{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:48:20Z","timestamp":1791841700762,"version":"4.3.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>As the incidence of malignancies in young adults is increasing, fertility preservation in cancer survivors arises as a major concern. Especially among female cancer patients, pregnancy rates are estimated to be 40% lower compared to women of the same age. Nowadays oncologists are to be preoccupied not only with their patients\u2019 successful treatment, but also with the maintenance of the potential of the latter to conceive and obtain children. Chemotherapy associated ovarian failure (COF), refers to disruption of ovarian function both as an endocrine gland and as a reproductive organ, due to previous exposure to chemotherapy agents. Although the underlying mechanism is not fully understood, it is supposed that chemotherapy agents may induce either DNA damage of premature ovarian follicle or early activation and apoptosis of them, resulting into early exhaustion of available follicle deposit. Various chemotherapy agents have been associated with COF with the highest incidence being reported for patients undergoing combination regimens. Although a variety of alternatives in order to maintain ovarian function and fertility in female cancer survivors are available, adequately established practices to do so are lacking. Thus, it is of major importance to investigate further and collect sufficient evidence, aiming to guide patients and physicians in everyday clinical practice.<\/jats:p>","DOI":"10.3389\/fendo.2020.572388","type":"journal-article","created":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T02:38:29Z","timestamp":1607395109000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":101,"title":["Chemotherapy Associated Ovarian Failure"],"prefix":"10.3389","volume":"11","author":[{"given":"Davide","family":"Mauri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Gazouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Zarkavelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Papadaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Mavroeidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Gkoura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Ntellas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lea","family":"Amylidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lampriani","family":"Tsali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleftherios","family":"Kampletsas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/14737140.2017.1335199","article-title":"Anticancer treatments and female fertility: clinical concerns and role of oncologists in oncofertility practice","volume":"17","author":"Salama","year":"2017","journal-title":"Expert Rev Anticancer Ther"},{"key":"B2","article-title":"The Best Age for Pregnancy and Undue Pressures","volume":"10","author":"Bellieni","year":"2016","journal-title":"J Family Reprod Health"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26045","article-title":"Pregnancy after adolescent and adult cancer: a population-based matched cohort study","volume":"129","author":"Stensheim","year":"2011","journal-title":"Int J Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt199","article-title":"Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"24","author":"Peccatori","year":"2013","journal-title":"Ann Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.5694\/mja18.00190","article-title":"Preventing ovarian failure associated with chemotherapy","volume":"209","author":"Cui","year":"2018","journal-title":"Med J Aust"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.5888","article-title":"American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients","volume":"24","author":"Lee","year":"2006","journal-title":"J Clin Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2015.11.043","article-title":"Prevention of chemotherapy-induced ovarian damage","volume":"105","author":"Roness","year":"2016","journal-title":"Fertil Steril"},{"key":"B8","doi-asserted-by":"publisher","first-page":"185ra62","DOI":"10.1126\/scitranslmed.3005402","article-title":"Cyclophosphamide triggers follicle activation and \u201cburnout\u201d; AS101 prevents follicle loss and preserves fertility","volume":"5","author":"Kalich-Philosoph","year":"2013","journal-title":"Sci Transl Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/er.2008-0048","article-title":"Molecular mechanisms underlying the activation of mammalian primordial follicles","volume":"30","author":"Adhikari","year":"2009","journal-title":"Endocr Rev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2016-0176","article-title":"Chemotherapy-induced damage to ovary: mechanisms and clinical impact","volume":"12","author":"Bedoschi","year":"2016","journal-title":"Future Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100363","article-title":"Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise","volume":"3","author":"Soleimani","year":"2011","journal-title":"Aging (Albany NY)"},{"key":"B12","volume-title":"Mechanisms of chemotherapy-induced primordial follicle death in human. Presented at: Society for the Study of Reproduction","author":"Titus","year":"2014"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e23492","DOI":"10.1371\/journal.pone.0023492","article-title":"In vivo bioimaging as a novel strategy to detect doxorubicin-induced damage to gonadal blood vessels","volume":"6","author":"Bar-Joseph","year":"2011","journal-title":"PloS One"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2014-0016","article-title":"Estimates of young breast cancer survivors at risk for infertility in the U.S","volume":"19","author":"Trivers","year":"2014","journal-title":"Oncologist"},{"key":"B15","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1001\/jamaoncol.2015.3251","article-title":"Gonadotropin-Releasing Hormone Agonists for Ovarian Function Preservation in Premenopausal Women Undergoing Chemotherapy for Early-Stage Breast Cancer: A Systematic Review and Meta-analysis","volume":"2","author":"Munhoz","year":"2016","journal-title":"JAMA Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2011.991","article-title":"Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial","volume":"306","author":"Del Mastro","year":"2011","journal-title":"JAMA"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1413204","article-title":"Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy","volume":"372","author":"Moore","year":"2015","journal-title":"N Engl J Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"p.vi1","DOI":"10.1093\/annonc\/mdv335.01","article-title":"Long-term outcome results of the phase III PROMISE-GIM6 study evaluating the role of LHRH analog (LHRHa) during chemotherapy as a strategy to reduce ovarian failure in early breast cancer patients","volume":"26","author":"Lambertini","year":"2015","journal-title":"Ann Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx184","article-title":"GnRHa agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial","volume":"28","author":"Leonard","year":"2017","journal-title":"Ann Oncol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"iv19","DOI":"10.1093\/annonc\/mdy080","article-title":"Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"29","author":"Eichenauer","year":"2018","journal-title":"Ann Oncol"},{"key":"B21","article-title":"Surveillance, Epidemiology and End Results programme (SEER), supported by the National Cancer Institute (NCI) of the USA","year":""},{"key":"B22","doi-asserted-by":"publisher","first-page":"e80444","DOI":"10.1371\/journal.pone.0080444","article-title":"Gonadotropin-releasing hormone for preservation of ovarian function during chemotherapy in lymphoma patients of reproductive age: a summary based on 434 patients","volume":"8","author":"Zhang","year":"2013","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.65.8864","article-title":"No evidence for the benefit of gonadotropin-releasing hormone agonist in preserving ovarian function and fertility in lymphoma survivors treated with chemotherapy: Final long-term report of a prospective randomized trial","volume":"34","author":"Demeestere","year":"2016","journal-title":"J Clin Oncol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1111\/j.1743-7563.2007.00089.x","article-title":"Ovarian preservation with gonadotropin-releasing hormone analog during chemotherapy","volume":"3","author":"Gilani","year":"2007","journal-title":"Asia Pacif J Clin Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2001.6181","article-title":"Use of GnRH Analogs for Functional Protection of the Ovary and Preservation of Fertility during Cancer Treatment in Adolescents: A Preliminary Report","volume":"81","author":"Pacheco","year":"2001","journal-title":"Gynecol Oncol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1757-2215-6-15","article-title":"Optimized protocol for cryopreservation of human eggs improves developmental competence and implantation of resulting embryos","volume":"6","author":"Wang","year":"2013","journal-title":"J Ovarian Res"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.011","article-title":"Further evidence on the safety and success of ovarian stimulation with letrozole and tamoxifen in breast cancer patients undergoing in vitro fertilization to cryopreserve their embryos for fertility preservation","volume":"23","author":"Oktay","year":"2005","journal-title":"J Clin Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.fertnstert.2015.10.026","article-title":"Successful elective and medically indicated oocyte vitrification and warming for autologous in\u00a0vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval","volume":"105","author":"Doyle","year":"2016","journal-title":"Fertil Steril"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)60025-9","article-title":"Over 900 oocyte cryopreservation babies born with no apparent increase in congenital anomalies","volume":"18","author":"Noyes","year":"2009","journal-title":"Reprod BioMed Online"},{"key":"B30","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.fertnstert.2012.09.028","article-title":"Mature oocyte cryopreservation: a guideline","volume":"99","year":"2013","journal-title":"Fertil Steril"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00600","article-title":"Oocyte Cryopreservation in Oncological Patients: Eighteen Years Experience of a Tertiary Care Referral Center","volume":"10","author":"Specchia","year":"2019","journal-title":"Front Endocrinol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dey321","article-title":"Elective and Onco-fertility preservation: factors related to IVF outcomes","volume":"33","author":"Cobo","year":"2018","journal-title":"Hum Reprod"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1159\/000499054","article-title":"Cryopreservation of Human Ovarian Tissue: A Review","volume":"46","author":"Rivas Leonel","year":"2019","journal-title":"Transfus Med Hemother"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1177\/1933719117702251","article-title":"Current Success and Efficiency of Autologous Ovarian Transplantation: A Meta-Analysis","volume":"24","author":"Pacheco","year":"2017","journal-title":"Reprod Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu353","article-title":"Successful fertility preservation following ovarian tissue vitrification in patients with primary ovarian insufficiency","volume":"30","author":"Suzuki","year":"2015","journal-title":"Hum Reprod"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1312830110","article-title":"Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment","volume":"110","author":"Kawamura","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/80442","article-title":"Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy","volume":"6","author":"Morita","year":"2000","journal-title":"Nat Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2033","article-title":"Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapy-induced death","volume":"15","author":"Gonfloni","year":"2009","journal-title":"Nat Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.08.017","article-title":"DNA Damage-Induced Primordial Follicle Oocyte Apoptosis and Loss of Fertility Require TAp63-Mediated Induction of Puma and Noxa","volume":"48","author":"Kerr","year":"2012","journal-title":"Mol Cell"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den481","article-title":"Protective effect of theimmunomodulator AS101 against cyclophosphamide-induced testicular damage inmice","volume":"24","author":"Carmely","year":"2009","journal-title":"Hum Reprod"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1016\/j.fertnstert.2013.01.135","article-title":"Granulocyte colony-stimulating factor with or without stemcell factor extends time to premature ovarian insufficiency in female mice treatedwith alkylating chemotherapy","volume":"99","author":"Skaznik-Wikiel","year":"2013","journal-title":"Fertil Steril"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-010-9463-y","article-title":"Tamoxifen decreases ovarian follicular loss from experimentaltoxicant DMBA and chemotherapy agents cyclophosphamide and doxorubicin inthe rat","volume":"27","author":"Ting","year":"2010","journal-title":"J Assist Reprod Genet"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2019.03.010","article-title":"EUropeanREcommendations for female FERtility preservation (EU-REFER): A joint collaboration between oncologists and fertility specialists","volume":"138","author":"Dolmans","year":"2019","journal-title":"Crit Rev Oncol\/Hematol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2020.572388\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T02:38:32Z","timestamp":1607395112000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2020.572388\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,8]]},"references-count":43,"alternative-id":["10.3389\/fendo.2020.572388"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2020.572388","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,8]]},"article-number":"572388"}}