title: Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks.
abstract: OBJECTIVE
  Germline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility. Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments.
  
  
  METHODS
  We performed ovarian stimulation in 126 women with breast cancer by using letrozole and gonadotropins for the purpose of fertility preservation by embryo or oocyte cryopreservation. As surrogates of ovarian reserve, the oocyte yield and the incidence of low response were compared with ovarian stimulation according to BRCA mutation status.
  
  
  RESULTS
  Of the 82 women who met the inclusion criteria, 47 women (57%) had undergone BRCA testing, and 14 had a mutation in BRCA genes, of which two were of clinically undetermined significance. In BRCA mutation-positive patients, low ovarian response rate was significantly higher compared with BRCA mutation-negative patients (33.3 v 3.3%; P = .014) and with BRCA-untested women (2.9%; P = .012). All BRCA mutation-positive low responders had BRCA1 mutations, but low response was not encountered in women who were only BRCA2 mutation positive. Compared with controls, BRCA1 mutation- but not BRCA2 mutation-positive women produced lower numbers of eggs (7.4 [95% CI, 3.1 to 17.7] v 12.4 [95% CI, 10.8 to 14.2]; P = .025) and had as many as 38.3 times the odds ratio of low response (95% CI, 4.1 to 353.4; P = .001).
  
  
  CONCLUSIONS
  BRCA1 mutations are associated with occult primary ovarian insufficiency. This finding may, at least in part, explain the link between infertility and breast/ovarian cancer risks.
authors.affiliation: Institute for Fertility Preservation, Department of Obstetrics and Gynecology, New York Medical College-Westchester Medical Center, Valhalla, NY 10595, USA. koktay@fertilitypreservation.org
authors.forename: Kutluk
authors.initials: K
authors.lastname: Oktay
authors.forename: Ja Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Barad
authors.forename: Samir N
authors.initials: SN
authors.lastname: Babayev
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D007246:Infertility / Q000235:genetics*; D000077289:Letrozole; D009154:Mutation; D009570:Nitriles / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010053:Ovary / Q000502:physiology*; D010062:Ovulation Induction; D012306:Risk; D014230:Triazoles / Q000494:pharmacology
chemical_list: D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole