Ovaries: Organs or gametes?

Female cancer patients interested in preserving their fertility prior to treatment may choose from a variety of options including egg banking, embryo banking, or ovarian tissue cryopreservation. While some fertility preservation techniques, such as egg and embryo baking, require a 2 to 3 week delay in cancer treatment, ovarian removal and cryopreservation allow women to proceed with cancer treatment almost immediately. After the survivor is cancer-free and wants to have a child, pieces of her ovary can be transplanted back into her body to begin releasing eggs that are unaffected by chemotherapy and radiation. Most cases of ovarian tissue transplantation are called autografts since the donor and recipient are the same. In a few rare cases, women have received ovarian tissue from other individuals, usually sisters.

These rare cases raise an interesting question to ethicists at the Oncofertility Consortium; should ovarian transplantation between two women be legally treated like organs or gametes? The US government regulates organs listed under the National Organ Transplantation Act and sale of these organs is prohibited. In contrast, gametes, such as eggs and sperm, are unregulated and legally able to be purchased and sold. While ovaries are definitely organs, they also hold genetic material with the potential to become life. Oncofertility ethicist Lisa Campo-Engelstein, PhD, discusses these issues in a recent publication titled “Gametes or Organs? How Should we Legally Classify Ovaries Used for Transplantation in the USA?

The article, published in the Journal of Medical Ethics, discusses that the intended use of the ovary should play a major part in categorizing the donation. One 30-year-old woman identified in the article lost her fertility after cancer treatment for non-Hodgkins lymphoma. Her sister donated an ovary to her so she could carry and give birth to a child. In contrast, another patient requested autotransplantation of her own ovarian tissue not to have a child but to relieve early onset menopausal symptoms. While these two intended uses of ovarian tissue are quite different, they may play roles in the legal, ethical, and insurance designations of such transplants.

In the article, Dr. Campo-Engelstein suggests that ovarian tissue should be classified as a gamete because, in either case, once ovarian tissue is donated to a recipient, it may be used to produce offspring, even if that was not the original intent. It is important to remember that these cases are quite rare and it is unlikely that ovarian tissue donation will become common. However, the Oncofertility Consortium believes it is necessary to include ethical scholars into the discussion of any emerging technology as their insights can help guide the scientific research.

Pregnant with Cancer

Most of the time, this blog focuses on the effects of cancer and its treatment on fertility. But what happens if you are already pregnant and then diagnosed with cancer? Suddenly you are not only focused on fostering your pregnancy but also saving your life and your growing fetus.

Cancer diagnoses occur in approximately one out of every 1,000 pregnancies and while pregnant women may be diagnosed with any type of cancer, those that occur most during pregnancy are also commonly seen in young adults. These include cervical cancer, Hodgkin’s lymphoma, malignant melanoma, and thyroid cancer. Breast cancer is the most diagnosed cancer during pregnancy and is seen in one out of every 3,000 pregnant women. Though cancer during pregnancy is not uncommon, significant gaps remain in our knowledge of how cancer, and its treatment, can affect the mother, growing fetus, or the fertility of the child in utero.

While pregnant, a woman’s body is constantly changing and these changes can mask cancer symptoms and delay a diagnosis. Possible cancer symptoms such as bloating, headaches, or body aches commonly occur in pregnancy also and may prevent timely diagnosis. Once diagnosed, many treatments may be off-limits to pregnant patients. Patients diagnosed with cancer during pregnancy face complex treatment decisions. During the first trimester of pregnancy, chemotherapeutics are associated with significant risk for fetal malformation. Even after the first three months, cancer therapies may cause problems for the developing fetus. Some types of radiation therapy, such as radioiodine, damage specific tissues but other therapies are thought to be safer. The many types of cancer treatments and variables during pregnancy have prevented the standardization of care for these women.

Little research has examined the long-term effects of cancer treatment on a child exposed to cancer therapies in utero. Significant studies are needed to examine the fertility and long-term health of these offspring. This work would be used to develop guidelines to treat women who are pregnant and facing a cancer diagnosis. In conjunction with research, expert clinicians should be trained to treat pregnant cancer patients. Moreover, cancer during pregnancy presents a unique and complex scenario that must be carefully treated by a multidisciplinary team to to provide a bright future for both mother and child.

Emerging Treatments and Education for Blood Cancers

Ten percent of all cancer cases are classified as blood cancers because they originate in the blood, bone marrow, or lymphatic tissue that frequently spreads to bone marrow. These cancers, which include leukemia, lymphoma, and myeloma, cause uncontrolled division and growth of abnormal blood cells that can crowd out other necessary blood cells. While they can affect people of all ages, lymphomas are the third most common cancers in children.

One of the greatest problems with these cancers is diagnosis. The typical symptoms of blood born cancers are also common in many non-life threatening illnesses and, as such, can delay accurate diagnoses.  These include generalized tiredness, anemia, bone aches, or bruising. Many blood cells are involved in the immune response and may be reduced in patients, who may also experience frequent infections.

The most common treatments for leukemia, lymphoma, and myeloma are chemotherapy and radiation, which have significantly increased survival rates over the last decades. Remission for these cancers is positively correlated with the amount of chemotherapy used, meaning that the greater the chemotherapy dose, the more likely the cancer cells will be destroyed. Unfortunately, increased chemotherapy also increases the risk for future infertility.

Patients at high risk for relapse or those not responding to traditional cancer therapies are candidates for stem cell transplantation. During a stem cell transplant, cancer-free cells are introduced into a patient and become integrated into bone marrow cavities to begin making healthy bone marrow and stem cells. Stem cell transplants can be used with cells from the patient, called an autologous transplant, or from cells from a donor, called an allogenic transplant. Prior to transplantation, patients undergo significant chemotherapy and whole body irradiation to kill off any remaining cancer cells and inhibit the patient’s immune system to prevent rejection of donor cells. The significant amount of chemotherapy and radiation in stem cell transplantation put patients especially at risk for loosing their fertility and such patients should look into fertility preservation options if they are interested in having biological children later in life.

Fortunately, both oncology providers and patients have many opportunities to learn more about emerging research and treatments in blood born diseases. Last Friday, the Physicians’ Education Resources hosted an event at Northwestern University’s Feinberg School of Medicine to inform providers on “Current Trends in Leukemia, Lymphoma, and Myeloma.” Patients and their families can also learn from the experts in a series of free upcoming events for the public including the Leukemia Research Foundation’s Annual Town Hall Meeting on Sunday, January 30, 2011, which will include physician panelists who will discuss how to find a treatment center, the role of genetics in blood cancers, and clinical trials for patients. Gilda’s Club of Chicago is also holding a seminar on February 2, 2011, on Improving Treatments for Blood Cancers.

Premature Menopause: The Unexpected Symptoms of Cancer Treatment

When most younger women think of menopause, they think of their mothers having hot flashes at the dinner table or hearing about sleepless nights from their aunts but women dealing with cancer at many ages may experience these symptoms. Menopause can manifest in a variety of ways including hot flashes, mood swings, changes in sex drive, and memory loss. While the average age of menopause in the United States is 51, cancer treatments can induce premature menopause, either permanently or temporarily, in much younger women. Survivors of childhood cancer are also up to 13 times more likely to experience premature menopause than women without a cancer history.

The menopausal change is an important issue at any time in a woman’s life but women who are simultaneously dealing with a cancer diagnosis and treatment are even less prepared than older women. In ageing women, menopause is caused by a gradual shutting-down of the ovaries at the end of the reproductive years. With “the change,” the ovaries stop producing the hormones estrogen and progesterone. This hormonal withdrawal causes many of the symptoms of menopause. Young women undergoing a variety of cancer treatments may experience a sudden onset of menopause and its symptoms.

Chemotherapies that cause damage to the ovaries (and cause permanent or temporary infertility) can cause menopause. Some chemotherapies, such as those with alkylating agents, are more likely than others to increase the risk of infertility and menopause. In addition, radiation therapy to the pelvic areas or the brain can induce menopause by damaging the ovaries directly or disrupting the parts of the brain that control ovarian function. Women with ovarian cancer and some cases of breast cancer may have their ovaries surgically removed, which pushes them into a premature menopause termed “surgical menopause.” Some chemical methods of cancer prevention, such as tamoxifen, are prescribed to young women to reduce the risk for primary breast cancer or relapse. Tamoxifen works by interfering with estrogen signaling in the body that can increase the proliferation of cancerous cells but can also commonly cause menopausal side effects in women, though it does not cause menopause.

As with older women, symptoms for premature menopause due to cancer therapy may vary greatly between women. Cancer survivors with premature menopause experience a longer percentage of their lives without the natural protective effects of estrogens. These hormones are important for maintaining bone and heart health and cancer survivors may be at increased risks of long-term effects of premature menopause such as osteoporosis and cardiovascular disease. A new documentary, called Hot Flash Havoc, aims to explain some of these risks and includes interviews with women who experienced premature menopause in their 30s. The Institute for Women’s Health Research is hosting an event with a panel of experts and pre-screening of the documentary on Wednesday, February 2nd in Chicago, IL.

New Publication: Oncofertility and Gender Roles

Investigators at the Oncofertility Consortium recently published a discussion on historical perceptions of infertility in the Journal of Cancer Survivorship. The authors, Shauna Gardino, Sarah Rodriguez, PhD, and Lisa Campo-Engelstein, PhD, related this evidence to contemporary responses to real or perceived fertility loss by male and female cancer survivors. Since oncofertility is a new field, studying infertility and gender allows researchers to gain an understanding of the desire for fertility preservation in male and female cancer patients.

In “Infertility, Cancer, and Changing Gender Norms,” the authors identify that men and women may differently value their reproductive potentials and delve into historical views of infertility between genders. Infertility has often been considered a female problem-though both genders are equally likely to experience infertility. With the advent of modern-day medicine, infertility became a treatable condition for both men and women but, until recent times, almost all patients seeking infertility treatments were women.  The authors further explore the psychological reactions that men and women experience when receiving a diagnosis of infertility and how that has changed over time.

Recent studies have examined the value cancer survivors place on their fertility and it they are distressed by its potential loss. Interestingly, early research identified such values primarily in women but current literature increasingly finds fertility concerns in men, indicating that gender differences in infertility concerns may be decreasing. Perceptions of fertility, infertility, and parenthood have changed rapidly over the past few decades. In the United States, men are more active in child rearing than a generation ago and the authors stipulate that this may play a role on the changing values that men and women place on having biological children.

The National Institutes of Health, which funds the research of the Oncofertility Consortium, supports investigating the changing perception of fertility by cancer survivors, as it can guide fertility preservation recommendations to patients. This new information can help health care providers better care for cancer patients as they make fertility preservation decisions in the short time between diagnosis and treatment.

To learn more information about the history of fertility, join us online at the February 10th Oncofertility Consortium Virtual Grand Rounds with Margaret Marsh, PhD, and Wanda Ronner, MD, who will discuss “The Fertility Doctor: John Rock and the Reproductive Revolution.”

ASCO University for Cancer Providers

The American Society for Clinical Oncology provides continuing education for medical professionals on a range of topics. One recently-launched module, Focus Under Forty, disseminates information to help providers best care for patients between 15 and 39 years old. The free presentations identify the unique challenges that young cancer patients and survivors face in the realm of supportive and cancer care.

The seminars identify medical risks that cancer disease or its treatment may cause for young patients. Some issues, such as osteoporosis and blood clots, may affect adolescents and young adults more than children. Other problems identified in the module are caused by specific cancer therapies, such as anthracycline and high doses of cyclophosphamide, which can increase the risk of heart problems. These and other therapies may also impair the future fertility of cancer survivors. The module further discusses how women who are already pregnant when diagnosed with cancer face their own unique dilemmas, as many therapies may affect the development of a fetus.

The ASCO modules also provide sample questions for health care providers to ask young patients about various aspects of their health. In addition, it provides resources for clinicians and patients to support their needs. This information provides the framework for medical professionals to increase their understanding about cancer in young people and better care for them. Clinicians with detailed questions about fertility and cancer treatment can also call the Oncofertility Consortium‘s FERTline hotline at 866/708-FERT (3378).

National Cancer Institute Committed to Oncofertility

In 1971, the National Cancer Act was signed in to law to find a cure for cancer through research and clinical trials. Since that time, scientists have learned many nuances about cancerous cells and tissues and significantly increased survivorship rates for many cancers. Where a cancer diagnosis used to be a death warrant, today it can be a manageable disease.

As survival rates increase, the National Cancer Institute (NCI), which coordinates federal funding of research, training, and education about cancer, has increased their efforts in survivorship issues, such as secondary cancers and infertility. To support this mission, the NCI included the Oncofertility Consortium in a national list of organizations that provides services to cancer patients and caregivers.

In addition to providing information to patients, the NCI communicates to the larger broader cancer community through its biweekly online NCI Cancer Bulletin. The current version of the newsletter is the NCI’s 250th and includes the article, “Preserving Fertility While Battling Cancer.” The piece discusses the gap between clinical guidelines and fertility preservation care for patients. Fortunately, researchers around the country are developing new fertility preservation treatments and developing tools that will help young patients make significant decisions about their future in the short period of time between diagnosis and treatment. The article highlights some of these researchers, including the Oncofertility Consortium‘s director, Dr. Teresa Woodruff. Continued support from the NCI will someday allow all young cancer patients to spare their fertility and, simultaneously, receive life-saving cancer treatments.

Obesity, Oncology, and Oncofertility

A recent seminar about the role of obesity on breast cancer got me thinking about how weight affects all types of cancer. In the United States, where a third of people are obese, many patients experience weight-related complications in cancer diagnosis and treatment. Obesity increases the risk and mortality rates for colon, breast, endometrial, kidney, esophageal, and other cancers. As unhealthy weights are increasing throughout most of the world, it is important to understand the relationship weight plays on cancer occurrence, treatment, and oncofertility.

In some cases, the link between cancer and obesity is well understood. Adipose tissue, or fat, produces the hormone estrogen that can increase the proliferation of some cancer cells. Hormone-responsive breast tumors are especially sensitive to estrogen, causing obese women to have a 50% increased risk for breast cancer than healthy weight women. Weight loss is negatively correlated with breast cancers, which gives women an opportunity to immediately reduce their cancer risk. Persistently high insulin levels caused by weight gain may also increase the risk for some cancers, including colorectal cancer.

Other cancers are correlated with increased cancer risk but have unknown etiology. For example, a type of esophageal cancer, called adenocarcinoma, and some stomach cancers are linked to obesity, possibly through gastric reflux disease, but no biological mechanism has further explained this link.

In addition to increasing the prospect of developing cancer, obesity can reduce the ability to diagnose abnormally dividing cells. This is because a variety of cancers, including those of the prostate and breast, are less likely to be detected in obese men and women. Obesity is correlated with reduced survivorship in these types of cancers.

Once diagnosed, obesity may continue to impact treatment success. Many chemotherapy does are calculated by body surface area rather than weight, which may lead obese people to receive ineffective doses of chemotherapy. One study also suggests that cancerous cells might not receive full doses of radiation in obese people.

Survivors can benefit from weight loss even after beating cancer. Multiple studies describe an improved quality-of-life in cancer survivors of healthy rather than obese weights. As we all know, fertility is one of the most important issues to young cancer survivors, who already have reduced chances for achieving a spontaneous pregnancy. By itself, obesity can reduce testosterone levels in men and cause ovulation and other conception problems for women, thus inhibiting fertility. Fortunately, survivors can be proactive in this oncofertility issue by developing healthy eating and exercise habits to pass on to the next generation.

Testing Female Fertility After Cancer

Our recent blog on the reproductive options for cancer survivors who do not receive fertility preservation raised some interesting questions. As mentioned in the post, while there is no definitive way to determine if anyone is fertile prior to attempting to conceive, some medical testing can give a good indication of future reproductive potential. Dr. Jennifer Hirshfeld-Cytron, recently discussed these tests with us and said, “what a woman does if she had cancer is the same as if she is over age 40,” and wants to learn about her fertility. A variety of hormonal tests are available that may give such clues for women, often as indicators of the ovarian reserve, the potential of an ovary to produce eggs capable of fertilization.

Two hormone tests, for follicle-stimulating hormone (FSH) and estrogen, are often initially performed to determine reproductive potential in women. FSH is a hormone that stimulates the growth of follicles in the ovary and, when measured the third day after a woman begins her menstrual flow, can indicate potential fertility. Most fertile women have FSH levels below 10 mIU/ml at Day 3, although exact clinical determinations can vary. Menopausal women and cancer survivors who have lost reproductive ability may have elevated FSH levels at this time. Estradiol, the primary type of estrogen in women, is also low at Day 3 in most fertile women.

Another important hormone, inhibin B, can be measured to indicate fertility. Inhibin B is produced by antral follicles, small follicles that require FSH to survive. Interestingly, as small antral follicles grow, they produce inhibin B, which then inhibits FSH production. Three days after menstruation begins, inhibin B is normally elevated but these tests are harder to interpret and, therefore, used less regularly than FSH and estrogen.

The two gold-standard measurements for ovarian reserve test anti-Müllerian hormone (AMH) levels and a woman’s antral follicle count. While AMH testing has been in existence for years, research resulted in its increased utility during recent years. AMH is a less variable hormone that  increases during puberty and remains constant until menopause. Granulosa cells, specialized “nurse cells” within follicles, produce AMH that also remains relatively stable across the menstrual cycle. Thus, this test can be used at any point in the menstrual cycle and even when a woman is taking hormonal birth control.

An additional reproductive test for cancer survivors interested in preserving their fertility is a count of their antral follicles at the beginning of the menstrual cycle. These follicles can be viewed near the surface of the ovary with an ultrasound. It is important to note that these counts are good indicators of the number of eggs that may be retrieved through hormonal stimulation during in vitro fertilization procedures, rather than the spontaneous pregnancies that may be an option for cancer survivors.

Future research will determine if these tests can be tailored to cancer survivors. One effect of cancer treatment can be temporary or permanent infertility begining during therapy that continues for months, years, or forever. Clarisa Gracia MD, an Oncofertility Consortium investigator, examines how fertility measurements change during and after active cancer treatment. Potentially, such measurements could provide personalized treatment to women that would destroy their cancers and, simultaneously, allow them to retain reproductive ability.

Fertility Options AFTER Cancer

We at the Oncofertility Consortium spend much of our time developing new techniques and options for young cancer patients who wish to preserve their fertility before undergoing cancer therapy. But what options are available to cancer survivors who did not undergo fertility-sparing treatments?

Cancer patients may not protect their reproductive potential before beginning cancer treatment for many reasons including an immediate need for care, unavailable options near a patient’s home, and young age at cancer diagnosis, among others. Once they successfully beat cancer and start thinking about the future, young people may begin to wonder about their reproductive options. Since tailored treatments are used to combat each distinct case of cancer, fertility is also differently affected in every case. Treatments that may affect fertility include surgery, radiation, and chemotherapy. Even the doses, locations, and combinations of these treatments may affect later reproductive ability. Finally, these variables can alter the fertility of individual cancer fighters in different ways.

Survivors who wonder about the impact of cancer treatment on their reproductive potential should talk with a physician or fertility counselor. Survivors with additional questions or need for referrals can contact the FERTline oncofertility patient navigators. Analysis of a man’s semen sample can determine if the number and mobility of sperm indicates diminished fertility. Women may have their ovaries, fallopian tubes, and uterus examined and their hormone levels measured. Though these tests may give an indication of fertility, there is no sure-fire way to determine person’s reproductive potential until he or she attempts to conceive a child.

Cancer survivors who find their fertility impaired may use one of the many options in assisted reproductive technology (ART) to have biological children. Men with reduced sperm count or mobility may undergo intrauterine insemination or intracytoplasmic sperm injection, which involves depositing sperm into the uterus or injected into an egg, respectively, to increase the chance of conceiving. Male or female cancer survivors can also fertilize their sperm or eggs through in vitro fertilization (IVF) to have a child.

Survivors who lose reproductive ability after cancer and its treatment can employ third party reproduction to have children. These include using donor sperm, eggs, or embryos to have a child. Women whose bodies are unable to support a pregnancy to term can also employ a surrogate, or gestational carrier, to carry the survivor’s biological children or with the use of donor gametes. Adoption is also an option that is becoming increasingly available to cancer survivors, in part, due to some of the research at the Oncofertility Consortium. Thus, cancer patients who did not undergo fertility preservation should not lose hope as they still have the ability to build a family.

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