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Special populations: Women considering childbearing
Age affects fertility. As women age, their ovaries release eggs that are not as healthy as those released in younger women, and in general, fewer eggs each menstrual cycle, making it harder for older women to become pregnant. Are BRCA mutation carriers less fertile? Previous research suggested that BRCA mutations might affect women's fertility. A recent study found that BRCA1 mutation carriers may have slightly lower fertility than women without the same mutation, but more research is needed before this finding is useful for medical decision-making. (5/24/16)
Whether having a BRCA mutation affects ovarian reserve, which in general describes the capacity of ovaries to provide eggs that will ultimately result in a successful pregnancy.
Age is the biggest factor that affects ovarian reserve—a woman has less healthy eggs (one that will result in a successful pregnancy) to release each month from her ovary the older she gets. Because of this, age is often a factor in family planning. If BRCA mutation status also affects their fertility, this would be more important information for women to take into account for family planning.
While the association between BRCA1 mutation carriers and lower ovarian reserve adds to previous data from mice that implicated BRCA in fertility and reproductive aging, it is not yet clinically relevant. BRCA1 mutation carriers do not need to rush and have children when they are not ready as it is not definitive that BRCA1 mutation carriers have a lower ovarian reserve.
Additionally, it is important to point out that the difference in ovarian reserve found in this study was relatively small. Women with BRCA mutations have many factors to consider when they are thinking about conceiving including the desire to have children before undergoing risk-reducing removal of the ovaries and fallopian and personal history of fertility problems. BRCA mutation carriers should keep in mind the same fertility issues that arise in the general population, such as—age does affect ovarian reserve.
Medical News Today
A woman is born with all of the eggs she will have throughout her life. Each month during her menstrual cycle, she releases one egg and in general, the healthier eggs are released when she is younger and the less healthy eggs are released later on. This is often referred to as lower ovarian reserve. Healthier eggs have a higher chance of resulting in a pregnancy, making it more difficult for women to get pregnant at older ages.
Some studies have suggested that BRCA genes are involved in reproductive aging, while others have not. Kelly-Anne Phillips and colleagues at the Peter MacCallum Cancer Centre in Australia and colleagues published findings in the journal Human Reproduction where they looked at how BRCA status affected ovarian reserve (as measured by concentration of the hormone called AMH (Anti-Müllerian hormone) in the blood.
The researchers used blood samples from 172 BRCA1 mutation carriers and 216 women from families with BRCA1 mutations who did not carry the mutation in their family, as well as 147 BRCA2 mutation carriers and 158 women from families with BRCA1 mutations who did not carry the mutation in their family. These women were between the ages of 25-45, had two intact ovaries and had no personal history of any cancer (except for non-melanoma skin cancer). Researchers measured AMH (Anti-Müllerian hormone) concentrations in the blood, which is a measurement of ovarian reserve as AMH is a hormone produced by eggs and represents a woman’s overall egg pool. AMH is a good measurement of ovarian reserve and is one of the most important tests that fertility specialists use when counseling patients.
The sample size used in this research study was relatively small. While the researchers saw that there was no difference in AMH concentrations between BRCA2 carriers and non-carriers, this may be because there were not enough BRCA2 patients in the study for the researchers to see a difference.
While this study suggests an association between BRCA1 mutation status and a lower ovarian reserve, more work needs to be done to confirm this finding, in addition to the BRCA2 finding, as it was a relatively small study. Additionally, because the difference in AMH concentrations between BRCA1 mutation carriers and non-carriers was not large, the authors write “…it is possible that the findings of our study might not translate to clinically relevant fertility implications for younger women, but may be important for the subgroup of BRCA1 mutation carriers who wish to conceive in their late 30s or 40s when fertility is reduced even in the general population.” Young BRCA1 mutation carriers do not need to rush to have children based on these findings alone. However, women in their late 30s and 40s do already have a reduced ovarian reserve due to age—may want to talk to a fertility expert, particularly if they are having trouble conceiving. These experts may suggest trying to conceive at an earlier age or freezing their eggs.
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Human Embryology. Retrieved from: “Gametogenesis.”
Phillips K, Collins IM, Milne RL, et al. “Anti-Mullerian hormone serum concentrations of women with germline BRCA1 or BRCA2 mutations.” Human Reproduction. Published online first on April 19, 2016.
The Society of Obstetricians and Gynecologists of Canada. Retrieved from: “Age and Fertility.”
Whitman-Elia, GF. Retrieved from: “Low Ovarian Reserve- What does it really mean?”
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