The Impact of Systemic Oncological Treatments on the Fertility of Adolescents and Young Adults-A Systematic Review

Overview

Journal Life (Basel)

Specialty Biology

Date 2023 May 27

PMID 37240854

Authors

Justine Himpe

Sander Lammerant

Lore Van den Bergh

Lore Lapeire

Chloe De Roo

Affiliations

Soon will be listed here.

Abstract

Background: Over the past decades, advancements in oncological treatments have led to major improvements in survival. Particularly for adolescents and young adults (AYAs), fertility is an important concern in cancer survivorship. The purpose of the review is to provide physicians with a practical overview of the current knowledge about the impact of systemic oncological treatments on the fertility of female and male AYAs.

Methods: A systematic review was performed based on relevant articles obtained from 4 databases up until 31 December 2022.

Results: The mechanisms of gonadotoxicity and the concurrent risk is described for the following categories: chemotherapy, targeted therapy and immunotherapy. For the category "chemotherapy", the specific effects and risks are listed for the different classes and individual chemotherapeutics. In the category "targeted therapy", a distinction was made between tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. Information concerning immunotherapy is scarce.

Conclusions: The effects of chemotherapy on fertility are well investigated, but even in this category, results can be conflicting. Insufficient data are available on the fertility effects of targeted therapy and immunotherapy to draw definitive conclusions. More research is needed for these therapies and their evolving role in treating cancers in AYAs. It would be useful to include fertility endpoints in clinical trials that evaluate new and existing oncological treatments.

Citing Articles

The potential role of exercise in mitigating fertility toxicity associated with immune checkpoint inhibitors (ICIs) in cancer patients.

Jamrasi P, Tazi M, Zulkifli N, Bae J, Song W J Physiol Sci. 2024; 74(1):57.

PMID: 39616333 PMC: 11607910. DOI: 10.1186/s12576-024-00950-3.

The Effects of Cancer Immunotherapy on Fertility: Focus on Hematological Malignancies.

Caserta S, Cancemi G, Murdaca G, Stagno F, Di Gioacchino M, Gangemi S Biomedicines. 2024; 12(9).

PMID: 39335619 PMC: 11428457. DOI: 10.3390/biomedicines12092106.

Menstrual Blood Stem Cells-Derived Exosomes as Promising Therapeutic Tools in Premature Ovarian Insufficiency Induced by Gonadotoxic Systemic Anticancer Treatment.

Cordeiro M, Roque R, Laranjeiro B, Carvalhos C, Figueiredo-Dias M Int J Mol Sci. 2024; 25(15).

PMID: 39126037 PMC: 11312895. DOI: 10.3390/ijms25158468.

The Low Survivability of Transplanted Gonadal Grafts: The Impact of Cryopreservation and Transplantation Conditions on Mitochondrial Function.

Moniz I, Soares M, Sousa A, Ramalho-Santos J, Branco A Biology (Basel). 2024; 13(7).

PMID: 39056734 PMC: 11274302. DOI: 10.3390/biology13070542.

The increasing burden of testicular seminomas and non-seminomas in adolescents and young adults (AYAs): incidence, treatment, disease-specific survival and mortality trends in the Netherlands between 1989 and 2019.

van der Meer D, Karim-Kos H, Elzevier H, Dinkelman-Smit M, Kerst J, Atema V ESMO Open. 2024; 9(2):102231.

PMID: 38244349 PMC: 10937200. DOI: 10.1016/j.esmoop.2023.102231.

References

Lambertini M, Del Mastro L, Pescio M, Andersen C, Azim Jr H, Peccatori F . Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med. 2016; 14:1. PMC: 4700580. DOI: 10.1186/s12916-015-0545-7. View

Cameron D, Piccart-Gebhart M, Gelber R, Procter M, Goldhirsch A, de Azambuja E . 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017; 389(10075):1195-1205. PMC: 5465633. DOI: 10.1016/S0140-6736(16)32616-2. View

Goldhirsch A, Gelber R, Castiglione M . The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. The International Breast Cancer Study Group. Ann Oncol. 1990; 1(3):183-8. DOI: 10.1093/oxfordjournals.annonc.a057718. View

You L, Lv Z, Li C, Ye W, Zhou Y, Jin J . Worldwide cancer statistics of adolescents and young adults in 2019: a systematic analysis of the Global Burden of Disease Study 2019. ESMO Open. 2021; 6(5):100255. PMC: 8417345. DOI: 10.1016/j.esmoop.2021.100255. View

Budman D, Berry D, Cirrincione C, Henderson I, Wood W, Weiss R . Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B. J Natl Cancer Inst. 1998; 90(16):1205-11. DOI: 10.1093/jnci/90.16.1205. View

Bang Y, Van Cutsem E, Feyereislova A, Chung H, Shen L, Sawaki A . Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010; 376(9742):687-97. DOI: 10.1016/S0140-6736(10)61121-X. View

Eichenauer D, Aleman B, Andre M, Federico M, Hutchings M, Illidge T . Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018; 29(Suppl 4):iv19-iv29. DOI: 10.1093/annonc/mdy080. View

Chatzidarellis E, Makrilia N, Giza L, Georgiadis E, Alamara C, Syrigos K . Effects of taxane-based chemotherapy on inhibin B and gonadotropins as biomarkers of spermatogenesis. Fertil Steril. 2009; 94(2):558-63. DOI: 10.1016/j.fertnstert.2009.03.068. View

MILLER 3rd J, Williams G, LEISSRING J . Multiple late complications of therapy with cyclophosphamide, including ovarian destruction. Am J Med. 1971; 50(4):530-5. DOI: 10.1016/0002-9343(71)90341-x. View

10.

Scovell J, Benz K, Samarska I, Kohn T, Hooper J, Matoso A . Association of Impaired Spermatogenesis With the Use of Immune Checkpoint Inhibitors in Patients With Metastatic Melanoma. JAMA Oncol. 2020; 6(8):1297-1299. PMC: 7303895. DOI: 10.1001/jamaoncol.2020.1641. View

11.

Bujan L, Walschaerts M, Moinard N, Hennebicq S, Saias J, Brugnon F . Impact of chemotherapy and radiotherapy for testicular germ cell tumors on spermatogenesis and sperm DNA: a multicenter prospective study from the CECOS network. Fertil Steril. 2013; 100(3):673-80. DOI: 10.1016/j.fertnstert.2013.05.018. View

12.

Tham Y, Sexton K, Weiss H, Elledge R, Friedman L, Kramer R . The rates of chemotherapy-induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane. Am J Clin Oncol. 2007; 30(2):126-32. DOI: 10.1097/01.coc.0000251398.57630.4f. View

13.

Garutti M, Lambertini M, Puglisi F . Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review. ESMO Open. 2021; 6(5):100276. PMC: 8487000. DOI: 10.1016/j.esmoop.2021.100276. View

14.

Hoelder S, Clarke P, Workman P . Discovery of small molecule cancer drugs: successes, challenges and opportunities. Mol Oncol. 2012; 6(2):155-76. PMC: 3476506. DOI: 10.1016/j.molonc.2012.02.004. View

15.

Morgan S, Lopes F, Gourley C, Anderson R, Spears N . Cisplatin and doxorubicin induce distinct mechanisms of ovarian follicle loss; imatinib provides selective protection only against cisplatin. PLoS One. 2013; 8(7):e70117. PMC: 3726485. DOI: 10.1371/journal.pone.0070117. View

16.

Bines J, Oleske D, Cobleigh M . Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer. J Clin Oncol. 1996; 14(5):1718-29. DOI: 10.1200/JCO.1996.14.5.1718. View

17.

Tulchiner G, Pichler R, Ulmer H, Staudacher N, Lindner A, Brunner A . Sex-specific hormone changes during immunotherapy and its influence on survival in metastatic renal cell carcinoma. Cancer Immunol Immunother. 2021; 70(10):2805-2817. PMC: 8423679. DOI: 10.1007/s00262-021-02882-y. View

18.

Loren A, Senapati S . Fertility preservation in patients with hematologic malignancies and recipients of hematopoietic cell transplants. Blood. 2019; 134(9):746-760. DOI: 10.1182/blood.2018846790. View

19.

Pryzant R, Meistrich M, Wilson G, Brown B, McLaughlin P . Long-term reduction in sperm count after chemotherapy with and without radiation therapy for non-Hodgkin's lymphomas. J Clin Oncol. 1993; 11(2):239-47. DOI: 10.1200/JCO.1993.11.2.239. View

20.

Silva C, Ribeiro Rama A, Soares S, Moura-Ramos M, Almeida-Santos T . Adverse reproductive health outcomes in a cohort of young women with breast cancer exposed to systemic treatments. J Ovarian Res. 2019; 12(1):102. PMC: 6824094. DOI: 10.1186/s13048-019-0581-6. View