Fertility Preservation Options Vary by Cancer Type
With continued improvement in assisted reproductive technology, the landscape for fertility preservation in the female cancer patient has changed for the better, said Nicole Noyes, MD, Professor and Codirector of the Oocyte Cryopreservation Program at New York University Fertility Center, at the 2010 meeting of the American Society for Reproductive Medicine (ASRM).
More women are pursuing fertility preservation than ever before, and the 2006 guidelines from the American So ciety of Clinical Oncology (ASCO) rec ommend that patients who are interested in fertility preservation options be referred to fertility preservation expertise.
Considerations in the choice of fertility preservation include the patient’s age, type of cancer and planned treatment, available time before starting cancer treatment, overall health of the patient and, if a single woman, her willingness to use donor gametes. More than 1 option may be possible for a given patient, said Dr Noyes.
Cryopreservation May Offer an Advantage
Embryo banking is still considered the standard of care, and has a live birth rate of approximately 33%. By comparison, oocyte cryopreservation, which is still considered experimental by ASRM, has a live birth rate of 39.3%, and appears to have no increase in birth anomalies compared with natural conception.
Approximately 50% of in vitro fertilization centers in the United States offer oocyte cryopreservation, she said. Oocyte cryopreservation has the advantage of reproductive autonomy, because it does not require the use of donor sperm.
A recent randomized controlled comparison that included 600 donor egg recipients showed no difference in implantation rates and clinical pregnancy rates between vitrified and fresh oocytes (Cobo A, et al. Hum Reprod. 2010;25:2239-2246).
And in a series of 90 patients with cancer who underwent ovarian hyperstimulation and oocyte cryopreservation, Dr Noyes and colleagues found that adequate ovarian stimulation could be achieved (Noyes N, et al. J Assist Reprod Genet. 2010;27:495-499). There were no differences between cryopreservation cycles performed in patients with cancer and in women without cancer. “We can complete stimulation very quickly—within 2 weeks,” she said. “We tend to dose up with gonadotropins.”
Newer Options Require More Data
Some of the newer technologies for fertility preservation have limited data on effectiveness, said Clarissa Gracia, MD, Director of Fertility Preservation at Penn Fertility, University of Pennsylvania.
In vitro maturation of immature oocytes is considered experimental. In a study of women with normal ovaries, in vitro maturation with follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) priming was associated with higher clinical pregnancy rates than without priming or with FSH or hCG priming alone (Fadini R, et al. Reprod Biomed Online. 2009;19:343-351).
There have been few successes with ovarian tissue banking, which is also considered experimental, said Dr Gracia. Ovarian tissue banking re quires surgical removal of ovarian tissue. Ovarian stimulation is not necessary, no partner is required, and delays in treatment are minimal. A review of published data using orthotopic transplants of cryopreserved ovarian tissue reveals 10 live births in 8 patients with cancer.
Other challenges to fertility preservation in the patient with cancer are fitting fertility preservation into the cancer treatment schedule and uncertainties about ovarian stimulation, such as the safety of stimulating close to administration of gonadotoxic chemotherapy or with a tumor present.
Dr Noyes provided an overview of fertility preservation options for patients with specific cancer diagnoses.
Patients with Breast Cancer
In patients with breast cancer, if surgery is performed first (before adjuvant chemotherapy), there is usually time for fertility preservation between the surgery and the start of chemotherapy, Dr Noyes said. If chemotherapy is administered first, ovarian stimulation is performed with a full tumor load.
Continuation and return of menstrual bleeding depends on the chemotherapy regimen, the age of the patient, and the use of tamoxifen in women treated for breast cancer. Month ly bleeding returned within 1 month after standard courses of chemotherapy more often with a regimen of cyclophosphamide, methotrexate, and fluor ouracil than with doxorubicin and cyclo phosphamide.
Dr Noyes urged caution in interpreting these results, saying that “menses does not mean motherhood.” Tamoxifen use was associated with a decrease in bleeding after completion of chemotherapy.
Patients with Hematologic Malignancies
Patients with hematologic malignancies require rapid treatment (sometimes before fertility preservation), and they usually have a full tumor load at the time of fertility preservation treatment. “They may have relapse after first fertility-sparing cancer treatment and require a more gonadotoxic protocol with chemotherapy or bone marrow transplantation,” Dr Noyes said.
Ovarian stimulation may be challenging in women with hematologic cancers because ovarian follicles (particularly antral and larger) may be destroyed during chemotherapy. Ovarian stimulation is not possible during chemotherapy and can be challenging shortly after chemotherapy. Also, it is not clear how long to wait after cancer therapy to see the response to ovarian stimulation. Further more, the safety of in vitro fertilization immediately after cancer therapy is unclear with respect to embryo de velopment and implantation, as well as the risks of aneuploidy and malformation.
Ovarian tissue cryopreservation before chemotherapy may be an option for fertility preservation in women with hematologic cancers. Among the 10 births resulting from autologous transplantation of follicles or strips of cryopreserved ovarian cortical tissue, 5 have been by women with Hodgkin’s or non-Hodgkin’s lymphoma, all of whom were in their 20s at the time. “Ovarian tissue pieces are more resilient in younger women; this is not a treatment for women who are 40 or older,” Dr Noyes noted.
Reimplanting cryopreserved ovarian tissue from women with certain hematologic cancers runs the risk of reseeding the cancer and therefore may not be safe, said Dr Noyes. (In 2006, ASCO recommended ovarian tissue screening to detect malignant cells to minimize the risk of cancer cell transfer with the ovary.)
Gynecologic Malignancies
Gynecologic cancers have their own unique considerations for fertility preservation, because they often require removal of organs associated with reproduction.
Removal of the uterus in the management of gynecologic cancers warrants a thorough discussion, because implantation at the uterine level is not affected by a woman’s age.
In the case of endometrial cancer, “if it can’t be treated with hormones, the uterus will have to come out, in which case we can either make eggs or embryos that can go into a gestational carrier,” Dr Noyes pointed out. “The use of gestational carriers is much more common now than it was a few years ago.” She said that there are approximately 800 known cases of gestational carriers in the United States.
Patients with ovarian cancer often have decreased ovarian reserve. Various modalities can assess ovarian reserve, the most common being assessment of FSH and estradiol. In addition, noninvasive sonographic evaluation can help in the assessment of ovarian function.