Cancer awareness campaigns and effective screening strategies have allowed for early detection of breast cancer. Due to effective modern treatment over 85% - 90% of breast cancer sufferers may survive beyond 5 years after their diagnosis.
Since 5% of breast cancer is diagnosed in women <40years old, young breast cancer survivors may desire to have children after remission of cancer. Pregnancy is safe in women who have survived breast cancer independent of estrogen receptor status of the tumor. The ability to have children naturally is significantly reduced after breast cancer treatment in some women. Even though young women (<35years) with a good ovarian reserve have a greater chance of return of spontaneous menstruation and/ or natural pregnancy than older women, all women undergoing chemotherapy should consider fertility preservation.
The treatments for breast cancer that reduce ovarian reserve and the ability to have children are:
1. Chemotherapy especially cyclophosphamide based treatments
2. Surgery that removes the ovaries (known as oophorectomy)
3. Radiotherapy for breast cancer is directed on the chest away from the reproductive organs and has less impact on fertility
There are options for improving fertility after surviving breast cancer. These are called “Fertility preservation strategies”:
1. Oocyte cryopreservation also known as egg freezing. A woman is given hormonal injections (containing FSH/ LH, HCG, like the process of IVF) to stimulate the ovaries to produce many mature eggs. These eggs are then harvested and cryopreserved (frozen). The eggs may be thawed (defrosted) and fertilized many years later when the woman has been cured of breast cancer and desires to have children. The process of egg freezing may be performed soon after diagnosis of breast cancer and before chemotherapy is begun. It delays the start of chemotherapy by 2 to 3 weeks. This time delay and the ovarian stimulation do not worsen treatment outcomes of breast cancer therapy. The Reproductive Endocrinologist will utilize measures that reduce peak estrogen levels and other complications during ovarian stimulation such as concurrent letrozole administration, GnRH antagonist for downregulation and GnRH agonist trigger.
2. Embryo cryopreservation (embryo freezing). It involves the same steps as oocyte cryopreservation except that the mature eggs are fertilized immediately after harvest to form embryos using partner or donor sperm. The disadvantage of embryo freezing is that if there is a change in the relationship between the woman and her partner (eg-divorce), then the woman may not be able to use these embryos in future as she will require his consent to do so.
Oocyte and embryo cryopreservation are established fertility procedures that are no longer considered experimental by several international bodies such as ESHRE and ASRM and are available in most fertility clinics.
3. In vitro maturation of immature eggs (IVM). This is suitable for women that cannot wait to undergo ovarian stimulation to produce mature eggs before starting cancer treatment (eg- those with locally advanced breast cancer) or those with safety concerns. IVM involves harvesting immature eggs which may be matured within the laboratory and then frozen.
4. Ovarian tissue cryopreservation (OTC). OTC is indicated in women who cannot delay the start of chemotherapy or those whose ovaries are being removed as part of their treatment (eg BRCA gene carriers). Portions of or a whole ovary is removed and cryopreserved. When the woman is ready to have a child after survival, this ovarian tissue may be transplanted back into her pelvis through an operation (laparoscopic surgery). Pregnancy can be achieved naturally or through IVF. Alternatively, this ovarian tissue may be cultured in the laboratory (artificial ovary) to harvest mature eggs, or immature eggs may be harvested from this tissue at the time of OTC and cultured to maturity in the laboratory. OTC is becoming recognized as an established fertility preserving procedure but is not yet available in many countries.
5. Gonadotropin releasing hormone analogues (GnRHa) suppress ovarian function and are thought to protect it from insults by chemotherapy. GnRHa are administered 2 to 3 weeks before chemotherapy and are continued throughout chemotherapy till the end of treatment. GnRHa significantly reduced the risk of developing chemotherapy-induced early menopause. They were associated with a higher number of post-treatment pregnancies in women that desired fertility and had no negative impact on cancer survival outcomes. The main adverse events associated with GnRHa administration are hot flushes and vaginal dryness. GnRHa do not replace the more effective fertility preserving measures such as oocyte and embryo cryopreservation.
It is important to note that fertility preservation methods are not a guarantee of a live birth in future. They however increase the possibility of having a child after breast cancer treatment. In order to prevent adverse effects on pregnancy outcome, a woman may attempt pregnancy at least 1 year after completing chemotherapy, at least 3 months after stopping endocrine therapy and at least 7 months after completing anti-HER2 agents.
References
1. Female Fertility Preservation: Guideline of the European Society of Human Reproduction and Embryology (2020)
2. Fertility preservation and reproduction in patients facing gonadotoxic therapies: an Ethics Committee opinion Ethics Committee of the American Society for Reproductive Medicine (2018)
3. Burning Questions in the Oncofertility Counseling of Young Breast Cancer Patients, Arecco et al, 2020, Breast Cancer Basic & Clinical Research
