Background: Young, healthy women carrying a pathogenic or likely pathogenic variant (P/LPV) in genes configuring the hereditary breast and/or ovarian cancer (HBOC) syndrome face several non-oncological issues. Among these, the implications on fertility are not yet entirely understood.

Methods: Aiming to explore the ovarian reserve in young, healthy women with HBOC syndrome, we conducted a monocentric, prospective, observational cohort trial between January 2020 and September 2023. Eighty-seven healthy women aged less than 42 years with a P/LPV in HBOC predisposition genes were enrolled: 32 BRCA1 P/LPV carriers, 47 BRCA2 P/LPV carriers, and 8 carriers of P/LPV in other genes (TP53, RAD50, CHECK2, RAD51D, PALB2, ATM). AMH levels and antral follicular count (AFC) were evaluated as fertility biomarkers.

Results: No significant differences in demographic characteristics or mean levels of AMH or in AFC are observed between BRCA1 and BRCA2 P/LPV carriers. The distribution of AMH values is significantly lower compared to the general population (p = 0.019). The significant decrease in AMH levels is mostly ascribable to BRCA1 P/LPV carriers (p = 0.03). Both in the overall population and in BRCA1/2 P/LPV carriers, AFC decreases faster compared to those reported in the nomogram.

Conclusions: A consistent trend for reduced reproductive potential in young, healthy women with HBOC syndrome is observed, particularly in BRCA1 P/LPV carriers. These findings need to be confirmed by larger studies including also women carrying P/LPV in other HBOC syndrome-related genes.