BRCA1 germline mutations may be associated with reduced ovarian reserve

BRCA1 carriers have a decreased ovarian reserve, as evidenced by lower age- and body mass index–adjusted serum anti-Mullerian hormone levels, compared with women without BRCA mutations.


Erica T. Wang, M.D., M.A.S., Margareta D. Pisarska, M.D., Catherine Bresee, M.S., Yii-Der Ida Chen, Ph.D., Jenny Lester, M.P.H., Yalda Afshar, M.D., Carolyn Alexander, M.D., Beth Y. Karlan, M.D.

Volume 102, Issue 6, Pages 1723-1728



To determine whether BRCA carriers have a decreased ovarian reserve compared with women without BRCA mutations, because BRCA mutations may lead to accelerated oocyte apoptosis due to accumulation of damaged DNA.


Cross-sectional study.


Academic tertiary care center.


A total of 143 women, aged 18–45 years, who underwent clinical genetic testing for BRCA deleterious mutations because of a family history of cancer, were included. The cohort was classified into three groups: BRCA1 carriers, BRCA2 carriers, and women without BRCA mutations (controls). None had a personal history of breast or ovarian cancer.



Main Outcome Measure(s):

The main outcome was serum anti-Müllerian hormone (AMH) level. Linear and logistic regression models adjusting for age and body mass index (BMI) were performed to determine the association between BRCA mutations and AMH.


BRCA1 mutation carriers had a significant decrease in AMH levels compared with controls after adjusting for age and BMI (0.53 ng/mL [95% confidence interval (CI) 0.33–0.77 ng/mL] vs. 1.05 ng/mL [95% CI 0.76–1.40 ng/mL]). Logistic regression confirmed that BRCA1 carriers had a fourfold greater odds of having AMH


BRCA1 carriers have lower age- and BMI-adjusted serum AMH levels compared with women without BRCA mutations. Our results contribute to the current body of literature regarding BRCA carriers and their reproductive outcomes. Larger prospective studies with clinical outcomes such as infertility and age at menopause in this population are needed to further substantiate our findings.

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