{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:02:00Z","timestamp":1791993720313,"version":"4.4.0"},"reference-count":103,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T00:00:00Z","timestamp":1511136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Adult survivors of childhood cancers are more prone to developing poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. Chemotherapy drugs exert cytotoxic effects systemically and therefore can damage the ovaries, leading to infertility, premature ovarian failure, and, to a lesser extent, spontaneous abortions. They have very limited or no deleterious effects on the uterus that can be recognized clinically. By contrast, radiation is detrimental to both the ovaries and the uterus, thereby causing a greater magnitude of adverse effects on the female reproductive function. These include infertility, premature ovarian failure, miscarriage, fetal growth restrictions, perinatal deaths, preterm births, delivery of small-for-gestational-age infants, preeclampsia, and abnormal placentation. Regrettably, the majority of these adverse outcomes arise from radiation-induced uterine injury and are reported at higher incidence in the adult survivors of childhood cancers who were exposed to uterine radiation during childhood in the form of pelvic, spinal, or total-body irradiation. Recent findings of long-term follow-up studies evaluating reproductive performance of female survivors provided some reassurance to female cancer survivors by documenting that pregnancy and live birth rates were not significantly compromised in survivors, including those who had been treated with alkylating agents and had not received pelvic, cranial, and total-body irradiation. We aimed in this narrative review article to provide an update on the impact of chemotherapy and radiation on the ovarian and uterine function in female survivors of childhood cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications for Practice<\/jats:title>\n                  <jats:p>Adult survivors of childhood cancers are more prone to developing a number of poor reproductive and obstetrical outcomes than their siblings and the general population as a result of previous exposure to chemotherapy and radiation during childhood. The impact of radiation therapy on the female genital system is greater than chemotherapy regimens because radiation is detrimental to both the uterus and the ovaries, whereas toxic effects of chemotherapy drugs are confined to the ovaries. Therefore, radiation-induced uterine damage accounts for most poor obstetrical outcomes in the survivors. These include infertility, miscarriages, stillbirths, fetal growth restrictions, preeclampsia, and preterm deliveries.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2017-0201","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T14:55:28Z","timestamp":1511189728000},"page":"214-224","source":"Crossref","is-referenced-by-count":63,"title":["Ovarian and Uterine Functions in Female Survivors of Childhood Cancers"],"prefix":"10.1093","volume":"23","author":[{"given":"Ozgur","family":"Oktem","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Koc University, Istanbul, Turkey"},{"name":"Assisted Reproduction Unit, Fertility Preservation Program, American Hospital Women's Health Center, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Kansas University, Kansas City, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugur","family":"Selek","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Koc University School of Medicine and MD Anderson Cancer Center, Houston, Texas, USA"},{"name":"Department of Radiation Oncology, Comprehensive Cancer Care Program, American Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Schatmann","sequence":"additional","affiliation":[{"name":"Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bulent","family":"Urman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, School of Medicine, Koc University, Istanbul, Turkey"},{"name":"Assisted Reproduction Unit, Fertility Preservation Program, American Hospital Women's Health Center, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,11,20]]},"reference":[{"key":"2021122509424979200_onco12299-bib-0001","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3322\/caac.20073","article-title":"Cancer statistics, 2010","volume":"60","author":"Jemal","year":"2010","journal-title":"CA Cancer J Clin"},{"key":"2021122509424979200_onco12299-bib-0002","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3322\/caac.21349","article-title":"Cancer treatment and survivorship statistics, 2016","volume":"66","author":"Miller","year":"2016","journal-title":"CA Cancer J Clin"},{"key":"2021122509424979200_onco12299-bib-0003","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer statistics, 2016","volume":"66","author":"Siegel","year":"2016","journal-title":"CA Cancer J Clin"},{"key":"2021122509424979200_onco12299-bib-0004","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1196\/annals.1429.033","article-title":"Preservation of menstrual function in adolescent and young females","volume":"1135","author":"Oktem","year":"2008","journal-title":"Ann NY Acad Sci"},{"key":"2021122509424979200_onco12299-bib-0005","doi-asserted-by":"crossref","first-page":"4477","DOI":"10.1200\/JCO.2007.11.2003","article-title":"Long-term health status among survivors of childhood cancer: Does sex matter?","volume":"25","author":"Armstrong","year":"2007","journal-title":"J Clin Oncol"},{"key":"2021122509424979200_onco12299-bib-0006","doi-asserted-by":"crossref","first-page":"10159","DOI":"10.1158\/0008-5472.CAN-07-2042","article-title":"A novel ovarian xenografting model to characterize the impact of chemotherapy agents on human primordial follicle reserve","volume":"67","author":"Oktem","year":"2007","journal-title":"Cancer Res"},{"key":"2021122509424979200_onco12299-bib-0007","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/jncimonographs\/lgi022","article-title":"Impact of cancer treatment on uterine function","author":"Critchley","year":"2005","journal-title":"J Natl Cancer Inst Monogr"},{"key":"2021122509424979200_onco12299-bib-0008","doi-asserted-by":"crossref","first-page":"2917","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":"2021122509424979200_onco12299-bib-0009","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1200\/JCO.2013.49.2678","article-title":"Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update","volume":"31","author":"Loren","year":"2013","journal-title":"J Clin Oncol"},{"key":"2021122509424979200_onco12299-bib-0010","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1097\/01.AOG.0000452746.44206.18","article-title":"Committee opinion no. 607: Gynecologic concerns in children and adolescents with cancer","volume":"124","year":"2014","journal-title":"Obstet Gynecol"},{"key":"2021122509424979200_onco12299-bib-0011","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.fertnstert.2013.08.012","article-title":"Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: A committee opinion","volume":"100","author":"Practice Committee of American Society for Reproductive Medicine","year":"2013","journal-title":"Fertil Steril"},{"key":"2021122509424979200_onco12299-bib-0012","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1002\/cncr.23071","article-title":"Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function","volume":"110","author":"Oktem","year":"2007","journal-title":"Cancer"},{"key":"2021122509424979200_onco12299-bib-0013","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/0041-008X(91)90310-B","article-title":"Phosphoramide mustard is responsible for the ovarian toxicity of cyclophosphamide","volume":"107","author":"Plowchalk","year":"1991","journal-title":"Toxicol Appl Pharmacol"},{"key":"2021122509424979200_onco12299-bib-0014","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1093\/humrep\/dem027","article-title":"Cortical fibrosis and blood-vessels damage in human ovaries exposed to chemotherapy. 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