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Understanding BRCA & HBOC > FORCE Publications > Newsletter > Archives > Fertility, Reproduction, and Menopause in BRCA Carriers

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FORCE Publications

Fertility, Reproduction, and Menopause in BRCA Carriers

by Lauren N. C. Johnson, MD and Clarisa R. Gracia, MD, MSCE

Preliminary research suggests that BRCA mutations may affect women's fertility. One study showed that women with BRCA1 mutations had fewer eggs retrieved when undergoing in vitro fertilization (IVF) compared to women without BRCA mutations. Researchers at the University of California at San Francisco studied women with BRCA1/2 mutations who had not had prophylactic surgery, chemotherapy, or radiation, to determine when they went through natural menopause. Compared to women without known mutations, mutation carriers experienced menopause three years sooner than women who had not been tested for the mutation. A separate study performed by a large hereditary cancer research consortium observed that on average, BRCA carriers underwent natural menopause about a year sooner than non-carriers.

A woman's fertile window and time to menopause depends on the number of eggs she carries in her ovaries. Earlier onset of menopause in women with BRCA mutations suggests that they may have fewer eggs than women without a mutation, and may therefore be at higher risk for infertility. While these findings warrant further investigation, current evidence is inconclusive.

BRCA carriers face unique reproductive challenges. The recommendation for riskreducing oophorectomy by age 35 to 40 narrows women's timespan to complete their families. Some women with BRCA mutations choose to pursue fertility treatments such as IVF to expedite pregnancy and then undergo recommended prophylactic surgery. Women with mutations who are not in a position to become pregnant before ovary removal is recommended may decide to freeze their eggs and/or embryos for future use. Some pursue preimplantation genetic diagnosis of embryos to reduce the chance of passing their mutation to their children. All these options can be affected by the number of eggs available.

If women with BRCA mutations are truly at higher risk of infertility than the general population, this may influence their decisions about family planning. Early referral to fertility specialists may be beneficial to BRCApositive women so that they may pursue fertility treatments or fertility preservation. Researchers at the University of Pennsylvania have teamed up with FORCE to conduct the AFFIRM (Assessment of Fertility and Factors Influencing Reproduction and Menopause in BRCA Mutation Carriers) study. Supported by a grant from the Basser Research Center for BRCA of Penn Medicine's Abramson Cancer Center, this study will collect information regarding fertility, pregnancy history, and timing of menopause among women with and without BRCA mutations. Results will help researchers better understand fertility and reproduction in the BRCA population, which will help women make informed decisions about their reproductive options. Ultimately, we hope that all women with BRCA mutations can fulfill their reproductive goals. Visit the FORCE website for more information or to participate in this important study.

References

Oktay K, et al. Association of BRCA1 mutations with occult primary ovarian insufficiency: A possible explanation for the link between infertility and breast/ovarian cancer risks. Journal of Clinical Oncology 2010; 28(2):240-44.

Lin WT, et al. Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non-clinic-based sample of women in Northern California. Cancer epub, Jan. 2013.

Finch A, et al. Frequency of premature menopause in women who carry a BRCA1 or BRCA2 mutation. Fertility and Sterility epub, Feb. 2013.

Dr. Lauren Johnson is a fellow in Reproductive Endocrinology and Infertility at the University of Pennsylvania. Dr. Clarisa Gracia is an associate professor and director of the fertility preservation program at the University of Pennsylvania in the division of reproductive endocrinology and infertility.

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