PURPOSE

To determine whether germline (g) pathogenic variants are associated with decreased ovarian reserve.

MATERIALS AND METHODS

An individual patient-level data meta-analysis was performed using five data sets on 828 evaluable women who were tested for g. Of those, 250 carried g, whereas 578 had tested negative and served as controls. Of the women with g four centers studied those affected with breast cancer (n = 161) and one studied unaffected individuals (n = 89). The data were adjusted for the center, age, body mass index, smoking, and oral contraceptive pill use before the final analysis. Anti-Müllerian hormone (AMH) levels in affected women were drawn before presystemic therapy.

RESULTS

The mean age of women with versus without g (34.1 ± 4.9 34.3 ± 4.8 years; = .48) and with g versus g (33.7 ± 4.9 34.6 ± 4.8 years; = .16) was similar. After the adjustments, women with g had significantly lower AMH levels compared with controls (23% lower; 95% CI, 4 to 38; = .02). When the adjusted analysis was limited to affected women (157 with g 524 without, after exclusions), the difference persisted (25% lower; 95% CI, 9 to 38; = .003). The serum AMH levels were lower in women with g (33% lower; 95% CI, 12 to 49; = .004) but not g compared with controls (7% lower; 95% CI, 31% lower to 26% higher; = .64).

CONCLUSION

Young women with g pathogenic variants, particularly those affected and with g, have lower serum AMH levels compared with controls. They may need to be preferentially counseled about the possibility of shortened reproductive lifespan because of diminished ovarian reserve.