Since the 1990s, researchers have published conflicting results about the connection between cancer risk and fertility drugs. As a result, there has been a lingering concern among women that using fertility drugs may increase their risk for later developing hormone receptor positive cancers. Hormone receptor positive tumors consist of cells that express receptors for certain hormones such as estrogen or progesterone, but are most commonly known as estrogen receptor tumors. These types of tumors depend on the presence of estrogen in order to grow and spread throughout the body, making the risk for gynecologic cancers cause for concern in some women undergoing IVF treatment.

Fertility drugs have come under scrutiny because they stimulate hyper-ovulation, meaning they cause a woman’s body to produce more eggs. They have been linked to certain gynecologic cancers, such as breast and ovarian cancer. One reason research published in the 1990s may have suggested a link between fertility drugs and cancer risk, is due to the drugs that were being prescribed 20 years ago. Researchers have also blamed the mixed nature of the findings on the studies’ relatively short length, or on including women who have not given birth as they are known to have an increased risk of some cancers.

New research, however, suggests that using fertility drugs does not have an impact on your risk for developing ovarian cancer down the line. Lead author of the study and clinical fellow in the Division of Reproductive Endocrinology at the Mayo Clinic in Rochester, Minnesota, Dr. Albert Asante and his colleagues gathered medical information on 1900 women from an ongoing ovarian cancer study at the Mayo Clinic. The researchers compared 1,028 women with ovarian cancer to 872 women of similar age who did not have cancer. As reported in Fertility and Sterility, approximately 24 percent of the women who did not have ovarian cancer reported having used fertility drugs, while roughly 17 percent of women who had ovarian cancer had used fertility drugs.

The researchers took into account factors that can influence the risk for ovarian cancer, such as age and use of the birth control pill, and found no difference in cancer rates between the groups. Dr. Asante looked specifically at whether women in the study who reported being infertile- whether or not they had taken fertility drugs – had a greater chance of developing ovarian cancer, and found no added risk. He said one explanation for the result is that most of the women in his study had infertility issues, but eventually became pregnant. According to Dr. Albert Asante, “One important message [from this study] is women who need to use fertility drugs to get pregnant should not worry about using these fertility drugs.”

To read more about this new study, click HERE for the full text. To learn more about your reproductive options when faced with a cancer diagnosis, please visit www.SaveMyFertility.org.

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.

Below is an excerpt from an article in the University of Colorado Cancer Center Fund E-News featuring Oncofertility Consortium member and Northwestern University alumna, Laxmi Kondapalli, MD, MSCE. To learn more about Dr. Kondapalli, read our three-part blog series, Training the Next Generation in Oncofertility.

By Jerry Sinning

Dr. Laxmi A. Kondapalli is a unique member of the University of Colorado Cancer Center. She joined the University of Colorado faculty in 2011 as Assistant Professor and Women’s Reproductive Health Research Scholar in the Division of Reproductive Endocrinology and Infertility. She came to the Cancer Center after finishing her education in the Northeast – receiving her Bachelor’s Degree from the University of Michigan, her Medical Degree at the University of Vermont College of Medicine, and a Master of Science in clinical epidemiology from the University of Pennsylvania. She completed her residency in obstetrics and gynecology at Northwestern University and fellowship in reproductive endocrinology and infertility at the University of Pennsylvania.

Dr. Kondapalli is the leader of the Oncofertility Program at CU Cancer Center. She does not see patients to discuss their cancer treatment options, but rather their family planning options as cancer survivors. Dr. Kondapalli’s program is one of only a handful in the country that provides an interdisciplinary approach to cancer treatment planning and care that includes clear family planning options for patients, community support services, research, education and outreach…

Read the rest of the article here.

Talking with teenagers about fertility can be awkward and uncomfortable. Talking with teenagers and their families about a cancer diagnosis is devastating. How do we do both at the same time and ensure that the importance of fertility preservation is understood in light of the traumatic timing? Studies among adult cancer survivors show that fertility is their most prevalent concern, thus we need to develop a method for relaying this information to young cancer patients and their families in a timely and sensitive manner. In the article, “The Birds and the Bees and the Bank: Talking with Families Amidst a Cancer Diagnosis,” by Gwendolyn P. Quinn, Caprice A. Knapp, and Devin Murphy, in Oncofertility Medical Practice: Clinical Issues and Implementation, the authors propose using a new method for initiating these discussions.

Patients and their families often look to health care providers to guide them in their decision-making process. Receiving a cancer diagnosis is very traumatic and can leave both the patient and their parents in a highly emotional state. They may not remember all that they were told in that initial discussion, but unfortunately decisions need to be made in that moment that will have an impact on their life many years later. Depending on the cancer diagnosis and the treatment protocol, loss of fertility may be a consequence., and needs to be addressed.

Studies show that communicating with patients using interactive tools, increases a patients understanding of the information being presented. Additionally, understanding is further increased, specifically when individual decision-making is involved, using a values clarification exercise or tool. According to the authors, “A values clarification tool (VCT) is often used in environments in which a common shared vision or purpose is required, the goal of which may be to develop the common vision, define roles, or develop long-range plans.” A VCT serves as a primer for future decision-making because it does not asks participants to ponder hypothetical situations, but instead aids them in defining the values and beliefs that influence their behavior. The authors maintain, “The open-ended statements of the VCT encourage patient/parent and administrator to begin a dialogue so that the patient/parent may process the idea of having children first, and then consider their feelings about possibly not being able to have children in their future.”

Allowing young patients to take an active role in making decisions about their fertility by evaluating their own beliefs and behaviors, and processing the idea of potential infertility, can actually serve to empower their decision-making process. Studies show that adolescent and teenage cancer survivors have clear expectations about parenthood and having biological children, yet are not always able to fully express these desires. The VCT can be a helpful tool in initiating these types of discussions. Read, “The Birds and the Bees and the Bank: Talking with Families Amidst a Cancer Diagnosis.” Learn more about your fertility options by visiting our Virtual Patient Navigator.

Over the last twenty years, advances in fertility preservation techniques have made oncofertility more accessible to women diagnosed with cancer or other fertility impacting diseases. Despite this good news, the academic journal, Cancer, recently reported that between 1993 and 2007, only 4% of women between the ages of 18-40 diagnosed with cancer, sought out fertility preservation. In Cancer Today, a medical magazine issued by the American Association for Cancer Research, addresses this disparity in a new article entitled, “Fertility Preservation Catches On, But Slowly,” arguing that new cancer patients need information and referrals to reproductive specialists immediately after diagnosis to ensure they have the best possible chance of preserving their fertility if they choose to do so.

Studies show that discussing fertility preservation with a cancer patient may depend on several factors including education, socioeconomic status, sexual orientation, and whether or not the cancer patient already has children. According to Cancer Today, “college graduates [are] up to 40% more likely to be counseled than those without a bachelors degree.” Teresa K Woodruff, reproductive endocrinologist and director of the Oncofertility Consortium maintains that this disparaging information highlights the gap between getting fertility preservation counseling and taking action.  She also argues that “cancer patients need to be seen on that same day as diagnosis or within the next 24 hours,” by a reproductive specialist.

So what can we do to ensure that every young cancer patient has the same opportunity to preserve his or her fertility prior to treatment? The Oncofertility Consortium has led the way not only research, but also in advocacy, making fertility preservation a public discussion so that both clinicians and patients are aware of the potential damage cancer treatment can have on fertility. The more knowledge one has, the more likely they are to make an informed decision in that critical timeframe between diagnosis and treatment.

To read, “Fertility Preservation Catches On, But Slowly,” in Cancer Today, please click here. If you or someone you know needs information on fertility preservation, including options, techniques, clinics, cost, etc., please click on links below for more information.

• National Fertility Hotline (866.708.FERT) to speak with a Fertility Preservation Patient Navigator
• SaveMyFertility: an authoritative resource for adult cancer patients and the parents of children with cancer who want to learn more about preserving their fertility before and during cancer treatment, and protecting their hormonal health after treatment.
• Fertility Preservation Patient Navigator: A website designed to help patients learn more about their options for family building.
• MyOncofertility: A patient education resource provided by the Oncofertility Consortium.

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.

Infertility is serious and often underestimated side effect of cancer treatment. Ensuring cancer patients are equipped with the necessary health information to protect and preserve their fertility in a time sensitive manner is a critical component to comprehensive cancer care. In a new article in Nursing: Research and Reviews, by Angela Jukkala, Karen Meneses, Andres Azuero, June Cho and Patrick McNees, entitled, “Development of the Knowledge of Fertility and Fertility Preservation Scale,” the authors reported on a process used to develop and examine the reliability and validity of an instrument to measure a breast cancer survivor’s self-assessed knowledge of fertility and fertility preservation.

In their study, 92 breast cancer survivors between the ages of 25-45 were asked to complete the Knowledge of Fertility and Fertility Preservation (KF) Scale as part of their participation in a larger study, the Fertility Cancer Project (FCP). The KF Scale is a new instrument designed to measure a breast cancer survivor’s self-assessed level of knowledge of fertility and fertility preservation. The content of the KF Scale was developed through a comprehensive review of the literature, researcher clinical expertise, and expert review to meet the fertility and fertility preservation knowledge needs of young breast cancer survivors. The KF Scale included 13 content areas grouped into three subscales: Treatment Factors Affecting Fertility, Infertility Information, and Alternative Parenting Options.  All items were scored on a 1–3 rating scale with 1 representing “a little”, 2 representing “some”, and 3 representing “a lot” of knowledge.

The results of the KF Scale analysis were consistent: many participants self-assessed their overall knowledge of fertility and fertility preservation as “a little” and the majority rated their knowledge for the Infertility Information subscale as “a little.” What this means is that most patients completed their chemotherapy treatment having only “a little” knowledge of cancer treatment’s impact on their fertility and only “a little” knowledge about fertility preservation options beforehand. These results suggest that more health-related communication and information about fertility impacting cancer treatment is needed prior to undergoing treatment. According to the authors, “Health care professionals providing care for young women newly diagnosed with breast cancer must be able to provide needed health information on a wide range of topics (eg, surgery, chemotherapy, fertility preservation) in a relatively short period of time.”

To ensure that patients receive quality nursing care, they need to be informed of the long-term side effects of chemotherapy, including infertility. The KF Scale could be used to develop individualized teaching plans to meet patient-specific fertility and fertility preservation health information needs. The KF Scale could also be used to examine the effectiveness of educational interventions if used before and after the intervention. Read “Development of the Knowledge of Fertility and Fertility Preservation Scale.”

Pediatric cancer, a disease once thought to be primarily incurable, now has an 80% cure rate as a result of clinical advances in technology, pharmaceuticals and screening. For many young patients and their families, survival takes precedence over all other issues immediately following a cancer diagnosis. As a result, late effects such as fertility loss, are often not addressed until remission or after fertility impacting cancer treatments have already begun. A new publication in the journal, Pediatrics, by Gwendolyn Quinn, Caprice Knapp, Devin Murphy, Kelly Sawczyn, and Leonard Sender entitled, “Congruence of Reproductive Concerns Among Adolescents with Cancer and Parents: Pilot Testing an Adapted Instrument,” the authors conducted a pilot study to test a 10-item reproductive concerns scale adapted for female adolescent cancer patients and their parents, to determine the congruence between parent and adolescent fertility cancers as a result of cancer diagnosis.

The authors hypothesized that adolescent patients would struggle to actualize long term cancer effects as a result of their young age and inexperience with parenthood; therefore, have fewer reproductive concerns than their parents. Parents on the other hand, would view their child’s fertility loss more negatively and dramatically due to their experience as parents. The authors also hypothesized that age would play a factor in the congruence of fertility concerns between parent and child with older adolescents sharing similar reproductive concerns with their parents.

In order to obtain accurate and unfiltered feedback from adolescents, they were interviewed in rooms separate from their parents. Findings showed that the majority of parents provided inaccurate predictions of their daughters’ responses regarding their reproductive concerns.  Overall, parents underestimated their child’s desire to have children of their own one day and expected that their children would be satisfied with survivorship.

As a result of this study, two key issues regarding adolescent reproductive concerns and parent perceptions were highlighted: 1) that creating and administering pediatric instruments must be done with pediatric patients for accuracy, without parental involvement which often inhibits free expression, and 2) parents often underestimated their daughters concern about future reproduction when impacted by a cancer diagnosis.  This study demonstrates that adolescents have strong reproductive concerns that are not being captured in current quality-of-life instruments and may be further neglected because of parents’ unawareness of their child’s concerns.  Thus, patient discussions regarding fertility concerns should be conducted before treatment begins, during and after.

Read: “Congruence of Reproductive Concerns Among Adolescents with Cancer and Parents: Pilot Testing an Adapted Instrument.”

Recently my colleague and office buddy, Nadia Johnson, was featured in the Spring 2012 issue of Inquiry, Northwestern University’s School of Education and Social Policy’s (SESP) quarterly magazine, in an article entitled, “Higher Education Student Nadia Johnson: Motivating Girls to Study Science.” Nadia is the Co-Director for the Women’s Health Science Program (WHSP) and a graduate student at Northwestern pursuing a master’s degree in SESP’s Higher Education Administration and Policy program. Inquiry featured her as a student and Northwestern staff member who is making a difference in the lives of young women through science education.

As the Co-Director for WHSP, Nadia runs the Oncofertility Saturday Academy, along with programs in cardiology, physical science, and infectious diseases. The programs focus on bringing in girls who are under-represented in science and medicine, namely African American and Latina women, for a series of workshops open to high school juniors and seniors.  According to Nadia, “ When it comes to teaching science, we must better understand how boys and girls experience the science setting differently and how we can manage this so that girls can get just as far as boys.”

This past November, the WHSP program received the prestigious Presidential Award for Excellence in Science, Mathematics and Engineering demonstrating the enormous impact this program has had on young women in science. For Nadia, the formula is simple, “If you excel in something and you have praise, you tend to go down that path,” as was the case for her. She also emphasizes the importance of having young women mentored by female scientists and clinicians so they see firsthand, women who are working and exceling in science fields.

Not one to rest on her morals, Nadia is using her graduate research to improve the WHSP program and make the experience not only significant for the high school students, but also for program mentors (health care providers, medical students, faculty, etc…) who also participate.  Regardless of what the data shows, Nadia knows from experience that these kinds of programs, are a win-win for everyone involved.  Read, “Higher Education Student Nadia Johnson: Motivating Girls to Study Science.”

We talk a lot about the importance of collaborative care at the Oncofertility Consortium. Often cancer patients have a variety needs that require multiple specialists, thus the need to consult and collaborate to ensure the patient is receiving comprehensive care is pertinent. In a new article in the journal Familial Cancer entitled, “The Consequences of Risk Reducing Salpingo-Oophorectomy: The Case for a Coordinated Approach to Long-Term Follow Up Post Surgical Menopause,” the authors Carmel Pezaro, MD, Paul James, MD, Joanne McKinley, Mary Shanahan, Mary-Anne Young and Gillian Mitchell, MD argue that young women who have had risk reducing salpingo-oophorectomy (RRSO) need improved support services from their healthcare team in the long-term aftermath of this surgery.

First of all, let’s start by going over what salpingo-oophorectomy is for those of you who don’t know. Salpingo-oophorectomy is the removal of the ovary(ies) together with the fallopian tube(s).  For young women with mutations in BRCA1 and BRCA2 genes, an RRSO is often recommended as a preventative measure against the increased risk for breast and ovarian cancer prior to natural menopause.  Up to this point, no long-term studies have been done on pre-menopausal women who have undergone RRSO  focusing on the wider physical consequences of the surgery (aside from sexual dysfunction) such as the severity of menopause symptoms and risk factors like osteoporosis.

The significance of menopause systems in RRSO patients is important to investigate due to research suggesting  that surgical menopause “may result in a more rapid decrease in bone density when compared to natural menopause, it’s association with cognitive impairment or dementia, and an increased risk of cardiovascular mortality.”  Often health care providers emphasize the importance of RRSO in preventative cancer care, but it is unclear whether or not the long-term consequences of this surgery and the management of those symptoms are addressed. Furthermore, symptom severity was markedly higher in women who were less than 50 years old prior to surgery regardless of their menopause status.  The authors hypothesize that one reason for this may be that younger women are more affected by the sexual consequences of menopause because they are engaged in a greater amount of sexual activity.

The results of this study demonstrate that women are not receiving appropriate structured support for their symptoms post surgery. The authors suggest that because their follow-up care crosses many disciplines, it falls between the cracks as providers assume someone else is taking care of it, therefore the medical team providing the long-term genetic follow-up should also be reasonable for coordinating the long-term post RRSO management in conjunction with general practitioners. Read the article, “The Consequences of Risk Reducing Salpingo-Oophorectomy: The Case for a Coordinated Approach to Long-Term Follow Up Post Surgical Menopause.”