The most recent healthbeat from the US Department of Health and Human Services briefly discussed the topic of survivors of childhood cancer having children. The point made is that these patients had no increased risk of having children with birth defects, though they were at higher risks for having preterm births and low birth weights. You can listen to this blurb at the HHS site here.
Francesca Duncan, PhD
Applying emerging Assisted Reproductive Techonology (ART) procedures in an Oncology setting may help cancer survivors attain their desire to have a child spared of the very cancer that they themselves battled. Preimplantation Genetic Testing (PGT) is a prenatal screen performed prior to the initiation of pregnancy. In this procedure, cell(s) from embryos derived from ART procedures (either in vitro fertilization or intracytoplasmic sperm injection) are biopsied and used for genetic testing so that only unaffected embryos are transferred to the recipient uterus. Since its inception in the 1990s to screen for sex-linked disorders, PGT has been used to screen embryos for a wide range of abnormalities including single gene disorders, chromosomal abnormalities, and aneuploidies. More controversial uses of PGT include HLA-typing, sex selection for family balancing, and screening for non-medical genetic traits. PGT has a 2% misdiagnosis rate and is generally considered to be successful. Approximately 7,000 cycles of PGT have been reported worldwide, resulting in more than 1,000 live births.
In the past few years there has been an increasing use of PGT to screen for cancer syndromes because the five-year survival rate for most cancers is improving for reproductive-aged men and women. Thus, starting a family post-cancer is becoming a reality for many. Furthermore, strides in basic research have uncovered the genetic links to many cancers, therefore allowing a technology such as PGT to be applied to this disease. According to a 2006 paper published by Dr. Kenneth Offit and colleagues in the Journal of the American Medical Association, there are 55 published reports of using PGT to screen for 22 common cancer predisposition syndromes including hereditary breast, ovarian, and colon cancers (1). Of the thirteen PGT centers that provide clinical or research services, nine perform cancer-related screening.
Although using PGT to screen for cancer predisposition syndromes could be a promising option for Oncofertility patients seeking to start a healthy family, caution needs to be exercised before making it standard for several reasons. First, although the embryos selected for implantation may not harbor specific genetic mutations that will predispose the children to cancer, the embryos may have other genetic defects that were not screened for. Second, it is important to realize that many cancers are sporadic, so PGT will not offer a protective benefit against these forms. Finally, PGT has only been in existence for about twenty years, so we do not know the effects of this procedure on the long-term health and well-being of the offspring. Studies in mice have demonstrated that simply culturing embryos in vitro can have subtle but statistically significant consequences on the gene expression profiles, imprinting, and long-term behavior in the resulting animals (2-4). In contrast, my work using a mouse model of PGT demonstrates that removing a single cell from an 8-cell embryo does not affect the global patterns of gene expression in the resulting blastocyst (5). Although these results are encouraging for demonstrating the safety of PGT, they are still preliminary and more research needs to be done.
(1) K Offit et al. JAMA (2006); 296: 2727-2730.
(2) P Rinaudo et al. Reproduction (2004); 128: 301-311.
(3) AS Doherty et al. Biology of Reproduction (2000); 62: 1526-1535.
(4) DJ Ecker et al. PNAS (2004); 101: 1595-1600.
(5) FE Duncan et al. Fertility Sterility (2009); 91: 1462-1465.
From the NCI Cancer bulletin (www.cancer.gov):
NCI has launched a new Web portal that provides a single access point to information for adolescent and young adult (AYA) cancer patients aged 15 to 39. About 70,000 AYAs are diagnosed with cancer each year in the United States.
Cancer is the second leading cause of death in this age group. Yet, substantially less attention has been given to young adults with cancer than to children and older adults, and improvement in the survival rate of young adults has not kept pace with that achieved in other patient groups. Reasons for this lack of progress include issues specific to this age group: differences in biology or intolerance of therapy, delay in diagnosis, physicians unfamiliar with the disease, a lack of both available clinical trials and access to these trials, and, often, the psychosocial condition of the patient. Additionally, AYA patients often have special concerns that differ from those of older cancer patients, such as preserving fertility, being able to obtain health insurance and access health care following a cancer diagnosis, and feeling isolated because of a lack of peers who can relate to fighting cancer at their age.
The portal was developed in response to a report by the Adolescent and Young Adult Oncology Progress Review Group (PRG). This PRG, a collaborative effort between NCI and the Lance Armstrong Foundation, was followed by Closing the Gap: A Strategic Plan, developed to address recommendations in the PRG report. The AYA cancer portal is designed to reach newly diagnosed AYA patients with evidence-based information that will help them learn more about their treatment options and participate in treatment-related decisions, explore clinical trial options, get emotional/coping support, and learn about organizations that provide information and support to AYAs.
We are excited to announce that the www.myoncofertility.org, is featured as a prominent resource on the portal, linking young cancer patients with the information they need to best navigate the difficult fertility preservation decisions that they face when confronting a cancer diagnosis’s patient-facing website,
The portal can be accessed at http://www.cancer.gov/cancertopics/aya.
Tampa, FL (Oct. 9, 2009) — Moffitt Cancer Center will celebrate the honor of being named a center of excellence by Fertile Hope from 5:30 to 8:30 p.m. Oct. 26 in the Ted & Marty Couch Auditorium at the Vincent A. Stabile Research Building, 12902 Magnolia Drive.
Fertile Hope is a national nonprofit fertility organization providing resources and support for cancer patients. The Fertile Hope Center of Excellence Program is the first of its kind to address fertility preservation and parenthood options. It is designed to ensure that all age-appropriate cancer patients are informed of their fertility risks before treatment.
Moffitt is being honored for the information received by all patients on the issues of reproductive risks and fertility preservation options.
Quinn will speak on behalf of Moffitt and the newly developed LIVESTRONG Fertility Advisory Committee. The Lance Armstrong Foundation and Fertile Hope united to develop the committee. Quinn has been appointed for a two-year term and will help guide the foundation on how to best meet the reproductive needs of those affected by cancer.
Quinn will discuss fertility and options for cancer patients. Other experts from Moffitt, Fertile Hope, the Lance Armstrong Foundation and USF IVF & Reproductive Endocrinology will share the latest information on cancer and fertility.
Patients, families, friends and medical staff are invited to celebrate the acceptance of the award and to hear the latest information on cancer and fertility.
Please R.S.V.P. by Oct. 20 at 1-888-MOFFITT.
To qualify as a Fertile Hope Center of Excellence, cancer centers must demonstrate that:
All individuals of reproductive age who are treated for cancer are given complete information, both verbally and in writing, about their reproductive risks and options for preserving fertility before cancer therapy, radiation, chemotherapy and surgery are initiated.
Educational resources are available for health care professionals, patients and survivors.
Referrals are provided to appropriate specialists for fertility preservation and parenthood after cancer.
About Fertile Hope
Fertile Hope is a national, nonprofit organization dedicated to providing reproductive information, support and hope to cancer patients whose medical treatments present the risk of infertility. In addition to robust programs in areas of awareness, education and support, Fertile Hope operates the only fertility preservation financial assistance program for cancer patients, including a program for men to help reduce the cost of sperm banking. For more information, to apply for financial assistance or to make a donation, please visit www.fertilehope.org or call (888) 994-HOPE.
About the Lance Armstrong Foundation
At the Lance Armstrong Foundation, we fight for the 28 million people around the world living with cancer today. There can be – and should be – life after cancer for more people. That’s why we kick in at the moment of diagnosis, giving people the resources and support they need to fight cancer head-on. We find innovative ways to raise awareness, fund research and end the stigma about cancer that many survivors face. We connect people and communities to drive social change, and we call for state, national and world leaders to help fight this disease. Anyone anywhere can join our fight against cancer. Join us at www.livestrong.org.
About H. Lee Moffitt Cancer Center & Research Institute
Located in Tampa, Florida, Moffitt Cancer Center is an NCI Comprehensive Cancer Center — a designation that recognizes Moffitt’s excellence in research and contributions to clinical trials, prevention and cancer control. Moffitt currently has 15 affiliates in Florida, one in Georgia and two in Puerto Rico. Additionally, Moffitt is a member of the National Comprehensive Cancer Network, a prestigious alliance of the country’s leading cancer centers, and is listed in U.S. News & World Report as one of “America’s Best Hospitals” for cancer. Moffitt’s sole mission is to contribute to the prevention and cure of cancer.
For the full story, and more on the Moffitt Cancer Center, visit this site.
I recently ran across an article by Fiona Macrae written on October 29, 2009 from Mail Online entitled “No men OR women needed: Scientists create sperm and eggs from stem cells”. I proceeded to read this article before I read the actual scientific manuscript that it was based on; the article itself makes several very big claims: 1) the research could change the face of parenthood, 2) the research could be the cure for infertility and 3) it may soon be possible for children to be born through entirely artificial means. For the last few years, there have been several outrageous media outlets that make a practice of taking an interesting scientific manuscript and sensationalizing it as a cure for infertility, etc.
I continued on and read the original scientific paper they were describing in the column, “Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation;” an article published in this month’s issue of Nature. It truly is a super paper describing the role the DAZL, DAZ, and BOULE genes play in the progression of embryonic stem cells to primordial germ cells (PGCs) and the subsequent development into a haploid gamete. Interestingly, this group isolated fluorescently-tagged PGCs that were developed from embryonic stem cells in culture (previously shown), but for the first time demonstrated that DAZL, DAZ, and BOULE are upregulated in order to induce these PGCs to begin meiosis and then arrest at early prophase of meiosis I.
What the scientific paper did not describe, or even hint at, was that this science would be a cure for infertility. What this paper does, however, is attempt to clarify another step in the process of early germ cell formation that may be used as a tool for elucidating critical steps in male and female infertility. There is not one simple solution to infertility. I urge all scientists and non-scientists to be objective about outrageous claims that are made about cures and answers and to read the actual scientific papers and find the true messages behind the science.
The Fall 2009’s Virtual Grand Rounds hosted Dr. David Wildt of the Center for Species Survival at the Smithsonian National Zoo for his talk entitled “Sex, Wildlife and Intensive Management”. Joining him in giving this seminar were Dr. Nucharin Songsasen and Dr. Pierre Comizzoli, also of the National Zoo. Dr. Wildt began by addressing the role of the reproductive sciences in wildlife management and the challenges faced in this field. One of the main challenges is the lack of knowledge that is compounded by the incredible diversity that exists. For example, of 5500 mammalian species, only about 100 have been studied with respect to reproductive biology. This is partially reflected in the reproductive biology literature: approximately 10% of publications in the field relate to wildlife, compared to 36% relating to the “role model” species, rodents and cattle. Of the species that have been studied, there are great differences in reproduction. To illustrate this, Dr. Wildt described both the Great Pandas which spend less than 1% of their lives in estrus, the time it is possible for them to become pregnant, and bats which have the capability of storing sperm, not just for days or weeks, but for months! This diversity can also be found within species such as canids: the domestic dog has spontaneous estrus with no seasonality however, the Maned Wolf only ovulates in the first half of the year and only in the presence of males. Dr. Wildt talked at length of how the information gathered is put to practical use in species management, as well. In 1996, Dr. Wildt was part of a multidisciplinary team that went to China to work on reversing the stagnation of the panda population. By applying the knowledge gained from this research team, the number of pandas (in captivity) has been increased from 104 in 1998 to 292 in 2009. Soon this population will be self sustaining and reintroduction of pandas to the wild will commence. Dr. Wildt stressed that reproductive science is more than just ARTs and that often species management can be done purely by understanding the factors that affect an animal’s fertility, such as environmental influences. For example, switching from small cages to a more natural enclosure lowered the stress of a colony of Clouded Leopards in Thailand, enabling natural reproduction to occur.
Dr. Wildt then turned it over to his colleagues Dr. Songsasen and Dr. Comizzoli to describe what is on the horizon for reproductive sciences in wildlife and species management. Dr. Songsasen and Dr. Comizzoli updated us to the latest advances at the bench using the domestic dog and cat as models for wild canids and felids, respectively. These species are important because they can serve as a model for many human diseases such as diabetes, retinitis pigmentosa and cancer. There are also parallels with humans and fertility. For example, teratospermia is seen in cats with very high frequency (~60%). Dr. Songsasen described her work with the domestic dog and the successes with in vitro follicle culture. Using the alginate culture system developed by the Woodruff lab, preantral follicles can be cultured and demonstrate hormone production. Dr. Songsasen discussed the impacts of including various additives to the culture system including FSH and LH and also how the age of the animal affects the culturing. Dr. Comizzoli then went on to describe his work with in vitro maturation of domestic cat oocytes and with vitrification of ovarian tissue. Upon thawing of cortical strips, they are able to demonstrate that about 80% of the original structure is preserved and about 70% of the primordial follicles are viable.
Thanks to Drs. Wildt, Songsasen, and Comizzoli for excellent examples of how non-typical animal models can be used for oncofertility research, and the ways we can pay these animals back by using our findings to help sustain their populations!
The presentation will be posted for viewing here within the next few days!
Writing for parenting.com, Erin Zammett Ruddy wrote an article1 today about her experiences of getting pregnant while being on Gleevac as a way to treat her chronic myelogenous leukemia (CML). Her first hand account really sums up many of the choices we’ve discussed from a clinician’s point of view: is it ok to halt cancer treatment for the duration or remainder of a pregnancy? How do the patient and clinician come to the right decision on this topic? I think we will all be happy to read that Erin’s team of doctors included endocrinologists, fertility specialists, and oncologists, and Erin herself says that her doctor’s support was instrumental in her decision to continue her pregnancy. I highly encourage you to read Erin’s story; it very nicely outlines many of the issues that the was designed to address.
The options available to couples facing infertility are increasing, whether or not a cancer diagnosis is involved. Assisted reproductive technologies (ARTs), such as in vitro fertilization (IVF), are becoming more and more common, and millions of healthy babies have been born with their help. With all this success, we might start to forget about the biology of it all–that the “in vitro” part of IVF litterally means “in glass”–IVF embryos go through fertilization and the first few days of embryonic development outside of their mother’s body. We need to make sure we consider the effects that growing an embryo outside the body for a few days might have.
A few weeks ago world leaders came together for a meeting at the United Nations building in New York to discuss a whole host of issues facing the global community ranging from the proliferation of nuclear weapons to climate change. While, weeks later, the conference still may be most famous for its discussion of mushroom clouds the meeting also yielded a less covered but equally important fallout for the way policy makers address women’s issues.
The UN, at the conference, consolidated four separate agencies focussed on women’s issues into one much more powerful group, UNIFEM. In addition to improving organizational efficiency, the new über-agency hopes to more quickly and effectively address global issues that disproportionately affect women. Chief among these issues are health concerns. UNIFEM cites, among other statistics that women in sub-Saharan Africa aged 15-24 are 6 times more likely than their male counterparts to test positive for HIV.
UNIFEM, though, is extending its sights far beyond HIV and even beyond addressing sexual assaults, poverty, and political representation, all of which are most certainly on the to-do list. The agency seeks to expose and attack gender inequality issues wherever they exist, whether it be on the battlefield, in the halls of congress, or within the walls of a hospital.
This is, in many ways, an ambition shared by Oncofertility Consortium and The Institute for Women’s Health Research. These two organizations have put their full efforts behind expanding clinical trials on women’s health issues and improving women’s fertility preservation options, already to tremendous success. Whether it’s a new international agency, a nationwide collaboration between basic science researchers and clinicians, or as an ever-growing database in the state of Illinois, the potential of this increased attention to women’s issues on all levels and in all arenas is should be exciting to women (and men) everywhere.