Chemotherapy-induced Damage to Ovary: Mechanisms and Clinical Impact

Overview

Journal Future Oncol

Specialty Oncology

Date 2016 Jul 13

PMID 27402553

Citations 129

Authors

Giuliano Bedoschi

Paula Andrea Navarro

Kutluk Oktay

Affiliations

Soon will be listed here.

Abstract

Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility.

Citing Articles

Effects of Anticancer Therapy on Osteoporosis in Breast Cancer Patients: A Nationwide Study Using Data from the National Health Insurance Service-National Health Information Database.

Kwon M, Kim B, Min S, Chae S J Clin Med. 2025; 14(3).

PMID: 39941403 PMC: 11818878. DOI: 10.3390/jcm14030732.

Human hair follicle-derived mesenchymal stem cells improve ovarian function in cyclophosphamide-induced POF mice.

Mo J, Hu H, Li P, Ye Y, Chen W, Chen L Stem Cell Res Ther. 2025; 16(1):67.

PMID: 39934888 PMC: 11816600. DOI: 10.1186/s13287-024-04097-1.

Diminished ovarian reserve is associated to euploidy rate: a single center study.

Carnesi E, Castellano S, Albani E, Busnelli A, Smeraldi A, Bulbul O Front Endocrinol (Lausanne). 2025; 15:1535776.

PMID: 39897960 PMC: 11783844. DOI: 10.3389/fendo.2024.1535776.

Exosomes derived from hypoxic mesenchymal stem cells restore ovarian function by enhancing angiogenesis.

Qu Q, Liu L, Wang L, Cui Y, Liu C, Jing X Stem Cell Res Ther. 2024; 15(1):496.

PMID: 39709481 PMC: 11663355. DOI: 10.1186/s13287-024-04111-6.

Nicotinamide mononucleotide improves the ovarian reserve of POI by inhibiting NLRP3-mediated pyroptosis of ovarian granulosa cells.

Ma Y, Nong W, Zhong O, Liu K, Lei S, Wang C J Ovarian Res. 2024; 17(1):236.

PMID: 39593096 PMC: 11590476. DOI: 10.1186/s13048-024-01534-w.

References

Bath L, Wallace W, Shaw M, Fitzpatrick C, Anderson R . Depletion of ovarian reserve in young women after treatment for cancer in childhood: detection by anti-Müllerian hormone, inhibin B and ovarian ultrasound. Hum Reprod. 2003; 18(11):2368-74. DOI: 10.1093/humrep/deg473. View

Meirow D, Assad G, Dor J, Rabinovici J . The GnRH antagonist cetrorelix reduces cyclophosphamide-induced ovarian follicular destruction in mice. Hum Reprod. 2004; 19(6):1294-9. DOI: 10.1093/humrep/deh257. View

Tarlatzis B, Zepiridis L . Perimenopausal conception. Ann N Y Acad Sci. 2003; 997:93-104. DOI: 10.1196/annals.1290.011. View

Tschudin S, Bitzer J . Psychological aspects of fertility preservation in men and women affected by cancer and other life-threatening diseases. Hum Reprod Update. 2009; 15(5):587-97. DOI: 10.1093/humupd/dmp015. View

Kevenaar M, Meerasahib M, Kramer P, van de Lang-Born B, de Jong F, Groome N . Serum anti-mullerian hormone levels reflect the size of the primordial follicle pool in mice. Endocrinology. 2006; 147(7):3228-34. DOI: 10.1210/en.2005-1588. View

Lie Fong S, Lugtenburg P, Schipper I, Themmen A, de Jong F, Sonneveld P . Anti-müllerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies. Hum Reprod. 2008; 23(3):674-8. DOI: 10.1093/humrep/dem392. View

Bedoschi G, Oktay K . Current approach to fertility preservation by embryo cryopreservation. Fertil Steril. 2013; 99(6):1496-502. PMC: 3970911. DOI: 10.1016/j.fertnstert.2013.03.020. View

van Beek R, van den Heuvel-Eibrink M, Laven J, de Jong F, Themmen A, Hakvoort-Cammel F . Anti-Mullerian hormone is a sensitive serum marker for gonadal function in women treated for Hodgkin's lymphoma during childhood. J Clin Endocrinol Metab. 2007; 92(10):3869-74. DOI: 10.1210/jc.2006-2374. View

Soleimani R, Heytens E, Oktay K . Enhancement of neoangiogenesis and follicle survival by sphingosine-1-phosphate in human ovarian tissue xenotransplants. PLoS One. 2011; 6(4):e19475. PMC: 3084884. DOI: 10.1371/journal.pone.0019475. View

10.

Oktay K, Turan V, Titus S, Stobezki R, Liu L . BRCA Mutations, DNA Repair Deficiency, and Ovarian Aging. Biol Reprod. 2015; 93(3):67. PMC: 4710189. DOI: 10.1095/biolreprod.115.132290. View

11.

Hall J, Welt C, Cramer D . Inhibin A and inhibin B reflect ovarian function in assisted reproduction but are less useful at predicting outcome. Hum Reprod. 1999; 14(2):409-15. DOI: 10.1093/humrep/14.2.409. View

12.

Tsepelidis S, Devreker F, Demeestere I, Flahaut A, Gervy C, Englert Y . Stable serum levels of anti-Müllerian hormone during the menstrual cycle: a prospective study in normo-ovulatory women. Hum Reprod. 2007; 22(7):1837-40. DOI: 10.1093/humrep/dem101. View

13.

Lie Fong S, Laven J, Hakvoort-Cammel F, Schipper I, Visser J, Themmen A . Assessment of ovarian reserve in adult childhood cancer survivors using anti-Müllerian hormone. Hum Reprod. 2009; 24(4):982-90. DOI: 10.1093/humrep/den487. View

14.

Anderson R, Wallace W . Antimüllerian hormone, the assessment of the ovarian reserve, and the reproductive outcome of the young patient with cancer. Fertil Steril. 2013; 99(6):1469-75. DOI: 10.1016/j.fertnstert.2013.03.014. View

15.

Penarrubia J, Fabregues F, Manau D, Creus M, Casals G, Casamitjana R . Basal and stimulation day 5 anti-Mullerian hormone serum concentrations as predictors of ovarian response and pregnancy in assisted reproductive technology cycles stimulated with gonadotropin-releasing hormone agonist--gonadotropin treatment. Hum Reprod. 2005; 20(4):915-22. DOI: 10.1093/humrep/deh718. View

16.

Meirow D, Epstein M, Lewis H, Nugent D, Gosden R . Administration of cyclophosphamide at different stages of follicular maturation in mice: effects on reproductive performance and fetal malformations. Hum Reprod. 2001; 16(4):632-7. DOI: 10.1093/humrep/16.4.632. View

17.

Oktay K, Bedoschi G, Pacheco F, Turan V, Emirdar V . First pregnancies, live birth, and in vitro fertilization outcomes after transplantation of frozen-banked ovarian tissue with a human extracellular matrix scaffold using robot-assisted minimally invasive surgery. Am J Obstet Gynecol. 2015; 214(1):94.e1-9. PMC: 4707043. DOI: 10.1016/j.ajog.2015.10.001. View

18.

Kerr J, Hutt K, Cook M, Speed T, Strasser A, Findlay J . Cisplatin-induced primordial follicle oocyte killing and loss of fertility are not prevented by imatinib. Nat Med. 2012; 18(8):1170-2. PMC: 3517916. DOI: 10.1038/nm.2889. View

19.

Lee S, Ozkavukcu S, Heytens E, Moy F, Alappat R, Oktay K . Anti-Mullerian hormone and antral follicle count as predictors for embryo/oocyte cryopreservation cycle outcomes in breast cancer patients stimulated with letrozole and follicle stimulating hormone. J Assist Reprod Genet. 2011; 28(7):651-6. PMC: 3162058. DOI: 10.1007/s10815-011-9567-z. View

20.

Weenen C, Laven J, von Bergh A, Cranfield M, Groome N, Visser J . Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod. 2004; 10(2):77-83. DOI: 10.1093/molehr/gah015. View