More than 500,000 women of reproductive age (20-49) are diagnosed with cancer each year. Fortunately, given advances in timely detection and effective therapy, more than 83% of these women will survive at least 5 years (SEER Cancer Statistics Review, 1975-2011). As a result, more women are concerned about their child-bearing potential after undergoing chemotherapy or radiation, and as reproductive technology advances, the issue of fertility preservation becomes even more salient.
Potential candidates for fertility preservation
The importance of considering fertility preservation for any reproductive-aged woman with a new cancer diagnosis cannot be overemphasized. This is especially true for women who may be receiving gonadotoxic therapies, such as alkylating agents or abdominal/pelvic radiation.
To assess the risk of various cancer treatments to fertility, patients and providers can access the Fertility Risk Tool at www.livestrong.org. The Fertility Risk Tool compiles known data about the risk of amenorrhea from specific cancers, chemotherapy agents, and radiation treatments, based on the woman’s age. The risk for infertility is likely higher than the stated incidence of amenorrhea, but the chart provides an initial counseling tool for health care providers and an overview for patients.
Discussions regarding fertility preservation are essential for any woman from menarche through mid-40s. However, as technological advances are rapidly occurring in reproductive medicine, options such as ovarian tissue cryopreservation are becoming available for prepubescent girls. Counseling these young patients with a new cancer diagnosis should not be overlooked.
Fertility preservation options
In vitro fertilization (IVF) with embryo banking is currently the most successful fertility preservation option and the standard of care. The process involves an IVF cycle, including monitored ovarian stimulation, transvaginal oocyte retrieval, fertilization of the oocytes, and cryopreservation of embryos.
The entire process takes a minimum of 12 days, and usually starts shortly after the onset of menses. The embryos can survive for years in liquid nitrogen and the survival rate of frozen embryos is greater than 95%. The pregnancy rate per embryo transfer cycle depends on the age of the woman when the embryos were created, with women under age 35 having higher live-birth rates compared with women older than 42 (live-birth rates 42.4% versus 17.8%, respectively, according to national summary data from the Society for Assisted Reproductive Technology).
Another option, which may be more attractive for women without a committed male partner, involves egg banking. This process also involves ovarian stimulation and egg retrieval, but fertilization is not performed. Instead the oocytes are cryopreserved, often by way of a vitrification technique shown to have a higher percentage of oocytes that survive the thaw (Fertil. Steril. 2011;96:277-85).
While the data regarding live birth after egg banking are limited, studies have shown reassuring birth outcomes for more than 900 babies from this technology (Reprod. Biomed. Online 2009;18:769-76).
Timing of treatment must be coordinated with the help of an oncologist. For example, many women with breast cancer opt to have their oncological surgery and undergo ovarian stimulation during the 4-6 week recovery period before initiating chemotherapy.
Ovarian tissue banking is considered experimental, but may be the only option available for women who must initiate treatment immediately, or for prepubescent girls. This technology involves surgical removal of part of an ovary, which is divided into small sections and frozen. The options for reproductive potential may include in vitro maturation of the immature oocytes in the strips of ovarian tissue with subsequent fertilization in the laboratory versus transplantation of the segments of ovarian tissue with the goal of some restoration of ovarian function (Hum. Reprod. 2014;29:1931-40).
Another option is the use of a gonadotropin-releasing hormone (GnRH) agonist during therapy to induce a prepubertal state, with the hypothetical goal to decrease damage to immature oocytes. A recent meta-analysis of randomized trials found that suppression with a GnRH agonist during chemotherapy significantly decreased premature ovarian failure in young women (Cancer Treat. Rev. 2014;40:675-83).
To date, the available literature does not address the effect of GnRH agonist use on rates of infertility in cancer survivors.
Special considerations for hormone sensitive cancers
Women with hormone sensitive cancers, such as breast cancer, often have understandable concerns about preserving their fertility and the impact that ovarian stimulation and future pregnancy may have on their prognosis.
For breast cancer patients, an effective adjuvant treatment during ovarian stimulation is an aromatase inhibitor, which lowers the peak estrogen levels compared to a standard ovarian stimulation cycle, with a similar oocyte yield (J. Clin. Endocrinol. Metab. 2006;91:3885-90).
There does not appear to be a difference in recurrence of breast cancer in women who pursued egg or embryo banking versus those who did not (J. Clin. Oncol. 2008;26:2630-5). Even after subsequent successful pregnancies, recurrence risk in hormone sensitive cancers, including breast cancer, is not increased (Cancer 2004;100:465-9). It is important to note that many women with breast cancer are placed on tamoxifen for many years. These women may consider a surrogate or a “tamoxifen break” after consultation with their oncologists.