Fertility in women carrying BRCA gene abnormality may be reduced
Women carrying BRCA gene abnormality frequently consult with reproductive endocrinologists for fertility treatment or preservation. Women referred to test the BRCA gene for mutations based on ancestry, family history and type of cancer diagnosed in her family. If a mutation is found the lifetime risk for breast cancer is 70% and ovary cancer is 40%.
Fertility in women with BRCA mutations maybe reduced in reproductive age women because of the mutation itself, procedures used to reduce the risk of cancer or cancer treatment if they develop cancer.
Ovarian Reserve and Response to Ovarian Stimulation
Women carrying a BRCA mutation may require ovarian stimulation using fertility medications for
- Preservation of fertility through egg freezing or embryo freezing prior to prophylactic removal of both ovaries,
- Preservation of fertility after the diagnosis of breast cancer and before chemotherapy or
- An incidental fertility problem unrelated to BRCA mutation.
Ovarian reserve and response to fertility medication is one of the most determinants of success of fertility treatment or preservation.
Although it was suggested that women with BRCA mutations respond more modestly to fertility medications, this was not proven. When women carrying these mutations were compared to relatives with no mutations, there were no differences in the number of deliveries and the need for fertility treatment. Also in a study of 260 Ashkenazi Jewish women with ovarian cancer and 331 controls, unselected for age or family history of the disease. Pregnancy success was similar for 96 mutation carrier and 164 non-carrier cases and controls.
Fertility & fertility treatment
Its unlikely that fertility or fertility treatment will increase the risk for breast cancer in women with BRCA mutations. 1380 women diagnosed with breast cancer and carrying BRCA mutations were matched 1380 women without breast cancer and carrying BRCA mutations. 16% reported fertility problems, 4% used fertility medications and 1% used IVF. There was no difference between women who developed breast cancer and those who did not regarding history of infertility and the use of fertility medication. The type of fertility medicine-oral or injection medication also did not change the risk for breast cancer, irrespective if women had children before or not.
Interestingly, there is significant excess of females among the offspring of female carriers of BRCA1 and BRCA2 mutations-higher female to male ratio.
Avoiding BRCA transmission to babies (PGD)
Women interested in getting pregnant should be counseled to the risk of transmission of mutation to future children. Both men and women carrying the mutation are at a significantly increased risk of cancer. It is very possible to prevent this transmission if the eggs or embryos are tested before replacement into the uterus in women undergoing in vitro fertilization – IVF Eggs are tested by polar body biopsy (this is a small cell attached to the egg and carry chromosomes representative to those of the egg). Embryos are tested by testing one cell of a 6 to 8 cell embryo. Testing has many medical and ethical dimensions and is better handled by providers specializing in these areas.
The risk of breast cancer may increase with multiple pregnancies and deliveries in women carrying BRCA2 mutations. In BRCA1 mutation carriers, late menarche and breast feeding reduces the risk for breast cancer. The effect of pregnancy on cancer risk though was not confirmed in multiple studies.