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ASCO convened an Expert Panel to conduct a systematic review of the literature available through March 2005 to develop guidance to oncologists about available fertility preservation methods and related issues in cancer patients.
The following recommendations are based on the available evidence and address several questions posed by the Panel. Oncologists should address the possibility of infertility with patients treated during their reproductive years. Fertility preservation is often possible, but to preserve the full range of options, fertility preservation approaches should be considered as early as possible during treatment planning.
See Table 1 for a summary of fertility preservation options in male patients.
Sperm cryopreservation. Sperm cryopreservation is effective, and oncologists should discuss sperm banking with appropriate patients. It is strongly recommended that sperm are collected prior to initiation of treatment because the quality of the sample and sperm DNA integrity may be compromised even after a single treatment session. Although planned chemotherapy may limit the number of ejaculates, intracytoplasmic sperm injection allows the successful freezing and future use of a very limited amount of sperm.
Hormonal gonadoprotection. Hormonal therapy in men is not successful in preserving fertility when highly sterilizing chemotherapy is administered.
Other considerations. Men should be advised of a potentially higher risk of genetic damage in sperm stored after initiation of therapy. Testicular tissue or spermatogonial cryopreservation and transplantation or testis xenografting have not yet been tested successfully in humans. Of note, such approaches are also the only methods of fertility preservation potentially available to prepubertal boys.
See Table 2 for a summary of fertility preservation options in female patients.
Embryo cryopreservation. Embryo cryopreservation is considered an established fertility preservation method because it has routinely been used for storing surplus embryos after in vitro fertilization. Approximately 2 weeks of ovarian stimulation with daily injections of follicle-stimulating hormone is required and must be started within the first 3 days of the menstrual cycle.
Cryopreservation of unfertilized oocytes. Cryopreservation of unfertilized oocytes is an option, particularly for patients without a partner or those with religious or ethical objections to embryo freezing. Ovarian stimulation is required as described in the preceding section. Oocyte cryopreservation should be performed only in centers with the necessary expertise, and the Panel recommends participation in institutional review board (IRB) –approved protocols.
Ovarian tissue cryopreservation. Ovarian tissue cryopreservation and transplantation procedures should be performed only in centers with the necessary expertise under IRB-approved protocols that include follow-up for recurrent cancer. A concern with reimplanting ovarian tissue is the potential for reintroducing cancer cells, although in fewer than 20 procedures reported thus far, there are no reports of cancer recurrence.
Ovarian suppression. Currently, there is insufficient evidence regarding the safety and effectiveness of gonadotropin-releasing hormone analogs and other means of ovarian suppression on fertility preservation. Women interested in this technique are encouraged to participate in clinical trials.
Ovarian transposition. Ovarian transposition (oophoropexy) can be offered when pelvic radiation is administered as cancer treatment. Because of the risk of remigration of the ovaries, this procedure should be performed as close to the radiation treatment as possible.
Conservative gynecologic surgery. It has been suggested that radical trachelectomy be restricted to stage IA2-IB disease with diameter less than 2 cm and invasion less than 10 mm. In the treatment of other gynecologic malignancies, interventions to spare fertility have generally centered on doing less-radical surgery and/or lower-dose chemotherapy with the intent of sparing the reproductive organs as much as possible.
Other considerations. Of special concern in breast and gynecologic malignancies is the possibility that fertility preservation interventions and/or subsequent pregnancy may increase the risk of cancer recurrence. Although several studies have not shown a decrement in survival or an increase in risk of breast cancer recurrence with pregnancy, the studies are all limited by significant biases, and concerns remain for some women and their physicians.
Use of established methods of fertility preservation (semen cryopreservation and embryo freezing) in postpubertal minor children requires patient assent and parental consent. The modalities available to prepubertal children to preserve their fertility are limited by the sexual immaturity of the children and are essentially experimental. Efforts to preserve fertility of children using experimental methods (e.g., gonadal tissue cryopreservation) should be attempted only under IRB-approved protocols.
As with other potential complications of cancer treatment, oncologists have a responsibility to inform patients about the risk that their cancer treatment will permanently impair fertility. An algorithm for triaging fertility preservation referrals is presented in Figure 1, and suggested talking points are illustrated in the sidebar.
Oncologists should answer basic questions about whether fertility preservation options decrease the chance of successful cancer treatment, increase the risk of maternal or perinatal complications, or compromise the health of offspring. Patients should be encouraged to participate in registries and clinical studies as available to define further the safety of these interventions and strategies. Currently, women with a history of cancer and cancer treatment should be considered high risk for perinatal complications and would be prudent to seek specialized perinatal care.
Oncologists should refer interested and appropriate patients to reproductive specialists as soon as possible. Referral to psychosocial providers may be beneficial when a patient has moderate to severe distress about potential infertility.
The literature review found many cohort studies, case series, and case reports, but relatively few randomized or definitive trials examining the success and impact of fertility preservation methods in people with cancer.
Fertility preservation methods are still applied relatively infrequently in the cancer population, limiting greater knowledge about success and effects of different potential interventions. Other than risk of tumor recurrence, less attention is paid to the potential negative effects (physical and psychological) of fertility preservation attempts.
In addition to the full text of the guideline (http://www.asco.org/guidelines/fertility), further resources include a Patient Guide (http://www.plwc.org/patientguides) and a PowerPoint slide set (http://www.asco.org/guidelines/fertility/slides).
The American Society for Reproductive Medicine has both a Mental Health Professional Group (http://www.asrm.org/Professionals/PG-SIG-Affiliated_Soc/MHPG/index.html) and a Fertility Preservation Special Interest Group (http://www.asrm.org/Professionals/PG-SIG-Affiliated_Soc/fpsig/fpsig_index.html).
Cancer patient advocacy organizations such as fertileHOPE (www.fertilehope.org), Lance Armstrong Foundation/LIVESTRONG (www.livestrong.org), and the Susan G. Komen Breast Cancer Foundation (www.komen.org) provide patient information.
It is important to realize that many management questions have not been comprehensively addressed in randomized trials, and guidelines cannot always account for individual variation among patients. A guideline is not intended to supplant physician judgment with respect to particular patients or special clinical situations and cannot be considered inclusive of all proper methods of care or exclusive of other treatments reasonably directed at obtaining the same results.
Accordingly, ASCO considers adherence to this guideline to be voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. In addition, the guideline describes administration of therapies in clinical practice; it cannot be assumed to apply to interventions performed in the context of clinical trials, given that clinical studies are designed to test innovative and novel therapies in a disease and setting for which better therapy is needed. Because guideline development involves a review and synthesis of the latest literature, a practice guideline also serves to identify important questions for further research and those settings in which investigational therapy should be considered.
The Guideline Recommendations on Fertility Preservation in Cancer Patients were developed and written by Stephanie J. Lee (co-chair), MD, MPH, Kutluk Oktay (co-chair), MD, Leslie R. Schover, PhD, Ann H. Partridge, MD, MPH, Pasquale Patrizio, MD, MBE, W. Hamish Wallace, MD, Karen L. Hagerty, MD, Lindsay N. Beck, and Lawrence V. Brennan, MD.