From Medscape Medical News
Jim Kling
October 14, 2010 — Correction: The original text of this article described the daily iron dose for infants 6 to 12 months as 11 mg/kg. This is incorrect.
The dose should be 11 mg/day.
October 5, 2010 (San Francisco, California) — Iron deficiency is one of the most common, yet undetected, problems among children. Here at the American Academy of Pediatrics (AAP) 2010 National Conference and Exhibition, the American Association of Pediatrics released a clinical report, with guidelines for iron intake in infants and children and to improve screening methods.
The clinical report, entitled Diagnosis and Prevention of Iron Deficiency and Iron Deficiency Anemia in Infants and Young Children (0–3 Years of Age), was published online October 5 in Pediatrics. It is a revision of a 1999 policy statement.
Iron deficiency can have long-term irreversible effects on a child's cognitive and behavioral development. By the time a child develops iron-deficiency anemia, it might be too late to prevent future problems. "The body has a preferential tracking of iron. Red blood cells take precedence over the iron requirements of the brain. By the time you get iron-deficiency anemia, you've been iron-deficient for a long time," said Frank Greer, MD, professor of pediatrics at the University of Wisconsin School of Medicine and Public Health in Madison, and a coauthor of the report.
The 1999 guidelines call for children to have their hemoglobin checked sometime between 9 and 12 months of age, and again between 15 and 18 months of age. However, the existing test misses many children with iron deficiency and iron-deficiency anemia. Even those found to be iron deficient frequently receive no follow-up testing or treatment, according to Dr. Greer.
Although supplementing all children with iron would reduce iron deficiency, such a program does not have widespread support in the medical community at this point. That's partly because toddlers, who are the most widely affected group, have a wide range of diets and it is unclear what foods to fortify.
Liquid iron supplements or vitamins could be used, but there is a risk for iron overload in some populations, according to Michael K. Georgieff, MD, professor of pediatrics and child psychology and director of the Center for Neurobehavioral Development at the University of Minnesota in Minneapolis. Dr. Georgieff was on the AAP's committee on nutrition from 1993 to 1999 and played a key role in the 1999 guidelines.
"Iron supplementation and awareness of iron nutrition has probably been one of the most successful public health programs in the United States. In the 1960s, iron deficiency was probably 30% to 40%. Today, it may be under 10%. But in trying to eliminate that last 10%, you have to consider it in terms of exposing kids to [too much] iron," said Dr. Georgieff.
No single screening test is available that will accurately characterize the iron status of a child, he noted. In the report, the AAP recommends 4 protocols for screening for iron deficiency and iron-deficiency anemia, including combinations of several tests and follow-up protocols. "It's burdensome," Dr. Greer admitted.
"Since we're not going to do universal supplementation, we need to identify kids who are at risk for iron deficiency and start targeting them," said Dr. Georgieff, who studies the neurodevelopmental effects of iron deficiency in children.
The AAP report identified several factors associated with iron deficiency and iron-deficiency anemia, including prematurity or low birth-weight, lead exposure, exclusive breastfeeding past 4 months of age without iron supplements, and weaning to foods that don't include iron-fortified cereals or iron-rich foods. Infants with special healthcare needs might also be at risk. Children of low economic status, particularly those of Mexican American descent, are also of concern, according to the report, which recommends selective screening for these individuals.
The guidelines also address means to prevent iron deficiency through a diet of foods naturally rich in iron, such as meat, shellfish, legumes, iron-rich fruits and vegetables, and iron-fortified cereals. Fruits rich in vitamin C help iron absorption. Some children might require liquid iron supplements or chewable vitamins to get sufficient iron.
The AAP recommends varying amounts of iron based on a child's age:
* Term, healthy infants have sufficient iron for the first 4 months of life. Because human breast milk contains very little iron, breastfed infants should be supplemented with 1 mg/kg per day of oral iron from 4 months of age until iron-rich foods (such as iron-fortified cereals) are introduced.
* Formula-fed infants will receive adequate iron from formula and complementary foods. Whole milk should not be used before 12 months.
* Infants 6 to 12 months of age need 11 mg/day of iron a day. When infants are given complementary foods, red meat and vegetables with high iron content should be introduced early. Liquid iron supplements can be used if iron needs are not met by formula and complementary foods.
* Toddlers 1 to 3 years of age need 7 mg per day of iron. It is best if this comes from foods such as red meats, iron-rich vegetables, and fruits with vitamin C, which enhance iron absorption. Liquid supplements and chewable multivitamins can also be used.
* All preterm infants should have at least 2 mg/kg of iron per day until 12 months of age, which is the amount of iron in iron-fortified formulas. Preterm infants fed human milk should receive an iron supplement of 2 mg/kg per day by 1 month of age; this should be continued until the infant is weaned to iron-fortified formula or begins eating foods that supply the required 2 mg/kg of iron.
American Academy of Pediatrics (AAP) 2010 National Conference and Exhibition. Presented October 5, 2010.
Wednesday, January 19, 2011
Recommendation of 6 Months of Breast-Feeding Scrutinized
From Medscape Medical News
Emma Hitt, PhD
January 18, 2011 — The evidence in favor of 6 months of exclusive breast-feeding has come under scrutiny in a new study published by the BMJ.
A review article assessing the evidence was published by researcher Mary Fewtrell, MD, from the Child Nutrition Research Center at the University College London Institute of Child Health, United Kingdom, and colleagues was published online January 13 in the BMJ.
Current World Health Organization guidelines recommend that infants be exclusively breast-fed for 6 months; that is, with a diet that excludes solids or any fluids other than breast milk, including infant formulas. These guidelines, announced in 2001, were adopted by the United Kingdom in 2003.
Exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months.
"The critical question is whether the United Kingdom should alter its advice on the introduction of complementary foods while new evidence is assembled," the authors note.
The current report maintains that this change in policy occurred without formal consideration of the scientific evidence. Since the announcement of the World Health Organization guidelines, findings from a number of studies suggest that breast milk may not be a reliable single source of nutrition for the first 6 months of life. In addition, the European Food Safety Authority recently concluded that it was safe to introduce complementary foods between 4 and 6 months' of age for infants residing in the European Union.
In the current study, Dr. Fewtrell and colleagues reassessed the evidence in favor of 6 months of exclusive breast-feeding and concluded that exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months. Higher rates of iron deficiency anemia are an additional concern, having been linked to poorer long-term mental, motor, and social development. Furthermore, existing data suggest an increased risk for reaction to certain allergens (eg, gluten, which has been linked to celiac disease) when their introduction is delayed past 6 months.
Even in the case of protection from infection — considered to be a clear benefit of breast-feeding — a study conducted in Spain showed that these benefits largely accrue to infants breast-fed for 3 months, providing little "extra" benefit thereafter. However, a large study based in the United States did find that infants breast-fed exclusively for more than 6 months had a lower risk for otitis media and pneumonia when compared with infants who were breast-fed exclusively for 4 to 6 months.
Dr. Fewtrell and colleagues conclude that, in light of data that have accumulated during the last 10 years (ie, since the World Health Organization guidelines came out in 2001), the time is ripe for an evidence-based reappraisal of the United Kingdom's stance in this important, yet controversial, area.
According to independent commentator Richard Aubry, MD, MPH, a professor of obstetrics and gynecology at Upstate Medical University in New York, this work does not add any new evidence about the pros and cons regarding adding other foods earlier than 6 months' age.
He told Medscape Medical News that clinicians "need to keep the message clear: Exclusive breast-feeding is the preferred method for feeding the baby until approximately 6 months of age, and then mothers should be encouraged to continue breast-feeding as long as they can. These are the specific terms and overall advice by [the American Congress of Obstetricians and Gynecologists]."
This study was not commercially funded. Three of the 4 authors of the study report having performed consultancy work and/or received research funding in the past 3 years from companies that manufacture infant formulas and baby foods.
BMJ. Published online January 13, 2011.
Emma Hitt, PhD
January 18, 2011 — The evidence in favor of 6 months of exclusive breast-feeding has come under scrutiny in a new study published by the BMJ.
A review article assessing the evidence was published by researcher Mary Fewtrell, MD, from the Child Nutrition Research Center at the University College London Institute of Child Health, United Kingdom, and colleagues was published online January 13 in the BMJ.
Current World Health Organization guidelines recommend that infants be exclusively breast-fed for 6 months; that is, with a diet that excludes solids or any fluids other than breast milk, including infant formulas. These guidelines, announced in 2001, were adopted by the United Kingdom in 2003.
Exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months.
"The critical question is whether the United Kingdom should alter its advice on the introduction of complementary foods while new evidence is assembled," the authors note.
The current report maintains that this change in policy occurred without formal consideration of the scientific evidence. Since the announcement of the World Health Organization guidelines, findings from a number of studies suggest that breast milk may not be a reliable single source of nutrition for the first 6 months of life. In addition, the European Food Safety Authority recently concluded that it was safe to introduce complementary foods between 4 and 6 months' of age for infants residing in the European Union.
In the current study, Dr. Fewtrell and colleagues reassessed the evidence in favor of 6 months of exclusive breast-feeding and concluded that exclusive breast-feeding may not adequately meet infants' energy needs for a full 6 months. Higher rates of iron deficiency anemia are an additional concern, having been linked to poorer long-term mental, motor, and social development. Furthermore, existing data suggest an increased risk for reaction to certain allergens (eg, gluten, which has been linked to celiac disease) when their introduction is delayed past 6 months.
Even in the case of protection from infection — considered to be a clear benefit of breast-feeding — a study conducted in Spain showed that these benefits largely accrue to infants breast-fed for 3 months, providing little "extra" benefit thereafter. However, a large study based in the United States did find that infants breast-fed exclusively for more than 6 months had a lower risk for otitis media and pneumonia when compared with infants who were breast-fed exclusively for 4 to 6 months.
Dr. Fewtrell and colleagues conclude that, in light of data that have accumulated during the last 10 years (ie, since the World Health Organization guidelines came out in 2001), the time is ripe for an evidence-based reappraisal of the United Kingdom's stance in this important, yet controversial, area.
According to independent commentator Richard Aubry, MD, MPH, a professor of obstetrics and gynecology at Upstate Medical University in New York, this work does not add any new evidence about the pros and cons regarding adding other foods earlier than 6 months' age.
He told Medscape Medical News that clinicians "need to keep the message clear: Exclusive breast-feeding is the preferred method for feeding the baby until approximately 6 months of age, and then mothers should be encouraged to continue breast-feeding as long as they can. These are the specific terms and overall advice by [the American Congress of Obstetricians and Gynecologists]."
This study was not commercially funded. Three of the 4 authors of the study report having performed consultancy work and/or received research funding in the past 3 years from companies that manufacture infant formulas and baby foods.
BMJ. Published online January 13, 2011.
Wednesday, January 12, 2011
Frozen Hope: Fertility Preservation for Women with Cancer
From Journal of Midwifery & Women's Health
Gwendolyn P. Quinn, PhD; Susan T. Vadaparampil, PhD, MPH; Paul B. Jacobsen, PhD; Caprice Knapp, PhD; David L. Keefe, MD; Geri E. Bell, BS
Posted: 03/12/2010; J Midwifery Womens Health. 2010;55(2):175-180. © 2010 Elsevier Science, Inc.
Abstract
Young women diagnosed with cancer have the option of preserving their fertility by using assisted reproductive technology (ART) techniques prior to undergoing cancer treatment. This article presents a composite case of a young woman with cancer who had many unanswered emotional and ethical questions about her future as a parent. Fertility preservation techniques, including preimplantation genetic diagnosis (PGD), and related patient education are described.
Current literature regarding reproductive counseling for cancer survivors is reviewed. Resources for providing psychosocial support for decisions about fertility preservation are lagging behind the rapid pace of scientific advancements in cancer treatment and ART.
As more young women are surviving cancer and taking steps to preserve fertility, there is great need for the provision of psychologic support services and the establishment of ethical guidelines to aid them on this path.
Women's health care providers can provide support to cancer survivors facing fertility and parenting issues by becoming knowledgeable about the long-term aspects of decision making and developing educational materials and guidelines for these patients.
Introduction
The number of young women diagnosed with cancer is increasing.[1] Recent data indicate the most common types of cancer occurring among women aged 15 to 29 are cancers of the female genital system, lymphoma, thyroid cancer, melanoma, and breast cancer.[1] Advances in cancer treatment have resulted in an increased number of long-term survivors. Young women who are diagnosed with cancer must make decisions about their reproductive future at a time when they are emotionally fragile. In addition to processing the cancer diagnosis and associated treatment choices, the decisions required concerning preserving future fertility and the time constraints associated with judgments can understandably be emotionally distressing. Women without cancer who are diagnosed with infertility have typically had at least a year in which to process their desire for a child and understand the barriers and benefits for each of the assisted reproductive technologies that may be available to their unique situation. The traditional reproductive counseling and the time frame for decision making offered to a woman or a couple experiencing infertility may not be available to a woman with a cancer diagnosis. This article presents a composite case of a young woman with cancer who faced infertility due to her cancer treatment but hoped to have a biologic child in the future. The case is examined in light of what is known and not yet known about the medical and psychosocial aspects of fertility preservation for women with cancer.
Cancer and Infertility
The best treatment for cancer may lead to impaired fertility or the complete loss of fertility. However, rates of infertility vary depending on a number of factors, including cancer site, type of treatment, and the age of the patient. Infertility in cancer patients can be caused by the cancer or the type of cancer treatment received. Exact infertility rates are not known, because there are no valid measures for women to establish that fertility was present prior to treatment. Women who undergo chemotherapy or radiation for malignancies during reproductive years have a 40% to 80% chance of losing fertility. The treatments that produce the greatest risk for infertility include alkylating agents such as cyclophosphamide, methotrexate, and fluorouracil in chemotherapy; total body radiation; and external beam radiation in a field that includes the ovaries. Both chemotherapy and radiation can cause premature ovarian failure for females, often leading to premature menopause.
Fertility Preservation
Rapidly improving assisted reproductive technologies and therapies offer some opportunities to preserve the fertility of female patients receiving chemotherapy and/or radiation. The emerging field of proteomics is leading the way toward the identification of proteins involved in oocyte maturation, embryo development, and implantation that could improve assisted reproduction techniques. Assisted reproductive technology (ART) consists of clinical treatments and laboratory procedures that include the handling of human oocytes, sperm, or embryos, with the intent of establishing a pregnancy. This includes, but is not limited to, in vitro fertilization (IVF), intracytoplasmic sperm injection, gamete intrafallopian transfer, zygote intrafallopian transfer, embryo biopsy, preimplantation genetic diagnosis (PGD), embryo cryopreservation, oocyte or embryo donation, and gestational surrogacy. Table 1 includes definitions of each type of procedure.
There are currently only two established options for fertility preservation for women with cancer: 1) oophoropexy, moving the ovaries out of the range of radiation, and 2) embryo cryopreservation, the freezing of fertilized eggs via IVF for later use. Additional techniques for fertility preservation, such as oocyte cryopreservation (freezing unfertilized eggs) and ovarian tissue cryopreservation (freezing strips of ovarian tissue, which may be transplanted either orthotopically within the pelvis or heterotopically within subcutaneous tissue), are less established and not widely available. All options must typically be considered and undertaken prior to the initiation of treatment.
There are also ethical, spiritual, and legal issues related to decision making about fertility preservation, such as the disposition of stored embryos. These issues often concern health care professionals as well and may pose barriers to the discussion of or assistance with the use of ART.Some patients and their families choose to consider posthumous parenting, that is, they intend to use the stored embryos whether or not the patient survives. Although this is an ethically charged situation, the American Society for Reproductive Medicine recommends that health care professionals do not deny patients assistance for this form of reproduction and also advises that "precise instructions" be given by the patient in the event of his or her death. The precise instructions for the disposition of DNA are part of the informed consent counseling, and patients are required to outline the procedures for future use of the stored embryos (e.g., willed to a spouse or parent, discarded, donated, etc.) If these procedures are followed, this can reduce the need for legal involvement to determine ownership of the stored embryos in the event of the patient's death or in the case of divorce. The United Kingdom also regulates the disposition of embryos through informed consent. Information about this practice is not readily available from other countries.
Preimplantation Genetic Diagnosis for Hereditary Cancers
The concerns of individuals affected with cancer regarding biologic parenthood are often focused on the health risks for future children. Carriers of genetic mutations, such as women with mutations in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. For those survivors who are concerned about the possibility of transmitting a serious hereditary cancer to their future children, limited biologic parenting options are available. Preimplantation genetic diagnosis is one option for parents who want to avoid this dilemma.
Preimplantation genetic diagnosis is a procedure used in conjunction with IVF to screen for specific genetic or chromosomal abnormalities before transferring the fertilized eggs into the woman. Preimplantation genetic diagnosis involves microsurgical removal of one or two blastomeres (embryos) at the six- to eight-cell stage, usually 3 days after fertilization. At this stage, the cells of the embryo have not differentiated into particular body tissues, and there is not likely to be damage to the resulting embryo. Biopsies of embryos are analyzed to detect genetic abnormalities arising from the maternal or paternal chromosomes. However, since diagnostic tests are performed on a single cell, the possibility of misdiagnosis must be considered. Preimplantation genetic diagnosis results are usually available within 48 hours after biopsy, which corresponds to day 5 after egg retrieval. Depending on their original quality, embryos may or may not reach the blastocyst stage, which is the final stage of in vitro development.[9] Usually on day 5, embryos free of genetic defects are transferred into the patient; however, some women or couples may choose to cryopreserve affected embryos. Currently data are not collected on the health of offspring born through the use of PGD, so it is unknown if there are related long-term health consequences.
Preimplantation genetic diagnosis has been accomplished for both cancer-specific disorders such as adenomatous polyposis coli, BRCA1/2, retinoblastoma, Li-Fraumeni syndrome, and von Hippel-Lindau syndrome, as well as disorders predisposing to neoplasia (Fanconi anemia, Wiskott-Aldrich syndrome).[11–13] The PGD procedure has been performed for a little over a decade and involves the use of IVF so parents can select the embryos that are implanted into the uterus. Embryos are tested for genetic status at the early stages of development. The ability to use PGD testing for all cancer types is not currently possible. The regulations developed for PGD testing and the types of cancers for which embryos can be tested vary by country and availability within each country. For example, the ability to use PGD for BRCA became available in 2006; however, other hereditary cancers, such as familial adenomatous polyposis, have been tested for in the Netherlands since 2004, although BRCA testing of embryos is not allowed there.[13] Thus, although the availability of PGD testing for certain cancer types varies by country and facility, the psychosocial issues women face over certain issues such as embryo selection are quite similar. One option for PGD is to implant only those embryos that are found to be unaffected. Some parents still may choose to implant affected embryos with the knowledge that the potential for hereditary syndromes is high. In the past, options for hereditary cancer mutation carriers included not having children or undergoing amniocentesis or other forms of prenatal diagnosis. Preimplantation genetic diagnosis allows parents to avoid terminating a pregnancy and/or risking the health of the fetus or the mother.
In Europe, guidelines regulate which clinics can perform PGD and for which diseases they can screen. In the United Kingdom, the Human Fertilisation and Embryology Authority (HFEA) governs which procedures are acceptable and provides guidelines as to how these procedures should be performed. It also licenses clinics that wish to use any type of ART. Currently, no such oversight exists in the United States.[14] At present, HFEA has approved PGD to test for 50 disorders, including hereditary breast and ovarian cancers, which can be caused by a mutation in the BRCA1/2 genes. Mutations in BRCA1/2 are passed down in families in an autosomal dominant pattern, and children of individuals with a BRCA1/2 mutation have a 50% chance of inheriting it. Women who carry the BRCA1/2 gene have an 80% lifetime risk of developing breast cancer and approximately a 40% risk of developing ovarian cancer. With such a high risk for developing cancer, the HFEA considers it appropriate to allow PGD for this cancer predisposition gene.
The use of PGD in the United States is predicted to be approximately 20% across all embryos created via IVF; however, it is not known specifically which abnormalities or conditions PGD testing has been used for.[11] Almost 2000 babies have been born after the process of PGD since it was developed in 1989.[15] There are no published reports of increased fetal defects or late effects in babies born using PGD, but it is possible abnormalities may occur later in life as a result of the procedure.[9,10,13] Preimplantation genetic diagnosis cannot detect all genetic irregularities because only a limited number of chromosomes can be tested per procedure, and misdiagnosis may still occur.Prenatal diagnosis (amniocentesis or chorionic villus sampling) may still need to be considered after use of PGD to determine if the fetus carries a genetic abnormality.
Cancer and Parenting
Although cancer presents obstacles to becoming a parent, an experience with a major illness can also make survivors excellent parents, with greater emotional resilience and appreciation for parenthood. However, the decision to become a biologic parent after cancer must be weighed with the obstacles of the time and expense of fertility preservation procedures such as IVF. Adoption remains an option, but cancer survivors may experience difficulty in becoming qualified as adoptive parents. Survivors seeking adoption may encounter discrimination from US adoption agencies because of the survivor's physical health and condition.Some US agencies require an applicant to be at least 5 years post-treatment before he or she can qualify as a potential adoptive parent. Some cancer survivors have had success qualifying for the adoption of foreign-born children through international adoption agencies. Additionally, infertility treatments and adoption procedures may be too costly for some survivors, especially after an expensive battle with cancer.
In addition to concerns about cancer recurrence and parenting, survivors often have psychosocial concerns related to pregnancy and parenting, many of which mirror issues faced by any woman considering the use of ART. These concerns focus primarily on risks of birth defects or cancer in offspring; anxiety about hormonal factors related to pregnancy or infertility treatment increasing a risk of cancer recurrence, leaving the spouse/partner to raise the child if the parent with cancer dies; and conflicts about using ART because of ethical beliefs or religious beliefs, as some religions prohibit the use of donor gametes
Reproductive Counseling for Cancer Survivors
Canada and Schover[22] identified the need for research to promote improved patient education regarding cancer and reproductive health. Although the researchers indicate oncologists would probably be the ideal health care professionals for cancer patients to have in-depth discussions with regarding fertility preservation and future parenting, they further note that time constraints may make this unrealistic. However, their objective is to promote better information about the risks of infertility to the newly diagnosed cancer patient, a communication initiative for which other researchers have made a similar plea. Although this is a crucial first step on the road to improved quality of life in cancer survivors and risk management for infertility, it does not fully address the decision-making issues the patient must consider in rapid time.
There is little research about the psychosocial decision making of newly diagnosed cancer survivors regarding fertility and PGD choices. Unlike infertility in couples without a cancer diagnosis, the impending infertility of a cancer patient and the need for treatment provides a narrow window of time for patient counseling. Although some patients, similar to the woman in this case study, perceive stored embryos and oocytes as "frozen hope," decisions about the future of the stored embryo can be agonizing. Recent studies have begun to examine patient choices for the donation or destruction of stored embryos.
One study conducted in an Australian population among 235 couples with banked embryos found 27% would donate to stem cell research or infertility research, whereas 15% would consider donating to another couple.
However, the disagreement rate among the couples was high, with more than 40% disagreeing over each of the options.Additionally, 90% of the couples indicated they would want to discuss donation with a health care professional rather than make the decision alone. The majority preferred a fertility specialist or scientist as their choice for the discussions. This study highlights the fact that deciding to pursue ART is only the beginning of the decision-making process that may span several years.
Other researchers have begun to examine how patients feel about stored embryos and oocytes in fertility clinics. An emerging trend indicates patients may enter reproductive counseling with one set of ideas about stored embryos and feel differently after a successful pregnancy or failed attempts.[26–28] However, no studies have examined this meaning among women who stored embryos or oocytes due to cancer treatment.
There are currently no guidelines specifically tailored for the reproductive counseling needs of newly diagnosed cancer patients, especially for those who may have concerns about hereditary cancer syndromes. Peshkin et al.suggest strong support for such guidelines and continued collaborations among providers who work in oncology, cancer genetics, and ART.Conclusion
Finishing cancer treatment and transitioning from patient to survivor does not end the psychologic trauma of cancer. There are a plethora of issues that survivors often face after their cancer is in remission that affect quality of life. This case report illustrates the loss of fertility often experienced by a cancer survivor as a result of treatment. Young women with genetic mutations, such as those in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. Considering PGD to avoid passing the mutation may allow parents to select only healthy embryos, but decisions about the fate of embryos that are mutation carriers remain perplexing.
Decisions about using fertility preservation typically must be made at the same time as other decisions about treatment of a life-threatening diagnosis. Ethical, religious, financial, and other implications of preserving her fertility confront the woman before she begins cancer treatment. This leaves limited time for the patient to consider the implications of her choices and how she may feel about her reproductive options at a later date.
Given that 2.5 million young adults in the United States have survived cancer, more research is needed on the psychosocial aspects of parenthood, particularly to identify the psychosocial needs of survivors regarding cryopreservation and PGD. The resources for providing support for using ART and PGD lag behind the rapid advance of technology. Table 2 provides a list of online sources of information for patients and health care professionals. Communication guidelines should be developed for informing cancer patients of the emotional and psychosocial impact of fertility preservation, with particular regard to future decision making. More research is needed to develop educational resources specific to this population that will aid the women newly diagnosed with cancer in decision making. Although social support is an important aspect of survivorship, the medical community can also provide support by assigning social workers or counselors to survivors and to the newly diagnosed who are facing fertility and parenting issues.
Gwendolyn P. Quinn, PhD; Susan T. Vadaparampil, PhD, MPH; Paul B. Jacobsen, PhD; Caprice Knapp, PhD; David L. Keefe, MD; Geri E. Bell, BS
Posted: 03/12/2010; J Midwifery Womens Health. 2010;55(2):175-180. © 2010 Elsevier Science, Inc.
Abstract
Young women diagnosed with cancer have the option of preserving their fertility by using assisted reproductive technology (ART) techniques prior to undergoing cancer treatment. This article presents a composite case of a young woman with cancer who had many unanswered emotional and ethical questions about her future as a parent. Fertility preservation techniques, including preimplantation genetic diagnosis (PGD), and related patient education are described.
Current literature regarding reproductive counseling for cancer survivors is reviewed. Resources for providing psychosocial support for decisions about fertility preservation are lagging behind the rapid pace of scientific advancements in cancer treatment and ART.
As more young women are surviving cancer and taking steps to preserve fertility, there is great need for the provision of psychologic support services and the establishment of ethical guidelines to aid them on this path.
Women's health care providers can provide support to cancer survivors facing fertility and parenting issues by becoming knowledgeable about the long-term aspects of decision making and developing educational materials and guidelines for these patients.
Introduction
The number of young women diagnosed with cancer is increasing.[1] Recent data indicate the most common types of cancer occurring among women aged 15 to 29 are cancers of the female genital system, lymphoma, thyroid cancer, melanoma, and breast cancer.[1] Advances in cancer treatment have resulted in an increased number of long-term survivors. Young women who are diagnosed with cancer must make decisions about their reproductive future at a time when they are emotionally fragile. In addition to processing the cancer diagnosis and associated treatment choices, the decisions required concerning preserving future fertility and the time constraints associated with judgments can understandably be emotionally distressing. Women without cancer who are diagnosed with infertility have typically had at least a year in which to process their desire for a child and understand the barriers and benefits for each of the assisted reproductive technologies that may be available to their unique situation. The traditional reproductive counseling and the time frame for decision making offered to a woman or a couple experiencing infertility may not be available to a woman with a cancer diagnosis. This article presents a composite case of a young woman with cancer who faced infertility due to her cancer treatment but hoped to have a biologic child in the future. The case is examined in light of what is known and not yet known about the medical and psychosocial aspects of fertility preservation for women with cancer.
Cancer and Infertility
The best treatment for cancer may lead to impaired fertility or the complete loss of fertility. However, rates of infertility vary depending on a number of factors, including cancer site, type of treatment, and the age of the patient. Infertility in cancer patients can be caused by the cancer or the type of cancer treatment received. Exact infertility rates are not known, because there are no valid measures for women to establish that fertility was present prior to treatment. Women who undergo chemotherapy or radiation for malignancies during reproductive years have a 40% to 80% chance of losing fertility. The treatments that produce the greatest risk for infertility include alkylating agents such as cyclophosphamide, methotrexate, and fluorouracil in chemotherapy; total body radiation; and external beam radiation in a field that includes the ovaries. Both chemotherapy and radiation can cause premature ovarian failure for females, often leading to premature menopause.
Fertility Preservation
Rapidly improving assisted reproductive technologies and therapies offer some opportunities to preserve the fertility of female patients receiving chemotherapy and/or radiation. The emerging field of proteomics is leading the way toward the identification of proteins involved in oocyte maturation, embryo development, and implantation that could improve assisted reproduction techniques. Assisted reproductive technology (ART) consists of clinical treatments and laboratory procedures that include the handling of human oocytes, sperm, or embryos, with the intent of establishing a pregnancy. This includes, but is not limited to, in vitro fertilization (IVF), intracytoplasmic sperm injection, gamete intrafallopian transfer, zygote intrafallopian transfer, embryo biopsy, preimplantation genetic diagnosis (PGD), embryo cryopreservation, oocyte or embryo donation, and gestational surrogacy. Table 1 includes definitions of each type of procedure.
There are currently only two established options for fertility preservation for women with cancer: 1) oophoropexy, moving the ovaries out of the range of radiation, and 2) embryo cryopreservation, the freezing of fertilized eggs via IVF for later use. Additional techniques for fertility preservation, such as oocyte cryopreservation (freezing unfertilized eggs) and ovarian tissue cryopreservation (freezing strips of ovarian tissue, which may be transplanted either orthotopically within the pelvis or heterotopically within subcutaneous tissue), are less established and not widely available. All options must typically be considered and undertaken prior to the initiation of treatment.
There are also ethical, spiritual, and legal issues related to decision making about fertility preservation, such as the disposition of stored embryos. These issues often concern health care professionals as well and may pose barriers to the discussion of or assistance with the use of ART.Some patients and their families choose to consider posthumous parenting, that is, they intend to use the stored embryos whether or not the patient survives. Although this is an ethically charged situation, the American Society for Reproductive Medicine recommends that health care professionals do not deny patients assistance for this form of reproduction and also advises that "precise instructions" be given by the patient in the event of his or her death. The precise instructions for the disposition of DNA are part of the informed consent counseling, and patients are required to outline the procedures for future use of the stored embryos (e.g., willed to a spouse or parent, discarded, donated, etc.) If these procedures are followed, this can reduce the need for legal involvement to determine ownership of the stored embryos in the event of the patient's death or in the case of divorce. The United Kingdom also regulates the disposition of embryos through informed consent. Information about this practice is not readily available from other countries.
Preimplantation Genetic Diagnosis for Hereditary Cancers
The concerns of individuals affected with cancer regarding biologic parenthood are often focused on the health risks for future children. Carriers of genetic mutations, such as women with mutations in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. For those survivors who are concerned about the possibility of transmitting a serious hereditary cancer to their future children, limited biologic parenting options are available. Preimplantation genetic diagnosis is one option for parents who want to avoid this dilemma.
Preimplantation genetic diagnosis is a procedure used in conjunction with IVF to screen for specific genetic or chromosomal abnormalities before transferring the fertilized eggs into the woman. Preimplantation genetic diagnosis involves microsurgical removal of one or two blastomeres (embryos) at the six- to eight-cell stage, usually 3 days after fertilization. At this stage, the cells of the embryo have not differentiated into particular body tissues, and there is not likely to be damage to the resulting embryo. Biopsies of embryos are analyzed to detect genetic abnormalities arising from the maternal or paternal chromosomes. However, since diagnostic tests are performed on a single cell, the possibility of misdiagnosis must be considered. Preimplantation genetic diagnosis results are usually available within 48 hours after biopsy, which corresponds to day 5 after egg retrieval. Depending on their original quality, embryos may or may not reach the blastocyst stage, which is the final stage of in vitro development.[9] Usually on day 5, embryos free of genetic defects are transferred into the patient; however, some women or couples may choose to cryopreserve affected embryos. Currently data are not collected on the health of offspring born through the use of PGD, so it is unknown if there are related long-term health consequences.
Preimplantation genetic diagnosis has been accomplished for both cancer-specific disorders such as adenomatous polyposis coli, BRCA1/2, retinoblastoma, Li-Fraumeni syndrome, and von Hippel-Lindau syndrome, as well as disorders predisposing to neoplasia (Fanconi anemia, Wiskott-Aldrich syndrome).[11–13] The PGD procedure has been performed for a little over a decade and involves the use of IVF so parents can select the embryos that are implanted into the uterus. Embryos are tested for genetic status at the early stages of development. The ability to use PGD testing for all cancer types is not currently possible. The regulations developed for PGD testing and the types of cancers for which embryos can be tested vary by country and availability within each country. For example, the ability to use PGD for BRCA became available in 2006; however, other hereditary cancers, such as familial adenomatous polyposis, have been tested for in the Netherlands since 2004, although BRCA testing of embryos is not allowed there.[13] Thus, although the availability of PGD testing for certain cancer types varies by country and facility, the psychosocial issues women face over certain issues such as embryo selection are quite similar. One option for PGD is to implant only those embryos that are found to be unaffected. Some parents still may choose to implant affected embryos with the knowledge that the potential for hereditary syndromes is high. In the past, options for hereditary cancer mutation carriers included not having children or undergoing amniocentesis or other forms of prenatal diagnosis. Preimplantation genetic diagnosis allows parents to avoid terminating a pregnancy and/or risking the health of the fetus or the mother.
In Europe, guidelines regulate which clinics can perform PGD and for which diseases they can screen. In the United Kingdom, the Human Fertilisation and Embryology Authority (HFEA) governs which procedures are acceptable and provides guidelines as to how these procedures should be performed. It also licenses clinics that wish to use any type of ART. Currently, no such oversight exists in the United States.[14] At present, HFEA has approved PGD to test for 50 disorders, including hereditary breast and ovarian cancers, which can be caused by a mutation in the BRCA1/2 genes. Mutations in BRCA1/2 are passed down in families in an autosomal dominant pattern, and children of individuals with a BRCA1/2 mutation have a 50% chance of inheriting it. Women who carry the BRCA1/2 gene have an 80% lifetime risk of developing breast cancer and approximately a 40% risk of developing ovarian cancer. With such a high risk for developing cancer, the HFEA considers it appropriate to allow PGD for this cancer predisposition gene.
The use of PGD in the United States is predicted to be approximately 20% across all embryos created via IVF; however, it is not known specifically which abnormalities or conditions PGD testing has been used for.[11] Almost 2000 babies have been born after the process of PGD since it was developed in 1989.[15] There are no published reports of increased fetal defects or late effects in babies born using PGD, but it is possible abnormalities may occur later in life as a result of the procedure.[9,10,13] Preimplantation genetic diagnosis cannot detect all genetic irregularities because only a limited number of chromosomes can be tested per procedure, and misdiagnosis may still occur.Prenatal diagnosis (amniocentesis or chorionic villus sampling) may still need to be considered after use of PGD to determine if the fetus carries a genetic abnormality.
Cancer and Parenting
Although cancer presents obstacles to becoming a parent, an experience with a major illness can also make survivors excellent parents, with greater emotional resilience and appreciation for parenthood. However, the decision to become a biologic parent after cancer must be weighed with the obstacles of the time and expense of fertility preservation procedures such as IVF. Adoption remains an option, but cancer survivors may experience difficulty in becoming qualified as adoptive parents. Survivors seeking adoption may encounter discrimination from US adoption agencies because of the survivor's physical health and condition.Some US agencies require an applicant to be at least 5 years post-treatment before he or she can qualify as a potential adoptive parent. Some cancer survivors have had success qualifying for the adoption of foreign-born children through international adoption agencies. Additionally, infertility treatments and adoption procedures may be too costly for some survivors, especially after an expensive battle with cancer.
In addition to concerns about cancer recurrence and parenting, survivors often have psychosocial concerns related to pregnancy and parenting, many of which mirror issues faced by any woman considering the use of ART. These concerns focus primarily on risks of birth defects or cancer in offspring; anxiety about hormonal factors related to pregnancy or infertility treatment increasing a risk of cancer recurrence, leaving the spouse/partner to raise the child if the parent with cancer dies; and conflicts about using ART because of ethical beliefs or religious beliefs, as some religions prohibit the use of donor gametes
Reproductive Counseling for Cancer Survivors
Canada and Schover[22] identified the need for research to promote improved patient education regarding cancer and reproductive health. Although the researchers indicate oncologists would probably be the ideal health care professionals for cancer patients to have in-depth discussions with regarding fertility preservation and future parenting, they further note that time constraints may make this unrealistic. However, their objective is to promote better information about the risks of infertility to the newly diagnosed cancer patient, a communication initiative for which other researchers have made a similar plea. Although this is a crucial first step on the road to improved quality of life in cancer survivors and risk management for infertility, it does not fully address the decision-making issues the patient must consider in rapid time.
There is little research about the psychosocial decision making of newly diagnosed cancer survivors regarding fertility and PGD choices. Unlike infertility in couples without a cancer diagnosis, the impending infertility of a cancer patient and the need for treatment provides a narrow window of time for patient counseling. Although some patients, similar to the woman in this case study, perceive stored embryos and oocytes as "frozen hope," decisions about the future of the stored embryo can be agonizing. Recent studies have begun to examine patient choices for the donation or destruction of stored embryos.
One study conducted in an Australian population among 235 couples with banked embryos found 27% would donate to stem cell research or infertility research, whereas 15% would consider donating to another couple.
However, the disagreement rate among the couples was high, with more than 40% disagreeing over each of the options.Additionally, 90% of the couples indicated they would want to discuss donation with a health care professional rather than make the decision alone. The majority preferred a fertility specialist or scientist as their choice for the discussions. This study highlights the fact that deciding to pursue ART is only the beginning of the decision-making process that may span several years.
Other researchers have begun to examine how patients feel about stored embryos and oocytes in fertility clinics. An emerging trend indicates patients may enter reproductive counseling with one set of ideas about stored embryos and feel differently after a successful pregnancy or failed attempts.[26–28] However, no studies have examined this meaning among women who stored embryos or oocytes due to cancer treatment.
There are currently no guidelines specifically tailored for the reproductive counseling needs of newly diagnosed cancer patients, especially for those who may have concerns about hereditary cancer syndromes. Peshkin et al.suggest strong support for such guidelines and continued collaborations among providers who work in oncology, cancer genetics, and ART.Conclusion
Finishing cancer treatment and transitioning from patient to survivor does not end the psychologic trauma of cancer. There are a plethora of issues that survivors often face after their cancer is in remission that affect quality of life. This case report illustrates the loss of fertility often experienced by a cancer survivor as a result of treatment. Young women with genetic mutations, such as those in the BRCA1/2 genes, may have additional concerns about passing on hereditary cancers to future offspring. Considering PGD to avoid passing the mutation may allow parents to select only healthy embryos, but decisions about the fate of embryos that are mutation carriers remain perplexing.
Decisions about using fertility preservation typically must be made at the same time as other decisions about treatment of a life-threatening diagnosis. Ethical, religious, financial, and other implications of preserving her fertility confront the woman before she begins cancer treatment. This leaves limited time for the patient to consider the implications of her choices and how she may feel about her reproductive options at a later date.
Given that 2.5 million young adults in the United States have survived cancer, more research is needed on the psychosocial aspects of parenthood, particularly to identify the psychosocial needs of survivors regarding cryopreservation and PGD. The resources for providing support for using ART and PGD lag behind the rapid advance of technology. Table 2 provides a list of online sources of information for patients and health care professionals. Communication guidelines should be developed for informing cancer patients of the emotional and psychosocial impact of fertility preservation, with particular regard to future decision making. More research is needed to develop educational resources specific to this population that will aid the women newly diagnosed with cancer in decision making. Although social support is an important aspect of survivorship, the medical community can also provide support by assigning social workers or counselors to survivors and to the newly diagnosed who are facing fertility and parenting issues.
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