Fertility preservation must be an ‘integral part’ of early cancer care

In 2006, ASCO published guidelines that encouraged clinicians to address fertility preservation with reproductive-age patients as early as possible in the cancer treatment continuum.

Six years later, however, data continue to suggest a significant percentage of patients are not informed about how treatment could affect their fertility or the options they have to preserve it.

In a study published in Cancer in March, Letourneau and colleagues evaluated 1,041 women aged 18 to 40 years who were diagnosed with cancer. Nearly 40% of the women did not receive fertility counseling from their oncology team or other specialists. Their findings also indicated sociodemographic disparities, suggesting women with higher income and more education, as well as those who were aged 35 years or younger, were more likely to receive counseling.

Researchers point to several barriers. Some clinicians contend they are not experts in fertility and are not qualified to discuss it, whereas others point to lack of time, noting conversations about treatment and survival supersede those about long-term quality of life.

Other studies indicate that patients may not raise the subject because they fail to understand the breadth of available fertility preservation options. They may believe those options are cost prohibitive, or — depending on the patient’s age — they simply are uncomfortable talking about it.

Still, the ASCO guidelines are clear, and although data indicate the percentage of patients who receive fertility preservation counseling has increased slightly in recent years, the subject does not arise nearly as consistently as it should, according to several clinicians who spoke with HemOnc Today.

“As clinicians, our job is not only to cure the disease, but to put patients back on the road of their life,” said Charles L. Shapiro, MD, director of breast medical oncology and leader of the Breast Cancer Research Program at the Ohio State University-James Comprehensive Cancer Center. “In many cases, that road involves having a family, which should make the fertility conversation an integral part of the initial consultation. When you get the diagnosis, everything is a rush. But in most cases, you have time to have this conversation.”

Cure comes first

A study by Forman and colleagues, who emailed surveys to oncologists at major academic medical centers in the United States, showed that — as recently as 2009 — more than half of respondents indicated they “rarely” referred patients to reproductive endocrinologists.

Time may be a significant factor, said Lynda Kwon Beaupin, MD, assistant professor of oncology at Roswell Park Cancer Institute.

“When you meet a family for the first time, the first focus is the disease,” Beaupin, coordinator of the adolescent and young adult program (AYA) at Roswell Park, said in an interview. “Then it is too late.”

Beaupin and her team often address fertility preservation during conversations about side effects of therapy.

“This is when the conversation can — and should — happen,” Beaupin said.

Shapiro agreed; however, he said financial considerations may be one reason why that dialogue does not always take place.

“The reality is that doctors need to see many patients to meet salary requirements, and they need to maximize both their time and the number of patients they see,” he said. “With this in mind, it is understandable that something like fertility has traditionally not been part of the initial consultation.”

Clinicians also sometimes struggle to help patients think much beyond the next step in their treatment, said Marcia Leonard, RN, PNP, co-director of the University of Michigan Comprehensive Cancer Center Survivorship Program.

“This is an incredibly hard time for patients. They worry that they may not survive,” Leonard said. “We have to help get them in the mindset of, ‘I’m going to survive. Let’s think in longer terms.’”

A ‘go-to’ person

A common personality trait among oncologists also may help explain why fertility preservation is not always discussed during cancer treatment, according to Ann H. Partridge, MD, MPH, director of the Adult Survivorship Program at Dana-Farber Cancer Institute in Boston and a member of the 2006 ASCO panel on fertility preservation.

“Most oncologists are perfectionists who want to do everything the right way, largely because their job demands it,” Partridge said in an interview. “If they feel the least bit uncomfortable with this subject, or if they feel they do not absolutely have all of the information, they might avoid it.”

That does not mean they do not consider it a priority, John P. Mulhall, MD, director of the Male Sexual and Reproductive Medicine Program at Memorial Sloan-Kettering Cancer Center, told HemOnc Today.

“The average oncologist believes this is an important issue,” Mulhall said. “However, we also know the average oncologist would prefer someone else to have this conversation.”

Some medical centers have taken steps to make sure “someone else” is readily available, creating subdivisions dedicated to fertility preservation, or designating specialists in AYA programs, urology departments or reproductive endocrinology departments who are trained to counsel patients about their options.

“Many individual clinicians and health care systems have identified someone locally who is the go-to person for male and female reproductive medicine,” Mulhall said. “This person or these people can manage patients and direct them in the right way.”

When those structures are created, patients — and other members of the care team — are better informed, Leonard said.

“Ten years ago, we didn’t have the technology to successfully initiate pregnancy with small numbers of sperm, women did not know what their options were, and oncologists often did not even consider these issues,” she said. “That is beginning to change.”

Men vs. women

The rate at which clinicians discuss fertility preservation with patients, however, still varies based on several factors.

In a study published in May in BJOG, Peddie and colleagues evaluated 16 men and 18 women aged 17 to 49 years who were recently diagnosed with cancer, and 15 health care professionals involved with their care. Results showed significant gaps in information provided to young women, which suggests “the need for an early appointment with a fertility expert,” according to the researchers.

Another study published in May in the Journal of Clinical Oncology evaluated 484 cancer survivors aged 18 to 45 years. In that study, Armuand and colleagues discovered marked differences between the delivery of fertility-related information to men and women.

The researchers found men were more than three times as likely to receive information about how treatment could affect their fertility (OR=3.2) and more than 14 times as likely to receive information about fertility preservation options (OR=14.4).

Armuand and colleagues suggested the differences were due to the relative ease and commonality of sperm banking as compared with female fertility preservation. In addition, sperm banking is relatively quick, whereas female fertility preservation options may delay commencement of cancer treatment.

“I don’t think you can even compare males and females in terms of fertility preservation,” Jennifer Keating Litton, MD, assistant professor in the department of breast medical oncology in the division of cancer medicine at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “It is such a completely different process. It is so much more complicated for women.”

Men can bank sperm within 24 or 48 hours of diagnosis. Researchers also are investigating the effectiveness of a procedure in which testicle tissue is removed and preserved.

The most common approach in women involves embryo or oocyte freezing. Daily, self-administered hormone injections stimulate multiple oocytes, a process that can take anywhere from 10 days to several weeks. Once matured, the eggs are harvested transvaginally, usually under light sedation. The harvested oocytes are fertilized with the partner’s sperm or donor sperm and then frozen. Alternatively, the unfertilized oocytes can be frozen.

Researchers also have explored the freezing of ovarian tissue. Early investigations have yielded varying success.

“With this procedure, no hormonal stimulation is needed. We can take the ovarian tissue prior to therapy, cryopreserve it and replace the tissue when therapy is complete,” Leonard said.

This process would be advantageous because restoring ovarian function restores estrogen production, as well. However, ovarian tissue cryopreservation is in the very early stage of development and must be considered an experimental measure.

Another investigational procedure is in vitro maturation, in which eggs are removed and matured outside of the body using gonadotropin. If perfected, this strategy could benefit young girls because it does not require patients to have gone through puberty.

Despite efforts to improve the effectiveness of fertility preservation in women, cancer often presents a reality that is impossible to combat, Litton said.

“Sometimes there is time to do a cycle of fertility preservation without changing OS,” Litton said. “Breast cancer, as opposed to other forms of cancer such as leukemia, does not progress as fast, and it is an appropriate conversation to have. But with women in life-threatening situations, often waiting 3 weeks for the cycle is not an option.”

The age factor

A patient’s age also can complicate fertility preservation efforts.

The NCI and National Comprehensive Cancer Network define adolescence and young adulthood as between 15 and 39 years.

The NCCN published guidelines earlier this year that offer recommendations about fertility for AYA patients, which provides clinicians with an entry point for conversations about reproductive issues. Still, the subject remains delicate when teenagers are involved, Beaupin said.

“Many of them have probably never even thought about having children,” she said. “We try to let them know that the cancer may prevent them from having children when they are older and, even though they may not know it at the moment, they may want children down the line. We try to put it in terms they can understand.”

Patients in their 20s and 30s who do not have a partner also may struggle with the issue, Partridge said.

“Some women in this age group may not know who they want to be the father of their children, or even if they want children,” she said. “With men it is a little easier, but they may still be uncertain and we have to guide them through the process.”

Patient regret

Regardless of patients’ ages, all of the clinicians interviewed agreed the least desirable outcome is when someone completes cancer treatment and does not know he or she could have preserved their fertility.

“The last thing we want to see is regret among patients,” Mulhall said.

The study by Letourneau and colleagues evaluated how pretreatment fertility counseling and fertility preservation improved post-treatment quality of life in reproductive-age women with cancer.

“Receiving specialized counseling about reproductive loss and pursuing fertility preservation is associated with less regret and greater quality of life for survivors, yet few patients are exposed to this potential benefit,” Letourneau and colleagues wrote. “Women of reproductive age should have expert counseling and should be given the opportunity to make active decisions about preserving fertility.”

The data collected by Letourneau and colleagues showed patients who received pretreatment counseling from an oncologist and a fertility specialist reported higher Satisfaction with Life Scale scores than patients who did not receive pretreatment counseling (23 vs. 19.8).

The results also showed patients who received pretreatment counseling from an oncologist and a fertility specialist demonstrated lower Decision Regret Scale scores than patients who received counseling from an oncologist alone (8.4 vs. 11, P<.0001).

The findings suggest a multidisciplinary approach may help patients feel they have an opportunity to make active decisions about preserving their fertility, according to researchers.

“Of course, there are some patients who are at such risk that it is not an option,” Beaupin said. “But we have others who go through procedures, their fertility is gone, and they feel that they lost out or were misinformed. We need to make sure they have as much information as possible at the outset.”

Additional obstacles

Although certain fertility preservation can be expensive, particularly for women, misinformation can be as much of a barrier as cost, Leonard said.

“Many people think fertility preservation is much more expensive than it really is. [They believed] it was upward of $10,000 for both men and women,” Leonard said. “That is not the case. The cost for males is around $500 to $1,000, depending on the site and the number of samples banked.”

Oocyte and embryo cryopreservation costs are much higher, often $6,000 or more, but financial help is available.

“Although many insurance companies do not cover emergency fertility preservation as part of care, organizations such as Fertile Hope, through the Livestrong Foundation, Oncofertility.org, Be Bright Pink, FORCE and Cancer.net all offer assistance,” Litton said. “Many groups are honing in on this and including it as part of general patient care and the information package.”

Ethical dilemmas also can arise.

“When you create an embryo, there may be social and emotional implications,” Leonard said. “There are also legal issues, because the embryo belongs to both people. If a couple later divorces or they never marry in the first place, the man can refuse to allow use of those embryos. This obviously can spark further issues for clinicians who are trying to save a life.”

In the end, however, none of these issues is insurmountable, clinicians said.

“The worst thing, in my view, is letting cancer be the boss,” Shapiro said. “As clinicians, we should be getting control of the disease, but also helping our patients gain control of the situation. We need to empower them on the path to wellness and health throughout life. This is the message we need to promote, and fertility is part of it.” – by Rob Volansky

 

Is the oncology team responsible for providing pretreatment fertility counseling?

The discussion of the threat to infertility based on the cancer or treatment should begin with the oncology team.

These are the health care professionals who deliver the diagnosis and make treatment recommendations to patients and, therefore, are responsible for informing them about risk. Generally, the earlier this conversation happens, the more options a patient may have to preserve his or her fertility, if desired.

Without that initial dialogue, many patients will not be able to consider their present cancer-treatment decisions in light of their preferences for future fertility and family building.

However, the topic of reproductive health and fertility preservation with a patient of childbearing age who has been diagnosed with cancer is not a single conversation, but rather a series of discussions that happen over time.

In a truly multidisciplinary approach to patient care, this initial conversation must be followed with a referral to a fertility preservation team or reproductive endocrinologist. These specialists provide details to patients about the options available to them before, during and after treatment — not only for fertility preservation but also for contraception and timing of family building.

Many survivors say they appreciated the initial consultation with the fertility preservation team — in which they received tailored risks and options based on their own clinical situation — even if they chose to take no action.

Consultation with a fertility preservation team also encourages patients to consider these options in light of their emotional status and social circumstances.

Without both oncology and fertility preservation teams working together to have these discussions, patients may not benefit from the advances in oncofertility.

Susan Thomas Vadaparampil, PhD, MPH, is an associate member of the Health Outcomes and Behavior Program at Moffitt Cancer Center, and an associate professor of oncologic sciences at the University of South Florida. She may be reached at H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612; email: susan.vadaparampil@moffitt.org. Gwendolyn P. Quinn, PhD, is an associate member of the Health Outcomes and Behavior Program at Moffitt Cancer Center, and an associate professor of oncologic sciences at the University of South Florida. She may be reached at Gwen.Quinn@moffitt.org. Vadaparampil and Quinn are co-principal investigators of an R25 training grant funded by NCI to train nurses in the oncology care setting about reproductive health issues in cancer care. For more information, go to www.rhoinstitute.org. Disclosure: Vadaparampil and Quinn report no relevant financial disclosures.

Decisions about fertility should be made in conjunction with a fertility preservation team.

Fertility preservation is an emerging discipline that provides future childbearing options for reproductive-age patients undergoing treatment for cancer or other serious illnesses. Improved therapeutic regimens for many types of cancer have resulted in more survivors than ever before, and quality-of-life issues — such as the ability to have children — have become increasingly important.

Furthermore, rapid scientific advancements over the past decade have helped fertility therapies such as oocyte cryopreservation, once considered experimental, become established options for many women. Thus, the need to provide comprehensive, accurate and current fertility preservation information is more critical than ever.

Patients newly diagnosed with cancer often need to make many difficult treatment decisions within a short amount of time. Health care providers are obligated to give patients the best information available to make these choices. Fertility preservation counseling should emphasize key messages, such as the potential impact of cancer treatment on fertility and options available to patients, as well as the time and effort required to complete them. The counseling also must include a discussion of parenthood after cancer. Given these considerations, fertility specialists are best equipped to counsel patients about fertility preservation.

Even when decision making seems relatively straightforward, subtleties exist. For example, sperm banking is a long-standing therapy for postpubertal males before cancer treatment. However, systemic illness may negatively affect sperm counts even prior to initiation of therapy, and banked specimens may be of poor quality.

Counseling patients about whether additional collections are required and potential use of the specimens — for intrauterine insemination or in vitro fertilization — is essential. Long-term storage costs, shipment of specimens to other facilities for future use, and specimen ownership in the event of death should also be addressed.

Fertility specialists have experience in these areas and also can also answer questions about risks to offspring born via assisted reproductive technologies and the procedures themselves. Complex ethical issues, such as posthumous reproduction, also should be considered, and legal or spiritual counsel may be sought. These conversations are familiar territory for fertility specialists.

In the end, informed decision making needs to be just that: informed. Cancer patients deserve the best opportunity not only for cancer treatment and survival, but also for a fulfilled life as a survivor — which, for many people, includes having children. Thus, informed decisions about future fertility are ideally made in conjunction with a fertility preservation team.

Jani R. Jensen, MD, is an assistant professor of reproductive endocrinology and infertility at Mayo Clinic in Rochester, Minn. She may be reached at Mayo Clinic, 200 First St. SW, Rochester, MN 55905; email: jensen.jani@mayo.edu. Disclosure: Jensen reports no relevant financial disclosures.