Blogs

By Marla Paul

A new gentler chemotherapy drug in the form of nanoparticles has been designed by Northwestern Medicine® scientists to be less toxic to a young woman’s fertility but extra tough on cancer. This is the first cancer drug tested while in development for its effect on fertility using a novel in vitro test.

The scientists designed a quick new in vitro test that predicts the toxicity of a chemotherapy drug to fertility and can be easily used to test other cancer drugs in development as well as existing ones. Currently the testing of cancer drugs for fertility toxicity is a time and resource intensive process.

“Our overall goal is to create smart drugs that kill the cancer but don’t cause sterility in young women,” said Teresa Woodruff, a co-principal investigator of the study and chief of fertility preservation at Northwestern University Feinberg School of Medicine. The paper was published March 20 in in the journal PLOS ONE.

The scientists hope their integration of drug development and reproductive toxicity testing is the beginning of a new era in which chemotherapy drugs are developed with an eye on their fertotoxity (fertility toxicity). As cancer survival rates increase, the effect of cancer treatments on fertility is critically important to many young patients.

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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.

Alice Crisci, founder of Fertile Action, and contributing author to the fourth upcoming Oncofertility book, Oncofertility Communication: Sharing Information and Building Relationships across Disciplines, has been in the news recently for her vocal opposition to a California bill that prohibits women from getting paid for donating their eggs for medical research. Now at 11 weeks pregnant, we asked her to tell to share her cancer story with us, including her advocacy and policy work.

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Q: Tell us a little bit about how you got involved in cancer and fertility advocacy?

I was diagnosed with breast cancer in 2008, and launched my non profit, Fertile Action, that same year. In 2009, I took my board to the National Breast Cancer Coalition (NBCC) annual conference. We were all shocked at the exclusionary policies of the NBCC towards young women, but had the good fortune of meeting with congress woman, Debbie Wasserman Shultz, about the Early Act (the Public Health Service Act to increase awareness of the risks of breast cancer in young women and provide support for young women diagnosed with breast cancer). We spent a day running around the Capitol lobbying for her bill, and I saw firsthand how I could be an influencer in setting or opposing policies. Since then I have worked at the California state level, and federal level on meaningful initiatives that support young adult cancer survivors.

Q: Based on your cancer diagnosis and treatment plan, how long were you advised to wait to start a family after you completed cancer treatment?

My treatment was very long – almost 3.5 years before I was taken off all medications. 2.5 years of that was spent in medical menopause so I was not producing hormones that could support a pregnancy. I started trying naturally about a year later and had three chemical pregnancies/early miscarriages. I finally decided to use the “totsicles” I created with a sperm donor when I was diagnosed. My first transfer was a success, and on my five year cancerversary I heard my baby’s heartbeat for the 2nd time and balled my eyes out! My doctor approved me going off tamoxifen early because of the additional treatment of medical menopause. It’s such a toxic medication that he recommended I wait six months before trying to get pregnant. That six month wait turned into almost a year before having my first pregnancy loss.

Q: How has your cancer survivorship care influenced your fertility story? 

Had anyone told me when I was first diagnosed that I would be in some form of treatment for over 3 years, I wouldn’t have started! I thought it was surgery, chemo and done. Six months of my life, and that was that. I was very sick from all the treatment for so many years, then dealing with so many side effects after ending treatment, My fertility plans continued to get delayed. I was also financially devastated from going through cancer, and it took a long time to start rebuilding to the level where I thought I could afford a family.

Q: You have been a vocal critic of the CA bill prohibiting compensation to women for donating their eggs to medical research. How do you think a reversal of this bill would impact cancer care?

To date, we have focused more on quantity, but there are ample women like me who have eggs left that don’t produce a live birth. If we can study chemo’s impact on quality then we can also discover new interventions for preventing that impact. Fertility preservation is still prohibitive for many patients so we need to keep innovating in other areas. California’s current bill prevents any of the amazing researchers in this great state from conducting this type of study. Institutional Review Boards (IRB), especially at the university setting, do a great job of overseeing ethics, and preventing exploitation of vulnerable populations. In many cases IRB’s are much more restrictive than legislation!

To learn more about your fertility options following a cancer diagnosis, please visit www.SaveMyFertility.org.