Do women with BRCA1 or BRCA2 mutations have reduced ovarian reserve?

Abstract

1537 Background: It is uncertain whether mutations in the DNA repair genes, BRCA1 or BRCA2, result in reduced ovarian reserve. AMH is a surrogate marker of ovarian reserve. This study examined AMH levels of BRCA1 and BRCA2 mutation carriers and their non-carrier blood relatives. Methods: Eligible women were from families segregating BRCA1 or BRCA2 mutations enrolled in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). Each woman had been tested for the family mutation and had completed an epidemiological questionnaire and provided a blood sample at cohort entry. Women were aged 25-45 years, had no personal history of invasive cancer, had two intact ovaries and were not pregnant or breastfeeding at the time of blood draw. AMH was tested on stored plasma samples using an electrochemiluminescence immunoassay platform. Higher AMH levels are associated with greater ovarian reserve. Associations between AMH level and carrier status were tested by linear regression, using the natural logarithm of AMH as the outcome variable, carrier status as the explanatory variable, and adjusting for age at blood draw, oral contraceptive use, BMI and cigarette smoking. Robust standard errors were estimated to account for the inclusion of multiple members from the same family. Results: AMH level was measured for 172 carriers and 216 non-carriers from families carrying BRCA1 mutations, and 147 carriers and 158 non-carriers from families carrying BRCA2 mutations. Within both groups, mutation carriers were younger at blood draw than non-carriers (p ≤ 0.031). Age was negatively associated with AMH level for carriers and non-carriers of BRCA1 and BRCA2 mutations (p < 0.001). BRCA1 mutation carriers had, on average, 25% lower AMH levels than non-carriers (p = 0.022). There was no evidence of an association for BRCA2 mutation carriers (p = 0.94). Results did not change substantially after excluding women who were post-menopausal or taking oral contraceptives at blood draw. Conclusions: This study suggests that women with a germline mutation in BRCA1 have reduced ovarian reserve. This could have implications for their fertility and family planning.