P-364 Ovarian follicular density in women with BRCA1 and BRCA2 mutations: new insights into the negative impact on ovarian reserve

Abstract

Study question Assessing follicular density in ovarian biopsies from women with breast cancer carrying BRCA1 and BRCA2 mutations who underwent ovarian tissue cryopreservation (OTC). Summary answer Follicular density appeared to be lower in women with BRCA1/BRCA2 mutations compared to those without the mutation; however, this difference did not reach statistical significance. What is known already BRCA1 mutation carriers have been reported to experience a 25% reduction in AMH levels, whereas evidence regarding the association between BRCA2 mutations and AMH levels remains inconsistent. Only one study has examined follicular density in ovarian biopsy tissue from women with breast cancer carrying BRCA1 or BRCA2 mutations. In this study, no significant differences were reported in follicular density between BRCA-positive women and BRCA-negative patients undergoing ovarian tissue cryopreservation (OTC) for fertility preservation. Study design, size, duration A single center, observational, cross-sectional study carried out in a tertiary level referral center for fertility preservation treatment. All patients who underwent OTC for breast cancer and met inclusion criteria, from January 1st, 2002 (date of establishment of the biobank) to September 30th, 2024, were included in the study. 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. Participants/materials, setting, methods The study was carried out in a tertiary level referral center for fertility preservation treatment. The whole study was reported according to the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and checklist. Medical reports were searched for extraction of the following patient data: age at OTC, BMI, breast cancer treatments before OTC, antral follicular count on preoperative transvaginal ultrasound, anti-müllerian hormone concentration (ng/ml) prior to surgery, follicular density of ovarian tissue sample. Main results and the role of chance 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). Limitations, reasons for caution The first limit was the relatively small sample size due to the low prevalence of women with BRCA1 and BRCA2 mutations. Another limitation of the study was the absence of preoperative AMH values in nearly half of the patients. Wider implications of the findings Our study might suggest that, although it did not reach statistical significance, there could be a negative clinical impact of BRCA1 and BRCA2 mutations on fertility. This warrants further investigation to provide women carring germline mutations of BRCA1 or BRCA2 more appropriate therapeutic guidance in the field of fertility preservation. Trial registration number No