{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:02:33Z","timestamp":1790730153903,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,5]]},"abstract":"Abstract<\/jats:title>\n \n STUDY QUESTION<\/jats:title>\n Does chemotherapy exposure affect IVM potential of immature oocytes retrieved from the ovarian cortex following ovarian tissue cryopreservation (OTC) for fertility preservation?<\/jats:p>\n <\/jats:sec>\n \n SUMMARY ANSWER<\/jats:title>\n The IVM potential of oocyte retrieved from ovarian cortex following OTC is not affected by prior exposure to chemotherapy but primarily dependent on patient\u2019s age, while successful retrieval of immature oocytes from the ovarian tissue is negatively affected by chemotherapy and its timing.<\/jats:p>\n <\/jats:sec>\n \n WHAT IS KNOWN ALREADY<\/jats:title>\n The potential and feasibility of IVM in premenarche patients was previously demonstrated, in smaller studies. The scarce data that exist on the IVM potential of oocytes retrieved during OTC following chemotherapy support the feasibility of this process, however, this was not previously shown in the premenarche cancer patients population or in larger cohorts.<\/jats:p>\n <\/jats:sec>\n \n STUDY DESIGN, SIZE, DURATION<\/jats:title>\n A retrospective cohort study evaluating 229 cancer patients aged 1\u201339\u2009years with attempted retrieval of oocytes from the ovarian tissue and the medium following OTC in a university affiliated fertility preservation unit between 2002 and 2021.<\/jats:p>\n <\/jats:sec>\n \n PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n A total of 172 chemotherapy na\u00efve and 57 chemotherapy exposed patients aged 1\u201339\u2009years underwent OTC in university affiliated tertiary infertility and IVF center. OTC and IVM outcomes were compared between the chemotherapy na\u00efve and exposed groups. The main outcome measure was mean IVM rate per patient in the chemotherapy na\u00efve and exposed groups, with subgroup analysis of a 1:1 chemotherapy exposed group matched for age at OTC and type of malignancy. We additionally analyzed premenarche and postmenarche patients\u2019 outcomes separately and investigated the effect of time from chemotherapy to IVM, malignancy type and chemotherapy regimen on oocyte number and IVM outcomes in the chemotherapy exposed group.<\/jats:p>\n <\/jats:sec>\n \n MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n While the number of retrieved oocytes and percentage of patients with at least one oocyte retrieved was higher in the chemotherapy na\u00efve group (8.7\u2009\u00b1\u20097.9 versus 4.9\u2009\u00b1\u20095.6 oocytes and 87.2% versus 73.7%, P\u2009&lt;\u20090.001 and P\u2009=\u20090.016, respectively), IVM rate and number of mature oocytes were comparable between the groups (29.0\u2009\u00b1\u200925.0% versus 28. 9\u2009\u00b1\u200929.2% and 2.8\u2009\u00b1\u20093.1 versus 2.2\u2009\u00b1\u20092.8, P\u2009=\u20090.979 and P\u2009=\u20090.203, respectively). Similar findings were shown in subgroup analyses for premenarche and postmenarche groups. The only parameter found to be independently associated with IVM rate in a multivariable model was menarche status (F\u2009=\u20098.91, P\u2009=\u20090.004). Logistic regression models similarly showed that past chemotherapy exposure is negatively associated with successful retrieval of oocytes while older age and menarche are predictive of successful IVM. An age and the type of malignancy matched (1:1) chemotherapy na\u00efve and exposed groups were created (25 patients in each group). This comparison demonstrated similar IVM rate (35.4\u2009\u00b1\u200930.1% versus 31.0\u2009\u00b1\u200925.2%, P\u2009=\u20090.533) and number of matured oocytes (2.7\u2009\u00b1\u20093.0. versus 3.0\u2009\u00b1\u20093.9 oocytes, P\u2009=\u20090.772). Type of malignancy and chemotherapy regimen including alkylating agents were not associated with IVM rate.<\/jats:p>\n <\/jats:sec>\n \n LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n This study\u2019s inherited retrospective design and the long study period carries the possible technological advancement and differences. The chemotherapy exposed group was relatively small and included different age groups. We could only evaluate the potential of the oocytes to reach metaphase II in vitro but not their fertilization potential or clinical outcomes.<\/jats:p>\n <\/jats:sec>\n \n WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n IVM is feasible even after chemotherapy broadening the fertility preservation options of cancer patients. The use of IVM for fertility preservation, even after exposure to chemotherapy, should be further studied for optimal postchemotherapy timing safety and for the in vitro matured oocytes potential for fertilization.<\/jats:p>\n <\/jats:sec>\n \n STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n No funding was received for this study by any of the authors. The authors report that no competing interests.<\/jats:p>\n <\/jats:sec>\n \n TRIAL REGISTRATION NUMBER<\/jats:title>\n N\/A.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/humrep\/dead142","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T01:09:37Z","timestamp":1688692177000},"page":"1705-1713","source":"Crossref","is-referenced-by-count":6,"title":["Prior exposure to chemotherapy does not reduce the in vitro<\/i> maturation potential of oocytes obtained from ovarian cortex in cancer patients"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1848-4560","authenticated-orcid":false,"given":"Gilad","family":"Karavani","sequence":"first","affiliation":[{"name":"In-Vitro Fertilization Unit, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"},{"name":"Department of Obstetrics and Gynecology, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koral","family":"Vedder","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einat","family":"Gutman-Ido","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raizl","family":"Gruda Sussman","sequence":"additional","affiliation":[{"name":"Division of Haematology\/Oncology, Department of Paediatrics, The Hospital for Sick Children , Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neta","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Hematology, Hadassah Ein-Kerem Medical Center, Hebrew University of Jerusalem , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talya","family":"Mordechai-Daniel","sequence":"additional","affiliation":[{"name":"In-Vitro Fertilization Unit, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"},{"name":"Department of Obstetrics and Gynecology, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2442-4938","authenticated-orcid":false,"given":"Assaf","family":"Ben-Meir","sequence":"additional","affiliation":[{"name":"In-Vitro Fertilization Unit, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"},{"name":"Department of Obstetrics and Gynecology, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-1596","authenticated-orcid":false,"given":"Tal","family":"Imbar","sequence":"additional","affiliation":[{"name":"In-Vitro Fertilization Unit, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"},{"name":"Department of Obstetrics and Gynecology, Hadassah Ein-Kerem Medical Center and Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,6]]},"reference":[{"key":"2023090508445386700_dead142-B1","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1093\/humrep\/dem413","article-title":"Selection of patients before and after anticancer treatment for ovarian cryopreservation","volume":"23","author":"Abir","year":"2008","journal-title":"Hum Reprod"},{"key":"2023090508445386700_dead142-B2","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/humrep\/dew007","article-title":"Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy","volume":"31","author":"Abir","year":"2016","journal-title":"Hum Reprod"},{"key":"2023090508445386700_dead142-B3","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1002\/cncr.31255","article-title":"Fertility preservation options in pediatric and adolescent patients with cancer","volume":"124","author":"Burns","year":"2018","journal-title":"Cancer"},{"key":"2023090508445386700_dead142-B4","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.fertnstert.2023.01.027","article-title":"Future potential of in vitro maturation including fertility preservation","volume":"119","author":"Cadenas","year":"2023","journal-title":"Fertil Steril"},{"key":"2023090508445386700_dead142-B5","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.fertnstert.2013.01.141","article-title":"In vitro maturation of human immature oocytes for fertility preservation","volume":"99","author":"Chian","year":"2013","journal-title":"Fertil Steril"},{"key":"2023090508445386700_dead142-B6","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.2217\/fon-2022-0078","article-title":"Ovarian failure risk in post-pubertal patients with cancer: a prognostic model","volume":"18","author":"Cioffi","year":"2022","journal-title":"Future Oncol"},{"key":"2023090508445386700_dead142-B7","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1093\/humrep\/des143","article-title":"Ovarian reserve and response to IVF and in vitro maturation treatment following chemotherapy","volume":"27","author":"Das","year":"2012","journal-title":"Hum Reprod"},{"key":"2023090508445386700_dead142-B8","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.fertnstert.2013.03.027","article-title":"Risk of transferring malignant cells with transplanted frozen-thawed ovarian tissue","volume":"99","author":"Dolmans","year":"2013","journal-title":"Fertil Steril"},{"key":"2023090508445386700_dead142-B9","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.fertnstert.2021.03.008","article-title":"Transplantation of cryopreserved ovarian tissue in a series of 285 women: a review of five leading European centers","volume":"115","author":"Dolmans","year":"2021","journal-title":"Fertil Steril"},{"key":"2023090508445386700_dead142-B10","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1056\/NEJMra1614676","article-title":"Fertility preservation in women","volume":"377","author":"Donnez","year":"2017","journal-title":"N Engl J Med"},{"key":"2023090508445386700_dead142-B11","doi-asserted-by":"crossref","first-page":"e0208576","DOI":"10.1371\/journal.pone.0208576","article-title":"Comparison of GnRH agonist and hCG for priming in vitro maturation cycles in cancer patients undergoing urgent fertility preservation","volume":"13","author":"El Hachem","year":"2018","journal-title":"PLoS One"},{"key":"2023090508445386700_dead142-B12","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/1477-7827-9-150","article-title":"Vitrification of in vitro matured oocytes collected from antral follicles at the time of ovarian tissue cryopreservation","volume":"9","author":"Fasano","year":"2011","journal-title":"Reprod Biol Endocrinol"},{"key":"2023090508445386700_dead142-B13","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.rbmo.2020.07.015","article-title":"In-vitro maturation of oocytes recovered during cryopreservation of pre-pubertal girls undergoing fertility preservation","volume":"41","author":"Fouks","year":"2020","journal-title":"Reprod Biomed Online"},{"key":"2023090508445386700_dead142-B14","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.1182\/blood-2012-01-403022","article-title":"Cryopreserved ovarian cortex from patients with leukemia in complete remission contains no apparent viable malignant cells","volume":"120","author":"Greve","year":"2012","journal-title":"Blood"},{"key":"2023090508445386700_dead142-B15","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s10815-015-0490-6","article-title":"Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study","volume":"32","author":"Gao","year":"2015","journal-title":"J Assist Reprod Genet"},{"issue":"5","key":"2023090508445386700_dead142-B16","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1093\/humrep\/dev020","article-title":"Follicle activation and \u2018burn-out\u2019 contribute to post-transplantation follicle loss in ovarian tissue grafts: the effect of graft thickness","volume":"30","author":"Gavish","year":"2015","journal-title":"Hum Reprod"},{"key":"2023090508445386700_dead142-B17","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1126\/science.aav7321","article-title":"Chromosome errors in human eggs shape natural fertility over reproductive life span","volume":"365","author":"Gruhn","year":"2019","journal-title":"Science"},{"key":"2023090508445386700_dead142-B18","doi-asserted-by":"crossref","first-page":"682470","DOI":"10.3389\/fonc.2021.682470","article-title":"Follicle rescue from prepubertal ovaries after recent treatment with cyclophosphamide-an experimental culture system using mice to achieve mature oocytes for fertility preservation","volume":"11","author":"Hao","year":"2021","journal-title":"Front Oncol"},{"key":"2023090508445386700_dead142-B19","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1093\/humrep\/dex040","article-title":"Efficacy of ovarian tissue cryopreservation for fertility preservation: lessons learned from 545 cases","volume":"32","author":"Jadoul","year":"2017","journal-title":"Hum Reprod"},{"key":"2023090508445386700_dead142-B20","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12905-021-01343-z","article-title":"Chemotherapy-based gonadotoxicity risk evaluation as a predictor of reproductive outcomes in post-pubertal patients following ovarian tissue cryopreservation","volume":"21","author":"Karavani","year":"2021","journal-title":"BMC Womens Health"},{"key":"2023090508445386700_dead142-B21","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.fertnstert.2019.03.026","article-title":"In vitro maturation rates in young premenarche patients","volume":"112","author":"Karavani","year":"2019","journal-title":"Fertil Steril"},{"key":"2023090508445386700_dead142-B22","doi-asserted-by":"crossref","first-page":"667682","DOI":"10.3389\/fcell.2021.667682","article-title":"Age-dependent in vitro maturation efficacy of human oocytes - is there an optimal age?","volume":"9","author":"Karavani","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2023090508445386700_dead142-B23","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/S0015-0282(99)00067-9","article-title":"A laparoscopic technique for obtaining ovarian cortical biopsy specimens for fertility conservation in patients with cancer","volume":"71","author":"Meirow","year":"1999","journal-title":"Fertil Steril"},{"key":"2023090508445386700_dead142-B24","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1093\/humrep\/den055","article-title":"Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients","volume":"23","author":"Meirow","year":"2008","journal-title":"Hum Reprod"},{"key":"2023090508445386700_dead142-B25","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1093\/humupd\/7.6.535","article-title":"The effects of radiotherapy and chemotherapy on female reproduction","volume":"7","author":"Meirow","year":"2001","journal-title":"Hum Reprod Update"},{"key":"2023090508445386700_dead142-B26","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s10815-020-01724-7","article-title":"Improving the maturation rate of human oocytes collected ex vivo during the cryopreservation of ovarian tissue","volume":"37","author":"Nikiforov","year":"2020","journal-title":"J Assist Reprod Genet"},{"key":"2023090508445386700_dead142-B27","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.ctrv.2011.10.002","article-title":"Options on fertility preservation in female cancer patients","volume":"38","author":"Rodriguez-Wallberg","year":"2012","journal-title":"Cancer Treat Rev"},{"key":"2023090508445386700_dead142-B28","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.fertnstert.2020.03.037","article-title":"Evaluation of ovarian tissue transplantation: results from three clinical centers","volume":"114","author":"Shapira","year":"2020","journal-title":"Fertil Steril"},{"key":"2023090508445386700_dead142-B29","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.fertnstert.2017.09.001","article-title":"First delivery in a leukemia survivor after transplantation of cryopreserved ovarian tissue, evaluated for leukemia cells contamination","volume":"109","author":"Shapira","year":"2018","journal-title":"Fertil Steril"},{"issue":"4","key":"2023090508445386700_dead142-B30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"2023090508445386700_dead142-B31","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1007\/s10815-018-1315-1","article-title":"Cryopreservation and transplantation of ovarian tissue: results from one center in the USA","volume":"35","author":"Silber","year":"2018","journal-title":"J Assist Reprod Genet"},{"key":"2023090508445386700_dead142-B32","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1016\/j.fertnstert.2009.12.073","article-title":"Duration of fertility after fresh and frozen ovary transplantation","volume":"94","author":"Silber","year":"2010","journal-title":"Fertil Steril"},{"key":"2023090508445386700_dead142-B33","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/humupd\/dmz027","article-title":"Ovarian damage from chemotherapy and current approaches to its protection","volume":"25","author":"Spears","year":"2019","journal-title":"Hum Reprod Update"},{"key":"2023090508445386700_dead142-B34","doi-asserted-by":"crossref","first-page":"F45","DOI":"10.1530\/REP-19-0077","article-title":"Fertility preservation: progress and prospects for developing human immature oocytes in vitro","volume":"158","author":"Telfer","year":"2019","journal-title":"Reproduction"},{"key":"2023090508445386700_dead142-B35","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.fertnstert.2021.03.004","article-title":"In vitro growth and maturation of primordial follicles and immature oocytes","volume":"115","author":"Telfer","year":"2021","journal-title":"Fertil Steril"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/38\/9\/1705\/51345266\/dead142.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/38\/9\/1705\/51345266\/dead142.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T08:48:12Z","timestamp":1693903692000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/38\/9\/1705\/7220733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,6]]},"references-count":35,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,7,6]]},"published-print":{"date-parts":[[2023,9,5]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/dead142","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,9,1]]},"published":{"date-parts":[[2023,7,6]]}}}