Department of Obstetrics and Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT.
Department of Obstetrics and Gynecology, Health and Technology University School of Medicine, Istanbul, Turkey.
J Clin Oncol. 2021 Jun 20;39(18):2016-2024. doi: 10.1200/JCO.20.02880. Epub 2021 Apr 23.
To determine whether germline (g) pathogenic variants are associated with decreased ovarian reserve.
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.
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).
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.
确定种系（g）致病性变异是否与卵巢储备减少有关。
对 828 名接受 g 检测的可评估女性进行了一项基于个体患者水平数据的荟萃分析，其中 250 名携带 g，578 名检测结果为阴性作为对照。在携带 g 的女性中，有 4 个中心研究了患有乳腺癌的个体（n = 161），1 个中心研究了未受影响的个体（n = 89）。在最终分析前，对中心、年龄、体重指数、吸烟和口服避孕药使用情况进行了调整。在进行全身治疗前，采集了患有乳腺癌的 g 携带者的抗苗勒管激素（AMH）水平。
携带 g 的女性与不携带 g 的女性（34.1 ± 4.9 34.3 ± 4.8 岁； =.48）和携带 g 的女性与 g 的女性（33.7 ± 4.9 34.6 ± 4.8 岁； =.16）的平均年龄相似。经过调整后，携带 g 的女性的 AMH 水平明显低于对照组（低 23%；95%CI，4 至 38； =.02）。当调整后的分析仅限于患有乳腺癌的女性（157 名携带 g 524 名不携带 g，排除后）时，这种差异仍然存在（低 25%；95%CI，9 至 38； =.003）。携带 g 的女性的血清 AMH 水平较低（低 33%；95%CI，12 至 49； =.004），而 g 携带者的 AMH 水平与对照组相比没有差异（低 7%；95%CI，低 31%至高 26%； =.64）。
携带 g 致病性变异的年轻女性，尤其是患有乳腺癌和携带 g 的女性，其血清 AMH 水平低于对照组。由于卵巢储备减少，她们可能需要优先咨询生殖寿命缩短的可能性。
