What methods are available to preserve fertility in breast cancer patients? There are several methods that can be used today to preserve fertility: the most effective and certain method is embryo cryostorage, but this method requires a delay of up to 6 weeks in adjuvant therapy to allow for ovarian stimulation of the patient. If a referral to a fertility specialist is made prior to breast cancer surgery, this appears to not only increase the likelihood of obtaining adequate numbers of oocytes, but also does not delay adjuvant breast cancer treatment. Although more than 500 successful cases of safe delivery of babies with cryopreserved mature oocytes have been reported, and pregnancy success rates have improved with technical improvements. However, this method is still considered experimental. Although oocytes can be collected without ovarian stimulation, the amount of embryos formed is extremely low. In hormone-sensitive tumors (e.g., hormone receptor (HR) positive patients), letrozole or tamoxifen may be chosen as an alternative to estrogen for ovarian stimulation to reduce the potential risk of estrogen exposure to tumor cells. New methods, such as in vitro follicle culture and ovarian tissue cryostorage and transplantation methods, are being actively investigated. Can GnRH analogs protect against ovarian damage caused by chemotherapy? In premenopausal women, GnRH analogs cause a temporary, reversible decrease in estrogen production by reducing pituitary FSH and LH secretion. possible mechanisms of fertility protection by GnRH analogs include ovarian suppression, preservation of early follicles that have begun to grow, interruption of FSH-induced follicular replenishment, and reduction of ovarian blood flow. Until now, most clinical studies of GnRH analogs have been small, uncontrolled and retrospective, comparing differences between ages, tumor types and chemotherapy regimens. Therefore, these studies cannot provide definitive safety conclusions, and this limitation has prevented the widespread use of GnRH analogs for ovarian protection. A recent randomized controlled study of 80 young breast cancer patients, which used the presence of regular cycles of menstrual resumption as an endpoint and serum gonadotropin levels as a criterion, and patients who took chemotherapy only as a control, showed a significant improvement in ovarian protection in patients who took chemotherapy plus a GnRH agonist (goserelin). However, the study had some limitations, such as the short follow-up period (8 months) and the lack of information on other adjuvant treatments, which prevented the identification of patients whose ovarian function would later recover. Several prospective randomized controlled studies are underway: the results of the ZORO trial found no statistically significant difference (p = 0.28) in the protection of ovarian function between the goserelin group (70%) and the observation-only control group (56.7%) in young patients with hormone-sensitive breast cancer treated with anthracycline chemotherapy. The Italian PROMISE trial was completed in 2008 with 280 patients enrolled, but the results of this study have not yet been published. Another prospective randomized controlled study, led by the Southwest Oncology Organization (SWOG 0230) in the United States with participation from the North American Breast Cancer Organization and Breast Cancer Research International, included a population of hormone receptor-negative premenopausal breast cancer patients to assess the rate of ovarian failure after 2 years of adjuvant, and showed a significant positive effect of GnRH agonist (goserelin) in terms of ovarian protection (the study was published at the 2014 ASCO meeting —- translator’s note). The Ovarian Protection in Premenopausal Breast Cancer Patients Trial (OPTION trial), led by Celtic Oncology UK, is assessing menstruation at 12 months post-treatment. Given the limited and conflicting data available, there are currently no recommendations for the routine use of GnRH analogs for ovarian protection outside of clinical trials. (This opinion represents the prevailing view prior to the publication of the results of the SWOG 0230 trial in 2014 —- translator’s note) The American Society of Clinical Oncology published evidence-based guidelines for protecting fertility in cancer patients. They strongly recommend that “oncologists discuss the risk that cancer treatment may lead to infertility with patients as soon as possible, arguing that in many cases there are insufficient data to give any one patient an accurate expectation of whether future pregnancies will occur. If a patient is at risk for infertility and is interested in considering reproductive protection options, early referral to an appropriate specialist should be recommended”. Can we assess a patient’s fertility with certainty and reliability? There is a lack of reliable and reproducible methods to accurately assess the fertility of a patient after antineoplastic therapy. The presence or absence of menstrual periods does not accurately reflect ovarian reserve function: women with reduced ovarian reserve have shorter and more regular menstrual cycles due to accelerated follicular development. The use of hormone levels (e.g. FSH, LH, estradiol, inhibin B, anti-mullerian hormone = AMH) to assess female fertility may be a better method. The most promising is AMH because it reflects earlier folliculogenesis, which may more closely reflect the number of primordial ovarian follicles, and because AMH does not change substantially during the menstrual cycle. AMH is increasingly becoming an indicator of follicular reserve at older ages and a potential tool to assess fertility prospectively before and after chemotherapy. The widespread use of hormone levels as a method of assessing fertility is not recommended due to cost issues, sensitivity issues, and reproducibility issues. In addition, a single assessment method only reflects ovarian function at a specific time point and therefore does not predict the potential for future ovarian recovery. Evaluation of cystic follicle count and ovarian volume on vaginal ultrasound may be an optional predictor of ovarian function. However, many of these indicators have been interfered with by endocrine therapy for breast cancer. In addition, there are no specific laboratory tests or imaging tests that can perfectly reflect a woman’s ability to have a future pregnancy, even if she is not receiving endocrine therapy. How long after breast cancer diagnosis and or treatment should a woman consider pregnancy? Available data suggest that even an earlier pregnancy (even within 2 years of breast cancer diagnosis or treatment) is unlikely to affect a patient’s prognosis in patients with a low risk of recurrence, but it is not clear whether this is true for both hormone receptor (HR) negative or positive cases. However, it is generally recommended in clinical practice to wait at least 2 years after diagnosis before trying to conceive, primarily to survive the early high-risk period of recurrence. When patients inquire about how soon they can get pregnant after breast cancer treatment, the following factors should also be considered: such as risk of breast cancer recurrence, duration of adjuvant therapy, preservation of fertility and age. Considering the oocyte maturation time, it is reasonable to recommend waiting at least 6 months after chemotherapy. However, there are few summary data as to when endocrine therapy actually leads to pregnancy: since tamoxifen and aromatase inhibitors (Als) are used in all methods of adjuvant fertility to enhance oocyte production. The practical recommendation is to wait at least 2 months after stopping endocrine therapy and not to try to conceive until 3-6 months.