This Sunday is Mother’s Day. Many of you may have plans with your family doing your best to ensure that the day is celebrated, and the women in your life who fit this profile, past and present, are honored in some way. It goes without saying that being a mom is rewarding, but it can also have its challenges so it’s only right that we have one calendar day each year designated to showing gratitude for motherhood. That being said, what constitutes motherhood, comes in all different shapes and sizes…

In 2008, at age 26, Melissa Brown was diagnosed with breast cancer. Cancer was no stranger to her family – her mother had been battling breast cancer on and off since she was two years old.  Melissa had been giving herself breast exams since she was 12 so when she found the pea-sized lump in her breast, she knew something was amiss.  Within days of finding that lump, she was diagnosed with breast cancer and would eventually undergo chemotherapy (side by side with her mother) and have a bilateral mastectomy. Thankfully in Melissa’s case, her oncologist, the same one who had been treating her mother for 20 years, encouraged her to preserve her fertility before she began treatment for her cancer. Following his advice, she began taking fertility drugs to produce multiple eggs for fertilization, and with the help of her fiancée Steve, banked 4 embryos prior to cancer treatment.

Melissa’s cancer treatment was filled with highs and lows – she married Steve, and lost her mom to cancer. Following treatment, she wanted to have a baby with her new husband, however her oncologist recommended that if she wanted to have children, she use a gestational carrier or surrogate due to the possibility of cancer recurrence. Melissa was at a crossroads, until her younger sister Jessica, 25 at the time, said that she would carry Melissa’s babies for her. Melissa realizing the breadth of Jessica’s kindness and the responsibility she would undertake, agreed, but only after lengthy discussions and a little bit of soul searching.

Months earlier, Melissa and Steve banked their embryos at UPenn with the assistance of Oncofertility Consortium member, Dr. Clarisa Gracia. Now, under different circumstances, Melissa (with her sister in tow) was meeting with Dr. Gracia to discuss surrogacy. Dr. Gracia recognized that Jessica was not the ideal surrogate – she was young and had not given birth before, having no children yet. Complications could arise from a pregnancy, potentially leaving Jessica unable to have her own children one day. According to Gracia, “I was very concerned from the get-go, [but] she just really wanted to do this for her sister.”

In 2010, Dr. Gracia transferred two of the 4 embryos into Jessica’s uterus – both implanted, resulting in twins. Nine months later, Melissa and Steve were parents to Brendan and Gabriella via C-section. This Mother’s Day, as the twins are learning to walk, Melissa and Jessica will celebrate their mother’s memory and the bond that they have, which has only been strengthened through this journey. Read Melissa and Jessica’s entire story on Time.com, by author Bonnie Rochman, entitled, “My Sister, My Surrogate: After Battling Cancer, One Woman Receives the Ultimate Mother’s Day Gift.”

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.

A newly released memoir from cancer survivor, Michelle Whitlock, delves into her experiences with HPV, cervical cancer, fertility preservation and love in a book that you will read from start to finish in one sitting. How I Lost My Uterus and Found My Voice is an honest and (very) candid account of what her 20s looked like, replete with all the things you might expect out of a 20 something: falling in love, travel, finding oneself, heartbreak, etc… Now throw in a whole lot of cancer, embryo banking, chemo, radiation, incontinence and a play by play of “getting your groove” back after your vagina has done a total 180 from what it once was, and you have a very unique story.

At the age of 26, Michelle found out that she had HPV, a sexually transmitted virus infecting 50-60% of sexually active people. Shortly after finding this out, she received the biggest blow of her life – she was diagnosed with invasive cervical cancer.   From that point forward, Michelle made it her mission to ensure her treatment plan was something that worked for her, meaning not only was she going to do everything in her power to beat the cancer, but she was also going to fight just as hard to preserve her fertility for her “maybe babies” one day. At a time when little information was offered regarding fertility preservation, Michelle had to take the reins into her own hands and become her best advocate. Unsure of whether or not she even wanted children, she was not going to let cancer take her options away.

After successfully beating cancer the first time around and avoiding a total hysterectomy by electing to undergo an experimental surgery to eradicate the disease, she was diagnosed with the same cancer just a few years later.  She was left with no other option except chemo, radiation and a total hysterectomy, but as a result of her research and commitment to finding the best care possible, she found a doctor who understood the importance of her fertility just as much as she did. Thus, her “maybe babies” came to fruition and were put on ice for a date… TBD.

I don’t want to giveaway any more of her story, but this is a must read for cancer patients, survivors, caregivers or anyone that wants to know what cancer, fertility issues, and sexuality really look like. I highly recommend it for its rawness and the openness with which she shares her experience. Nothing is sugar-coated in these pages – Michelle talks about things that will make you blush from time to time, but they’re the things no one talks about, and should be.  It’s an inspirational story that reads like a conversation with your girlfriends so if you haven’t already, please pick up a copy of How I Lost My Uterus and Found My Voice, by Michelle Whitlock, and see what I have been raving about!

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.

Earlier this year, I blogged about a young woman and volunteer with Bright Pink, Kristin Nelson, who had preventative ovarian removal after she tested positive for BRCA1. BRCA1 and BRCA2 genes are a class of genes otherwise known as tumor suppressors, and a mutation of these genes has been linked to a significantly increased risk for the development of breast and ovarian cancer at an early age. Kristin had enough of a family history of breast and ovarian cancer to want to take measures to protect herself, should she develop cancer as well. Knowing this would impact her fertility, she decided to bank eggs and embryos prior to her oophorectomy.

Luckily, Kristin knew enough about her fertility risks with BRCA1 to pursue fertility preservation prior to her surgery, but not everyone has the same experience. In an attempt to raise awareness and education about fertility preservation in high-risk young women, Bright Pink has partnered up with the Oncofertility Consortium to present, Fertility Preservation for High-Risk Young Women National Teleconference on November 15^th at 8:00EST. The teleconference seeks to help high-risk young women understand the basics of fertility concerns, their options for fertility perseveration and parenthood, and provide valuable resources that are available. Leading the information session will be Oncofertility Consortium Director, Teresa K Woodruff, along with Kristin Nelson and Melissa Synder from Bright Pink. To learn more about how you can participate in this teleconference or to register, please visit www.bebrightpink.org.

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!

At the Oncofertility Consortium, it’s no secret that we believe in the importance of fertility preservation for young cancer patients – it’s what we’re all about. Research, education, advocacy, clinical care, you name it, we’re on top of it and constantly looking for ways we can improve the fertility outcomes of cancer patients. There is a lot that goes into this kind of work, and we receive a tremendous amount of support from the greater cancer community, individuals, academic institutions, clinicians, etc… In other words, it takes a village, and one of those villagers just so happens to be Playboy, Inc. Let me explain…

Men hoping to preserve their fertility before undergoing treatment for cancer or another fertility-threatening disease can cryopreserve, or freeze, their sperm. This is the most established fertility preservation method for males and samples are obtained in what is called a “male production room.” Before going into the room, the men are supplied with a “visual tool” to help facilitate this process and in general, a Playboy magazine is what they get.

Due to the fact that many of our male cancer patients are immuno-compromised, meaning that their immune systems are in a fragile state, they need to be provided with a visual tool that is unopened and still wrapped in plastic. This ensures that their health is not compromised in any way.  Hey, it’s giggle-inducing I know (I’m smiling as I type this post up), but it’s still a link in the chain – a part you may not give much thought to.

Which leads me to this – a big thank you to Playboy, Inc for generously donating a years worth of magazines to the Oncofertility Consortium for our male cancer patients undergoing fertility preservation! Not only are they helping out our patients, but they’re also demonstrating their belief in the importance of oncofertility by choosing to support us among the numerous opportunities they have to donate to non-profit organizations. Sometimes, it’s the little things that count the most!

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!

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. 

Religion and oncofertility strive to maintain an open and mutually beneficial dialogue in order to meet somewhere in the middle.  Oddly enough, science and theology often overlap, albeit outside of the lab, so it’s important to bridge any gaps that may exist in the current debate surrounding reproductive technology and certain faiths.  The benefits that fertility preserving techniques can have on the quality of life of a cancer patient needs to align with their religious beliefs if that proves to be an issue in their decision-making process.

One of the many religions that are open to the relationship between science and faith is Judaism. Judaism, specifically Orthodox Judaism, has many different movements that adhere to common principles.  One key feature that these different movements share is their dedication to both the written and the oral Torah. The Torah refers to the first 5 books of both the Jewish and Christian bible and Judaism teaches that the Torah is of divine origin and represents the word of G-d. (In this blog, we will practice the Jewish custom of spelling G-d as a measure of respect for the religion, which comes from the tradition of never spelling the Hebrew equivalent of the name).

The Torah contains 613 miztvot, or commandments, with the first stating to “be fruitful and multiply.”  One of the hallmarks of orthodoxy is that it encourages intellectual questioning in order to live morally and ethically in a way that G-d requires of his followers. Thus, one could presume that for an Orthodox Jew facing a cancer diagnosis, it is a religious obligation to preserve their fertility and their ability to bear children – that science and religion are not in fact in conflict, but working together to sustain G-d’s commandment, “be fruitful and multiply.”

According to Sherman Silber, MD, in “Judaism and Reproductive Technologies,” even the  “strictest orthodox Jewish theology maintains that the Torah is not in conflict with reproductive technologies…for cancer patients of reproductive age, Jewish law ultimately requires every effort to safeguard the possibility for future parenthood.” This even holds true in some cases of gamete donation, specifically ovarian tissue cryopreservation. In Judaism, religious leaders may not encourage egg or sperm donation because their use may be seen as breaking the marital bond; however, ovarian tissue donation is allowable because “the egg is being ovulated within the body of the intended mother.”

Many followers of Judaism agree that mankind needs to find it’s way to G-d through intellectual reasoning and mindful conflict resolution, in order to live their lives the way G-d intended. From that we can deduce that Judaism, although not aligned with all fertility preservation techniques, engages in an open and thoughtful dialogue with the science of oncofertility To learn more about Judaism’s relationship with reproductive technologies, please read Sherman Silber’s, “Judaism and Reproductive Technologies,” 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).

Mary Zelinski, PhD finishes her reports from the annual meeting of the Society for Cryobiology held from Corvallis, Oregon with a final blog about the keynote talk from Alison Ting, PhD. In this post, she relay’s Dr. Ting’s findings about advancing ovarian tissue cryopreservation techniques in one species of monkey.

________

By Mary Zelinski, PhD-Dr. Alison Ting, Post-doctoral Fellow, Division of Reproductive Science and Development, Oregon National Primate Research Center, wound up this interesting session with an update on “Optimization of Rhesus Macaque Ovarian Tissue Cryopreservation.”  She outlined the importance of ovarian tissue cryopreservation as an important option for fertility preservation in prepubertal cancer survivors or those without partners.  She also pointed out that in vitro development of follicles from cryopreserved ovarian tissue was an important method of fertility preservation that would not transmit cancerous cells back to the patient, a current risk of tissue transplantation in patients with blood-born cancers.

Dr. Ting summarized various conditions that she and her colleagues examined to develop cryopreservation of the ovarian cortex in a closed system using high security tissue straws to circumvent the clinical issue of cross-contamination between samples in open systems during liquid nitrogen storage.  She determined the threshold cryoprotectant concentration for vitrifying solutions in straws, compared vitrification solutions containing various concentrations of permeating cryprotectants, such as glycerol and ethylene glycol, in the presence or absence of nonpermeating cryoprotectants (with awesome names like super-cool X-1000, polyvinylpyrrolidone K12 and supercool Z-1000, PXZ) and determined the time needed for vitrification of samples at various temperatures (4 degrees Celsius, room temperature, and 37 degrees Celsius).  She reported preservation of both follicular and stromal morphology (based on histology), and noted that the addition of the non-permeating PXZ cyroprotectants preserved not only primordial and primary follicles, but also secondary and multilayered follicles. In addition, growth, survival and antrum formation of secondary follicles derived from thawed tissue cryopreseved with PXZ polymers was achieved using an encapsulated, 3-dimensional culture system.

Through careful and systematic experimentation,Dr. Ting identified a vitrification protocol for macaque ovarian tissue in a closed system using 54% cryoprotectant in the presence of PXZ polymers with gentle cooling and warming.  Vitrification of ovarian tissue in a closed system with minimal tissue toxicity can be achieved with effective dehydration and cryoprotectant penetration, which are tissue- and cryoprotectant-specific and also dependent on cryoprotectant exposure time and temperature.

Efforts continue to optimize the 3D encapsulated follicle culture system to yield mature oocytes derived from cryopreseved follicles, develop methods for vitrification of individual secondary follicles in closed systems, and examine follicular function in vivo following heterotopic transplantation of ovarian cortex in macaques.  This is the first demonstration of vitrification of primate ovarian tissue in a closed system and offers a significant technical advancement as a method for fertility preservation in cancer survivors.

___________

Read the earlier posts on Cryo2011 here:

• Reports from the 2011 Society for Cryobiology Conference
• Steven Mullen Discusses History of Oocyte Cryopreservation
• Fertility Preservation for Endangered Species

Thanks for the reports Dr. Zelinski! We look forward to hearing more from the Society for Cryobiology.