Assessment of ovarian reserve and reproductive outcomes in BRCA1 or BRCA2 mutation carriers

Introduction The clinical impact on fertility in carriers of BRCA1 and BRCA2 mutations remains unclear. The aim of this study was to assess ovarian reserve as measured by anti-mullerian hormone levels in BRCA1 or BRCA2 mutation carriers, as well as to investigate the impact of anti-mullerian hormone levels on reproductive outcomes. Methods The study involved a cohort of women who tested positive for BRCA1 and BRCA2 screening or were tested for a BRCA1 or BRCA2 family mutation. Blood samples were collected for anti-mullerian hormone analysis and the reproductive outcomes were analyzed after a mean follow-up of 9 years. Participants were classified into BRCA mutation-positive versus BRCA mutation-negative. Controls were healthy relatives who tested negative for the family mutation. All patients were contacted by telephone to collect data on reproductive outcomes. Linear regression was used to predict anti-mullerian hormone levels by BRCA status adjusted for a polynomial form of age. Results Results of anti-mullerian hormone analysis and reproductive outcomes were available for 135 women (BRCA mutation-negative, n=66; BRCA1 mutation-positive, n=32; BRCA2 mutation-positive, n=37). Anti-mullerian hormone curves according to BRCA status and adjusted by age showed that BRCA2 mutation-positive patients have lower levels of anti-mullerian hormone as compared with BRCA-negative and BRCA1 mutation-positive. Among the women who tried to conceive, infertility was observed in 18.7% of BRCA mutation-negative women, in 22.2% of BRCA1 mutation-positive women, and in 30.8% of BRCA2 mutation-positive women (p=0.499). In the multivariable analysis, there were no factors independently associated with infertility. Discussion BRCA2 mutation-positive carriers showed more diminished anti-mullerian hormone levels than BRCA1 mutation-positive and BRCA mutation-negative women. However, these differences do not appear to have a negative impact on reproductive outcome. This is important to consider at the time of reproductive counseling in women with BRCA1 or BRCA2 mutations.