In 2007, I was asked by the Medical Sciences Graduate Students Association at the University of Calgary to participate in a symposium called “Pushing the Boundaries – Advances That Will Change the World in 20 Years.” My presentation topic was oncofertility—a word I had just coined to describe the intersection of two disciplines, oncology and fertility—and I was thrilled to share my thoughts and passion for this new field and the goal of helping young women with cancer protect their future reproductive health.
Oncofertility was just an idea 10 years ago. Today it is a distinct field of medicine, offering new hope to cancer patients who will survive their disease and have fertility options that prior generations lacked. In the last year alone, 90 percent of young cancer patients at my institution received information about fertility as part of their cancer care. I cannot describe just how monumental this shift is for medical practice, with reproductive specialists and oncologists working together to improve patient care. For the patients at my institution, the discussions taking place between these two very different disciplines have led to interventions—banking eggs, sperm, embryos or tissue—with the goal of preserving the option to have a future family. For some of our cancer survivors, that future is now, and they are the proud parent of a child they thought they might not be able to have.
Bench to bedside to babies – oncofertility – is now part of the normal lexicon of centers of excellence around the globe as oncologists and reproductive specialists make fertility after cancer a priority at the time of diagnosis. Yet, when I delivered my remarks in Calgary less than a decade ago, I presented this kind of collaborative patient care as the future of medicine. So, what is my prediction for 2034?
Simply put, within the next 20 years, I expect to preside over the elimination of my field.
It sounds odd to create and then hope to eliminate an entire field of science and medicine, but that is my prediction and my hope. Let me tell you why. Even as science has created a medical arsenal of early diagnostics (genetic and blood-based), and more effective chemotherapeutics and radiation therapy approaches, I believe there is much more to come. Through science we will create new, smarter therapeutics that will treat the disease without causing collateral damage to the ovary and testes. We are learning more and more about the way the female egg and the male sperm respond to toxic drugs. Additionally, new technologies to better target drugs and radiation, as well as biologics that are specific to the disease, are on the horizon. Couple these technological advancements with a concerted effort to identify the triggers of cancer and to refocus our efforts on preventive measures that will either reduce the incidence of disease or diagnose it earlier and we will achieve better outcomes for patients. All of these advances – in cancer prevention, diagnosis, and treatment – will one day make it possible to address cancer without affecting future reproductive health, making the word oncofertility obsolete.
So, by 2034, I hope to once again become a regular reproductive scientist, continuing to work out the complexities of oocyte quality, ovarian follicle biology, and reproductive health; knowing that young women and men with cancer around the world need not worry about their ability to have a family one day; looking back fondly on the days when we needed oncofertility; and recognizing how continuing advances in cancer research allowed us to ultimately place oncofertility within the archives of medical history.
Dr. Teresa Woodruff is the Thomas J. Watkins Professor of Obstetrics & Gynecology, the Vice Chair of Research (OB/GYN), the Chief of the Division of Reproductive Science in Medicine, Feinberg School of Medicine and Professor of Molecular Biosciences at the Weinberg College of Arts and Sciences at Northwestern University. She is also the Director of the Northwestern University Women’s Health Research Institute. Her work has been supported by the National Institutes of Health and the National Science Foundation.
The Centers for Disease Control and Prevention released the final version of its National Public Health Action Plan for the Detection, Prevention and Management of Infertility. The National Action Plan developed over the course of seven years and began with an ad hoc working group that included members of the Oncofertility Consortium that started at Northwestern. A draft National Action Plan was released in May 2012. ASRM provided input at each step of process under which the National Action Plan was developed and will continue to be involved as the National Action Plan is implemented.
The goals of the National Action Plan are to:
• Promote healthy behaviors to maintain and preserve fertility;
• Promote prevention and early detection and treatment of medical conditions that can threaten fertility; and
• Reduce exposures to environmental, occupational, infectious and iatrogenic agents that can threaten fertility.
The National Action Plan is available at www.cdc.gov/reproductivehealth/Infertility/PublicHealth.htm.
The CDC will host a Public Health Grand Rounds on August 19, 2014 on infertility.
For more information please see www.cdc.gov/cdcgrandrounds.
A recent report in Fertility & Sterility has indicated that among women between the ages of 18 and 40, there is a significant amount of misconception regarding fertility and becoming pregnant. Dr. Illuzzi, an OB/GYN at Yale University School of Medicine, led a study in which 1,000 women of various ages and backgrounds completed a survey about their knowledge of reproductive health. The results showed a lack of knowledge across the board, with higher educated women knowing only slightly more than less educated women.
Over one-third of the women surveyed believed that specific positions during intercourse, such as elevating the pelvis, increase the odds of conception, although there is no scientific evidence to back this up. Additionally, only 10 percent of women know when the best time of the month to conceive is. The majority of women thought that sex must take place after ovulation to become pregnant, while in reality, pregnancy is most optimal when intercourse occurs 1 to 2 days prior to ovulation.
Other notable findings in the study include women’s thoughts on what can decrease fertility and prevent conception. Around 25% of surveyed women were unaware that factors such as obesity, smoking, and a history of sexually transmitted disease can cause infertility. In fact, the number one factor women cited as causing infertility was stress. Stress can have many negative side-effects, but according to Dr. Illuzzi, research does not currently support that it leads to infertility. While most of the women surveyed were aware that conception becomes more difficult with age, many did not know that later pregnancies are also more likely to result in miscarriage and chromosomal defects.
If you are concerned about fertility, or have questions about becoming pregnant, it is best to talk to your doctor, but you can get more information on websites such as the American College of Obstetricians and Gynecologists.
As today's cancer treatments increase survivorship, many young cancer patients now look at their potential for parenting children. The decision to have children, if fertility is sustained, is complicated and filled with legal, ethical and financial considerations. The Oncofertility Consortium based at Northwestern University hosts a monthly webcast that explores a variety of reproductive options for individuals who have been treated for cancer and everyone is welcome. Tomorrow's CME lecture will discuss: Contraceptive Options during and following Cancer Treatment. It will begin on March 7, 2013 at 9:50 AM Central US Time and last for one-hour.
To view a detailed flyer on this event including how to connect, click HERE
A new study shows that the biological clock is not the only clock women trying to conceive should consider. The circadian clock needs attention, too.
Epidemiological studies have shown female shift workers, such as nurses, and female flight attendants who work on long-distance east-west routes (i.e., those with constant jet lag) have fertility and menstrual issues. They are habitually out of sync with the external light cycle. But the role circadian rhythm disruption may play in their reproductive problems is a poorly studied area.
Research led by Northwestern U. circadian rhythm expert Fred W. Turek now draws a clear line between disrupted circadian rhythms and reproductive physiology. Turek and his colleagues are the first to show that if you disrupt the circadian clock environmentally in mice, with repeated changes in their light-dark cycles, there are problems with pregnancy outcomes.
And the effect can be dramatic. The researchers found evidence suggesting the severity of circadian disruption may be linked to the severity of pregnancy disruption: mice subjected to advances of the light-dark cycle had greater circadian clock disruption and lower reproductive success. This group’s pregnancy success rate was only 22 percent.
“Our results have important implications for the reproductive health of female shift workers, women with circadian rhythm sleep disorders and/or women with disturbed circadian rhythms for other reasons,” Turek said.
“If you disrupt your internal rhythms, there will be negative consequences -- that is very clear,” said Keith Summa, first author of the paper and an M.D./Ph.D. candidate working in Turek’s lab. “Our results suggest people should consider their biological rhythms for optimal health.”
The repeated shifting of the light-dark cycle shifts the biological clock throughout the body. This environmental disturbance is more relevant to shift workers and those frequently flying across time zones, the researchers note, than genetic disruption of the circadian clock, which also negatively influences reproductive function.
Turek, Summa and their colleague and co-author Martha H. Vitaterna studied three sets of normal laboratory female mice, all who had recently mated. The study was conducted over the course of 21 days, the duration of a typical pregnancy.
One set was a control group of 12 mice that experienced normal days of 12 hours of light, followed by 12 hours of darkness. The two other groups, of 18 mice each, also experienced days of 12 hours of light and 12 hours of darkness. But the phase-advanced group had its 12 hours of light start six hours earlier every five days. The phase-delayed group had its light start six hours later every five days. (There were a total of four phase shifts over the duration of the study.)
The researchers monitored the mice throughout the gestation period to count the number of full-term pregnancies. The results surprised them.
In the control mice, 90 percent of the matings led to full-term pregnancies. But in the phase-delay group, the pregnancy success rate was 50 percent, while in the phase-advanced group, it was only 22 percent.
“We were surprised at how dramatic the effect of manipulating the light-dark cycle was, especially in the phase-advanced group,” Summa said. “We expected a negative effect from the circadian clock disruption, but not this much.”
They next looked at a separate group of females in the phase-delay and phase-advance protocol to see how the animals responded to the repeated phase shifts. The researchers found the phase-advanced animals required one to two days longer, on average, to return to normal rhythms. This suggests the magnitude of circadian disruption is associated with the severity of pregnancy loss.
The next steps, the researchers say, are to identify specifically the stage at which pregnancy is affected and to understand exactly how circadian disruption results in the observed adverse effects.
“We’ve made an interesting observation, but what’s causing the reduced fertility?” Summa said. “We would like to determine where exactly the phase shifts and internal rhythm disruptions are having an effect.”
The March of Dimes Foundation and the Institute for Women’s Health Research at Northwestern University (the sponsor of this blog) supported the research.
The paper is titled “Environmental Perturbation of the Circadian Clock Disrupts Pregnancy in the Mouse.”
Megan Fellman is the science and engineering editor. Contact her at firstname.lastname@example.org
Researchers have identified a key step in the establishment of a pregnancy. The discovery may shed light on fertility disorders and diseases of the uterus, including endometrial cancer. At the start of each menstrual cycle, levels of the hormone estrogen begin to rise, which causes the uterine lining to grow and thicken. When the ovary releases an egg, levels of another hormone, progesterone, increase. Higher progesterone levels put the brakes on the estrogen-driven growth of the uterine lining, allowing the lining to mature and egg implantation to take place. Because of this function, progesterone is sometimes given to women to treat infertility and prevent premature birth. However, it carries some unpleasant side effects. A greater understanding of how progesterone works could lead to better treatments. It could also shed light on disorders such as endometrial cancer and endometriosis, which is marked by uncontrolled growth of the uterine lining. To clarify how progesterone stops the growth of the uterine lining, the study's first author, Dr. Quanxi Li of the University of Illinois at Urbana-Champaign, led a group of researchers from several institutions. Their findings were published in the February 28, 2011, issue of Science. The team focused on the role of a protein called Hand2 in halting the growth of the uterine lining. They had previously found that blocking the progesterone receptor decreased Hand2 expression in uterine cells, indicating a link between Hand2 and progesterone.In their new study, the team genetically engineered mice to lack Hand2 in the uterus, and then gave them progesterone. They then stimulated uterine lining growth with estrogen. In normal mice, progesterone prevents the uterine lining from growing. In the mice without Hand2, however, the lining grew in spite of the progesterone treatment. The scientists found that uterine cells beneath the lining express Hand2 during egg implantation. Further experiments revealed that estrogen stimulates the production of molecules called growth factors, which cause the uterine lining to grow. High levels of Hand2, brought on by progesterone, stop the production of these growth factors. Therefore, the uterine lining stops growing, allowing egg implantation. The discovery of Hand2's role in halting growth of the uterine lining may spur development of treatments for diseases like endometriosis and endometrial cancer. "This information helps us understand how the interplay of hormones prepares the uterus to host and support the embryo as it grows," says Dr. Milan Bagchi, a senior author of the study. "Our next priority will be to examine whether Hand2 plays a critical role in the human uterus as well." Related Links: Pregnancy Infertility Endometriosis Source: National Institutes of Health