Opening the Discussion
Patients value fertility counseling and there is evidence that it can reduce patients’ later levels of regret and dissatisfaction, improving quality of life.1
There are not yet widely used, validated questionnaires to guide oncofertility discussions but the American Society of Clinical Oncology (ASCO) and other national organizations recommend such patient/clinician discussions as well as fertility referrals and consultations for patients of reproductive age at the time of diagnosis, “when all potential options can be discussed with the patient,” Dr McKenzie said.3
Fertility preservation options vary by cancer type, tumor location and stage, treatment history, and comorbidities. Patient age is also relevant, when considering radiotherapy.
“Younger, when with more ‘reserve,’ are slightly more resilient on average,” explained Dr McKenzie. “The dose associated with 50% loss of fertility is lower closer to menopause than for very young women — those who are younger than 30, for example.”
Clinicians must convey to patients that even when fertility preservation is the goal and guides treatment decision-making, no one can be certain that fertility can always be maintained. Intensity-modulated radiotherapy (IMRT) is increasingly used to spare radiosensitive nontarget reproductive tissues and to direct increased radiation doses to target tumors. But even IMRT cannot entirely eliminate the oocyte toxicity of pelvic radiotherapy, Dr McKenzie cautioned. Ovaries are so sensitive that even minimal doses of radiation can impact fertility for some women.
The odds of preterm, low-weight, or small-for-gestational-age births increase with radiation dose to the uterus.1 Radiation dose to ovaries is directly correlated with the risk of subsequent infertility, due in part to increased risk of impaired pelvic blood flow.1 Lower doses of ionizing radiation to the ovaries, less than 2.0 Gy, can cause irregular menses but not necessarily sterility, whereas half of women receiving 2.5 Gy or higher radiation doses to the ovaries will experience persistent sterility.1
A dose of 20 Gy can induce premature ovarian function in younger women (younger than 40 years), whereas as little as 6 Gy can trigger premature ovarian insufficiency in older (older than 40 years), premenopausal women, Dr McKenzie noted.1
Chemotherapy agents used in chemoradiation regimens, particularly those involving alkylating chemotherapy with cyclophosphamide, ifosfamide, or busulfan-melphalan, can also cause ovarian toxicity.1 Platinum-based chemotherapy regimens involve a lower, moderate risk of gonadotoxicity, while methotrexate, vincristine, and bleomycin carry lower risks of gonadotoxicity.1 (Gonadotropin-releasing hormone analogue prophylaxis before chemotherapy might reduce the risk of premature ovarian failure.1)