Potential implications on female fertility and reproductive lifespan in BRCA germline mutation women

Women who carry a mutation in the BRCA1 or BRCA2 genes not only have an increased lifetime risk of developing breast and ovarian cancer, but also a complicated reproductive future. Based on the hypothesis that BRCA germline mutations (BRCAm) are associated with accelerated follicular loss and early menopause, the aim of this paper is to discuss and review the most outstanding recently published articles about BRCA gene and fertility.

A literature research in PubMed was conducted, using the keywords “anti-Müllerian hormone”, “BRCA1/2 gene”, “female fertility”, “ovarian reserve” and “premature ovarian failure”, selecting outstanding articles published since 2010.

BRCA genes, mainly BRCA1, play a role in the maintenance of double-stranded DNA breaks and telomere length, a factor associated with reproductive lifespan and early depletion of ovarian reserve. BRCAm women have a decreased ovarian reserve and worse response in fertility preservation. In the case of being given chemotherapy or tamoxifen, that would increase the apoptosis of follicular reserve. Low Anti-Müllerian hormone serum concentrations have not been shown to affect natural fecundability and fertility in BRCAm women below 30 s, but it does in women above that threshold. Surgical risk reduction salpingo-oophorectomy implies another important limitation in reproductive possibilities. Removal of the fallopian tubes with delayed oophorectomy could be a reasonable strategy in high-risk premenopausal women in the context of a clinical trial.

BRCAm women should not delay pregnancy, especially if they are BRCA1, older than 35 years or with previous gonadotoxic treatments. Future prospective studies on infertility outcomes in this population are needed.