- The goal of this 2018 pocket guide update is to provide current guidance regarding fertility preservation options for people with cancer anticipating treatment.
- People with cancer are interested in discussing fertility preservation. Health care providers caring for adult and pediatric patients with cancer (including medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, surgeons, and others) should address the possibility of infertility as early as possible before treatment starts.
- Health care providers should refer patients who express an interest in fertility preservation (and those who are ambivalent) to reproductive specialists.
- To preserve the full range of options, fertility preservation approaches should be discussed as early as possible, before treatment starts. The discussion can ultimately reduce distress and improve quality of life. Another discussion and/or referral may be necessary when the patient returns for follow-up after completion of therapy and/or if pregnancy is being considered. The discussions should be documented in the medical record.
- Sperm cryopreservation: Sperm cryopreservation is effective, and health care providers should discuss sperm banking with postpubertal males receiving cancer treatment.
- Hormonal gonadoprotection: Hormonal therapy in men is not successful in preserving fertility. It is NOT recommended.
- Other methods to preserve male fertility: Other methods, such as testicular tissue cryopreservation and reimplantation or grafting of human testicular tissue, should be performed only as part of clinical trials or approved experimental protocols.
- Post-chemotherapy: Men should be advised of a potentially higher risk of genetic damage in sperm collected after initiation of therapy. It is strongly recommended that sperm be collected before initiation of treatment because the quality of the sample and sperm DNA integrity may be compromised after a single treatment. Although sperm counts and quality of sperm may be diminished even before initiation of therapy, and even if there may be a need to initiate chemotherapy quickly such that there may be limited time to obtain optimal numbers of ejaculate specimens, these concerns should not dissuade patients from banking sperm. Intracytoplasmic sperm injection allows the future use of a very limited amount of sperm; thus, even in these compromised scenarios, fertility may still be preserved.
- Embryo cryopreservation: Embryo cryopreservation is an established fertility preservation method, and it has routinely been used for storing surplus embryos after in vitro fertilization.
- Cryopreservation of unfertilized oocytes: Cryopreservation of unfertilized oocytes is an option and may be especially well suited to women who do not have a male partner, do not wish to use donor sperm, or have religious or ethical objections to embryo freezing.
- Oocyte cryopreservation should be performed in centers with the necessary expertise. As of October 2012, the American Society for Reproductive Medicine no longer deems this procedure experimental.
Qualifying Statement: More flexible ovarian stimulation protocols for oocyte collection are now available. Timing of this procedure no longer depends on the menstrual cycle in most cases, and stimulation can be initiated with less delay compared with old protocols. Thus, oocyte harvesting for the purpose of oocyte or embryo cryopreservation is now possible on a cycle day-independent schedule. Of special concern in estrogen-sensitive breast and gynecologic malignancies is the possibility that these fertility preservation interventions (e.g., ovarian stimulation regimens that increase estrogen levels) and/or subsequent pregnancy may increase the risk of cancer recurrence. Aromatase inhibitor-based stimulation protocols are now well-established and may ameliorate this concern. Studies do not indicate increased cancer recurrence risk as a result of aromatase-inhibitor supplemented ovarian stimulation and subsequent pregnancy.
- Ovarian transposition: Ovarian transposition (oophoropexy) can be offered when pelvic irradiation is performed as cancer treatment. However, because of radiation scatter, ovaries are not always protected, and patients should be aware that this technique is not always successful.
- Because of the risk of remigration of the ovaries, this procedure should be performed as close to the time of radiation treatment as possible.
- Conservative gynecologic surgery: It has been suggested that radical trachelectomy (surgical removal of the uterine cervix) should be restricted to stage IA2 to IB cervical cancer with diameter <2 cm and invasion < 10 mm.
- In the treatment of other gynecologic malignancies, interventions to spare fertility have generally centered on doing less radical surgery with the intent of sparing the reproductive organs as much as possible. Ovarian cystectomy can be performed for early-stage ovarian cancer.
Recommendation 3.5 [Updated]
- Ovarian suppression: There is conflicting evidence to recommend GnRHa and other means of ovarian suppression for fertility preservation. The Panel recognizes that, when proven fertility preservation methods such as oocyte, embryo or ovarian tissue cryopreservation are not feasible, and in the setting of young women with breast cancer, GnRHa may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency. However, GnRHa should not be used in place of proven fertility preservation methods.
Recommendation 3.6 [Updated]
- Ovarian tissue cryopreservation and transplantation: Ovarian tissue cryopreservation for the purpose of future transplantation does not require ovarian stimulation and can be performed immediately. In addition, it does not require sexual maturity and hence may be the only method available in children. Finally, this method may also restore global ovarian function. However, it should be noted further investigation is needed to confirm whether it is safe in patients with leukemias.
Qualifying Statement: As of the time of this publication, ovarian tissue cryopreservation remains experimental. However, emerging data may prompt reconsideration of this designation in the future. (This technique is already considered non-experimental in some countries and its experimental status is undergoing evaluation in the U.S.)
Role of Health Care Providers
- All oncologic health care providers should be prepared to discuss infertility as a potential risk of therapy. This discussion should take place as soon as possible once a cancer diagnosis is made and can occur simultaneously with staging and the formulation of a treatment plan. There are benefits for patients in discussing fertility information with providers at every step of the cancer journey.
- Encourage patients to participate in registries and clinical studies, as available, to define further the safety and efficacy of these interventions and strategies.
- Refer patients who express an interest in fertility, as well as those who are ambivalent or uncertain, to reproductive specialists as soon as possible.
- Refer patients to psychosocial providers when they are distressed about potential infertility.
Special Considerations: Children
- Suggest established methods of fertility preservation (e.g., semen or oocyte cryopreservation) for postpubertal children, with patient assent and parent or guardian consent. For prepubertal children, the only fertility preservation options are ovarian and testicular cryopreservation, which are investigational.