患有遗传性乳腺癌和/或卵巢癌综合征的年轻健康女性生殖潜力降低。

Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome.

作者信息

Sighinolfi Giovanna, Grandi Giovanni, Barbieri Elena, Venturelli Marta, Piombino Claudia, Melotti Chiara, Lippi Bruni Rebecca, Costantini Cuoghi Riccardo, D'Amico Roberto, Lambertini Matteo, Peccatori Fedro A, Tenedini Elena, Dominici Massimo, Cortesi Laura, La Marca Antonio, Toss Angela

机构信息

Obstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.

出版信息

Commun Med (Lond). 2025 Mar 8;5(1):70. doi: 10.1038/s43856-025-00788-9.

DOI:10.1038/s43856-025-00788-9

PMID:40057639

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11890596/

Abstract

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.

摘要

背景

携带构成遗传性乳腺癌和/或卵巢癌（HBOC）综合征基因的致病性或可能致病性变异（P/LPV）的年轻健康女性面临若干非肿瘤学问题。其中，对生育能力的影响尚未完全明确。

方法

为探索患有HBOC综合征的年轻健康女性的卵巢储备情况，我们在2020年1月至2023年9月期间开展了一项单中心、前瞻性、观察性队列试验。纳入了87名年龄小于42岁、HBOC易感基因存在P/LPV的健康女性：32名BRCA1 P/LPV携带者，47名BRCA2 P/LPV携带者，以及8名其他基因（TP53、RAD50、CHECK2、RAD51D、PALB2、ATM）的P/LPV携带者。评估抗穆勒氏管激素（AMH）水平和窦卵泡计数（AFC）作为生育生物标志物。

结果

BRCA1和BRCA2 P/LPV携带者在人口统计学特征、AMH平均水平或AFC方面未观察到显著差异。与一般人群相比，AMH值的分布显著更低（p = 0.019）。AMH水平的显著降低主要归因于BRCA1 P/LPV携带者（p = 0.03）。在总体人群和BRCA1/2 P/LPV携带者中，AFC的下降速度均比列线图报告的更快。