{"paper_id":"119b531f-290e-43ad-85f9-633d24a1ab70","body_text":"Gonadotoxic treatment for both malignant and benign conditions, including chemotherapy, radiation therapy, and hematopoietic stem cell transplantation, can damage the ovarian reserve and possibly result in premature ovarian insufficiency (POI) and infertility ( Meirow, 2000 ;  Overbeek  et al. , 2017 ;  van Dorp  et al. , 2018 ;  Su  et al. , 2025 ). While the incidence of cancer among women of reproductive age is increasing, the overall survival rate after cancer is also rising ( Nordcan 2.0, 2024 ). Many women postpone childbearing, and as a result, may not have started or completed their family by the time they receive gonadotoxic treatment (Eurostat, 2025). The risk of treatment-induced infertility is a major concern among these women ( Partridge  et al. , 2004 ;  Peate  et al. , 2009 ;  Howard-Anderson  et al. , 2012 ;  Bentsen  et al. , 2023 ). The area of reproductive medicine focusing on fertility preservation (FP) prior to gonadotoxic treatment has evolved rapidly during the last few decades, and the number of clinics that guide women and offer FP treatments, including ovarian tissue cryopreservation (OTC), has increased worldwide ( Donnez and Dolmans, 2017 ;  Anderson  et al. , 2020 ).\nDonnez  et al.  (2004)  reported the first live birth after auto-transplantation of cryopreserved ovarian tissue, and OTC has been recognized as an option for FP by the American Society for Reproductive Medicine (ASRM) since 2019 ( Practice Committee of the American Society for Reproductive Medicine, 2019 ). OTC typically involves the removal of an entire ovary or ovarian cortical biopsies under general anesthesia usually via laparoscopic surgery. The excised ovary is then dissected into cortical strips which are cryopreserved ( Rosendahl  et al. , 2011 ). Slow freezing remains the current standard technique for OTC ( Anderson  et al. , 2017 ), whereas vitrification is emerging as an alternative approach ( Sänger  et al. , 2024 ). Autologous ovarian tissue transplantation (AOTT) can be performed in women exhibiting signs of POI following completion of gonadotoxic treatment, with the aim of restoring endocrine function and/or achieving pregnancy, either naturally or through ovarian stimulation and IVF. Live birth rates following AOTT have been reported ranging from 25% to 41% ( Colmorn  et al. , 2022 ;  Lotz  et al. , 2022 ;  Fraison  et al. , 2023 ) with no increased risk of perinatal complications compared with the general population except for preeclampsia ( Erden  et al. , 2024 ). Even though OTC in many clinics is not the first choice of FP ( Rodriguez-Wallberg  et al. , 2019 ), it is still considered relevant in premenarchal girls, post-menarche girls considered too young for ovarian stimulation and egg retrieval, and in women who are experiencing time constraints due to the urgency of initiating chemotherapy, and therefore do not have the time to go through ovarian stimulation. Although OTC is generally considered safe with little risk of complications ( Beckmann  et al. , 2018 ), surgery still carries risks that may delay the initiation of life-saving chemotherapy. Furthermore, a proportion of the women may never develop POI following gonadotoxic treatment, and therefore, the use of costly and potentially risky treatments as a precautionary measure should be carefully evaluated, particularly when it involves removing healthy ovarian tissue, which could potentially reduce the ovarian reserve further. These factors underscore the importance of evaluating return rates.\nA considerable number of years have passed since the first ovarian tissue was cryopreserved, and many studies are now able to report long-term follow-up data. This enables evaluation of FP treatment options and the populations to whom they are offered. The aim of this systematic review was to assess the return rates for the use of ovarian tissue cryopreserved as FP prior to gonadotoxic treatment.\n\nThe study was registered in PROSPERO (ID number CRD42024537107). We made no amendment after registration except from using an alternative risk of bias evaluation tool (described below). We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines in the development of the systematic review ( Page  et al. , 2021 ).\nWe searched PubMed (MEDLINE), EMBASE, and the Cochrane Library using medical subject headings (MeSH), Emtree Terms, and text words. Retrospective and prospective cohort studies, case-control studies, and randomized controlled trials that reported the proportion of women who returned for AOTT out of the total number who underwent OTC prior to gonadotoxic treatment were included. Studies that examined only the return rate for oocyte and/or embryo cryopreservation, and studies that investigated the outcomes from OTC without reporting the proportion of women who returned for AOTT were excluded. Furthermore, we excluded studies in languages other than English, abstracts without full text, letters to the editor, and case series involving fewer than 25 females undergoing OTC. Systematic reviews were screened for relevant references but not included in data extraction.\nWe developed the search strategy by combining search terms relating to FP, OTC and return rates in collaboration with a health science librarian, who specializes in systematic review searching. No filters or limits were used. The last search was run on 11 March 2025. We manually screened reference lists of selected studies for additional relevant articles. The following search strategy was conducted for the PubMed Search:\n(((“Fertility Preservation”[Mesh]) OR (“fertility preser*”[Title/Abstract])) AND (((ovar*[Title/Abstract]) AND (cryopreserv*[Title/Abstract])) OR ((“Cryopreservation”[Mesh]) AND (“Ovary”[Mesh])))) AND (((((((outcome*[Title/Abstract]) OR (“return rate*”[Title/Abstract])) OR (retransplant*[Title/Abstract])) OR (“autologous transplant*”[Title/Abstract])) OR (autotransplant*[Title/Abstract])) OR (transplant*[Title/Abstract])) OR (“Transplantation”[Mesh]))\nFor additional strategies, see  Supplementary Table S1 .\nWe imported the search results to Covidence (Veritas Health Innovation, Melbourne, Australia) to facilitate deselection of data duplicates, and the collaboration between reviewers regarding the screening process. Four reviewers took part in the screening process (A.M.Y., L.B.C., A.S.J., and K.T.M.). Each study was evaluated independently by two reviewers who were blinded to each other’s choices. Studies were screened according to relevance regarding the topic, content, and inclusion/exclusion criteria. In case of disagreement between reviewers in any point during the screening process, consensus was reached either through discussion or by consulting a third reviewer. In cases where more than one study was published using the same population or dataset, the most recent publication was included, and the other study/studies were excluded at the full-text screening stage due to ‘data duplication’. The study selection process is depicted in the PRISMA flowchart ( Fig. 1 ).\nFlow-chart for the study inclusion in a systematic review on the return rates for the use of cryopreserved ovarian tissue .\nA data extraction template was developed and agreed on by all reviewers. Data were extracted by one reviewer (A.M.Y.) and validated by a second reviewer (K.T.M.). From each included study, we extracted the following information: author, year of publication, title, country of publication, study design, and outcome details including the number of females receiving OTC prior to gonadotoxic treatment and the number of women returning for AOTT. When available, we also extracted the following data: age at OTC and AOTT, indication for OTC and AOTT, time interval from OTC to AOTT, follow-up time, proportion of participants aged ≥18 years at the end of follow-up (EOF), and the number of women lost to follow-up and mortality during the study period.\nWe performed a synthesis by summarizing the results through text and tables following the Synthesis Without Meta-Analysis (SWiM) in systematic reviews: reporting guideline ( Campbell  et al. , 2020 ). The outcome metric was the proportion of women who underwent AOTT among those who had their tissue cryopreserved (AOTT:OTC), presented as percentage. We generated a Forest plot ( Fig. 2 ) using the statistical software R (version 4.4.1; R Foundation for Statistical Computing, Vienna, Austria), including all eligible studies, illustrating the prevalence of the utilization rate with 95% CIs. Due to differences between children and adults (indications for OTC, risk of POI following gonadotoxic treatment, and the number of participants who were old enough to undergo AOTT or expressing a desire for pregnancy at the EOF), studies were grouped by age at OTC (children, adults, or both) within  Table 1 ,  Supplementary Table S2 , and  Fig. 2 . Due to substantial heterogeneity in study characteristics (age at OTC and AOTT, follow-up time, indications for OTC) we did not perform a meta-analysis, as it would not yield a meaningful summary estimate.\nForest plot of the return rates for the use of ovarian tissue cryopreserved prior to gonadotoxic treatment . Prevalence of women returning for autotransplantation out of those who had their tissue frozen with corresponding 95% CIs.\nStudy characteristics and results: return rates for the use of ovarian tissue cryopreserved prior to gonadotoxic treatment.\nBiasin  et al. , 2015\nItaly\n‘Ovarian tissue cryopreservation in girls undergoing hematopoietic stem cell transplant: Experience of a single center’\nDesign:  cohort study\nTime period of OTC:  August 2000–September 2013\nCohort:  n=47\nAge at OTC:  median age 13 years (range 2.7–20.3 years)\nPre-pubertal: n=24 (51%)\nPubertal: n=23 (49%)\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  Median age at last follow-up was 18.6 years (range 5.46–29.36 years)\nLost to FU and mortality during the study period:  deceased: n=7\nReason for OTC:  HSCT (Diamond-Blackfan anemia (n=1), Ewing sarcoma (n=3), immunodeficiency (n=2), AML (n=11), ALL (n=14), CML (n=5), non-Hodgkin lymphoma (n=2), MDS (n=2), thalassemia (n=7)).\nReason for AOTT:  not specified\nOTC:  n=47\nAOTT:  n=1 (2%)\nGrellet-Grün  et al. , 2023\nFrance\n‘A 16-year biocentric retrospective analysis of ovarian tissue cryopreservation in pediatric units: indications, results, and outcome’\nDesign:  retrospective cohort study\nTime period of OTC:  January 2004–May 2020\nCohort:  n=72\nAge at OTC:  mean age 9.3 years (range 0.2–17 years)\nPre-pubertal: n=51\nPost-pubertal: n=21\nTime from OTC to AOTT:  14 years\nProportion of participants aged ≥18 years at EOF:  14:72 ≥18 years (19%), 5:72 ≥23 years (7%)\nLost to FU and mortality during the study period:  deceased: n=15\nReason for OTC:  malignant disease: n=51 (70.8%) (malignant hematological diseases n=25 (35%), solid malignant tumors n=26 (36%)).\nnonmalignant disease: 21 (29.1%) (Hemoglobinopathies n=15 (21%), other non-malignant diseases n=6 (8%)).\nReason for AOTT:  not specified\nOTC:  n=72\nAOTT:  n=1 (1.4%)\nPoirot  et al. , 2019\nFrance\n‘Ovarian tissue cryopreservation for fertility preservation in 418 girls and adolescents up to 15 years of age facing highly gonadotoxic treatment. Twenty years of experience at a single center’\nDesign:  retrospective cohort study\nTime period of OTC:  April 1998–December 2018\nCohort:  n=418\nAge at OTC:  ≤15 years\nmedian age 6.9 years (range 0.3–15 years)\n<10 years: n=278 (66.5%)\n<5 years: n=150 (35.9%)\nTime from OTC to OTT:  not specified\nProportion of participants aged ≥18 years at EOF:  n=149\nLost to FU and mortality during the study period:  deceased: n=84 (20.1%)\nReason for OTC:  malignant diseases: n=313 (74.8%) (hematological malignancy n=97 (23.2%), solid tumor n=218 (51.7%))\nnon-malignant diseases: n=105 (25.2%) (hemoglobinopathies n=71 (68.9%)).\nReason for AOTT:  restore endocrine function: n=1\nrestore fertility: n=2\nOTC:  n=418\nAOTT:  n=3 (0.7%)\nLeflon  et al. , 2022\nFrance\n‘Experience, and gynecological and reproductive health follow-up of young adult women who have undergone ovarian tissue cryopreservation’\nDesign:  retrospective observational cohort study\nTime period of OTC:  2004–2018\nCohort:  n=113\nAge at OTC:  ≥18 years, mean age 29.5±4.8 years (range 18–37 years)\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  100%\nLost to FU and mortality during the study period:  deceased: n=14 (12%)\nReason for OTC:  hematological pathologies: n=49 (43%) (lymphoma n=36 (32%), leukemia n=6 (5%), non-malignant hematological disease requiring HSCT n=7 (6%)), breast cancer: n=34 (30%), gastrointestinal malignancies: n=8 (7%), sarcoma: n=5 (4%), gynecological malignancies n=4 (4%), larynx cancer: n=1 (0.9%), non-malignant disease requiring chemotherapy or radiotherapy: n=5 (4%), benign and borderline ovarian pathologies: n=7 (6.2%))\nReason for AOTT:  not specified\nOTC:  n=113\nAOTT:  n=9 (8.0%)\nBarral  et al. , 2024\nSpain\n‘Current status of fertility preservation in a Spanish tertiary public hospital: multidisciplinary approach and experience in over 1500 patients’\nDesign:  retrospective cohort study\nTime period of OTC:  2006–2022\nCohort:  n=703 (OTC: 115, OC: 304, GnRH agonist: 175, fertility sparing treatments for gynecological cancer: 109)\nAge at OTC:  mean age of the entire cohort: 31.8 years (range 16–40 years).\nTime from OTC to OTT:  mean 6.17 years\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: 15:115 (13%)\nReason for OTC (diagnoses):  breast cancer: 81%\nReason for AOTT:  not specified\nOTC:  n=115\nAOTT:  n=11 (9.5%)\nDiaz-Garcia  et al. , 2018\nSpain\n‘Oocyte vitrification versus ovarian cortex transplantation in fertility preservation for adult women undergoing gonadotoxic treatments: a prospective cohort study’\nDesign:  prospective cohort study\nTime period of OTC:  2005–2015\nCohort:  n=800 OTC (+1024 OV)\nAge at OTC:  28.2 years (±7.3 years)\nTime from OTC to AOTT:  mean storage time 5.5 years\nProportion of participants aged ≥18 years at EOF:  100%\nLost to FU and mortality during the study period:  not specified\nReason for OTC:  breast cancer: n=431 (53.9%), Hodgkin lymphoma: n=159 (19.9%), non-Hodgkin lymphoma: n=24 (3%), gynecological malignancies: n=25 (3.1%), sarcoma: n=52 (6.5%), leukemia: n=54 (6.8%), autoimmune disease: n=20 (2.5%), other solid organ tumors: n=35 (4.4%)\nReason for OTT:\nseeking pregnancy: n=44 (88%)\nendocrine purposes: n=6 (12%)\nOTC:  n=800\nAOTT:  n=50 (6.2%)\nKristensen  et al. , 2021\nDenmark\n‘Use of cryopreserved ovarian tissue in the Danish fertility preservation cohort’\nDesign:  retrospective cohort study\nTime period of OTC:  1999–2020\nCohort:  n=1186\nAge at OTC entire cohort:  mean age 25.1 years (±9 years), ranging from 4 months to 43 years.\n≤18 years: n=242 (21%)\n19–34 years: n=833 (70%)\n≥35: n=111 (9%)\nSubgroup 1: 24.6 years (±9 years)\nAge at AOTT:  not specified\nTime from OTC to AOTT: m ean storage time 4.3 years\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:\ndeceased total number: n=142 (12%)\ndeceased subgroup 1: n=135 (18%)\ndonated tissue for science: n=72 (6%)\nFU time:  Mean FU time was 8 years (entire cohort).\nMean FU time in subgroup 1 was 10.9 years, minimum 5 years\nReason for OTC:  malignant indications: breast cancer (38%), malignant hematologic diseases (25%) (lymphoma 18%, leukemia 7%), sarcoma (8%), gynecological malignancies (8%), neurological malignancies (5%), gastrointestinal malignancies (3%), other malignant diseases (e.g. kidney, nasopharyngeal cancer (1%))\nbenign indications, 12%: benign hematological diseases (5%), systemic diseases (rheumatologic and autoimmune disease (3%)), genetic diseases (2%).\nReason for AOTT:  achieve pregnancy: n=106\nrestore hormone production: n=10\ninduce puberty: n=1\nEntire cohort:\nOTC:  n=1186\nAOTT:  n=117 (10%)\nSubgroup 1:\nOTC:  n=759\nAOTT:  n=104 (14%)\nSubgroup 2\nOTC:  n=554\nAOTT:  n=103 (19%)\nSubgroup 1: >5 years FU\nSubgroup 2: alive and aged >24 years in July 2020\nJadoul  et al. , 2017\nBelgium\n‘Efficacy of ovarian tissue cryopreservation for fertility preservation: lessons learned from 545 cases’\nDesign:  retrospective cohort study\nTime period of OTC:  1997–2013\nCohort:  n=545\nAge at OTC:  ≤35 years.\nmean age 22.3±8.8 years (range 6 months–39 years)\n≤18 years: n=157 (29%)\nprepubertal: n=80 (15%)\n>18 to ≤35: n=388 (71%)\nAge at OTT:  not specified\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:\ndeceased: n=54 (10%)\nReason for OTC:  lymphomas (23%), leukemia (9%), benign hematological pathologies requiring bone marrow transplantation (3%), breast cancer (17%), sarcoma (9%), gynecological malignancies (6%), neurological malignancies (5%), gastrointestinal malignancies (3%), systemic diseases requiring chemotherapy (2%), benign and borderline ovarian pathologies (17.5%), genetic risk of POI (turner syndrome, family history of early menopause or galactosemia) (3.5%)\nReason for AOTT:  not specified\nOTC:  n=545\nAOTT:  n=21 (3.9%)\nRodriguez-Wallberg  et al. , 2019\nSweden\n‘A prospective study of women and girls undergoing fertility preservation due to oncologic and non-oncologic indications in Sweden-Trends in patients’ choices and benefit of the chosen methods after long-term follow up’\nDesign:  prospective cohort study\nTime period of OTC:  1998–2018\nCohort of women receiving FP counselling:  n=1254\nadults: n=1076\nchildren: n=178\nAge at OTC:\nadult women, n=221: mean age 28.1 years (range 18–39 years)\npost-pubertal teenagers, n=66: mean age 15.6 years (range 14–17 years)\npre-pubertal, n=48: mean age 11.2 years (range 3–13 years)\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:\ndeceased: n=97:1254 (7.7%)\nemigrated: n=18:1254 (1.4%)\nReason for FP counselling (entire cohort of women receiving FP counselling):\nmalignant diseases: n=852\nbenign diseases: n=402\nReason for AOTT:  not specified\nOTC:  n=335\nAOTT:  5%\nSchallmoser  et al. , 2023\nGermany\n‘Cryostorage of human ovarian tissue: evaluating the storage and disposal pattern over a 22-year period in 2475 patients’\nDesign:  retrospective cohort study\nTime period of OTC:  2000–2021\nCohort:  n=2475\nAge at OTC:  median age 28 years (min–max 0–44)\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: n=152\nFU Time:  FU-time was depicted as storage duration (years):\n≥5 years active storage: n=661 (median storage duration 7.4 years) (range 5–16.3 years)\n≥10 years active storage: n=148 (median storage duration 11.9 years) (range 10–16.3 years)\nEnded storage: n=1155 (median storage duration 3.8 years) (range 0–19.1 years)\nReason for OTC:  hematological malignancies: n=60 (8.4%), brain and nervous system: n=72 (2.9%), sarcoma: n=146 (5.9%), gynecological tumors: n=162 (6.5%, breast cancer: n=1108 (44.8%), lymphoma: n=555 (22.4%), Others: n=207 (8.4%)\nnon-specified: 165 (6.7%))\nReason for OTT:  not specified\nOTC:  n=2475\nAOTT:  n=124 (5%)\nTanbo  et al. , 2015\nNorway\n‘Autotransplantation of cryopreserved ovarian tissue after treatment for malignant disease—the first Norwegian results’\nDesign:  retrospective cohort study\nTime period of OTC:  2004–2014\nCohort:  n=164\nAge at OTC:  ≤35 years\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: n=15\nReason for OTC:  breast cancer: 40%, lymphomas: 25%, sarcomas: 15%, other malignant or benign conditions: 20%.\nReason for AOTT:  not specified\nOTC:  n=164\nAOTT:  n=2 (1.2%)\nHoekman  et al. , 2020\nNetherlands\n‘Ovarian tissue cryopreservation: Low usage rates and high live-birth rate after transplantation’\nDesign:  retrospective cohort study\nTime period of OTC:  2002–2015\nCohort:  n=69\nAge at OTC:  ≤36 years\nmean age 24 years (range 10.2–35.7 years)\n<18 years: n=19\n≥18: n=50\nTime from OTC to OTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: n=12 (17.4%)\nReason for OTC:  malignant diagnoses: n=56 (81.2%) (breast cancer n=25 (36.2%), other malignant diseases n=31 (44.9%))\nbenign indications: n=13 (18.9%)\nReason for AOTT:  not specified\nOTC:  n=69\nAOTT:  n=6 (8.7%)\nImbert  et al. , 2014\nBelgium\n‘Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis’\nDesign:  retrospective cohort study\nTime period of OTC:  March 1999–June 2011\nCohort:  n=225\nAge at OTC:  ≤36 years\naged 0.8–17 years: n=45 (20%)\naged ≥18 years: n=180 (80%)\nTime from OTC to OTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: n=28\nReason for OTC:\nprepubertal (n=27): hematological benign diseases (58%), lymphoma (4%), leukemia (27%), solid tumor (7%), immunological diseases (4%)\npost-pubertal (n=198): breast cancer (43%), lymphoma (22%), leukemia (6%), ovarian borderline tumor (8%), solid tumor (7%), pelvic tumor (8%), immunological disease (5%), hematological benign disease (1%)\nReason for AOTT:  not specified\nOTC:  n=225\nAOTT:  n=8 (3.6%)\nHulsbosch  et al. , 2018\nBelgium\n‘A real-life Analysis of Reproductive Outcome after Fertility Preservation in Female Cancer Patients’\nDesign:  retrospective cohort study\nTime period of OTC:  January 1999–December 2011\nCohort:  n=159\nAge at OTC:  post-menarche women, mean age 23 years (range 11–37 years)\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: n=15 (23%)\nReason for OTC:  based on the entire cohort (66 had OTC, the rest had GnRH agonist treatment only): hematological cancer: n=77 (48.4%), gynecological cancer: n=48 (30.2%), soft tissue sarcoma: n=16 (10.1%), gastro intestinal cancer: n=6 (3.8%), miscellaneous: n=12 (7.5%) (neuroblastoma, medulloblastoma, thymoma, adrenocortical carcinoma, glioma, mesothelioma)\nReason for AOTT:  not specified\nOTC:  n=66\nAOTT:  n=1 (1.5%)\nFabbri  et al ., 2022\nItaly\n‘Ovarian tissue cryopreservation and transplantation: 20 years experience in Bologna University’\nDesign:  retrospective cohort study\nTime period of OTC:  January 2002–January 2022\nCohort:  n=1026\nAge at OTC:  2–38 years\n≤17 years: 238 (23.2%) (group 1)\n18–38 years: 788 (76.8%) (group 2)\nmean age ±SD:\ngroup 1: 12.9 ± 4.14\ngroup 2: 28.0 ± 5.7\nTime from OTC to AOTT:  mean storage time 7.48 years ±3.5 years (range 2–17 years)\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: n=68 (6.6%) (group 1: n=27, group 2: n=41).\nReason for OTC:  malignant diseases: n=930 (91%) (lymphomas: n=419, leukemias: n=30, myelodysplasia: n=13, breast cancers: n=260, sarcomas: n=101, neurological malignancies: n=39, gastrointestinal malignancies: n=26, gynecological malignancies: n=22, Wilms tumor: n=9, others: n=11)\nnon-malignant diseases: n=96 (9%) (genetic diseases: n=52, autoimmune diseases: n=17, others: n=27)\nReason for OTT:\nrestore-and or improve ovarian function and seek pregnancy: n=20\nrestore steroidogenesis: n=4\nOTC:  1026\nAOTT:  24 (2.3%)\nSilber  et al. , 2022\nUSA\n‘ In vitro  maturation and transplantation of cryopreserved ovary tissue: understanding ovarian longevity’\nDesign:  retrospective cohort study\nTime period of OTC:  1997–2020\nCohort:  n=119\nAge at OTC:  1–42 years\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  not specified\nReason for OTC:\ncancer: n=85\npremature ovarian failure: n=8\nsocial reasons: n=13\nothers (turner syndrome, endometriosis, MS, aplastic anemia, massive ovarian bilateral teratoma or a daughter born with no ovary)\nReason for AOTT:  not specified\nOTC:  n=119\nOTT:  n=17 (14%)\nChoi  et al. , 2022\nKorea\n‘The experience of Fertility Preservation in a Single Tertiary Center in Korea’\nDesign:  retrospective cohort study\nTime period of OTC:  2010–October 2021\nCohort:  n=26\nAge at OTC:  11–41 years\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  not specified\nReason for OTC:  breast cancer n=2 (7.7%), hematologic cancer n=5 (19.2%), gynecologic cancer n=9 (34.6%), gastrointestinal cancer n=1 (3.9%), other malignancy n=5 (19.2%), benign ovarian cyst n=1 (3.9%), impending POI n=3 (11.5%)\nReason for OTT:  not specified\nOTC:  n=26\nOTT:  n=1 (3.8%)\nSánchez  et al. , 2008\nValencia\n‘The Valencia Programme for Fertility Preservation’\nDesign:  cohort study\nTime period of OTC:  not specified\nCohort:  n=200\nAge at OTC:  mean age 28.2 years (range 11–39 years)\nTime from OTC to OTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  not specified\nReason for OTC:  breast cancer: 55%, HD: 25%\nother malignant or non-malignant diseases: 20% (colorectal carcinoma, sarcoma, glomerulonephritis, cancer, lupus, other)\nReason for AOTT:  not specified\nOTC:  n=200\nAOTT:  4 (2%)\nOktay and Oktem, 2010\nUSA\n‘Ovarian cryopreservation and transplantation for fertility preservation for medical indications: report of an ongoing experience’\nDesign:  prospective longitudinal analysis\nTime period of OTC:  May 1997–March 2008\nCohort:  n=59\nAge at OTC:  mean age 26.7 years (±1.2 years) (range 4–44 years)\n0–18 years: 19%\n19–29 years: 42%\n30–39 years: 31%\n40–44 years: 8%\nTime from OTC to AOTT:  6 months–2 years\nProportion of participants aged ≥18 years at EOF:  pre-pubertal at FU: n=3\nLost to FU and mortality during the study period:  deceased: n=4 (8%)\nReason for OTC:  breast cancer: 22%, Hodgkin disease: 21%, non-Hodgkin lymphoma: 10.2%, acute myelitic leukemia: 10.2%, acute lymphocytic leukemia: 5.1%, early ovarian carcinoma: 5.1%, endometrial carcinoma: 3.4%, cervical carcinoma: 3.4%, others: 20.3% (aplastic anemia, diamond-blackfan syndrome, myelodysplasia, thalassemia major, hemophagocytic lymphohistiocytosis, lupus nephritis, ependymoma, synovial sarcoma, mosaic karyotype, vanishing bone disease, endometriosis, oophorectomy for dermoid cysts)\nReason for AOTT:  not specified\nOTC:  n=59\nAOTT:  n=3 (5%)\nDelattre  et al. , 2020\nBelgium\n‘Combining fertility preservation procedures to spread the eggs across different baskets: a feasibility study’\nDesign:  retrospective observational study\nTime period of OTC:  January 2012–December 2018\nCohort:  n=207\nAge at OTC:\nprepubertal: n=13\nOTC (n=4) mean age ±SD: 5.5 years (±7.1)\nOTC + OTO–IVM (n=9) mean age ±SD: 5.1 years (± 3.6)\npost-pubertal: n=55\nOTC + OTO–IVM (n=24) mean age ±SD: 27.9 years (±6.6)\nOPU–IVM + OTC + OTO–IVM (n=17) mean age ±SD: 25.9 years (± 4.8)\nOTC + OTO–IVM COS (n=13) mean age ± SD: 26.2 years (± 4.3)\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  not specified\nReason for OTC based on the entire cohort of the study:  breast cancer n=95, hematological cancer n=43, gynecological cancer n=31, neurological cancer n=18, colorectal cancer n=6, sarcoma n=8, other types, n=6.\nReason for AOTT:  not specified\nOTC:  n=68\nAOTT:  n=2 (2.9%)\nYap and Davies, 2007\nUK\n‘Fertility preservation in female cancer survivors’\nDesign:  retrospective cohort study\nTime period of OTC:  March 1995–March 2005\nCohort:  37\nAge at OTC:  mean age 27.0 years (range 2–42)\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: n=4\nReason for OTC (diagnoses):  breast cancer: n=14 (37.8%), gynecological cancer: n=9 (24.3%), other solid: n=2 (5.4%), hematological cancer: n=6 (16.2%), solid cancer child: =1 (2.7%)\nReason for AOTT:  not specified\nOTC:  n=37\nAOTT:  n=0 (0%)\nTakae  et al. , 2024\nJapan\n‘Survey on the implementation status and reproductive outcomes of oocyte and ovarian tissue cryopreservation in Japan: Historical comparison with nationwide surveys’\nDesign:  mailed-in questionnaire survey\nTime period of OTC:  December 2016–December 2020\nCohort:  n=198\nAge at OTC (for the ones receiving OTT):  mean age 36±3.9 years\nTime from OTC to AOTT:  Average 5±1.6 years (median, 5 years)\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  not specified\nReason for OTC:  not specified\nReason for AOTT:  not specified\nOTC:  n=198\nAOTT:  n=9 (4.5%)\nTakae  et al. , 2022\nJapan\n‘A practical survery of fertility preservation treatments in the startup phase in Japan’\nDesign:  mailed-in questionnaire survey\nTime period of OTC:  January 2006–November 2016\nCohort:  n=201\nAge at OTC:  mean age 29.7 ± 8.3 years (range 5–46 years).\n<10: n=3\n11–15: n=23\n16–20: n=17\n21–25: n=26\n26–30: n=37\n31–35: n=57\n36–40: n=33\n41–45: n=4\n46–50: n=1\n<15 years: 12.9%\nTime from OTC to AOTT:  not specified\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: n=14 (7%)\nReason for OTC (diagnoses):  breast cancer: n=89, malignant lymphoma: n=19, leukemia: n=18, bone and soft tissue tumor: n=8, brain tumor: n=7, ovarian tumor: n=7, uterine cervical cancer: n=7, autoimmune disease: n=7, myelodysplastic syndrome: n=5, ovarian cancer: n=5, ovarian tumor: n=5, endometrial cancer: n=5, ewing sarcoma: n=4, aplastic anemia: n=3, other hematological diseases: n=2, kidney cancer: n=2, colon cancer: n=2, others: n=7\nReason for AOTT:  not specified\nOTC:  n=201\nAOTT:  n=3 (1.4%)\nFinkelstein  et al. , 2025\nAustralia\n‘Pregnancy outcomes following ovarian tissue cryopreservation: an Australian cohort study’\nDesign:  retrospective cohort study\nTime period of OTC:  1995–2022\nCohort:  n=593\nAge at OTC:  mean age 27.2 years (SD 7.3) (range 9–44 years)\nTime from OTC to AOTT:  8.8 years (mean age at OTT 36.0 years)\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  deceased: n=107 (18.0%)\nReason for OTC:  transplant: solid tumor cancer 24:48 (50.0%), hematological cancer 13:48 (27.1%), autoimmune disorder 6:48 (12.5%), benign gynecological disorder 2:48 (4.2%), other benign disease 2:48 (4.2%), other cancer 1:48 (2.1%)\nnon-transplant: solid tumor cancer 275:545 (50.5%), hematological cancer 171:545 (31.4%), autoimmune disorder 24:545 (4.4%), benign gynecological disorder 21:545 (3.9%), other benign disease 21:545 (3.9%), other cancer 21:545 (3.9%), genetic disorder 8:545 (1.5%), donor 3:545 (0.6%), not reported 1:545 (0.2%)\nReason for AOTT:  not specified\nOTC:  n=593\nAOTT:  n=48 (8.1%)\nBeckmann  et al. , 2018\nFertiProtekt (Germany, Austria, Switzerland)\n‘Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue’\nDesign:  retrospective cohort study\nTime period of OTC:  2007–2016\nCohort:  n=1302\nReason for AOTT:  not specified\nAge at OTC:  not specified\nTime from OTC to AOTT:  average storage time: 3 years\nProportion of participants aged ≥18 years at EOF:  not specified\nLost to FU and mortality during the study period:  not specified\nReason for OTC:  breast cancer: n=552 (42.4%), Hodgkin’s disease: n=282 (21.7%), sarcoma: n=65 (5%), non-Hodgkin’s lymphoma: n=44 (3.4%), leukemia: n=40 (3.1%), cervical carcinoma: n=28 (2.2%), ovarian germ cell tumor: n=24 (1.8%), central nervous system tumors: n=16 (1.2%), rectal carcinoma: n=15 (1.2%), ovarian borderline tumor: n=14 (1.1%), ovarian carcinoma: n=14 (1.1%), anal carcinoma: n=5 (0.4%), vulvar carcinoma: n=4 (0.3%), gastric carcinoma: n=4 (0.3%), colon carcinoma: n=3 (0.2%), peritoneal carcinoma: n=3 (0.2%), endometrial carcinoma: n=2 (0.2%), renal cell carcinoma: n=2 (0.2%), chordoma: n=2 (0.2%), melanoma: n=1 (0.1%), carcinoma of unknown primary: n=1 (0.1%), synovial carcinoma: n=1 (0.1%), cholangiocarcinoma: n=1 (0.1%), carcinoma of the tongue: n=1 (0.1%), hydatiform mole: n=1 (0.1%), pharyngeal carcinoma: n=1 (0.1%), unavailable details on diagnoses: n=89 (6.8%)\nBenign disease: n=85 (6.5%)\nOTC:  n=1302\nAOTT:  n=58 (4.5%)\nOTC, ovarian tissue cryopreservation; AOTT, autologous ovarian tissue transplantation; EOF, end of follow-up; FU, follow-up; FP, fertility preservation; HSCT, hematopoietic stem cell transplantation; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; CML, chronic myeloid leukemia; MDS, myelodysplastic syndrome; OV, oocyte vitrification; OTO–IVM, ovarian tissue oocyte– in vitro  maturation; OPU–IVM, oocyte pick-up– in vitro  maturation; COS, controlled ovarian stimulation.\nWe assessed risk of bias for each included study using the Joanna Briggs Institute (JBI) Cohort Checklist. Although most of the included studies primarily investigated outcomes related to FP treatment success (e.g. pregnancy rate), secondary data on the return rate for the use of cryopreserved ovarian tissue were extracted for the purpose of this review. Risk of bias for this outcome was therefore assessed using the JBI Critical Appraisal Checklist for Cohort Studies, which is appropriate for evaluating studies reporting descriptive data on prevalence or return rates ( Joanna Briggs Institute, 2020 ). The overall certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE), considering risk of bias, inconsistency, indirectness, imprecision, and publication bias.\n\nAfter screening 2748 studies on title abstract and 94 studies on full text, 25 studies were found eligible for inclusion. The study selection process is depicted in the PRISMA flow chart ( Fig. 1 ). All studies were cohort studies.  Supplementary Tables S2 and S3  present the Risk of Bias Assessment according to JBI Critical Appraisal Checklist for Cohort Studies and quality assessment according to GRADE, respectively. Unspecified or insufficient follow-up time was a possible source of bias in all included studies ( Supplementary Table S2 ). Some studies addressed this limitation through sensitivity analyses. For example, Kristensen  et al.  performed sensitivity analysis by stratifying the population by >5 years of follow-up (subgroup 1) and by >5 years of follow-up, alive and aged >24 years (subgroup 2) ( Kristensen  et al. , 2021 ). The overall quality of the studies in reporting the return rate for the use of cryopreserved ovarian tissue was moderate ( Supplementary Table S3 ).\nTable 1  provides an overview of the study characteristics and outcomes across the 25 included studies. The studies were largely heterogeneous regarding cohort size, time period during which OTC was performed, indication for OTC, age at the time of OTC, and follow-up time.\nThe number of females undergoing OTC varied substantially across the included studies, ranging from 26 participants in the smallest study ( Choi  et al. , 2022 ), to 2475 in the largest ( Schallmoser  et al. , 2023 ). Three studies reported cohorts of ≤50 ( Yap and Davies, 2007 ;  Biasin  et al. , 2015 ;  Choi  et al. , 2022 ). Five reported cohorts of >50–100 ( Oktay and Oktem, 2010 ;  Hulsbosch  et al. , 2018 ;  Delattre  et al. , 2020 ;  Hoekman  et al. , 2020 ;  Grellet-Grün  et al. , 2023 ). Six reported cohorts of >100–200 ( Sánchez  et al. , 2008 ;  Tanbo  et al. , 2015 ;  Leflon  et al. , 2022 ;  Silber  et al. , 2022 ;  Barral  et al. , 2024 ;  Takae  et al. , 2024 ). Three studies reported cohorts of >200–400 participants ( Imbert  et al. , 2014 ;  Rodriguez-Wallberg  et al. , 2019 ;  Takae  et al. , 2022 ), and another three reported cohorts of >400–600 ( Jadoul  et al. , 2017 ;  Poirot  et al. , 2019 ;  Finkelstein  et al. , 2025 ). One study reported a cohort of 800 participants ( Diaz-Garcia  et al. , 2018 ). Additionally, three reported cohorts of >1000–1500 ( Beckmann  et al. , 2018 ;  Kristensen  et al. , 2021 ) and one reported a cohort of >2000 ( Schallmoser  et al. , 2023 ). All OTC procedures were performed between 1999 and 2022. In all studies, OTC was performed for both malignant and benign indications; however, malignant disease made up the more frequent indication for OTC. Fabbri  et al.  reported that among 1026 patients who underwent OTC, 91% (n = 930) did so for malignant indications, whereas 9% (n = 96) did so for non-malignant indications ( Fabbri  et al ., 2022 ), while Beckmann  et al.  reported that only 6.3% of the women had their tissue frozen for benign indications ( Beckmann  et al. , 2018 ) ( Table 1 ). The age at OTC ranged from 0 to 44 years. Three studies included only pediatric patients (aged ≤20 years at OTC) ( Biasin  et al. , 2015 ;  Poirot  et al. , 2019 ;  Grellet-Grün  et al. , 2023 ), three studies included only adolescent and adult patients (≥16 years) ( Diaz-Garcia  et al. , 2018 ;  Leflon  et al. , 2022 ;  Barral  et al. , 2024 ), 18 studies included both pediatric and adult patients at the time of OTC ( Yap and Davies, 2007 ;  Sánchez  et al. , 2008 ;  Oktay and Oktem, 2010 ;  Imbert  et al. , 2014 ;  Tanbo  et al. , 2015 ;  Jadoul  et al. , 2017 ;  Hulsbosch  et al. , 2018 ;  Rodriguez-Wallberg  et al. , 2019 ;  Delattre  et al. , 2020 ;  Hoekman  et al. , 2020 ;  Kristensen  et al. , 2021 ;  Choi  et al. , 2022 ;  Silber  et al. , 2022 ;  Takae  et al. , 2022 ,  2024 ;  Schallmoser  et al. , 2023 ;  Finkelstein  et al. , 2025 ), and 1 study did not specify the age of the patients at the time of OTC ( Beckmann  et al. , 2018 ).\nIn most included studies, the follow-up time was not clearly defined but occurred within the overall time frame of the study ( Table 1 ). For example, an Australian study by Finkelstein  et al. , which assessed return rates among women who underwent OTC between 1995 and 2022, reported that 48 of 593 women had returned for OTT (8.1%). However, the follow-up duration was not specified ( Finkelstein  et al. , 2025 ). Except from one study that reported a minimum follow-up duration of ≥3 years after primary cancer treatment ( Hulsbosch  et al. , 2018 ), none of the other studies reported a defined overall minimum follow-up duration ( Table 1 ). Most studies did not account for patient mortality when calculating overall return rates; however, in one study, the overall return rate was calculated as the proportion of women who returned out of those who were alive ( Rodriguez-Wallberg  et al. , 2019 ).\nThe return rate for use of cryopreserved ovarian tissue after completion of gonadotoxic treatment is depicted in the Forest plot ( Fig. 2 ) and ranged from 0% to 14%. Of the 25 studies, 18 reported a return rate of ≤5%, 6 reported a return rate of >5% to ≤10% while only 1 study reported a return rate of 14%.\nWhen stratified by age group at the time of OTC, studies including only pediatric patients reported return rates ranging from 0.7% to 2% ( Biasin  et al. , 2015 ;  Poirot  et al. , 2019 ;  Grellet-Grün  et al. , 2023 ), compared to return rates of 6.2–9.5% ( Diaz-Garcia  et al. , 2018 ;  Leflon  et al. , 2022 ;  Barral  et al. , 2024 ) in studies including only adolescents and adults (≥16 years).\n\nOverall, we found a low return rate of 0–14% after OTC, with most of the studies reporting return rates of ≤5%. In most studies, follow-up occurred within the time frame of the study, with only 8 studies explicitly reporting the follow-up duration, which ranged from 0 to 19.1 years ( Oktay and Oktem, 2010 ;  Biasin  et al. , 2015 ;  Diaz-Garcia  et al. , 2018 ;  Rodriguez-Wallberg  et al. , 2019 ;  Hoekman  et al. , 2020 ;  Leflon  et al. , 2022 ;  Grellet-Grün  et al. , 2023 ;  Schallmoser  et al. , 2023 ) ( Table 1 ). The reasons for the modest return rates can be manyfold. Key factors influencing the return rate for AOTT include: 1) length of follow-up, 2) need for AOTT (development of POI after OTC), 3) desire to undergo AOTT, and 4) the actual feasibility of AOTT, including mortality among those who had undergone OTC.\nSince AOTT may occur several years after OTC, limited follow-up time may bias the results. In all included studies, a subset of participants remained within reproductive age at EOF. Furthermore, most of the studies included both children and adults who underwent OTC and did not exclude individuals younger than 18 years of age at EOF when calculating return rates. Consequently, these analyses may underestimate true utilization rates by not accounting for participants who were not yet eligible for tissue transplantation (e.g. actively undergoing gonadotoxic therapy or in convalescence) or had not reached reproductive age or expressed a desire for pregnancy yet. Consistent with this,  Emrich  et al.  (2025)  examined storage patterns across age groups at the time of OTC and found that children and adolescents had a significantly higher proportion of active storage beyond 10 years compared with adults.\nThe risk of POI and infertility following cancer treatment depends, among others, on the type and cumulative dose of chemo and radiation therapy and therefore varies depending on the primary cancer diagnosis ( Schüring  et al. , 2018 ;  Van Den Berg  et al. , 2018 ). A substantial proportion of women who underwent OTC had been diagnosed with breast cancer. In the study by Schallmoser  et al ., women diagnosed with breast cancer accounted for 44.8% of patients who underwent OTC (1108 out of 2475), whereas in the study by Diaz-Garcia  et al ., it was 53.9% (431 out of 800) ( Diaz-Garcia  et al. , 2018 ;  Schallmoser  et al. , 2023 ). However, many clinics no longer offer OTC as the first choice of FP to women with breast cancer, partly because the likelihood of natural pregnancy after treatment in this patient group is high ( Partridge  et al. , 2023 ;  Magaton  et al. , 2025 ), and partly because oocyte or embryo cryopreservation provides additional benefits, such as the possibility of pre-implantation genetic testing (PGT) for individuals carrying BRCA 1/2 gene mutations ( Macklon and De Vos, 2024 ).\nIn a sub-analysis of a Danish cohort, Kristensen  et al . reported the use of cryopreserved ovarian tissue among patients who were alive and >24 years in 2020, stratified by diagnosis. They found a lower return rate among women diagnosed with breast cancer (18%) compared to that of women diagnosed with other malignant diseases (gastrointestinal malignancies (27%), gynecological malignancies (22%), sarcoma (21%)) ( Kristensen  et al. , 2021 ).\nYoung age at cancer treatment has a mitigating effect on the risk of POI ( Schüring  et al. , 2018 ;  Anderson  et al. , 2022 ) and therefore, utilization rate for AOTT may be higher among women diagnosed at a more advanced age. Kristensen et al. (2021) assessed the impact of age at the time of OTC on subsequent return rates. They found that women who underwent OTC aged ≥30 years had a return rate of 15%, nearly twice that of those aged 18–29 years (8%) ( Kristensen  et al. , 2021 ). In many facilities, OTC is recommended only for women aged <35 years ( Anderson  et al. , 2020 ), due to unfavorable results in those >35 years, and the lower risk of infertility after gonadotoxic treatment in younger patients may therefore also contribute to the overall low return rate. This may also partially explain the low return rates reported in studies that include only pediatric patients.\nPatients undergoing OTC for FP prior to gonadotoxic treatment may experience a change in their desire to have children following cancer treatment. For many cancer survivors, fear of disease recurrence is a significant concern and the possibility of bringing a child into the world who might lose a parent at an early age may also play an important role in their decision-making regarding attempts to conceive ( Liu  et al. , 2025 ). A Belgian study by Hulsbosch  et al . showed that among women in remission who had undergone OTC±GnRH agonist (n = 39), 46% (n = 18) expressed a desire for pregnancy, while 54% (n = 21) did not, after a minimum of 3-year follow-up ( Hulsbosch  et al. , 2018 ). A Danish study by Macklon  et al . found that among those who requested disposal of their cryopreserved ovarian tissue after an initial period of at least 5 years (17%), 19% did so because they decided not to have children ( Macklon  et al. , 2014 ). Furthermore, following a prolonged treatment period, often including both surgical and medical interventions, patients may be reluctant to undergo additional surgical procedures required for transplantation of the cryopreserved tissue. Schallmoser  et al . assessed the reason for ending storage among 224 patients who had undergone OTC for FP. They showed that 25.9% ended storage due to a lack of desire to have children, while 3.1% cited fear of future surgery as a reason. Additional reasons for discontinuing storage included pregnancy (natural or after IVF treatment), cancer recurrence, high storage costs, or patient death ( Schallmoser  et al. , 2023 ).\nThe low return rate, when reported without accounting for mortality, may be further influenced by the fact that some of the diagnoses associated with a high risk of infertility also carry a high mortality risk.  Macklon (2019)  found a mortality rate of 13% in a Danish cohort of 927 girls and women who underwent OTC with the most deaths observed in the group with upper gastro-intestinal cancers and sarcomas. Furthermore, oocyte and embryo cryopreservation have partly replaced OTC as preferred FP method in recent times ( Anderson  et al. , 2020 ). Consequently, OTC is increasingly offered only to women with limited time before starting chemotherapy, often due to advanced cancer progression. Therefore, women undergoing OTC for FP, particularly in more recent times, may have a worse prognosis, potentially reducing the number of women who survive long enough to utilize the cryopreserved tissue and thereby contributing to the lower observed return rates.\nThe return rate for the use of cryopreserved ovarian tissue varied substantially across included studies, possibly explained by the heterogeneity between studies including age at OTC, follow-up time, indications for OTC, and country of FP. Stratified by age at OTC, the utilization rate among patients who had their tissue frozen as children (range 0.7–2%) was lower compared to the rate among those who had their tissue frozen as adolescents and adults (range 6.2–9.5%). As return for AOTT may occur several years after OTC, the lower return rate observed among children may be partly explained by the fact that they have not yet reached reproductive age or have not yet expressed desire for childbearing by the end of the follow-up period. Further studies with extended follow-up duration are needed.\nFurthermore, in a Belgian study by Delattre  et al.,  OTC was performed in addition to either controlled ovarian stimulation (COS), oocytes retrieved from ovarian tissue  ex vivo  (OTO-IVM), or transvaginal retrieval of oocytes for IVM. Consequently, the return rate for utilization of the cryopreserved ovarian tissue may be lower in these patients as they would likely choose to use their cryopreserved oocytes or embryos first in order to avoid another surgical procedure ( Delattre  et al. , 2020 ). This may also apply to some of the other included studies, as it is unclear whether they exclusively had OTC performed or if other FP methods were used simultaneously.\nOverall, studies have reported higher return rates for the use of cryopreserved oocytes, embryos, and semen compared to OTC. A review by  Wnuk  et al . (2023)  found that return rates for the use of oocytes, embryos, and semen cryopreserved prior to gonadotoxic treatment ranged from 3.1% to 8.7%, 9% to 22.4%, and 2.6% to 21%, respectively.\nVariations among countries concerning patient-borne cost of the treatment may result in differences between populations receiving OTC and the length of storage. In countries where patients must cover the costs themselves, OTC is more likely to be pursued by women with a clear intention to undergo AOTT, if needed. In contrast, in countries where the procedure is offered to patients free of charge, a greater proportion of women may choose to undergo it as a precautionary measure, even though they may never use it. This may partly explain the high return rate in the study by  Silber  et al.  (2022) .\nCultural and religious variations between countries regarding whether women are reluctant to undergo AOTT if they are unmarried may also contribute to variations in return rates between countries. Studies have shown that cancer survivors are less likely to marry, compared to the general population, and they may therefore, in some countries, have a reduced likelihood of becoming mothers ( Syse, 2008 ;  Kirchhoff  et al. , 2012 ).\nFurthermore, eligibility criteria for OTC may vary between countries, influenced by disease severity and associated mortality risk. This is particularly important, as most studies do not account for mortality when reporting return rates.\nAlthough this systematic review is up to date and methodologically robust, with broad search criteria, it has several limitations. Many of the included studies either lack follow-up information or fail to specify a minimum follow-up duration. The studies are also heterogeneous in their populations, particularly regarding patient age. Moreover, standardized definitions of ‘return’ are absent. These limitations may contribute to underreporting and bias. Return rate was not the primary outcome of most of the included studies, and therefore, there is a risk of underreporting or inconsistent outcome ascertainment. This may influence the reliability of the prevalence estimates reported.\n\nDespite the common practice of offering OTC as FP, the low utilization rates highlight the need for careful consideration to avoid subjecting women to potentially unnecessary and costly treatment. The procedure diminishes the ovarian reserve and, like all surgical interventions, carries risks of complications such as infection and bleeding, that could, if severe enough, delay subsequent cancer treatment. Reassuringly, however, studies have shown a high satisfaction rate and a low complication rate ( Beckmann  et al. , 2018 ). On the other hand, the importance of the hope that OTC represents for the patients during a very difficult time should not be underestimated either ( Bach  et al. , 2020 ;  Bentsen  et al. , 2023 ). The overall modest return rates for the use of ovarian tissue cryopreserved prior to gonadotoxic treatment found in this study emphasize the importance of future studies with longer follow-up time to assess patterns of tissue utilization in relation to diagnosis, treatment protocol, and age thereby setting criteria in the selection of patients who would actually benefit from OTC.","source_license":"CC-BY-4.0","license_restricted":false}