BRCA1 germline mutations may be associated with reduced ovarian reserve

Fertil Steril. 2014 Dec;102(6):1723-8. doi: 10.1016/j.fertnstert.2014.08.014. Epub 2014 Sep 23.


Objective: 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.

Design: Cross-sectional study.

Setting: Academic tertiary care center.

Patient(s): 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.

Intervention(s): None.

Main outcome measure(s): The main outcome was serum antimüllerian 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.

Result(s): 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 <1 ng/mL compared with controls (odds ratio 4.22, 95% CI 1.48-12.0). There was no difference in AMH levels between BRCA2 carriers and controls.

Conclusion(s): 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.

Keywords: Antimüllerian hormone; BRCA mutations; ovarian reserve.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / blood*
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Body Mass Index
  • Cross-Sectional Studies
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2
  • Germ-Line Mutation*
  • Humans
  • Logistic Models
  • Middle Aged
  • Mutation
  • Ovarian Reserve / genetics*


  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • Anti-Mullerian Hormone