PURPOSE: 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).
CONCLUSION: 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.