Clinical Question 1
Are Patients with Cancer Interested in Interventions to Preserve Fertility?
Recommendation 1.1. 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.
What Can Health Care Providers Do to Educate Patients about the Possibility of Reduced Fertility Resulting from Cancer Treatments and to Introduce Them to Methods to Preserve Fertility?
Recommendation 1.2. Health care providers should refer patients who express an interest in fertility preservation (and patients who are ambivalent) to reproductive specialists.
Recommendation 1.3. Fertility preservation is often possible, but 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 and if pregnancy is being considered. The discussions should be documented in the medical record.
Clinical Question 2
What Is the Quality of Evidence Supporting Current and Forthcoming Options for Preservation of Fertility in Males?
Recommendation 2.1. Sperm cryopreservation: Sperm cryopreservation is effective, and health care providers should discuss sperm banking with postpubertal males receiving cancer treatment.
Recommendation 2.2. Hormonal gonadoprotection: Hormonal therapy in men is not successful in preserving fertility. It is not recommended.
Recommendation 2.3. 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.
Recommendation 2.4. Postchemotherapy: 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 session. 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.
Clinical Question 3
What Is the Quality of Evidence Supporting Current and Forthcoming Options for Preservation of Fertility in Females?
Recommendation 3.1. Embryo cryopreservation: Embryo cryopreservation is an established fertility preservation method, and it has routinely been used for storing surplus embryos after in vitro fertilization.
Recommendation 3.2. Cryopreservation of unfertilized oocytes: Cryopreservation of unfertilized oocytes is an option, particularly for patients 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.
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.
Recommendation 3.3. 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.
Recommendation 3.4. 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. Ovarian suppression: Currently, there is insufficient evidence regarding the effectiveness of gonadotropin-releasing hormone analog (GnRHa) and other means of ovarian suppression in fertility preservation.
GnRHa should not be relied upon as a fertility preservation method. However, GnRHa may have other medical benefits such as a reduction of vaginal bleeding when patients have low platelet counts as a result of chemotherapy. This benefit must be weighed against other possible risks such as bone loss, hot flashes, and potential interference with response to chemotherapy in estrogen-sensitive cancers. Women interested in this method should participate in clinical trials, because current data do not support it. In a true emergency or rare or extreme circumstances where proven options are not available, providers may consider GnRHa an option, preferably as part of a clinical trial.
Recommendation 3.6. Ovarian tissue cryopreservation and transplantation: Ovarian tissue cryopreservation for the purpose of future transplantation does not require ovarian stimulation or sexual maturity and hence may be the only method available in children. It is considered experimental and should be performed only in centers with the necessary expertise, under institutional review board (IRB)-approved protocols that include follow-up for recurrent cancer.
A theoretic concern with reimplanting ovarian tissue is the potential for reintroducing cancer cells depending on the type and stage of cancer, although so far there have been no reports of cancer recurrence.
Recommendation 3.7. Other considerations: Of special concern in estrogen-sensitive breast and gynecologic malignancies is the possibility that fertility preservation interventions (e.g., ovarian stimulation regimens that increase estrogen levels) and/or subsequent pregnancy may increase the risk of cancer recurrence.
Ovarian stimulation protocols using the aromatase inhibitor letrozole have been developed and may ameliorate this concern. Studies do not indicate increased cancer recurrence risk as a result of subsequent pregnancy.
Clinical Question 4
What Is the Role of Health Care Providers in Advising Patients about Fertility Preservation Options?
Recommendation 4.1. 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 before a treatment plan is formulated. There are benefits for patients in discussing fertility information with providers at every step of the cancer journey.
What Should Providers Discuss with Patients about Fertility Preservation?
Recommendation 4.2. Encourage patients to participate in registries and clinical studies, as available, to define further the safety and efficacy of these interventions and strategies
Recommendation 4.3. Refer patients who express an interest in fertility, as well as those who are ambivalent or uncertain, to reproductive specialists as soon as possible.
Recommendation 4.4. Refer patients to psychosocial providers when they are distressed about potential infertility.
Special Considerations: Fertility Preservation in Children
Recommendation 5.1. Suggest established methods of fertility preservation (e.g., semen or oocyte cryopreservation) for postpubertal minor children, with patient assent and parent or guardian consent.
For prepubertal minor children, the only fertility preservation options are ovarian and testicular cryopreservation, which are investigational.