Options for Preserving Fertility Should Be Considered Early to Maximize the Likelihood of Success


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3.6.91_partridge.jpgMost cancer survivors prefer to have biologic offspring despite concerns about the possible effects of cancer treatment on the child, the child’s lifetime cancer risk, or their own longevity, according to an ASCO panel that developed guidelines on fertility preservation in patients with cancer.1 While sperm and embryo cryopreservation remain the methods of fertility preservation with the greatest likelihood of success—as they were when the guidelines were issued in 2006—newer methods have also shown success or promise. A constant, however, is the need for oncologists to discuss with patients in their reproductive years (or with the parents of younger patients) the risk of infertility and the options for fertility preservation.

In an interview with The ASCO Post, Ann Partridge, MD, MPH, Director of the Program for Cancer Survivorship at Dana Farber Cancer Center in Boston and a member of the 2006 ASCO panel on fertility preservation, discussed some changes and advances since the guidelines were issued.

Ovarian Suppression

Oocyte cryopreservation is “much improved,” Dr. Partridge said. “When we wrote the guidelines in 2006, it was very experimental, with very low success rates.” But now “some centers are finding better success rates with oocyte preservation,” and there is “more and more success in terms of having a pregnancy after oocyte cryopreservation,” she added.

“The jury is still out” on ovarian suppression, using hormonal therapies to prevent premature menopause and infertility in patients being treated with chemotherapy or radiation therapy, Dr. Partridge said. A randomized trial testing the potential benefits of using the gonadotropin-releasing hormone (GnRH) agonist triptorelin (Trelstar) to prevent chemotherapy-induced amenorrhea among premenopausal women with breast cancer found that amenorrhea rates were comparable in the triptorelin and control groups. That study was published in the Journal of Clinical Oncology 2 (JCO) and reported in the Los Angeles Times.

In an editorial3 accompanying the journal article and a podcast on the journal website, Dr. Partridge, who works mainly with patients who have breast cancer, noted that the use of GnRH agonists “is appealing, given that they are readily available and are generally less cumbersome than available alternative strategies including in vitro fertilization and embryo cryopreservation before treatment.” Data on GnRH agonists, however, “have been mixed,” Dr. Partridge noted.

The triptorelin study reported in JCO is one of six recently completed or ongoing studies on GnRH agonists. Two other studies also had negative results; two had positive results; and the results of one trial have not yet been reported. That trial, the Prevention of Early Menopause Study (POEMS; Southwest Oncology Group [SWOG] study 0230), is a large international multicenter trial testing goserelin (Zoladex) with standard adjuvant chemotherapy.

“Critically, the confounding effects of tamoxifen treatment should not be an issue in this study, which includes only women with hormone receptor–negative disease,” Dr. Partridge wrote in the editorial. “Given the current level of evidence,” she continued, “women who are interested in future fertility and the providers who are assisting them in these often difficult decisions should not rely on GnRH agonist treatment during chemotherapy for preservation of menstrual and ovarian function or fertility.”

More Limited Options for Prepubescent Patients

Sperm banking is still the most commonly used method of fertility preservation for male patients. “It’s easy and cheap and relatively reliable,” Dr. Partridge said. It is not an option, however, for prepubescent males with immature sperm.

“Testicular tissue freezing is the only option available before puberty,” according to Fertile Hope, a LIVESTRONG initiative “dedicated to providing reproductive information, support, and hope to cancer patients and survivors whose medical treatments present the risk of infertility.” As material posted on the Fertile Hope website notes, “While this procedure shows a lot of promise, it is still experimental. There has not been a successful pregnancy yet.”4 Testicular shielding prior to radiation therapy can also help preserve fertility.

Embryo or oocyte cryopreservation cannot be used to preserve fertility in females who have not entered puberty “For prepubescent girls, really the only option is to take pieces of the ovaries,” Dr. Partridge said, and then freeze the tissue until it can be reimplanted. “You would have to consider the risks of infertility from the regimen vs the risk of taking a piece of the ovary,” Dr. Partridge said, as well as dealing with the additional surgery.

“In successful transplants, the tissue starts producing hormones and maturing eggs,” according to Fertile Hope. “While ovarian tissue freezing holds a lot of promise, it is still experimental.”4

Ovarian shielding or ovarian transposition (oophoropexy) can be used to help decrease radiation to the ovaries and damage to fertility. If transposition is used to surgically reposition the ovaries away from the radiation field, it should be performed just before radiation therapy to prevent remigration of the ovaries to their former position, according to the ASCO guidelines.

Threats to Fertility

Fertility can be compromised by cancers directly affecting the reproductive organs and by cancer treatments. For women and men, the most common cause for concern is receiving sterilizing, systemic therapy, Dr. Partridge said. “Bone marrow transplants, radiation to the gonads, and regimens including alkylating agents are the most toxic to the gonads—anything that either systemically or directly kills off cells is going to have a propensity to kill off developing cells, and of course the ovaries and the testes have lots of developing cells.” Bone-marrow transplantation regimens “tend to be the most gonadotoxic—they cause immediate sterilization for most, but not all, patients,” she said.

Surgical treatment can affect fertility by removing organs directly involved with the production of eggs or sperm or parts of their pathways, such as the uterus or penis.  “The other way cancer treatment can interfere is by getting in the way of the hormonal axes,” Dr. Partridge said, citing pituitary surgery as an example. “If you have pituitary disruption, that would get in the way of the hormonal axes that prime the ovaries to make an egg each month in premenopausal women.”

The Fertile Hope website has a risk calculator tool that provides information about the risk of amenorrhea or azoospermia based on specific treatment regimens for selected cancers (see sidebar, Internet Tool to Calculate Risks to Fertility).

Additional Studies

Dr. Partridge is involved in several ongoing and upcoming studies of fertility issues among patients with cancer. One large study just starting is aimed at increasing awareness of these issues. Following up on a pilot study that addressed gaps in care for young women being treated for breast cancer, Dr. Partridge is launching a randomized controlled trial of educational and supportive care interventions.

“One of the additional questions we are asking in a longitudinal cohort study of very young women with breast cancer is whether or not they feel pressured to have additional children,” Dr. Partridge said. “So we’ll get at that question of who’s pushing this issue: patients? their loved ones? When considering this issue for young patients, it may be their parents, and maybe that is appropriate.”

The LIVESTRONG Cancer Clinical Trial Matching Service maintains a list of trials relevant to cancer and fertility that are currently seeking patient participation, and offers assistance in searching for clinical trial options that match a specific diagnosis and treatment history. To search for trials, go to www.fertilehope.org/learn-more/research-and-trials/ or call 800-620-6167, Monday to Friday, 7:00 AM to 5:30 PM Central Time (except holidays). ■

Disclosure: Dr. Partridge reported no potential conflicts of interest.

SIDEBAR: Expect and Encourage Questions from Your Patients

SIDEBAR: Internet Tool to Calculate ‘Risks to Fertility’

SIDEBAR: Oocyte Preservation

References

1. Lee SJ, Schover LR, Partridge AH, et al: American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients. J Clin Oncol 24:2917-2931, 2006.

2. Munster PN, Moore AP, Ismail-Khan R, et al: Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer. J Clin Oncol 30:533-538, 2012.

3. Partridge AH: Ovarian suppression for prevention of premature menopause and infertility: Empty promise or effective therapy? J Clin Oncol 30:479-481, 2012.

4. Fertile Hope/LIVESTRONG: Pediatrics: Information for Parents. Available at www.fertilehope.org. Accessed March 19, 2012.


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