Fertility after breast cancer treatment.

In many countries of the developed world, there is an increasing trend toward delay in childbearing from 30 to 40 years of age for various reasons. This is unfortunately concordant with an increasing incidence of breast cancer in women who have not yet completed their family. The current choice for premenopausal women with breast cancer is adjuvant therapy which includes cytotoxic chemotherapy, ovarian ablation (by surgery, irradiation, or chemical ovarian suppression), anti-estrogen therapy, or any combination of these. Although the use of adjuvant therapies with cytotoxic drugs can significantly reduce mortality, it raises issues of the long-term toxicity, such as induction of an early menopause and fertility impairment. The risk of infertility is a potential hardship to be faced by the patients following treatment of breast cancer. The offspring of patients who became pregnant after completion of chemotherapy have shown no adverse effects and congenital anomalies from the treatment, but sometimes high rates of abortion (29%) and premature deliveries with low birth weight (40%) have been demonstrated. Therefore, the issue of recent cytotoxic treatment remains controversial and further research is required to define a "safety period" between cessation of treatment and pregnancy. Preservation of fertility in breast cancer survivors of reproductive age has become an important issue regarding the quality of life. Currently, there are several potential options, including all available assisted technologies, such as in vitro fertilization and embryo transfer, in vitro maturation, oocyte and embryo cryopreservation, and cryopreservation of ovarian tissue. Because increased estrogen levels are thought to be potentially risky in breast cancer patients, recently developed ovarian stimulation protocols with the aromatase inhibitor letrozole and tamoxifen appear to provide safe stimulation with endogenous estrogen. Embryo cryopreservation seems to be the most established fertility preservation strategy, providing a 25-35% chance of pregnancy. In addition, oocyte freezing can be considered as an alternative in patients who are single and in those who do not wish a sperm donor. Although ovarian tissue harvesting appears to be safe, experience regarding ovarian transplantation is still limited due to low utilization, so the true value of this procedure remains to be determined. Nevertheless, in clinical situations in which chemotherapy needs to be started in young patients facing premature ovarian failure, ovarian tissue preservation seems to be a promising option for restoring fertility, especially in conjunction with other options like immature oocyte retrieval, in vitro maturation of oocytes, oocyte vitrification, or embryo cryopreservation. It seems that in vitro maturation is a useful strategy because it improves oocyte or cryopreservation outcome in breast cancer patients undergoing ovarian stimulation for fertility preservation.