Yesterday we posted a blog about the 36^th annual APHON (Association of Pediatric Hematology/Oncology Nurses) Conference being held right now in Pittsburgh, PA.  It’s an exciting time for us because not only do we have a member of the Oncofertility Consortium presenting on fertility perseveration at the conference (Barbara Lockart, MSN, RN, CPNP, CPON), but also because APHON has recently released a position statement entitled, Fertility Preservation for Pediatric and Adolescent Young Adult (AYA) Cancer Patients. The strides that have been made since the Oncofertility Consortium’s inception in 2007 are truly on display here and we couldn’t be more excited!

Nurses are often the thread connecting young cancer patients and their families to pertinent information that can sometimes be overlooked in the urgency of a cancer diagnosis and subsequent treatment planning process.  As studies have shown, fertility issues and options are often not addressed at diagnosis for several reasons (age of the patient, diagnosis, gaps in provider knowledge, etc.); however, several studies report childhood and AYA cancer patients are interested in learning about fertility preservation options, including those that are experimental.

It is APHON’s position that, “discussions regarding fertility preservation occur with all patients and families as early in the treatment trajectory as possible (prior to treatment whenever possible). These discussions should continue throughout treatment and follow-up care as patients continue to grow and develop.” Currently, many pediatric facilities do not have the resources available to offer fertility preservation in their institutions, but they have the option of partnering with reproductive or adult centers that provide fertility preservation services. Collaboration between centers is vital for a successful treatment experience for patients, families, and their healthcare team. The Oncofertility Consortium provides both patients and health care professionals with resources for locating established fertility preservation centers, as well as providing a national fertility hotline, FERTLINE, answered by a Fertility Preservation Patient Navigator who can provide you with additional information.

In addition to that, pediatric oncology nurses’ expertise may be needed to provide adult healthcare providers with information about the unique psychosocial and developmental needs of childhood and AYA oncology patients and their families. They can also be a great resource for patients and families who may not have enough information independently to inquire about specific issues such as cost, insurance coverage, success rates, and storage concerns.

As evidenced by their position statement, APHON is supporting the Oncofertility Consortium’s quest to ensure that all patients, providers, and caregivers have the ability to make informed decisions regarding fertility preservation in the face of a cancer diagnosis. Please take a moment to read, Fertility Preservation for Pediatric and Adolescent Young Adult (AYA) Cancer Patients, and learn more about fertility preservation resources nationwide.

Earlier this month fertility experts announced an important milestone for assisted reproductive technologies (ART).  Since the birth of Louise Brown in England 34 years, the first “test tube baby”, an estimated 5 million babies have been born as a result of in vitro fertilization (IVF) and similar technologies.

The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) presented their data in Istanbul, Turkey at the 28^th meeting of the European Society of Human Reproduction and Embryology based on values of IVF treatment cycles administered worldwide in 2008 and added probable numbers for the last three years.

IVF and similar treatments, such as intracytoplasmic sperm injection (ICSI), are the major forms of infertility treatment utilized when other methods have failed.   IVF and ICSI are procedures done in a laboratory setting.  During IVF, sperm is placed in a special petri dish with unfertilized eggs.  The sperm and eggs may belong to the male or female wishing to conceive or from a donor.  During ICSI, a form of IVF, sperm is directly injected into the egg.   After fertilization, the resulting embryos are transferred into the uterus of a woman or cryopreserved (frozen) for future use.

Success rates for IVF and ICSI have stabilized since 2008 at around a 32% pregnancy and live birth rate for each embryo that is transferred.

According to ICMART experts, approximately 1.5 million IVF and ICSI treatments are administered every year throughout the world.  The majority of treatments, one-third, are administered in Europe.  However, the US and Japan are the most active countries per capita.

Despite the overall success of IVF, the effectiveness of fertility treatments declines in women over the age of 32.  According to the Society for Assisted Technology (SART), a woman in her early 40s only has a 4% chance of achieving a healthy pregnancy using her own eggs for IVF.

Because of the poor success rates of IVF in women as they age, fertility experts warn against couples waiting to have children who may have a false sense of confidence for what ART can offer.

It is important to consider the IVF milestone in context.  It is currently estimated that 10% of the global population, within reproductive age, is infertile.   According to the Centers for Disease Control and Prevention (CDC), infertility affects both men and women.  In the United States alone, approximately 7.3 million women of childbearing age (15 to age 44) have difficulty getting pregnant or staying pregnant.   In the most recent CDC report, approximately 4.7 million sexually experienced men have sought fertility help in their lifetimes. Of these, 18.1% were diagnosed with male-related infertility problems.

The use of ART has doubled over the past decade in the US according to the CDC.   The current trend toward postponing the age of first pregnancy has brought attention to the natural limits of fertility.  However, there are numerous other known causes of infertility that affect both men and women including genetic abnormalities, certain diseases, such as cancers and their medical treatments, behavioral risk factors, as well as exposure to harmful environmental and occupational factors.   Although women’s infertility is given greater consideration, infertility is not solely a women’s health issue, rather a growing public health concern.

Infertility has been associated with psychological distress and can have a negative impact on quality of life in cancer survivors.  Reproductive concerns are often sited among young cancer survivors prior to, and following cancer treatment. A number of fertility preservation (FP) options are available to preserve patients’ future reproductive ability. For men, sperm banking is a clinically established method, and a relatively straightforward procedure in comparison to FP for women, which is more complex. In a new article published in the Journal of Clinical Oncology by authors Gabriela M. Armuand, Kenny A. Rodriguez-Wallberg, Lena Wettergren, Johan Ahlgren, Gunilla Enblad, Martin Ho ̈glund, and Claudia Lampic, entitled, “Sex Differences in Fertility-Related Information Received by Young Adult Cancer Survivors,” the authors investigate male and female cancer survivors’ perception of fertility-related information and use of FP in connection with cancer treatment during reproductive age.

The authors used a sample of 484 survivors diagnosed from 2003 to 2007 identified in population-based registry in Sweden. Inclusion criteria included survivors who were age 18 to 45 years at the time of diagnosis and had lymphoma, acute leukemia, testicular cancer, ovarian cancer, or female breast cancer treated with chemotherapy. Study participants were asked to fill out a questionnaire assessing their experience with FP and knowledge of FP techniques following a cancer diagnosis.

The majority of male participants reported having received information about treatment impact on fertility (80%) and more than half of the men banked frozen sperm (54%). Among women, less than half reported that they received information about treatment impact on fertility, and 14% reported that they received information about FP. Only seven women, or 2%, underwent FP.  Sex was the single most important predictor for receipt of information about FP; a man was 14 times more likely to report having received such information than a woman. The results of this study are even more interesting when you take into account that in Sweden, infertility treatment is part of the tax-funded health care system; therefore, FP is available to all patients with cancer. Nonetheless, this did not seem to have an impact on female access to FP information and services.

The results of this study suggest significant sex differences when conveying fertility-related information and the use of FP. As a result, the authors argue that there is an urgent need to develop fertility-related information adapted to female patients with cancer to improve their opportunities to participate in informed decision-making regarding their treatment and future reproductive options. In an effort to meet the needs of young female cancer patients, the Oncofertility Consortium developed educational materials to help young women and their families better understand their fertility preservation options. Read, “Sex Differences in Fertility-Related Information Received by Young Adult Cancer Survivors.”

At the Oncofertility Consortium, we stress the importance of collaboration among clinicians, basic scientists, and the humanities in an effort to ensure that cancer patients have fertility options after treatment. This is no small feat, but the emerging field of oncofertility is constantly evolving as new fertility preservation techniques are developed, existing ones are improved and the impact of gonadotoxic cancer treatment is examined. In a new article written by oncofertility researchers, Katherine E. Dillon and Clarisa R. Gracia, and edited by Jacqueline Jeruss, in the journal, Current Treatments in Oncology, entitled, “Pediatric and Young Adult Patients and Oncofertility,” the authors explore the various fertility preservation options available to pediatric and young adult patients and argue that a team approach is needed between oncologists and reproductive endocrinologists in order to provide the best outcomes for young patients.

Among the fertility preservation techniques currently available, the authors discuss options available for both males and females including lesser known options for females such as oophoropexy (relocating the ovaries out of the radiation field to protect them from exposure during treatment), and hormone replacement therapy for pre-pubertal cancer patients. Options available for males are sperm banking and testicular tissue banking for pre-pubescent males. Testicular tissue banking is still experimental and requires further scientific development.

Increasing numbers of pediatric and young adult cancer patients are surviving well into their reproductive years, therefore the authors state that clinicians need to be informed about the impact of cancer therapies on both males and females, as well as the available fertility preservation techniques for this demographic. They also maintain that it is imperative for clinicians to understand the most recent advances in oncofertility to better understand the future direction of the field and potential fertility preservation techniques that will one day be practiced in a clinical setting. To read, “Pediatric and Young Adult Patients and Oncofertility,” please click here.

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.

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.

We hope that all patients of reproductive age who are diagnosed with cancer have the opportunity to discuss oncofertility with their provider shortly after diagnosis. This conversation should include the options, risks, benefits and various outcomes of available fertility preservation techniques. Oncofertility decisions can have a big impact on a cancer patients life, both in the moment and as they move forward through treatment, recovery and remission.

One aspect of oncofertility decision-making that needs to be explored is the impact the actual conversation can have on a newly diagnosed cancer patient. This discussion may have a significant effect on patients who were previously ambivalent or not interested in having biological children.  What was not an issue in this individual’s life prior to their diagnosis may now become something with which they struggle.  It’s true that not everyone plans to have children and what you may feel in your mid-20s could certainly change as you age and your life circumstances change. Nonetheless, men and women often make a conscious decision not to have children.

Discussing fertility preservation may lead a cancer patient to struggle with a decision that was already made prior to their diagnosis because they feel it should be important to them.  A cancer patient’s journey is complex and although fertility preservation options provide so much hope and joy to some, it can be a mixed blessing for others.  According to Leonard Sender, MD in “Reading Between the Lines of Cancer and Fertility: A Providers Story,” “having children is no longer a default expectation of becoming an adult, or even of getting married.” Thus, a provider shouldn’t assume that just because a patient can have children, doesn’t necessarily mean they want to.

For a newly diagnosed cancer patient, all the decisions they make will have a big influence on their lives from the point of diagnosis onward.  It’s important for providers to consider that not all patients want fertility preservation and that these decisions may have been weighed and assessed long before the cancer diagnosis, not because the patient is focused on other aspects of their treatment. To read more about this, including a case study of a cancer patient who chose not to pursue fertility preservation, please read “Reading Between the Lines of Cancer and Fertility: A Providers Story,” by Leonard Sender, MD in Oncofertility: Ethical, Legal, Social and Medical Perspectives. 

The goal of oncofertility is to preserve the future fertility of cancer patients and ensure they have reproductive choice after they’ve finished treatment. Not all methods of fertility preservation are considered “established” techniques meaning they are viewed as experimental and must be offered under Institutional Review Board (IRB) protocols (an IRB is a committee that has been designated to approve, monitor, and review biomedical research involving humans in order to protect the rights and welfare of the research subjects).

Oocyte and ovarian tissue cryopreservation are two separate techniques that still need basic and clinical research before they can become established methods of fertility preservation. As a result, research participants are needed for the use of oocytes and ovarian tissue. This creates the question, “who is the most appropriate population to participate in investigational fertility preservation research?”

Populations who have participated in research or who have been suggested as good potential participants are: cancer patients, fertility patients, women who are already donating oocytes for reproduction and healthy research volunteers donating oocytes or ovarian tissue for the sole purpose of research.  Each group comes with their own ethical and theoretical challenges, but for the sake of time, we’ll focus specifically on cancer patients.

In the case of ovarian tissue cryopreservation, researchers rely primarily on cancer patients for ovarian tissue, allowing patients to donate up to 20% of their ovarian tissue for research purposes. According to Michelle McGowan, PhD, in “Participation in Investigational Fertility Preservation Research: A Feminist Research Ethics Approach,” there is a concern that cancer patients who participate in investigational fertility preservations studies “may raise the potential for false hope both for fertility preservation and for cancer treatment.” McGowan argues that even though cancer patients are in a position to benefit from the outcomes of the research, they are also the most vulnerable because they may not understand that a technique is still considered investigational.  This means that there is a possibility they may remain infertile after the procedure.

Nonetheless, while there are certain drawbacks associated with each potential research participant population, cancer patients are the most ideal candidates for research since they are the ones who will benefit from their outcomes the most.  Healthy research participants risk damaging their reproductive health by participating in investigational fertility preservation research whereas a cancer patient’s fertility is already at risk so participation may be the best option for preserving their future fertility.  To learn more about the ethical implications of participation in fertility preservation research, please read, “Participation in Investigational Fertility Preservation Research: A Feminist Research Ethics Approach,” by Michelle McGowan, PhD., in Oncofertility: Ethical, Legal, Social and Medical Perspectives. To learn about joining a research study involving ovarian tissue cryopreservation, contact the national FERTLINE at 866-708-FERT (3378).