From OncoLog, January 2006, Vol. 51, No. 1

Fertility After Cancer

by Stephanie Deming

Advances offer new hope for patients facing fertility-damaging treatment, but doctors need to inform patients early about their options.

Free of cancer but infertile. For cancer survivors who find themselves in this situation, happiness about conquering cancer is tempered by sadness about treatment-induced infertility. And for infertile survivors who feel that they weren’t given adequate information about infertility before cancer treatment began, sadness can become anger.

In two recent surveys of oncologists and patients at major centers, Dr. Leslie Schover, professor in the Department of Behavioral Science at The University of Texas M. D. Anderson Cancer Center, found that oncologists sometimes do a poor job of informing patients about the possibility that certain treatments might cause infertility. “Maybe they mention it quickly during informed consent and it goes right over the patient’s head, because they have so much information coming in,” Dr. Schover said. Later, once patients have recovered from cancer treatment and realize that they might have been able to preserve their fertility if only someone had informed them in time about their options, they can feel devastated.

“Given that oncologists’ primary focus is treating and hopefully curing the cancer, it’s not surprising that infertility is not discussed as often as it should be,” said Dr. Schover. Another factor could be that many oncologists may not be aware of recent advances that have made fertility preservation more practical, especially for men. But ideally, she said, every patient who may be facing infertility as a result of treatment should be informed about his or her options. Toward this end, Dr. Schover and colleagues at M. D. Anderson Cancer Center are working to heighten awareness about cancer-related infertility among oncology healthcare professionals and cancer patients and their families.

“Banking on Fatherhood”

Of all the interventions available to preserve cancer patients’ fertility, one of the most straightforward is sperm banking in advance of radiation therapy or chemotherapy. Unfortunately, many men who might benefit from this option don’t learn about it until it’s too late.

Sperm banking is “kind of like insurance,” said Dr. Schover. Many men who lose sperm function as a result of cancer treatment eventually become fertile again, but for those who don’t, sperm banking preserves the chance to father a child through in vitro fertilization (IVF). With older methods, IVF success rates were relatively low because some sperm die during freezing and the sperm that survive after thawing may have reduced motility. However, with the advent of intracytoplasmic sperm injection (ICSI), IVF success rates have greatly improved. With ICSI, a single sperm is injected into an egg. Thus, motility isn’t an issue, and few sperm are needed. With ICSI, said Dr. Schover, “the woman still has to go through IVF, which is no small thing.” But the higher success rates have made sperm banking much more attractive.

One of Dr. Schover’s major projects is an interactive, educational CD-ROM, “Banking on Fatherhood,” designed to raise awareness about sperm banking among both patients and healthcare providers. This project, funded by a small business grant from the National Cancer Institute, is a collaboration with Paul Martinetti, M.D., of AXIS Healthcare Communications, LLC. The section for healthcare professionals includes a medical update about cancer-related male infertility and sperm banking; information on major world religions and their views on masturbation for semen collection and the use of IVF to create children; and videos demonstrating good and bad communication with patients about sperm banking. The section for cancer patients and their families includes information about infertility and sperm banking, other options for fathering children, including adoption and donor insemination, and religious issues, along with videos of cancer patients describing their personal experiences with sperm banking and a decision aid to help patients clarify their feelings. “Banking on Fatherhood” also includes sections for female partners of men with cancer and parents of teenage boys with cancer, plus a national directory of sperm banks that will store samples for cancer patients.

Options for Women

For women facing the possibility of cancer-related infertility, many options are available, but none are as practical or successful as sperm banking. Overall, a greater proportion of women than men become infertile after cancer therapy. According to Dr. Schover, “It’s really sad, but it’s hard to know what to say to a young woman interested in preserving her fertility. To counsel her, we have to be really honest. We tell her how much it’s going to cost and what evidence there is that any of these things really work.”

In women, the closest parallels to sperm banking are embryo freezing, a standard infertility procedure, and egg freezing, which is considered experimental. However, whereas sperm banking is rapid and relatively straightforward, embryo freezing and egg freezing are time-consuming, complicated, and expensive, and must usually be funded out-of-pocket. According to the advocacy organization Fertile Hope, the chances of pregnancy with embryo freezing are approximately 10% to 25% per embryo stored. With egg freezing, rates of pregnancy are only about one-quarter to one-third what they are with embryo freezing. And there are concerns about the health of children created with frozen eggs: the spindle that keeps the chromosomes in the right alignment is sometimes damaged during freezing, raising concerns that embryos created from these frozen eggs could have genetic damage.

Embryo or egg freezing may be a reasonable option for women who can postpone cancer treatment the 3 or 4 weeks typically required for hormonal stimulation of the ovaries and egg retrieval, but many women—for example, women with acute leukemia—cannot afford to wait that long. And for breast cancer patients, the estrogen sensitivity of breast cancer cells raises concerns that high estrogen levels resulting from ovarian-stimulating hormones could promote the growth of the cancer. These women may be able to undergo ovarian stimulation with tamoxifen or letrozole, added to block estrogen from entering breast cancer cells. Another experimental option is to remove part of an ovary and freeze the tissue in the hope of transplanting it back to the woman in the future, so that it could grow new blood vessels and produce eggs.

There are also more personal issues. If a woman is considering embryo freezing but does not have a male partner when her cancer is diagnosed, would she be willing to use donor sperm? If she eventually enters into a relationship with a male partner and wants to become pregnant, will he mind using embryos created with someone else’s sperm?

Because embryo and egg freezing require the expertise of specialists in reproductive endocrinology and infertility (commonly referred to as REI), M. D. Anderson has a relationship with the REI experts at Baylor College of Medicine, another institution in the Texas Medical Center, so that patients who want to pursue assisted reproductive technologies before cancer treatment can be referred there.

In addition to assisted reproductive technologies, modified cancer treatments may be an option for a small group of women with cancer. These modified treatments include fertility-sparing surgery for women with gynecologic malignancies and chemoprotection of the ovaries for women undergoing chemotherapy.

One of the leading experts in fertility-sparing surgery for women with gynecologic cancers is David Gershenson, M.D., chair of the Department of Gynecologic Oncology at M. D. Anderson. “For anybody for whom future fertility might be a consideration, you always want to be very clear about discussing the options for preserving fertility,” said Dr. Gershenson.

For women with certain types of ovarian cancer, ovarian cystectomy (removal of just part of an ovary) might be an option; if not, surgeons might be able to spare an ovary, the uterus, or both. (Depending on which reproductive organs remain, a woman might require assisted reproductive technology to have a child.) For some women with early-stage cervical cancer, conization (removal of just a cone of tissue) or radical trachelectomy (removal of the cervix without hysterectomy) might be appropriate.

If a woman with cervical cancer requires radiation therapy, the ovaries can sometimes be moved out of the radiation field ahead of time in an effort to protect them. Finally, for some women with early-stage endometrial cancer, treatment with hormonal therapy rather than surgery might be possible. Of course, throughout the processes of counseling patients, balancing the risks and potential benefits of fertility-sparing treatment, and ultimately making decisions, the primary concern is curing the cancer.

Dr. Gershenson noted that the success of fertility-sparing surgery at M. D. Anderson is based on two essential elements. “One is that the operating surgeon is very familiar with the biologic behavior of what they think they’re dealing with. The second key is to have frozen section exam availability and a good gynecologic pathologist. It’s a combination of the knowledge base and skills of the operating surgeon and the pathologist.”

Because the gynecologist often isn’t sure until surgery what he or she will find and what type of operation will be needed, counseling patients before surgery is complex. According to Dr. Gershenson, in addition to explaining the indications for surgery and any alternatives to surgery (eg, chemoradiation or chemotherapy), the gynecologist lays out all the potential intraoperative scenarios, including the possibility that the uterus and both ovaries will have to be removed, leaving the patient sterile. “It’s important to explain how I’ll make those decisions during surgery, so that they have as clear a picture as they can of what is going to happen,” he said.

A new approach under investigation is based on the theory that chemically shutting down the ovaries—in effect, inducing a temporary menopause—may protect ovarian follicles from the damaging effects of chemotherapy. Naoto Ueno, M.D., Ph.D., associate professor in the Department of Blood and Marrow Transplantation, is conducting a phase II trial to determine whether this tactic will preserve the ovarian function of women undergoing hematopoietic stem cell transplantation. In the trial, women receive the gonadotropin-releasing hormone (GnRH) analogue leuprolide (Lupron) before and during high-dose chemotherapy. M. D. Anderson is also collaborating with a hospital in Tokyo to conduct a phase III trial to see whether another GnRH analogue, goserelin (Zoladex), protects ovarian function in young women receiving chemotherapy for breast cancer.

Multidisciplinary Conferences

To raise awareness in the medical community about issues related to infertility after cancer, Dr. Schover organized a conference, “Parenthood after Cancer,” held at M. D. Anderson in the spring of 2004. Funded in part by the National Cancer Institute and attended by medical professionals from 13 countries, the conference included sessions on causes and prevention of cancer-related infertility, cryopreserving gametes and embryos, psychosocial, ethical, and legal issues, and more. (The proceedings were published in an issue of the Journal of the National Cancer Institute Monographs in 2005.) This first conference was such a success that it led to a follow-up, invitation-only consensus conference in the spring of 2005 at which attendees reached consensus about research priorities and recommendations for clinical practice.

The Future

Asked about the future of research on cancer-related infertility, Dr. Schover said, “I think there’s a lot more attention now being given to this area. Just in the last year, the American Society of Reproductive Medicine published guidelines on fertility in cancer, and the American Society of Clinical Oncology is going to be publishing guidelines for oncologists soon.”

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

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