High impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age: A systematic review and meta-analysis

Introduction: The risk of infertility following breast cancer (BC) treatment is critical for women of reproductive age. Accurate risk assessment is essential for fertility counseling and preservation. Amenorrhoea as an infertility marker is unreliable due to endocrine therapies. Anti-Mullerian hormo...

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Main Authors: Susanna Weidlinger, Magdalena Weidlinger, Rose-Maria Schramm, Angela Vidal, Janna Pape, Tanya Karrer, Manuela Rabaglio, Michael von Wolff
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Breast
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Online Access:http://www.sciencedirect.com/science/article/pii/S0960977625005314
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author Susanna Weidlinger
Magdalena Weidlinger
Rose-Maria Schramm
Angela Vidal
Janna Pape
Tanya Karrer
Manuela Rabaglio
Michael von Wolff
author_facet Susanna Weidlinger
Magdalena Weidlinger
Rose-Maria Schramm
Angela Vidal
Janna Pape
Tanya Karrer
Manuela Rabaglio
Michael von Wolff
author_sort Susanna Weidlinger
collection DOAJ
description Introduction: The risk of infertility following breast cancer (BC) treatment is critical for women of reproductive age. Accurate risk assessment is essential for fertility counseling and preservation. Amenorrhoea as an infertility marker is unreliable due to endocrine therapies. Anti-Mullerian hormone (AMH) is a reliable fertility marker, but its role in assessing chemotherapy-induced loss of ovarian reserve in BC survivors remains underexplored. Objective: This systematic review and meta-analysis evaluates AMH decline and the prevalence of low (AMH <1 ng/mL) and very low (<0.5 ng/mL) ovarian reserve in BC survivors <40 years old, 12–24 months post-chemotherapy, to quantify the gonadotoxic impact of BC treatments. Methods: A systematic literature search of PubMed, Embase, and the Cochrane Library identified studies with AMH levels before and 12–24 months after chemotherapy in BC patients <40 years of age. Data on AMH levels were pooled using random-effects meta-analysis. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. This study is part of the FertiTOX project (www.fertitox.com). Results: Ten studies (860 BC survivors) were included. Mean AMH decline was −1.61 (95 % CI: -2.31; −0.91) post-chemotherapy. The pooled prevalence of AMH <1 ng/mL and <0.5 ng/mL was 58 % (46–70 %) and 53 % (41–64 %), respectively. High heterogeneity was observed (I2 >80 %). Conclusions: More than half of BC survivors have severely reduced ovarian reserve after chemotherapy, which is associated with a shortened fertile window and an increased risk of premature ovarian insufficiency. These findings highlight the need for pre-treatment fertility counseling and post-treatment ovarian insufficiency surveillance in routine oncology care.
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spelling doaj-art-3fa753e964a948acad042fb1e50436b12025-08-20T03:28:00ZengElsevierBreast1532-30802025-08-018210451410.1016/j.breast.2025.104514High impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age: A systematic review and meta-analysisSusanna Weidlinger0Magdalena Weidlinger1Rose-Maria Schramm2Angela Vidal3Janna Pape4Tanya Karrer5Manuela Rabaglio6Michael von Wolff7Division of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital, Inselspital Bern, University of Bern, 3010, Bern, Switzerland; Corresponding author. Division of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital, Inselspital Bern, University of Bern Theodor-Kocher-Haus Friedbühlstrasse 19, CH-3010, Bern, Switzerland.Division of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital, Inselspital Bern, University of Bern, 3010, Bern, SwitzerlandDivision of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital, Inselspital Bern, University of Bern, 3010, Bern, SwitzerlandDivision of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital, Inselspital Bern, University of Bern, 3010, Bern, SwitzerlandDivision of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital, Inselspital Bern, University of Bern, 3010, Bern, SwitzerlandMedical Library, University Library Bern, University of Bern, 3010, Bern, SwitzerlandUniversity Clinic for Medical Oncology, Inselspital Bern, University of Bern, 3010, Bern, SwitzerlandDivision of Gynecological Endocrinology and Reproductive Medicine, University Women's Hospital, Inselspital Bern, University of Bern, 3010, Bern, SwitzerlandIntroduction: The risk of infertility following breast cancer (BC) treatment is critical for women of reproductive age. Accurate risk assessment is essential for fertility counseling and preservation. Amenorrhoea as an infertility marker is unreliable due to endocrine therapies. Anti-Mullerian hormone (AMH) is a reliable fertility marker, but its role in assessing chemotherapy-induced loss of ovarian reserve in BC survivors remains underexplored. Objective: This systematic review and meta-analysis evaluates AMH decline and the prevalence of low (AMH <1 ng/mL) and very low (<0.5 ng/mL) ovarian reserve in BC survivors <40 years old, 12–24 months post-chemotherapy, to quantify the gonadotoxic impact of BC treatments. Methods: A systematic literature search of PubMed, Embase, and the Cochrane Library identified studies with AMH levels before and 12–24 months after chemotherapy in BC patients <40 years of age. Data on AMH levels were pooled using random-effects meta-analysis. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. This study is part of the FertiTOX project (www.fertitox.com). Results: Ten studies (860 BC survivors) were included. Mean AMH decline was −1.61 (95 % CI: -2.31; −0.91) post-chemotherapy. The pooled prevalence of AMH <1 ng/mL and <0.5 ng/mL was 58 % (46–70 %) and 53 % (41–64 %), respectively. High heterogeneity was observed (I2 >80 %). Conclusions: More than half of BC survivors have severely reduced ovarian reserve after chemotherapy, which is associated with a shortened fertile window and an increased risk of premature ovarian insufficiency. These findings highlight the need for pre-treatment fertility counseling and post-treatment ovarian insufficiency surveillance in routine oncology care.http://www.sciencedirect.com/science/article/pii/S0960977625005314Anti-Mullerian hormoneAMHChemotherapyBreast cancerOvarian reserveFertility
spellingShingle Susanna Weidlinger
Magdalena Weidlinger
Rose-Maria Schramm
Angela Vidal
Janna Pape
Tanya Karrer
Manuela Rabaglio
Michael von Wolff
High impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age: A systematic review and meta-analysis
Breast
Anti-Mullerian hormone
AMH
Chemotherapy
Breast cancer
Ovarian reserve
Fertility
title High impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age: A systematic review and meta-analysis
title_full High impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age: A systematic review and meta-analysis
title_fullStr High impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age: A systematic review and meta-analysis
title_full_unstemmed High impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age: A systematic review and meta-analysis
title_short High impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age: A systematic review and meta-analysis
title_sort high impact of chemotherapy on ovarian reserve in breast cancer survivors of reproductive age a systematic review and meta analysis
topic Anti-Mullerian hormone
AMH
Chemotherapy
Breast cancer
Ovarian reserve
Fertility
url http://www.sciencedirect.com/science/article/pii/S0960977625005314
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