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National Cancer Policy Forum; Board on Health Care Services; A Livestrong and Institute of Medicine Workshop; Institute of Medicine. Identifying and Addressing the Needs of Adolescents and Young Adults with Cancer: Workshop Summary. Washington (DC): National Academies Press (US); 2014 Jan 10.

Cover of Identifying and Addressing the Needs of Adolescents and Young Adults with Cancer

Identifying and Addressing the Needs of Adolescents and Young Adults with Cancer: Workshop Summary.

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INFERTILITY AND EFFORTS TO PRESERVE FERTILITY

Now that so many cancers diagnosed in children and AYAs are curable, there has been growing concern about how cancer treatment might affect their fertility and about ways to preserve that fertility. Jennifer Levine, assistant professor of clinical pediatrics and director of the Center for Survivor Wellness in the Division of Pediatric Oncology at Columbia University Medical Center, said that the American Society of Clinical Oncology (ASCO), the American Society of Reproductive Medicine, and the National Comprehensive Cancer Network have all developed guidelines that state that fertility preservation should be an integral part of cancer treatment for AYAs. One participant said, “I think it has gone from ‘I hope my doctor thinks about my fertility’ to a mandate, and hospitals like mine have policies in place so they provide information about the risk of infertility and offer potential preservation options.”

The 2010 AYA LIVESTRONG survey found that about one-quarter of AYAs took steps to preserve their fertility before their cancer treatment began. The most common steps taken were sperm banking for men and preserving eggs and embryos for women. Sixty-five percent of males who tried to father a pregnancy after treatment were successful, while 58 percent of females who tried to become pregnant after treatment were successful. The majority of those with successful pregnancies used natural means to become pregnant, Rechis reported.

The survey also assessed the reasons for not using fertility preservation and found that although some people were not interested in having children, many did not know their fertility was at risk, did not have enough time to pursue fertility preservation options, or thought the costs of such preservation were too prohibitive. “These are all things we can affect and make a change for AYA survivors,” Rechis said. Oeffinger agreed and said that there are psychological reasons to preserve fertility. “Infertility is the number one issue of our patient population because it ties into their body image, their sense of self-worth,” he said.

Male Fertility

Levine provided some background information on the biology of fertility and then outlined the causes of infertility in cancer patients. In males, the germ cells start maturing into sperm cells at puberty, and in a healthy male, who is generally fertile from puberty until time of death, they continuously self-renew. Cancer treatment can deplete these germ cells. Levine said that it is very common for males to experience a temporary lack of sperm during or after radiation or chemotherapy because of both the destruction of maturing sperm cells and a relative depletion of germ cells. The maturation process can resume post-therapy, and the amount of time that a male is infertile after treatment varies from months to years. Ultimately, males usually become fertile again, but permanent infertility can occur if there is such a sufficient depletion of germ cells that there is no possibility of the maturation process resuming.

Cancer treatment or surgery can also cause infertility by damaging the pituitary gland, the pelvic nerves, or the ductal system, which can interfere with ejaculation. Sometimes it is the cancer itself and not necessarily the treatment that affects male fertility. Men with testicular cancer or HL will sometimes lack viable sperm prior to treatment because of the effects of the disease process itself, Levine said.

Sperm banking is a well-established means to preserve male fertility. If viable sperm are produced, those sperm are frozen and stored for future use. It is generally recommended that men produce several specimens over the course of a number of days in order to maximize the volume of the sperm that can be stored. But it is possible that just one specimen will be sufficient for future fertility, Levine said. “There often is a lot of pressure to begin therapy, and people feel uncomfortable delaying the start of therapy to allow sperm banking,” she said. “But if sperm banking is thought of at the time of diagnosis, there may be time to produce multiple specimens before treatment starts.”

The cost of sperm banking can be a challenge for some patients. It costs between $500 and $700 to do a semen analysis, and annual storage costs range between $200 and $400. Fertile Hope's Sharing Hope Program8 enables cancer patients to get discounted rates for sperm banking, Levine said. However, some patients may be too sick or too young to bank sperm at the time of diagnosis, and some may decline due to religious beliefs, she said.

If producing an ejaculate is a problem, sperm can be collected under anesthesia. This outpatient procedure is becoming more common, Levine said. Another option is to remove testicular sperm tissue and freeze it or to freeze an entire testicular specimen that includes germ cells which will be matured at a later point in time. Such testicular extraction can also be attempted post therapy as a more targeted means of acquiring viable sperm for assisted reproduction. In males receiving radiation therapy, gonadal shielding is also a common procedure to help preserve their fertility.

“Almost any post-pubertal male who is willing or interested in sperm banking should do it because it is really not so invasive,” Levine said. The earlier that men bank their sperm the better, she stressed, because even men with a lower risk for infertility might relapse in a period of time in which they are not producing sperm due to their previous therapy, so they won't be able to bank sperm at that point. Levine said that although many patients may not require sperm banking, for the 10 or 15 percent of men who end up using banked sperm, “that is how they are going to start their biologic family.” She added that men can undergo a semen analysis for viable sperm post treatment to aid their decision about whether to continue to pay for sperm storage.

Female Fertility

A woman's fertility can be affected by a number of actions related to cancer treatment. Removing a woman's ovaries or her uterus will render her infertile. Uterine surgery can cause scar tissue that may prevent implantation of the embryo. And cancer treatments, including treatments that affect the pituitary, can cause infertility by disrupting normal hormonal regulation. Unlike men, women are born with all the eggs they will ever have, and there is no self-renewal of germ cells. At menarche, women start to lose their egg follicles, and by their mid- to late 30s, their fertility begins to decline. By their late 40s or early 50s, most women reach menopause and can no longer become pregnant.

Cancer treatment can cause acute ovarian failure, in which the number of follicles drops down to levels that impede fertility, and it can hasten menopause. Oeffinger presented a study that found that the older a woman is when she is diagnosed with cancer, the more likely it is that she will experience infertility from her cancer treatment (Letourneau et al., 2012). Nearly half of women treated at age 35 for cancer experience infertility. “In our country, with so many women moving the timing of their family to later years, this obviously is quite an important issue,” he said. Cancer treatments lead some women, especially those treated with high-dose alkylating-agent chemotherapy and those who undergo a stem cell transplant, to experience early menopause. Even women who resume menstruation after chemotherapy can experience infertility. Premature menopause can also lead to sexual dysfunction.

Embryo freezing is the most common method for preserving the fertility of women undergoing cancer treatment, Levine said. This technique requires ovarian hyperstimulation in order to create multiple follicles in the ovaries. The follicles are retrieved prior to ovulation and fertilized to create embryos that are then frozen. The older a woman is when she has the procedure, the less likely is it to be successful. Embryo preservation requires a partner or donor sperm, and is very expensive, costing between $10,000 and $15,000, not including implantation costs. Embryo preservation takes a minimum of 2 weeks.

Oocyte cryopreservation is similar to embryo preservation except that it does not require fertilizing the egg and thus does not require a partner or donor sperm. Last fall, the American Society of Reproductive Medicine deemed that this approach is no longer an experimental procedure. “It really is something that in general we are thinking more about for our patients,” Levine said, but she noted that oocytes are more susceptible to being damaged by the freeze-thaw cycle than embryos, so the success rate for this procedure is somewhat lower than for embryo preservation. It is just as expensive and requires just as much time, she added.

Another option is to remove ovarian strips, freeze them, and reimplant them later or use them for in vitro fertilization. This procedure can be done immediately and it is the only option for pre-pubertal females. But it is controversial because of the concern that cancer cells, particularly leukemia cells, might be reintroduced with the re-implanted tissue. There also is not much experience reported in the literature, with only about a dozen pregnancies known to have resulted from it, Levine said.

Some patients with cervical cancer are now being treated by removing only part of the uterus and cervix, Levine said; it is possible for these women to carry a pregnancy. In patients who receive radiation therapy, the ovaries can be protected with gonadal shielding and ovarian transposition, in which the ovaries are moved outside of the radiation field. Gonadotropin-releasing hormone agonists and antagonists are also commonly used to try to preserve female fertility, Levine said, although there is very little evidence to support that approach, and some studies suggest it may actually be detrimental to fertility.

Women may also want to consider pursuing similar actions to preserve fertility after their cancer treatment if they are not ready to have children at that time. Although there are tests that could potentially assess a woman's fertility, these are not yet adequate or fully validated, Levine said. The CCSS generated promising data indicating that survivors are able to become pregnant, although it appeared that they took longer than their sibling controls.

Once a woman has completed her cancer treatment, she can pursue natural, assisted, or surrogate reproduction, although the possibility of a cancer relapse occurring during the pregnancy must be taken into account, as the pregnancy will limit the treatment options and timing. It is also possible that various late effects of treatment, such as cardiovascular or pulmonary impairments, could affect a pregnancy; these, too, must be taken into account. As Levine noted, such impairments can pose problems during pregnancy, when there is increased blood volume, and their presence may indicate the need to be seen by an obstetrician who specializes in high-risk pregnancies.

There are no data to suggest that children of cancer survivors have any increased risk of congenital abnormalities compared to the general population. But cancer survivors might have a genetic disposition to cancer that could be screened for with pre-implantation genetic diagnosis. Such a procedure can identify, for example, embryos that carry a mutated BRCA gene, Levine pointed out.

Levine suggested that providers discuss fertility with AYA patients at the time of their cancer diagnosis and give them a referral to have a more in-depth consultation with a reproductive endocrinologist if they wish. Fertility preservation should also be considered post treatment if it was not considered before treatment. Levine also suggested having an established referral mechanism in place related to fertility preservation. “If someone comes in saying they want a sperm bank, and you do not know where there is one or what kind of specimen jar to give them, fertility preservation is not likely to happen,” she noted.

Insurance Coverage of Fertility Preservation and Treatments

Not all insurance plans will cover the cost of fertility preservation or infertility treatment for cancer patients. One AYA cancer survivor who spoke at the workshop said that such coverage is critical. After her treatment, she said, she stopped menstruating and sought treatment with testosterone pellets, which cost $500 and were not covered by her insurance. Due to a flexible spending program at her job, she was able to pay for the treatment and subsequently started having normal menstrual cycles. “For 5 years,” she said, “I was menopausal and thought I would never have kids, which is a big emotional toll for a female at the age of 25, and if I hadn't had money to pay for the testosterone treatment, I never would have tried it.”

Levine noted that LIVESTRONG has been encouraging insurance companies to cover the cost of fertility preservation for cancer patients and that the American Medical Association recently stated that insurance companies should cover fertility preservation in cases where the infertility is expected to occur as a result of cancer treatment. In addition, the California legislature recently introduced a bill to require insurance companies to cover fertility preservation. “If coverage can be obtained, this is going to make a tremendous difference for cancer survivors,” she said.

Footnotes

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Copyright 2013 by the National Academy of Sciences. All rights reserved.
Bookshelf ID: NBK179875

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