Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome
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. Method...
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Nature Portfolio
2025-03-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00788-9 |
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| author | Giovanna Sighinolfi Giovanni Grandi Elena Barbieri Marta Venturelli Claudia Piombino Chiara Melotti Rebecca Lippi Bruni Riccardo Costantini Cuoghi Roberto D’Amico Matteo Lambertini Fedro A. Peccatori Elena Tenedini Massimo Dominici Laura Cortesi Antonio La Marca Angela Toss |
| author_facet | Giovanna Sighinolfi Giovanni Grandi Elena Barbieri Marta Venturelli Claudia Piombino Chiara Melotti Rebecca Lippi Bruni Riccardo Costantini Cuoghi Roberto D’Amico Matteo Lambertini Fedro A. Peccatori Elena Tenedini Massimo Dominici Laura Cortesi Antonio La Marca Angela Toss |
| author_sort | Giovanna Sighinolfi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cffa830a74404097a10c0f7dcb174df1 |
| institution | DOAJ |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-cffa830a74404097a10c0f7dcb174df12025-08-20T03:05:48ZengNature PortfolioCommunications Medicine2730-664X2025-03-01511910.1038/s43856-025-00788-9Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndromeGiovanna Sighinolfi0Giovanni Grandi1Elena Barbieri2Marta Venturelli3Claudia Piombino4Chiara Melotti5Rebecca Lippi Bruni6Riccardo Costantini Cuoghi7Roberto D’Amico8Matteo Lambertini9Fedro A. Peccatori10Elena Tenedini11Massimo Dominici12Laura Cortesi13Antonio La Marca14Angela Toss15Obstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria di ModenaObstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria di ModenaDivision of Oncology, Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria di ModenaDivision of Oncology, Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria di ModenaDivision of Oncology, Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria di ModenaObstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria di ModenaObstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria di ModenaUnit of Statistical and Methodological Support to Clinical Research, Azienda Ospedaliero-Universitaria di ModenaDepartment of Medical and Surgical Sciences, University of Modena and Reggio EmiliaDepartment of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of GenovaGynecologic Oncology Department, European Institute of Oncology IRCCSDepartment of Medical and Surgical Sciences, University of Modena and Reggio EmiliaDepartment of Medical and Surgical Sciences, University of Modena and Reggio EmiliaDivision of Oncology, Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria di ModenaObstetrics and Gynecology Unit, Azienda Ospedaliero-Universitaria di ModenaDepartment of Medical and Surgical Sciences, University of Modena and Reggio EmiliaAbstract 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.https://doi.org/10.1038/s43856-025-00788-9 |
| spellingShingle | Giovanna Sighinolfi Giovanni Grandi Elena Barbieri Marta Venturelli Claudia Piombino Chiara Melotti Rebecca Lippi Bruni Riccardo Costantini Cuoghi Roberto D’Amico Matteo Lambertini Fedro A. Peccatori Elena Tenedini Massimo Dominici Laura Cortesi Antonio La Marca Angela Toss Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome Communications Medicine |
| title | Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome |
| title_full | Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome |
| title_fullStr | Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome |
| title_full_unstemmed | Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome |
| title_short | Reduced reproductive potential in young healthy women with hereditary breast and/or ovarian cancer syndrome |
| title_sort | reduced reproductive potential in young healthy women with hereditary breast and or ovarian cancer syndrome |
| url | https://doi.org/10.1038/s43856-025-00788-9 |
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