Did you know that this week is National Infertility Awareness Week (NIAW)? NIAW is a movement that began in 1989 to raise awareness about the disease of infertility and encourage the public to understand their reproductive health. RESOLVE: The National Infertility Association founded this movement to:

• Ensure that people trying to conceive know the guidelines for seeing a specialist when they are trying to conceive.
• Enhance public understanding that infertility is a disease that needs and deserves attention.
• Educate legislators about the disease of infertility and how it impacts people in their state.

Infertility is a disease of the reproductive system that impairs the body’s ability to perform this basic function.  Pediatric and young adult cancer patients undergoing treatment are at high risk of having impaired fertility as a result of their disease or its treatment. Reproductive medicine provides a number of sophisticated options for assisted reproductive technologies (ART) such as egg, embryo, and sperm banking, ovarian tissue cryopreservation, and third party reproduction options (egg, sperm, and embryo donation, and gestational carrier/surrogacy) which help many people achieve parenthood.

Studies show that fertility preservation can bring hope to a patient undergoing cancer treatment, that there will be options and renewed life beyond their cancer diagnosis. Studies also indicate that individuals who do not receive fertility preservation information or treatment options following a cancer diagnosis are more likely to experience profound emotional consequences once they began to navigate family planning. While adoption and third party options make parenting possible, it does not always eradicate the feeling of loss one can suffer as a result of impaired fertility.

In support of NIAW, we ask you to help us and join the movement to increase and protect access to all family building options, and to help make fertility preservation counseling part of comprehensive cancer care in pediatric and young adult patients. For more information about your fertility options, please visit www.SaveMyFertility.org.

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.

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

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.

Oncofertility is a multidisciplinary field requiring experts from a variety of different backgrounds including endocrinology, oncology, bioethics, urology, etc., in order to provide fertility options to cancer patients.  In the oncofertility book series, each edition focuses on a specific component of oncofertility, with the 3^rd book, Oncofertility Medical Practice: Clinical Issues and Implementation, addressing the clinical aspects of fertility preservation.  The entire book culminates with a 15^th chapter, “Clinical Cases in Oncofertility,” by Clarisa Gracia, MD, highlighting the most important concepts covered throughout the book through a series of case studies. Dr. Gracia states, “Because the number of complex fertility preservation cases at any single center may be limited, there is value in providing a series of cases from multiple contributors in this book.” Each oncofertility patient is different, stressing the importance of individualized care to minimize risks and maximize outcomes.

Often when discussing oncofertility, we are talking specifically about cancer patients; however, there are other diseases that may impact fertility. Dr. Gracia sites a specific case where an 8yr old pre-pubertal girl with a history of severe sickle cell disease was advised to pursue stem cell transplantation (SCT). Studies have shown that infertility and premature ovarian failure are potential risks of this procedure. Because of that, she was a good candidate for fertility preservation if her family chose to pursue that option. Due to her age, the only viable option for fertility preservation was ovarian tissue cryopreservation and after lengthy counseling sessions, her parents agreed to allow her to participate in this experimental procedure.

Dr. Gracia highlights 2 very important points this case brings into question about oncofertility. The first being that prepubertal girls have limited options for fertility preservation. Egg and/or embryo banking is not possible before puberty, and in this particular case, because the girl was not receiving pelvic radiation, she was not a good candidate for ovarian transposition. The second issue is that more and more cancer therapies are being used to treat non-malignant diseases. These patients are often very ill and can be at greater risk for fertility preservation complications. According to Dr. Gracia, in this case, “patients with sickle cell disease may be at higher risk of vaso-occlusive crises, thrombosis, and postoperative pain.”

Learn more about this and other unique oncofertility cases in, ”Clinical Cases in Oncofertility,” by Clarisa Gracia, MD, in Oncofertility Medical Practice: Clinical Issues and Implementation.

Fertility sparing procedures which were once infrequent and under utilized, are now more commonly performed in young men and women facing a cancer diagnosis. A recent article in the February issue of the American College of Surgeons Bulletin, entitled Gynecologic Oncology Surgeons Spare Patients’ Fertility, Enhance Quality of Life,” by Jeannie Glickson discusses some of the technological advances in gynecologic oncology which have produced more favorable outcomes for young people facing a cancer diagnosis and fertility loss. Glickson talks to several heavy hitters in fertility preservation care, including Kristin Smith, Fertility Preservation Patient Navigator, and Oncofertility Consortium member Dr. Julian Schink, who maintain that it takes a multidisciplinary approach and team effort to treat young cancer patients.

One of the many things that Northwestern University is known for is pioneering collaborative fertility preservation care, oncofertility, at a time when many other institutions were treating fertility loss as a side effect of cancer treatment. According to Dr. Schink, “You need an oncologist who believes that the patients’ survival is the first priority, and you need a fertility team that respects some cancer patients’ desires to have children. You need strong players on both sides.” Specifically for these reasons, the Oncofertility Consortium was established – to respond to an urgent need for comprehensive fertility preservation care, incorporating clinicians, researchers and social scientists, all committed to ensuring that patients understand and can utilize fertility sparing technology.

Currently, patients interested in preserving their fertility may have some options that coincide with their cancer care, but other techniques not yet available to patients are being researched at the Oncofertility Consortium for potential future use. One of these techniques, a process called in vitro maturation, is performed by harvesting immature eggs from ovarian tissue strips which are cultured outside of the mother’s womb, treated with hormones until they mature and then fertilized with sperm to create an embryo. This would be particularly useful to patients who are not candidates for ovarian tissue transplantation such as leukemia patients or those with ovarian cancer.

As a result of the efforts of the Oncofertility Consortium and its members, patients can now receive comprehensive fertility preservation care at several sites across the country and internationally. At Northwestern, there has been a slight decline in the demand for fertility preservation services because patients no longer need to travel to Chicago for their treatment – they can find an institution, with the help of our Fertility Preservation Patient Navigator, in their own areas and according to Dr. Schink, “that’s a good thing.”

To read more about Northwestern’s pioneering efforts in oncofertility in Gynecologic Oncology Surgeons Spare Patients’ Fertility, Enhance Quality of Life, please click here.

Laxmi Kondapalli being interviewed by Dayle Cedars from Channel 7 news in Denver

One of the many, if not one of the most, important aims of the Oncofertility Consortium and its emphasis on fertility preservation research and clinical care, is “training the next generation.” Not only is the mission of the Consortium to improve fertility outcomes for patients undergoing cancer treatment, but it is also to ensure that future basic scientists and clinicians continue to expand current knowledge, research, clinical practice, and training in fertility preservation outcomes.  Laxmi Kondapalli, MD, MSCE, Assistant Professor of Obstetrics and Gynecology at the University of Colorado and Women’s Reproductive Health Research Scholar in the Division of Reproductive Endocrinology and Infertility is a realization of this goal. Let’s start at the beginning…

In March 2006, Laxmi was finishing up her residency training at Northwestern University in Obstetrics and Gynecology when she met Teresa K Woodruff, PhD, Director of the Oncofertility Consortium. Laxmi shared her interest in Reproductive Endocrinology (REI) with Dr. Woodruff, but expressed her desire to do basic science/bench research first, before embarking on clinical training and practice. According to Laxmi, “Meeting Dr. Woodruff changed the trajectory of my career.  She has incredible vision, particularly for someone who is not a clinician, on how to bridge science with individual care.”

Shortly after her meeting with Dr. Woodruff, Laxmi started working in the Woodruff Lab in August 2006. It was at the start of her tenure in the lab when she found out that Dr. Woodruff was one of the finalists for the prestigious National Institutes of Health (NIH) Roadmap Grant (aka, the grant that brought the “idea” of the Oncofertility Consortium to fruition). Together, they put the 1,000 page grant together over a 10 week period with help from members of the Woodruff Lab and other academics from within Northwestern and around the country. Laxmi explains, “It was being at the right place at the right time and the Oncofertility Consortium was a perfect fit for me because of my interest in REI and because it was a way for me to really see how you can translate work that we do in the laboratory to really impact clinical and patient care.”

In 2007, the Oncofertility Consortium was funded by the NIH, and Laxmi was A) not only a first-time grant writer, but a grant writer for one of the biggest grants given out (“for me, it was a valuable experience on so many levels”), B) processing and freezing A LOT of ovarian tissue in her lab work and C) navigating patients with the Fertility Preservation Patient Navigator who was receiving referrals from all over the country to do tissue freezing. By 2008, after two years in the Woodruff Lab working hands on with tissue, Laxmi was ready to embark on an REI fellowship and she had her sights set on an institution that would allow her to expand her work in fertility preservation while ideally being involved with the Oncofertility Consortium.

Stay tuned for Part 2 of the amazing, fabulous Laxmi Kondapalli success story!

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.

At the Oncofertility Consortium, we are always trying to make sure that we have the most up-to-date and accessible information regarding fertility preservation, particularly for patients. Whether we are partnering with advocacy groups to let patients know about support services available to them or we are sharing the latest research being done in fertility preservation, we want to make sure that we reach as many people as we can. One way that we work to do this is by making sure fertility preservation information shared on our partner websites is accessible to non-English speakers.

Currently, both of our sister sites, www.SaveMyFertility.org and www.MyOncofertility.org, have Spanish translations. Spanish seemed like the logical next step to creating a larger readership and expanding our reach within the oncofertility and patient community. Now we’re on to phase 2: Italian via Dormant Buds Association and website!!

Dormant Buds is an association founded based on the ideas of a gynecologist who works at a public hospital and specializes in fertility.  After contact with dozens of patients who, because of aggressive therapies, lost their ability to have children, the doctor, along with the help of a group of volunteers, designed a reference website, www.gemmedormienti.it. In the Section “Domande,” are Italian translations of the MyOncofertility.org animations. Take a look at this new website to see the latest translation!

Are you a cancer survivor? Help oncofertility researchers study and prevent treatment-induced fertility loss by joining the FIRST online fertility registry for cancer survivors!

Motherhood has long been viewed as a valued role for women, regardless of whether or not every woman is a mother or plans on being one. In all fairness, it is a defining role for many women and something that gives their lives added meaning. I can certainly understand how this could be a principle role in one’s life – I feel as though motherhood, among other things, gives my life purpose and a completeness stemming from conceiving, carrying and raising a child.

Historically, women who did not have children were viewed as unfortunate (I am referring primarily to middle class, white women). Their primary role was in the home and children were a large part of “keeping a home.” Before women entered the paid workforce, their primary job was to have and care for children. As you can imagine, women who for whatever reason were unable to bear children, suffered socially and emotionally as a result of their infertility. The idea of being complete, of being a whole woman was challenged by their childless identity.

In a new article by Sarah Rodriguez, PhD and Lisa Campo-Engelstein, PhD, entitled, “Conceiving Wholeness: Women, Motherhood, and Ovarian Transplantation, 1902 and 2004,” they explore the idea of wholeness experienced though organ transplantation, specifically ovarian tissue transplantation in infertile women.  Women began requesting medical interventions for infertility as early as the beginning of the 20^th century suggesting the “cultural resonance of pregnancy and motherhood.”  As surgical interventions to correct infertility grew in popularity, infertility was no longer seen as a “personal misfortune… [but instead] a medically treatable condition.”

In their article, Rodriguez and Campo-Engelstein argue that ovarian tissue transplantation can serve, through the act of biological reproduction, to render women whole, meaning to conceive and carry a pregnancy naturally. By utilizing case studies that span over a century, they show that the idea of wholeness embodied in biological motherhood still permeates women’s identities thus, organ transplantation that restores fertility in women helps facilitate this idea of completeness.

To learn more about this and the history of ovarian transplantation, please read “Conceiving Wholeness: Women, Motherhood, and Ovarian Transplantation, 1902 and 2004,” by Sarah Rodriguez and Lisa Campo-Engelstein. You can also find their research on fertility in, Oncofertility: Ethical, Legal, Social, and Medical Perspectives.