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Ovarian reserves lower in BRCA1 mutation carriers
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Women with mutations in the BRCA1 gene may have fewer eggs than women who do not have the mutation, according to results of a cross-sectional study.
Germline mutations in the BRCA1 or BRCA2 genes increase a person’s risk for breast, ovarian, fallopian tube and primary peritoneal cancers. Limited data exist on potential noncancer-related implications of these mutations, but preliminary findings in mice suggested ovarian reserves may be reduced in BRCA1 mutation carriers.
Kelly-Anne Phillips
“If confirmed, this could have clinical consequences for pregnancy planning, reproductive lifespan and perhaps ovarian function following chemotherapy,” Kelly-Anne Phillips, MBBS(Hons), MD, FRACP, oncologist at Peter MacCallum Cancer Centre, and colleagues wrote.
Phillips and colleagues measured anti-Müllerian hormone (AMH) concentrations — an indicator of egg count — in women aged 25 to 45 enrolled in a familial breast cancer cohort study to compare ovarian reserves of BRCA1 or BRCA2 mutation carriers with noncarriers.
The analysis included 172 carriers of a pathogenic mutation in BRCA1; 216 noncarriers from families that carried BRCA1 mutations; 147 carriers of a pathogenic mutation in BRCA2; and 158 noncarriers from families that carried BRCA2 mutations.
Study participants’ mean age at the time of blood draw was 35.1 years, and mutation carriers were younger than noncarriers (P .03).
Mean AMH concentration was negatively associated with age (P < .001).
After adjusting for age at blood draw, BRCA1 mutation carriers on average demonstrated a 25% (95% CI, 5-41) reduction in AMH concentrations. They also were more likely to have AMH concentrations in the lowest quartile for age (OR=1.84; 95% CI, 1.11–3.03) than noncarriers.
The difference in average AMH concentration between BRCA1 carriers and noncarriers was approximately equivalent to that between a 37-year-old and a 35-year-old, researchers wrote.
Researchers observed no statistically significant difference in AMH concentrations between BRCA2 mutation carriers and noncarriers.
BRCA2 has a more limited role in double-strand DNA break repair. BRCA2 mutation carriers tend to develop fewer cancers — and develop cancers at a later age — than BRCA1 mutation carriers.
“So, it is credible that any effect of mutation status on ovarian reserve would be more pronounced in BRCA1 mutation carriers,” Phillips said in a press release. “There may be a lesser effect in BRCA2 mutation carriers, as well, but our study did not have adequate power to detect it.”
Because AMH does not directly measure the primordial follicle pool, the clinical implications of the lower AMH concentrations seen in BRCA1 mutation carriers could not be assessed, researchers wrote.
“However, our findings suggest that women carrying the BRCA1 mutation who wish to have children should avoid, where possible, delaying pregnancy until their late 30s or 40s when fertility is reduced anyway because of their age,” Phillips said in the release. “For women trying to conceive in their 20s, any difference in ovarian reserve between BRCA1 mutation carriers and noncarriers is unlikely to be of clinical significance.” — by Kristie L. Kahl
Disclosure: Phillips reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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