Women With BRCA Mutation
Recent studies have shown that women carrying the BRCA mutation may have a lower OR and experience earlier menopause. In patients who underwent a letrozole–FSH stimulation protocol for FP, a significantly lower number of oocytes was retrieved in BRCA1 mutation-positive patients compared with women without BRCA mutation. However, no significant differences in the number of oocytes retrieved were noted for BRCA2 mutation-positive patients. Nevertheless, these early reports indicate an initially altered OR in women with BRCA mutations, and even though confirmation is still required in larger studies, it should be taken into account when referring these patients for FP. Unfortunately, when BC patients are referred for FP, their BRCA mutation status is often unknown since mutation tests require several weeks to be confirmed. In addition, BRCA mutation positive women have an increased lifetime risk of developing ovarian cancer; therefore, ovarian tissue cryopreservation is not considered safe in this population of patients and the risk of transplanting an already cancerous frozen ovarian tissue should be discussed with these individuals. Finally, preimplantation genetic diagnosis (PGD) testing has recently been successfully used to test for BRCA mutations and this technique can be offered when discussing FP, depending on the country and legislation. PGD uses standard assisted reproduction technologies, including COS, oocyte retrieval, IVF/intracytoplasmic sperm injection and in vitro embryo culture. The developing embryo is then biopsied at the eight-cell cleavage stage, the biopsied material is tested for the genetic condition, and unaffected embryos are then transferred to the uterus, or cryopreserved in cases of FP. However, PGD for cancer predisposition divides opinion among health professionals worldwide. Indeed, even though BRCA mutations are associated with an increased lifetime risk of breast and ovarian malignancies, cancer development is not inevitably fatal. While primary prevention strategies (mastectomy and salpingo-oophorectomy) significantly decrease the risk of cancer, they do not eliminate it and could compromise the quality of life and psychological wellbeing. Studies have shown that BRCA mutations carriers express concerns about transmitting the mutation to their descendants, and should, therefore, be counseled on the available options. The decision whether to pursue PGD or not is a complex and sensitive one, and depends on many factors, such as the patient's social values, her psychological and cultural context. Reproductive specialists should take account of all these personal elements and offer significant psychosocial support when counseling these patients. Further research on the experience of going through PGD for BRCA is required.