertility preservation technique, making it easier for cancer patients to receive insurance coverage if they choose egg freezing as their method of fertility preservation. These developments stemmed from substantive evidence that fertility preservation among cancer patients facing fertility impairing treatment is an ethically sound practice, and in a new article entitled, “Lives in the Balance: Women With Cancer and the Right to Fertility Care,” by Clarisa Gracia, MD, and Jacqueline Jeruss, MD, the authors share a reproductive specialist’s view of oncofertility counseling that is important for the practicing oncologist to consider.

First, by discussing fertility preservation with their patients, oncology providers are allowing them to make informed decisions about their reproductive futures. To date, there is no evidence indicating that by discussing oncofertility with patients, it compels them to participate; rather, it demonstrates that they are receiving comprehensive cancer care, which includes survivorship care. In fact, according to the authors, “evidence indicates that patients with cancer who receive counseling about fertility preservation experience less long-term regret than those patients who do not receive counseling, even if the patients choose not to pursue fertility preservation.” Sharing this information with patients may also increase patient confidence in the medical community if they see that they are being treated as a whole person and not just a cancer diagnosis.

Next, an ethical concern raised surrounding oncofertility centers on the disposition of embryos and tissue, specifically as an increasing amount of biologic material is cryopreserved as a result of fertility preservation. Nonetheless, the authors argue that the burden on society will be minimal, since most cryopreserved material comes from healthy, infertile patients actively trying to conceive. They also claim that by striving for advances in fertility preservation options, fewer patients will choose to freeze embryos because they will have other options, reducing the potential ethical issues surrounding embryo ownership.

Finally, the authors address the argument that the allocation of funding and research dedicated to fertility preservation could be better utilized in other medical fields, since it affects such a small percentage of people. Gracia and Jeruss state, “although this may have been a legitimate concern in the past, the research accomplished under the auspices of fertility preservation thus far has furthered the understanding of reproductive physiology, leading to significant breakthroughs in the field of reproductive medicine.” It’s also important to note that these breakthroughs have a ripple affect and can lead to improved fertility options for healthy infertile patients, improved contraception methods, and the conservation efforts of endangered species. Read “Lives in the Balance: Women With Cancer and the Right to Fertility Care,” by Clarisa Gracia, MD, and Jacqueline Jeruss, MD, to learn more about reproductive medicine and the ethical concerns surrounding oncofertility.

By Yogesh Makanji

In an Australian first, Monash IVF specialists reported achieving pregnancy in a 43-year-old woman after transplanting her cryopreserved ovarian tissue. Professor Gab Kovacs, Director of Monash IVF, Melbourne Australia, reported that his team had restored fertility in a woman by transplanting her cryopreserved ovarian tissue, following which she resumed natural ovulation and was six weeks pregnant. In 2005, this woman had ovarian tissue cryopreserved prior to commencing breast cancer treatment. If successful pregnancy ensues then in another Australian first, this would be the first Australian baby born from transplanted ovarian tissue and 20^th in the world. In light of their success, Professor Kovacs went on further to recommend ovarian tissue cryopreservation as a reliable, cheaper and easier method of preserving fertility of cancer patients; compared to cryopreserving eggs or embryos.

Adding to the commentary, Dr. Lyndon Hale, Medical director of Melbourne IVF Clinic, Australia reported that they had successfully transplanted ovarian tissue in patients and only one had become pregnant. However, she had subsequently miscarried. Dr. Hale also sees the benefits of this technique for preserving fertility of cancer patients.

Another trend emerging from this article is the use of cryopreserved ovarian tissue as a way of preserving a women’s fertility indefinitely.  In addition, it has been suggested that ovarian tissue transplant in peri-menopausal women may delay or offset symptoms associated with menopause; hot flashes, osteoporosis, weight gain, etc. Neither Professor Kovacs nor Dr. Hale is advocating the use of ovarian tissue transplant for this purpose. Hormone replacement therapies are available to alleviate some of these menopausal symptoms.

Ovarian tissue cryopreservation is providing many young cancer patients the opportunity to preserve their fertility. Chemo and radiotherapy may adversely affect a women’s future fertility. Thereby, cryopreservation of ovarian tissue prior to cancer treatment protects a women’s future fertility.

Source: The Age http://www.theage.com.au/national/health/science-beats-fertility-clock-20121128-2aev2.html

Oncofertility is an interdisciplinary field at the intersection of oncology and reproductive science. While those two fields make up the breadth of this discipline, it only touches the surface of what future clinicians need in their academic repertoire to successfully navigate this field.  In “Preparing an Interdisciplinary Workforce in Oncofertility: A Suggested Educational and Research Training Program,” in Oncofertility Medical Practice: Clinical Issues and Implementation, author Christos Coutifaris, MD, PhD, argues that the education and training of oncofertility professionals should involve, “oncology, pediatrics, reproductive science and medicine, biomechanics, material science, mathematics, social science, bioethics, religion, policy research, reproductive health law, and cognitive and learning science.”

Going forward, the National Institute of Health (NIH) has an ambitious agenda requiring multifaceted scientists and clinicians properly trained in both research and medicine. Ideally, physicians would be trained not only clinically, but they would also be prepared for investigative careers. According to Dr. Coutifaris, “the ultimate goal is to prepare reproductive endocrinologists, pediatric and adult oncologists, and surgeons, for investigative careers that focus on the reproductive, endocrine, and fertility needs of cancer patients and survivors.” By doing so, oncofertility specialists would be at the forefront of translational medicine, further benefiting the reproductive outcomes of cancer patients.

Dr. Coutifaris presents a well-laid training program for future oncofertility specialists. This includes establishing an executive steering committee responsible for the overall direction of the program, an advisory board to aid and shape the content of the program, an expert and diverse group of faculty members to mentor trainees, and research training, specifically focusing on the human oocyte. There should also be a comprehensive program evaluation in place to monitor the success of the program.

Having a dedicated oncofertility program in place to ensure that fertility options for young cancer patients is factored into their cancer care, is imperative.  Training and educating the next generation of oncofertility specialists will lay the foundation for improved cancer care and reproductive outcomes. Read, “Preparing an Interdisciplinary Workforce in Oncofertility: A Suggested Educational and Research Training Program,” to learn more about educating the next generation of oncofertility specialists. Participate in our new series of CME-accredited Virtual Grand Rounds to increase communication and education among healthcare providers.

We are happy to be hosting Helen Picton, BSc, PhD, FSB for her Virtual Grand Rounds presentation tomorrow, October 25th, 2012, at 10 AM Central Time, entitled, “From Basic Science to Clinical Application- the Facts and Future of Ovarian Cryopreservation for Fertility Preservation.”  Dr. Picton’s work focuses on characterizing ovarian follicles during growth and maturation, and the developmental competence of in vitro oocytes, and will inform her discussion of the research behind ovarian tissue freezing and how to apply that technique in a clinical setting now, and as we move forward with advancements in the reproductive field.

Receive free CME’s tomorrow by participating in tomorrow’s Virtual Grand Rounds (VGR) with the Oncofertility Consortium. VGR’s are live videoconferences with experts in the fields of reproduction, cancer, and oncofertility. They provide researchers, clinicians, and others the opportunity to hear emerging research findings from anywhere across the globe and participate through a live videochat. This year, the Oncofertility Consortium is also able to offer free CME credits to health care providers through these live virtual events.

At 10 AM, Central Time, click here to watch Dr. Picton present her Virtual Grand Rounds.

Members of the Oncofertility team were invited to guest post on the NIH Team Science Toolkit blog and we are happy to announce that the blog was just posted. Read the beginning of the blog below.

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Over the past decade, federal funding has played a key role in encouraging the advancement of interdisciplinary team science.  The 2007 Roadmap for Medical Research Initiative, which was created by the National Institutes of Health, is one such example.  The Initiative was designed to bring diverse experts together to solve extremely challenging public health problems, from obesity to mental illness. The Initiative launched a number of programs, including the Oncofertility Consortium (oncofertility.northwestern.edu). The Consortium is an interdisciplinary team of researchers and clinicians created with the goal to expand the reproductive future of young cancer survivors through advanced research and improved clinical care. Given that 10% of cancer patients are diagnosed during or before their reproductive years and that survivorship rates exceed 80%, fertility is a significant survivorship consideration for the 135,000 patients under age 45 who are diagnosed each year and for their families. The subfield of oncofertility (at the intersection of oncology and reproductive medicine) was launched with federal financial support, and the participation of scientists, clinicians, social scientists, humanities scholars, and others to address this issue…Read the rest of this blog on the Team Science Toolkit blog.

The more we understand about our genes, the more we understand genetic diseases and eventually, how to best treat them.  The recent efforts of a nationwide consortium of researchers suggests that the origins of the type of breast cancer a patient is diagnosed with may inform the most effective course of treatment.

The study, published in Nature on September 23^rd, is one of the most comprehensive studies of breast cancer to date.  The study revealed that the gene expression profile for one of the most aggressive forms of breast cancer, basal-like carcinoma, is more similar with ovarian tumors than with other breast cancer subtypes.

The four main breast cancer subtypes: Luminal A, Luminal B, HER2, and basal-like, were confirmed and characterized by leading researchers at several institutions as part of The Cancer Genome Atlas Network.  The study is part of an NIH funded initiative with the Cancer Genome Atlas Network to build maps of genetic changes in common cancers.  While most historical studies of breast cancer have utilized one or two methods to analyze and characterize the gene profiles of breast cancers, six parallel technologies were used for this study to examine mutations and defects in DNA, RNA, and proteins.  Consortium scientists analyzed tumors from 507 women, with nearly 350 tumors being analyzed using all six technologies.

Basal-like breast tumors are also known as “triple negative” tumors.  Triple-negative tumors lack receptors for the hormones estrogen, progesterone, and human epidermal growth factor 2 (HER2), which are the gene targets of a number of approved chemotherapies such as Tamoxifen and Herceptin.  However, no receptor hormones means no drug targets.  Basal-like tumors are a considered high-grade, indicative of an abnormal appearance of the cells under a microscope and a tendency to grow and multiply more rapidly. These tumors have a poor prognosis for treatment and are more prevalent in younger women, women with BRCA1 and BRCA2 mutations, and women of African-American descent.

Currently, basal-like breast tumors are treated like most other breast cancers, using similar chemotherapy strategies.  However, basal-like breast tumors are aggressive and not been shown to respond well to therapies targeting hormone receptors or to standard chemotherapy regimens.  Consortium researchers found that each subtype could be identified by unique genetic markers, and that mutations in only three genes, TP53 (tumor suppressor gene 53), PIK3CA and GATA3, occurred in common with all four subtypes.  These findings suggest that not all breast tumors are alike and therefore, may not respond similarly to the same chemotherapy regimens.

Consortium scientists found that basal-like and HER2 tumor subtypes were characterized by the highest mutation rates.  Basal-like tumors shared common features with ovarian tumors and lung cancers, including high rates of TP53 mutations, BRCA1 inactivation, and a loss of RB1 and cyclin E genes, which are known to promote genome instability.  The study shows that 80% of basal-like tumors had TP53 mutations and approximately 20% also have mutations in the BRCA1 or BRCA2 genes. Mutations in the TP53 gene have been strongly linked to poor treatment outcomes, while BRCA1/2 mutations are known to increase breast and ovarian cancer.

A growing body of research suggests that tumors should be characterized and treated based on the presence of abnormal genes and abnormal gene expression profiles rather than on their location in the body.  Consistent with these findings, consortium researchers found that basal-like tumors are genetically more similar to ovarian tumors based on their genetic profiles.  Ovarian tumors are also characterized by a high frequency of TP53 mutations, widespread genomic instability and share other gene mutations in common with similar frequency.   These results give biologic reasoning to consider the potential benefits to patients with basal-like tumors to be treated with platinum-based chemotherapies currently approved for the treatment of ovarian cancer or PARP inhibitors which target tumors with BRCA1 and 2 defects.

Clinical trials are a lengthy but necessary step to determine if platinum-based compounds, currently used to treat cancers elsewhere in the body, and/or PARP inhibitors hold promise for patients diagnosed with basal-like breast carcinoma.  For now, this study offers much needed insight into the origins of the most aggressive form of breast tumor and promising possibilities for future personalized treatments.