We have exciting news to share – registration for the 7^th annual Oncofertility Conference: Cancer and Fertility Around the Globe is now open! Please visit the conference webpage to view the agenda, speaker biographies,  submit an abstract for the poster session, and to REGISTER.  This year’s highlights will include; small group courses on oncofertility lab and clinical tools, insights from the International Society for Fertility Preservation, mitigating fertility loss in cancer patients, and a new fertility preservation decision tool for young patients.

The first day of the conference centers around a series of presentations from leaders in the field of oncofertility, including breakout sessions over lunch and an evening cocktail reception/poster exhibit. Our keynote speakers this year include Samuel Kim, MD, from the International Society for Fertility Preservation, and Nao Suzuki, PhD, from the St. Marianna University School of Medicine in Kanagawa, Japan. Throughout the day and evening, invited speakers from across the globe will present cutting-edge information to attendees that is not to be missed.

The second day of the conference, the Oncofertility Consortium will be hosting a set of popular courses for basic scientists and healthcare professionals to help improve their research and clinical skills. The first course offered, Clinic 101: Building a Fertility Preservation and National Physicians Cooperative (NPC) Program, is a one-day, small-group training course to give health care providers the tools necessary to develop their own fertility preservation program or strengthen their existing program. The training includes the following:

• Overview of the Key Pieces in a Fertility Preservation Program
• The Ins and Outs of Setting Up a Local Oncofertility Community
• Timing, Turnaround, and Practical Considerations
• Discussing Fertility Preservation with Patients
• Pediatric Fertility Preservation
• Engaging the nursing community
• The Oncologist’s Perspective

The second course offered, Oncofertility 101: Training in Follicle Techniques, provides one-day, small-group training courses to provide researchers with the tools to study follicle growth in vitro. The training includes the following:

• Laboratory Exercise Part I: Follicle Isolation & Manipulation
• Laboratory Exercise Part II: Follicle Encapsulation in Alginate
• The Evolution of Biomaterials in Follicle Culture
• The Ins and Outs of Setting Up a Follicle Culture Laboratory
• Laboratory Exercise Part III: Follicle Imaging & Quality Analysis

These courses run concurrently so participants may only register for one. They fill up quickly so be sure to register at your earliest convenience.

Don’t miss out on this great opportunity to meet and network with renowned Oncofertility specialists from across the globe! CNE credit will be available for healthcare professionals, and for those that cannot attend in person, there will be a LIVE broadcast of the first day of the conference (9^th). REGISTER TODAY. We look forward to seeing you in September!

**This activity is being submitted to the Oncology Nursing Society for approval to award contact hours. ONS is accredited as an approver of continuing nursing education by the American Nurses Credentialing Center’s COA.**

by Megan Carlson, Guest Blogger for the Oncofertility Consortium

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

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

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

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

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

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

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

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

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 Cathryn Smeyers

This is the final installment in a two-part blog story featuring Oncofertility Consortium member, Gregory Dolin, MD, JD, focusing on his recent Oncofertility Virtual Grand Rounds presentation. To read the 1^st blog, click here.

In his presentation, Dr. Dolin highlighted some of the problems that exist within the legislative process that make it even harder for scientific issues to be successfully conveyed to lawmakers.  According to Dr. Dolin, the hearing process, which many assume involves full congressional engagement, the presentation of relevant information and lively debate, is often more like “kabuki theater.”  Only invited participants are allowed to testify, hearings are rarely and sparsely attended, and the chairman has a nearly complete control of the agenda and the text of any proposal discussed.  Furthermore, after the hearing, much work is done by the staff in secret, the House Rules Committee can amend or rewrite the bill in any way it sees fit, floor debates may be very limited, and Conference Committees once again have the opportunity to amend or rewrite the bill outside of public view.

So what’s the solution?  How can we ensure that the people in control of federal dollars are scientifically literate and well informed?  Dr. Dolin proposes the creation of an objective body of scientific advisors charged with evaluating all proposed bills and advising Congress of the likely effect of legislation.  This body would also have to solicit scientific input from members of the public, which would allow scientists to register their opinions.  Models of this currently exist in the form of the Congressional Budget Office and the late Office of Technology Assessment. The creation of such an office, however, is just a proposal, and we are unlikely to see it realized in the near future.  In the interim, Dr. Dolin advises that scientists involve themselves in the legislative process and do what they can to ensure that Congress hears and understands complex scientific research.

The Oncofertility Consortium whole-heartedly agrees with Dr. Dolin, and we feel that Dickey-Wicker underscores the necessity for scientists to not only have a voice in the political sphere but to be adept communicators who can appropriately relay complex scientific information to a lay audience.  We hope our blog, for example, allows us to relay scientific research in a way that is both comprehensible and meaningful to our readers. Repropedia (www.repropedia.org) is another tool that we use to clearly communicate scientific information.

Repropedia is a website that is edited by scientists across the globe and serves as an authoritative source of definitions for reproductive health terms. This site directly interacts with other website by providing pop-up definition boxes, so a reader gets the information in context.  Our blog serves as the perfect example!  Of course, we couldn’t let Dr. Dolin go without contributing to this valuable resource. He kindly agreed to contribute a video definition of the term “parthenote,” and we sincerely hope that the general public (Congress included!) will benefit from his explanation.  In the end, it is exactly this kind of clear communication by the scientific community that will educate the public and inform public policy.

Click here to see Dr. Dolin’s Repropedia definition.  Click here to read the chapter he co-authored in the second Oncofertility book, Oncofertility: Ethical, Legal, Social, and Medical Perspectives, entitled, “Medical Hope, Legal Pitfalls: Potential Legal Issues in the Emerging Field of Oncofertility,” and look for his contribution to the fourth Oncofertility book due out later this year entitled, Oncofertility Communication: Sharing Information and Building Relationships across Disciplines.

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

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

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

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

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.

Pain is a common symptom among cancer patients and a large percentage of cancer patients are treated with opioids to control this side effect. Some cancer therapies are very rigorous and require opioid analgesics on an ongoing basis to treat the pain resulting from aggressive treatment. Many cancer survivors also report having low energy, depression, anxiety and impaired sexual function as a result of their treatment. It is also known that cancer treatment, such as radiation to the brain, is associated with long term endocrine abnormalities, including hypogonadism and hypothyroidism, that may cause some of these symptoms. However, the relationship between long-term use of pain medication and hormonal disruption is still not well-understood in female cancer survivors.

Information from males was discussed in an older article in the journal, Cancer, by authors, Arun Rajagopal, MD, Rena Vassilopoulou-Sellin, J. Lynn Palmer, PhD, Guddi Kaur, RN, BSN, and Eduardo Bruera, MD, entitled, “Symptomatic Hypogonadism in Male Survivors of Cancer with Chronic Exposure to Opioids.” In the article, the authors explore the relationship between the chronic consumption of oral opioids during and after cancer treatment and the potential for hypogonadism (reduced testosterone levels) and whether or not hypogonadism is associated with symptoms of fatigue, anxiety, depression and sexual dysfunction.

In an effort to prove the prevalence of central hypogonadism and associated symptoms of sexual dysfunction, depression, anxiety and fatigue, cancer patients selected for the study were all adult males, who had been cancer free for a year, and  taking high does of opioids. The control population was selected based on matching diagnosis and treatment, albeit they had not consumed any opioids in the last 12 months.  Patients completed the Sexual Desire Inventory (SDI), the Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Chronic Illness Therapy (FACT-G/FACIT-F) and the Edmonton Symptom Assessment System (ESAS) questionnaires. The patients also had serum samples taken to monitor their testosterone levels.

The results of the study showed that testosterone levels in the study group were significantly lower than what was found in the control group. Sexual dysfunction was significantly higher in the opioid group and reports of depression and fatigue were also much higher in the study group. Reported anxiety between the two groups was insignificant. Thus, the results suggest that chronic consumption of opioids leads to clinically significant central hypogonadism, which also may lead to greater levels of depression, fatigue and sexual impairment.

The results of this study and potential implications for the quality of life in cancer patients is critical. Hypogonadism can have consequences that go beyond poor libido and affect other areas of men’s lives, including fertility. Unfortunately, there are a lack of studies examine the relationship between opioid use in female cancer survivors and endocrine health. As chemotherapy and radiation may already compromise a woman’s reproductive ability, this information would provide health care providers with critical information regarding how to treat two significant quality-of-life issues in young female cancer survivors: reproductive health and pain management.

Look of Repropedia.org from a smartphone

Last June, we discussed the launch of a new online dictionary dedicated to defining reproductive words in easy to understand terms. Since then, we’ve been linking our reproductive terms to the website, Repropedia.org, which is an authoritative website that provides short, jargon-free descriptions to the public. Recent updates have now made it easier than ever 1) for people to use the website, and 2) for blogs like ours to link to the website’s words.

The first change to the website is called “responsive design.” This means that the website responds to the type of computer device of a user. For example, if I’m on my smartphone, the website automatically configures itself one-way but if I go to the website on my iPad or my desktop computer, the website will change again to fit these devices. It’s almost like the developers have built their own app for the website!

The Repropedia.org screen changes format when viewed on a large screen

The second change to the website will affect how you read this blog. As you may have noticed, in the past when we wrote reproductive terms and linked them to Repropedia, the definition was opened in a brand new webpage. Now, you can click on the word and the definition will “pop-up” directly on the blog’s page. With this new system, you will be able to tell the Repropedia-linked words because they will appear purple and underlined. For example, you can see that here with the term fetus.

The Oncofertility Blog is currently beta-testing this technology for Repropedia so if you see anything you like (or don’t like), please tell us. Also, if you manage a website or blog and would like to incorporate these definitions into your own site, you can get on the list to integrate the Repropedia Tooltip when it becomes widely available.

A person’s health is influenced by many factors; including, sex, gender, culture, environment, and income. Researchers are discovering the critical roles that sex and gender identity play in health, wellness, and disease progression. The discoveries being made through the study of women’s health and sex differences are key to advancements in personalized medicine for both sexes.

The Office of Research on Women’s Health (ORWH) was established in September 1990 in response to congressional, scientific, and advocacy concerns that a lack of systemic and consistent inclusion of women in National Institutes of Health (NIH) supported clinical research could result in clinical decisions being made about health care for women based on findings from studies of men—without evidence that they were applicable to women. Since that time, the Office has been the focal point for guiding the national research effort on women’s health issues and is responsible for ensuring that women’s health research priorities are integrated into the wider NIH research agenda. The mission of ORWH is to:

• Advise the NIH Director on matters relating to research on women’s health
• Strengthen and enhance research related to diseases, disorders, and conditions that affect women
• Ensure that research conducted and supported by NIH adequately addresses issues regarding women’s health
• Ensure that women are appropriately represented in biomedical and biobehavioral research studies supported by NIH
• Develop opportunities for and support recruitment, retention, reentry, and advance- ment of women in biomedical careers
• Support research on women’s health issues.

ORWH works in partnership with the 27 NIH Institutes and Centers to ensure that research on women’s health is part of the scientific framework at NIH, and throughout the scientific community. ORWH develops and supports scientific seminars, symposia, and workshops that highlight scientific advances, career development, and promising as well as accomplished researchers in this expanding field. This Thursday, May 17^th, Oncofertility Consortium member, Dr. Clarisa Gracia is taking part in a seminar series sponsored by the ORWH entitled, Innovations in Reproductive Technologies from 1-3pm EST, which will be available to listeners live, via podcast. Highlights of the seminar include:

• Ethical Issues in Emerging Technologies in Reproductive Medicine; 
Alan Decherney, MD, Head, Section on Implantation and Oocyte Physiology
Program in Reproductive and Adult Endocrinology
• Emerging Technologies in Infertility; 
Clarisa Garcia, M.D., M.S.C.E, Assistant Professor Obstetrics and Gynecology
• Technology in Reproductive Medicine; 
Alicia Armstrong, M.D., Associate Fellowship Program Director
Reproductive Endocrinology and Infertility
• Multipurpose Prevention Technology for HIV, STIs, and Pregnancy
; Gustavo Doncel, M.D., Ph.D., Professor of Obstetrics and Gynecology
• New Technology in Contraception Research
; Regine Sitruk-Ware, M.D., Reproductive Endocrinologist

Mark your calendars and tune in tomorrow to http://videocast.nih.gov at 1pm EST to listen live!

The Oncofertility Consortium uses emerging technologies, such as Virtual Grand Rounds, to speed the pace of research. Read about a new way we are doing this to facilitate global collaboration between scientists.

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iExperiment technology gives overseas scientists direct view into Northwestern microscope during experiment, speeding efforts to grow human follicle into mature egg

Marla Paul is the health sciences editor at Northwestern University. Contact her at marla-paul@northwestern.edu