title: Association of BRCA1 Mutations with Impaired Ovarian Reserve: Connection Between Infertility and Breast/Ovarian Cancer Risk.
abstract: Mutations in the BRCA1/2 genes are associated with breast and ovarian cancer susceptibility. Recent studies have suggested that the BRCA mutation might be associated with occult primary ovarian insufficiency. To evaluate fertility, several studies have validated anti-Mullerian hormone (AMH) as a direct biomarker for ovarian aging and it is considered a quantitative marker of ovarian reserve. We hypothesize that BRCA1 gene mutations will be negatively associated with AMH levels.
  
  
  
  We evaluated 124 women aged 18-45 years participating in the Northwestern Ovarian Cancer Early Detection and Prevention Program. Patients with a history of cancer, ovarian surgery, or exposure to chemotherapy were excluded. Linear and logistic regression modeling were performed to evaluate the association between AMH levels, age, and BRCA1 mutation. In logistic models, the outcome 'low AMH' was defined as AMH <0.05 ng/mL. Logistic regression models were used to adjust for other factors, including body mass index (BMI), duration of birth control (BC), smoking, gravidity, and parity.
  
  
  
  Women with the BRCA1 mutation had a significant decline in AMH with age (p = 0.0011). BRCA1-positive women >35 years had 10 times the odds of a low AMH (<0.5 ng/mL) compared with women ≤35 years. With adjustment for BMI, duration of BC, smoking, gravidity, parity, and age >35, BRCA1 was still strongly associated with a low AMH (p = 0.037).
  
  
  
  Women >35 with the BRCA1 mutation have a lower AMH, and hence ovarian reserve, than women without a BRCA mutation. Therefore, young adults with the BRCA1 mutation should be counseled regarding this potential decrease in ovarian reserve.
authors: 1 Medical University of South Carolina , Hollings Cancer Center, Charleston, South Carolina.
authors: Sara
authors: S
authors: Giordano
authors: 1 Medical University of South Carolina , Hollings Cancer Center, Charleston, South Carolina.
authors: Elizabeth
authors: E
authors: Garrett-Mayer
authors: 2 AbbVie , Pharmaceutical Research and Development, Chicago, Illinois.
authors: Navdha
authors: N
authors: Mittal
authors: 3 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors: Kristin
authors: K
authors: Smith
authors: 4 Department of Obstetrics and Gynecology-Clinical Genetics, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors: Lee
authors: L
authors: Shulman
authors: 5 Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors: Carolyn
authors: C
authors: Passaglia
authors: 5 Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors: William
authors: W
authors: Gradishar
authors: 3 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
authors: Mary Ellen
authors: ME
authors: Pavone
mesh_terms: D000293:Adolescent; D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D007246:Infertility / Q000209:etiology*; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000150:complications / Q000235:genetics*; D065851:Ovarian Reserve / Q000235:genetics*; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human
keywords: BRCA; BRCA mutation; anti-Mullerian hormone; ovarian reserve