title: BRCA1 germline mutations may be associated with reduced ovarian reserve.
abstract: 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.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Academic tertiary care center.
  
  
  METHODS
  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.
  
  
  METHODS
  None.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: erica.wang@cshs.org.
authors.forename: Erica T
authors.initials: ET
authors.lastname: Wang
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Margareta D
authors.initials: MD
authors.lastname: Pisarska
authors.affiliation: Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bresee
authors.affiliation: Department of Pediatrics and Medicine, Harbor-UCLA Medical Center, Torrance, California.
authors.forename: Yii-Der Ida
authors.initials: YD
authors.lastname: Chen
authors.affiliation: Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Jenny
authors.initials: J
authors.lastname: Lester
authors.affiliation: Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Yalda
authors.initials: Y
authors.lastname: Afshar
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Alexander
authors.affiliation: Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Beth Y
authors.initials: BY
authors.lastname: Karlan
mesh_terms: D000328:Adult; D054304:Anti-Mullerian Hormone / Q000097:blood*; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D065851:Ovarian Reserve / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; D054304:Anti-Mullerian Hormone
keywords: Antimüllerian hormone; BRCA mutations; ovarian reserve