Fertility preservation is an important issue among patients diagnosed with cancer during or before their reproductive years. About 75% of patients without children at the time of their cancer diagnosis wish to have future offspring, according to data from one review article. Despite concerns about fertility among patients undergoing potentially sterilizing cancer treatments, oncologists may not always be discussing options for fertility preservation with their patients.

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This year at the ASCO Annual Meeting, researchers presented data from a national survey of physician practice patterns to determine whether oncologists communicate the risk for infertility with patients undergoing cancer treatment. Although the majority of oncologists discussed fertility preservation with their patients, less than 25% reported referring patients to reproductive specialists for fertility preservation.

“The damage that cancer drugs do to fertility is highly underestimated,” said Kutluk Oktay, MD, FACOG, professor of obstetrics and gynecology, director in the division of reproductive medicine and infertility at Westchester Medical Center at New York Medical College, and medical director at the Institute for Fertility Preservation. It is important that patients who face this risk are counseled properly and referred to experts who can inform them of their options.

To determine the importance of the oncologist’s role in fertility preservation and to explore the options available to patients with cancer, HemOnc Today spoke with experts in the fields of psychology, obstetrics and gynecology, reproduction, and oncology.

The oncologist’s role

“We, as medical oncologists, are generally the point guard for caring for patients for everything — at diagnosis, through the trajectory of their disease and into survivorship,” Ann H. Partridge, MD, MPH, assistant professor in medicine at Harvard Medical School, told HemOnc Today. “We continue to follow them, especially if we gave them chemotherapy or other medication; they rely on us to give advice about whether something is safe, whether it will compromise their cancer care and whether it will compromise their ultimate survival.”

In 2006, ASCO published Recommendations for Fertility Preservation in People Treated for Cancer to inform oncologists of available preservation options and to guide them through the discussion and referral processes. However, according to the data presented at the ASCO Annual Meeting, only 38% of oncologists were aware of the recommendations.

When discussing fertility preservation, the guidelines recommend that infertility be discussed as a potential risk of cancer therapy — much like cognitive or cardiac complications — because infertility can affect survivors indefinitely, sometimes making future reproduction virtually impossible.

Although ASCO’s recommendations encourage oncologists to use their clinical judgment to determine the best time to inform patients about fertility preservation, they also emphasize the importance of discussing and referring patients to specialists at the earliest possible opportunity to allow men to collect samples and women to undergo egg or embryo cryopreservation.

Marvin Meistrich, PhD, professor of experimental radiation oncology, Florence M. Thomas Professor of Cancer Research at The University of Texas M.D. Anderson Cancer Center, also stressed the importance of informing patients undergoing potentially sterilizing therapy as early as possible of their risk for infertility.

“In women [who are having eggs or embryos frozen], we have to start our treatments around the second or third day of the menstrual period,” Oktay told HemOnc Today. “Often times we see that oncologists might be waiting and we miss that window of opportunity and then have to wait about a month for the next menstrual cycle.”

Preservation of fertility in women

Currently, cryopreservation technologies are the most commonly used and the most effective forms of fertility preservation, according to Oktay. Women undergoing infertility-producing treatment for breast cancer, hematologic malignancies and other solid tumor cancers have two cryopreservation options: embryo freezing and egg freezing.

According to Christine Duffy, MD, MPH, assistant professor of medicine at The Warren Alpert Medical School of Brown University, embryo freezing is a good option for women who have a male partner or a donor they are willing to use. The technique works by stimulating the ovary to produce eggs that are fertilized in vitro and then stored for later use. The process takes two to six weeks, depending on where a woman is in her cycle, Duffy said.

Women who may not have a partner, those who are not ready to select a donor, or women with religious concerns about the creation of embryos may prefer egg freezing compared with embryo freezing. The process is similar to embryo cryopreservation but involves freezing the egg itself. According to Duffy, although success rates are a bit lower with this technique compared with embryo freezing, progress has been made in this area.

A third, but still experimental cryopreservation technique for women, is ovarian tissue freezing. This technique involves a biopsy of the ovarian tissue that is then frozen and implanted into the patient at a later time. According to Duffy, the hope is that the patient will regain ovarian function. Although live births have occurred using this technique, it is still under investigation. One important concern surrounding this technique, however, is the risk for reintroducing the cancer from the biopsied tissue back into the patient after treatment.

The future of ovarian tissue freezing, according to Teresa Woodruff, PhD, Watkins Professor of Obstetrics and Gynecology, director of the Oncofertility Consortium at the Feinberg School of Medicine at Northwestern University, involves taking the follicles from the tissue and growing them completely in vitro to produce a mature egg that can be fertilized and then transferred back to the patient.

“In that case, the theoretical advantage would be that you could have an embryo and no residual cancer cells, but of course it is still very experimental,” she told HemOnc Today. Woodruff and colleagues are currently working on this technique.

Another experimental and somewhat controversial technique uses gonadotropin-releasing hormone agonists to shut the ovaries down during cancer treatment. According to Duffy, women who view fertility preservation as important should not rely solely on this technique due to the lack of evidence regarding its efficacy.

Preservation options for men

According to Meistrich, sperm banking semen and cryopreservation are the most proven techniques for preserving fertility in men with cancer. Current assisted reproductive techniques are more advanced than they were several decades ago.

“Now with assisted reproductive techniques, you don’t need that many [semen] samples, you don’t need that high of a sperm count, and you don’t need high motility because you’re injecting the sperm directly into the egg,” he said. “In the past you needed several good quality semen samples; now any semen sample would be adequate.”

Although there is no proven way to protect fertility during treatment, the use of less toxic chemotherapies and shielding during radiotherapy can help. According to Meistrich, the higher the dose of treatment, the higher the chance for sterility.

Using lower dose chemotherapy and radiation may also allow fertility to return after a period of sterility following treatment. Men should be aware that after several months of azoospermia, spermatogenesis may resume, so it is important to use proper contraception, Meistrich said.

In addition, the genetic safety of sperm recovered after treatment should not be of great concern. “Currently there is little evidence for genetic risk when the sperm has recovered more than one year after therapy,” Meistrich said. “[Patients] shouldn’t be apprehensive that the sperm are going to carry long-term genetic damage. But we found that within the first three months — and others have found within the first year — there is some genetic damage in the sperm. So an important thing is not to conceive during or immediately after chemotherapy or radiotherapy but to wait a period of at least six months to a year.”

Fertility preservation does not solely apply to adult patients with cancer; this concept is also important to parents of boys who undergo cancer treatment. There is currently no proven option for fertility preservation in children, but researchers such as Meistrich are working to harvest and freeze spermagonial cells to be reimplanted later.

“Even though animal studies have shown some success, there are no clinical reports of success yet with humans; however, in prepubertal boys there’s really no other option,” Oktay said.

Despite not yet being clinically proven, some spermagonial cells have been frozen with the hope that this technology will be perfected and available in the future, Meistrich said.

Costs of becoming a parent

According to data from the national physician survey, some physicians reported not discussing fertility preservation with their patients because of the physician’s perceived high costs associated with the procedure. In addition, data published in 2002 in The Journal of Clinical Oncology demonstrated that 51% of oncologists believed that most men could not afford the out-of-pocket costs of sperm banking before cancer treatment.

However, a companion study published by the same group demonstrated that only 7% of men chose not to bank their sperm because of financial reasons.

“Oncologists feel bad about that; they feel bad about bringing up something they know a patient might not be able to afford,” Leslie R. Schover, PhD, professor of behavioral science at The University of Texas M.D. Anderson Cancer Center, and a researcher involved in the studies, told HemOnc Today. “But actually, when we looked at oncologists’ and patients’ perceptions, we found that the oncologists were much more likely to think it was unaffordable than the patients.”

Opening the lines of communication

Patients interested in banking sperm or freezing eggs or embryos who are in need of financial assistance may find it through patient advocacy groups such as Fertile Hope, a non-profit organization that provides information and support to cancer patients and survivors. Organizations such as this and the Oncofertility Consortium provide support not only to patients, but also to oncologists looking for the appropriate resources for fertility preservation.

The Oncofertility Consortium was developed to improve communication between oncologists and fertility specialists and ensure that each group is part of the solution to the fertility needs of patients with cancer. The consortium, which is funded by NIH grants, has more than 60 sites in the United States to provide rapid fertility treatment among patients with cancer.

“The word ‘oncofertility’ is meant to bridge the gap and ensure that there are teams of clinicians and scientists working together to effectively manage the men and women who have fertility threats associated with cancer treatment,” said Woodruff, director of the consortium.

According to Duffy, oncologists cannot be expected to know in-depth details of fertility preservation options. Resources for oncologists are vital.

To ensure that oncologists are equipped with these resources, the consortium established a hotline that allows oncologists from across the nation to connect with the nearest oncofertility site to help them navigate patients toward the appropriate information source and provide a seamless transition from cancer care to fertility care and back again.

More importantly, however, oncologists must discuss fertility preservation with patients undergoing cancer treatment. Although there are valuable resources for patients interested in fertility preservation, the best resource may be their oncologist.

According to the ASCO recommendations, “physician encouragement affects patient interest in fertility preservation options.” In addition, data from the 2002 study conducted by Schover and colleagues found that physician recommendations were strong predictors of whether or not a man banked sperm. The recommendation was almost as influential as the patient’s own desire for future children.

“Oncologists are really the critical link in this whole story; they are doing an extraordinary job of early detection of the disease and treating the disease, so there’s been a remarkable increase in the survivorships rate of cancer patients, and that’s really exciting,” Woodruff said. “But now what oncologists have to put into the equation is that their patient is going to survive the disease, in many cases, and young patients have expectations of what life will be like once they go back to their ordinary life.” – by Stacey L. Adams

Are GnRH-agonists effective for fertility preservation in women undergoing treatment for cancer?

For more information:

• Jeruss JS. N Engl J Med. 2009;360:902-911.
• Lee SJ. J Clin Oncol. 2009;doi:10.1200/jco.2006.06.5888.
• Quinn G. #CRA9508. Presented at: 2009 ASCO Annual Meeting; May 31-June 2, 2009; Orlando.
• Robbins WA. Nature Genetics. 1997;16:74-78.
• Schover LR. J Clin Oncol. 2002;20:1880-1889.
• Schover LR. J Clin Oncol. 2002;20:1890-1897.
• Schover LR. Pediatr Blood Cancer. 2009;53:281-284.
• For information regarding The Oncofertility Consortium, visit: www.oncofertility.northwestern.edu.