Gene mutation implicated in cancer also linked to lower fertility in women.

Now, researchers at Peter MacCallum Cancer Centre have identified a link between the BRCA1 gene mutation and lower levels of a hormone that is an indicator of the number of eggs left in a woman’s ovaries.  The team state that this means that women in their mid-30s, who carry the BRCA1 mutation, have, on average, ovarian reserves similar to those of non-carriers who are two years older.  The opensource study is published in the journal Human Reproduction.

Previous studies show that women who carry the BRCA1 and BRCA2 gene mutations have a higher risk of cancers in the breast, ovaries, fallopian tubes and peritoneum. The risk increases with age and is generally higher for those with the BRCA1 mutation as opposed to the BRCA2 mutation.  As mutation carriers enter their early 40s they are usually advised to have their ovaries and fallopian tubes removed in order to minimise their cancer risk. For this reason, many women who know they are carriers try to have their children when they are younger. However, until now, there has been little evidence as to the effects of these genetic mutations on non-cancer-related conditions such as fertility.  The current study investigates BRCA1 and BRCA2 genetic mutations and levels of anti-Müllerian hormone (AMH) in women who carry the mutated genes in relation to ovarian reserves.

The current study analysed AMH levels from 693 women, aged between 25-45 years, who had no personal history of cancer. A total of 172 women were carriers and 216 women non-carriers from families carrying the BRCA1 mutations, and 147 carriers and 158 non-carriers were from families with the BRCA2 mutations. The women retained both ovaries and were not pregnant or breast-feeding at the time that blood was drawn from them. The researchers adjusted their results to take account of age, oral contraceptive use, body mass index and smoking.

Results show that carrying the BRCA1 mutation is associated with AMH concentrations that were, on average, 25% lower than those in non-carriers; the effect was not seen in women with the BRCA2 mutation.  The lab explain that although AMH is a reliable marker of ovarian reserve, AMH is only one indicator of a woman’s potential fertility, and women with low AMH levels can sometimes still have a baby whilst, conversely, women with high AMH levels are sometimes unable to do so.  They go on to add that the ability to conceive and carry a baby to full term is affected by many other factors as well, including egg quality and whether the fallopian tubes are unobstructed, neither of which are measured by AMH.

The group state that their findings suggest that women carrying the BRCA1 mutation should try to avoid delaying pregnancy until their late 30s or 40s when fertility is reduced due to age. They go on to add that for women trying to conceive in their 20s, any difference in ovarian reserve between BRCA1 mutation carriers and non-carriers is unlikely to be of clinical significance.  Results show that in addition to BRCA1 mutations carriers having 25% lower AMH concentrations, on average, than non-carriers, they were also more likely to have AMH concentrations that placed them in the lowest quarter when the women were divided into four groups according to the AMH levels. Data finding show that this was not seen in BRCA2 mutation carriers.

The lab hypothesize that a possible mechanism for the link between the BRCA1 mutation and ovarian reserve may be the role played by both the mutations in DNA repair, inefficient DNA repair has been shown to contribute to the aging of a woman’s eggs. They go on to conclude that BRCA1 and BRCA2 are both integral to mending breaks that occur in both strands of the DNA helix.

The team surmise that their findings show that women with a germline mutation in BRCA1 have reduced ovarian reserve as measured by AMH.  For the future, the researchers state that their findings also raises the possibility that BRCA1 mutations carriers may have a higher risk of chemotherapy-induced menopause, as they have lower ovarian reserve than their non-carrier counterparts when they start chemotherapy; however, this is just a hypothesis at this stage and requires further research.

Source: Peter MacCallum Cancer Centre


This cross-section of a human ovary shows potential areas for stem cells -which can now be converted to oocytes - even in adult women; Credit: Shutterstock.
This cross-section of a human ovary shows potential areas for stem cells -which can now be converted to oocytes – even in adult women; Credit: Shutterstock.

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