Ovarian follicular density in women with BRCA1 and BRCA2 mutations: new insights into the negative impact on ovarian reserve.

Germline mutations of BRCA1 and BRCA2 may impair DNA repair in the ovarian cortex, leading to increased oocyte apoptosis, thus, affecting ovarian reserve. Aim of this study was to assess follicular density in ovarian biopsies from women with breast cancer carrying BRCA1 and BRCA2 mutations who underwent ovarian tissue cryopreservation (OTC) at our center. This was a single center, observational, cross-sectional study carried out in a tertiary level referral center for fertility preservation treatment. Exclusion criteria were: patients aged < 18 years or > 38 years, patients who had already undergone chemotherapy/pelvic radiotherapy at the time of OTC, patients without data on follicular density and those with unknown BRCA mutational status. Follicular density was defined as the number of primordial, intermediate primordial, small primary, large primary, secondary, preantral, and antral follicles per 1 mm2 of cortical section area. Out of 216 patients, 21 women reported germline mutation: 9 (4.2%) were carriers of the BRCA1 mutation and 13 (6%) of the BRCA2 mutation. The mean age at OTC was 31.5 ± 3.6 years, and the median age was 32.4 years (range, 21-38). No significant difference in follicular density was observed among women without BRCA mutations, those with BRCA1 mutations, and those with BRCA2 mutations. The median follicular density was 4.0/mm2 (range 0-74.5) in BRCA-negative women, 3.5/mm2 (range 0-20) in women with BRCA1 mutations, and 4.0/mm2 (range 0-32) in women with BRCA2 mutations (p = 0.272 and p = 0.703, respectively). After adjusting for age, no statistically significant differences in follicular density were observed according to BRCA1 and BRCA2 mutation status: the median follicular density was 4.6/mm2 in BRCA-negative women, 3.1/mm2 in women with BRCA1 mutations, and 3.6/mm2 in women with BRCA2 mutations (p = 0.428 and p = 0.385, respectively). No significant difference in follicular density was observed between women with BRCA1/BRCA2 mutations and those without. Our findings suggest that the presence of a BRCA mutation does not have a significant negative clinical impact on the follicular population of the ovarian cortex. Larger studies are needed to further validate these findings.