Uterine cancer incidence is rising among reproductive-age women, highlighting a critical need for fertility-sparing treatment options. This review examines current practices for conservative management with fertility preservation in patients with uterine malignancies and aims to support clinicians in delivering patient-centered care in this evolving field. Ideal candidates are those with early-stage, low-grade endometrioid tumors. Hormonal therapies such as oral progestins and levonorgestrel intrauterine devices remain the mainstay of fertility-sparing treatment and can be combined with hysteroscopic resection to improve efficacy. Adjunctive agents and emerging therapies such as glucagon-like peptide-1 receptor agonists show promise, but further research is needed to clarify their role in treatment protocols. Surveillance involves regular endometrial sampling to monitor response and detect recurrence or progression. Fertility outcomes in patients opting for this treatment appear favorable, though recurrence risk remains significant. Definitive surgical management with hysterectomy and additional procedures as indicated is recommended after childbearing is complete. Multidisciplinary collaboration is essential in balancing oncologic safety with reproductive goals to ensure fertility-preserving care is a viable and safe option for patients with uterine cancer.
Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Uterine Cancer. National Cancer Institute. Updated 2024. Available from: https://seer.cancer.gov/statfacts/html/corp.html
2.
WijayabahuAT, ShielsMS, ArendRC, et al.Uterine cancer incidence trends and 5-year relative survival by race/ethnicity and histology among women under 50 years. Am J Obstet Gynecol, 2024; 231(5):526.e1-526–e22; doi: 10.1016/j.ajog.2024.06.026
3.
SuHI, LacchettiC, LetourneauJ, et al.Fertility Preservation in People With Cancer: ASCO Guideline Update. J Clin Oncol, 2025; 43(12):1488–1515.
4.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Uterine Neoplasms. Version 3.2025. Available from: https://www.nccn.org Published [Last accessed: March7, 2025].
5.
OgunbiyiMO, OxleyS, GrahamR, et al.The oncological and reproductive outcomes of fertility-preserving treatments for stage 1 grade 1 endometrial carcinoma: A systematic review and meta-analysis. J Obstet Gynaecol, 2024; 44(1):2294329; doi: 10.1080/01443615.2023.2294329
6.
RodolakisA, ScambiaG, PlanchampF, et al.ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma. Hum Reprod Open, 2023; 2023(1):hoac057; doi: 10.1093/hropen/hoac057
7.
FalconeF, Leone Roberti MaggioreU, Di DonatoV, et al.Fertility-sparing treatment for intramucous, moderately differentiated, endometrioid endometrial cancer: A Gynecologic Cancer Inter-Group (GCIG) study. J Gynecol Oncol, 2020; 31(5):e74; doi: 10.3802/jgo.2020.31.e74
8.
MaheshwariE, NougaretS, SteinEB, et al.Update on MRI in Evaluation and Treatment of Endometrial Cancer. Radiographics, 2022; 42(7):2112–2130; doi: 10.1148/rg.220070
9.
LakhmanY, KatzSS, GoldmanDA, et al.Diagnostic Performance of Computed Tomography for Preoperative Staging of Patients with Non-endometrioid Carcinomas of the Uterine Corpus. Ann Surg Oncol, 2016; 23(4):1271–1278; doi: 10.1245/s10434-015-4410-x
10.
YoshidaM, SaidaT, MoriK, et al.Comparison of preoperative diagnostic performance between dual-energy CT, conventional CT, and MRI in endometrial cancer. Pol J Radiol, 2024; 89:e358–e367; doi: 10.5114/pjr/189487
11.
RizzoS, FemiaM, RadiceD, et al.Evaluation of deep myometrial invasion in endometrial cancer patients: Is dual-energy CT an option? Radiol Med, 2018; 123(1):13–19; doi: 10.1007/s11547-017-0810-2
12.
ReiM, BernardesJF, CostaA. Ultrasound in endometrial cancer: Evaluating the impact of pre-surgical staging. Oncol Rev, 2025; 19:1446850; doi: 10.3389/or.2025.1446850
13.
AlcázarJL, GastónB, NavarroB, et al.Transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial infiltration in patients with endometrial cancer: A systematic review and meta-analysis. J Gynecol Oncol, 2017; 28(6):e86; doi: 10.3802/jgo.2017.28.e86
14.
MadárI, SzabóA, VleskóG, et al.Diagnostic Accuracy of Transvaginal Ultrasound and Magnetic Resonance Imaging for the Detection of Myometrial Infiltration in Endometrial Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel), 2024; 16(5):907; doi: 10.3390/cancers16050907
15.
PalmérM, ÅkessonÅ, MarcickiewiczJ, et al.Accuracy of transvaginal ultrasound versus MRI in the PreOperative Diagnostics of low-grade Endometrial Cancer (PODEC) study: A prospective multicentre study. Clin Radiol, 2023; 78(1):70–79; doi: 10.1016/j.crad.2022.09.118
16.
ArezzoF, FanizziA, MancariR, et al.A Radiomic-based model to predict the depth of myometrial invasion in endometrial cancer on ultrasound images. Sci Rep, 2025; 15(1):15901; doi: 10.1038/s41598-025-00906-6
17.
Ben DavidC, SieglerY, LinderR, et al.Screening and prevention of gynecologic malignancies in patients with lynch syndrome: Following the guidelines. Front Oncol, 2025; 15:1563022; doi: 10.3389/fonc.2025.1563022
18.
TanosP, DimitriouS, GulloG, et al.Biomolecular and Genetic Prognostic Factors That Can Facilitate Fertility-Sparing Treatment (FST) Decision Making in Early Stage Endometrial Cancer (ES-EC): A Systematic Review. Int J Mol Sci, 2022; 23(5):2653; doi: 10.3390/ijms23052653
19.
WangY, LaiT, ChuD, et al.The association of molecular classification with fertility-sparing treatment of atypical endometrial hyperplasia and endometrial cancer: A retrospective study. Front Oncol, 2025; 15:1506639; doi: 10.3389/fonc.2025.1506639
20.
LvX, GuoL, WangC. Efficacy of fertility-sparing treatment with LNG-IUS is associated with different ProMisE subtypes of endometrial carcinoma or atypical endometrial hyperplasia. J Gynecol Oncol, 2024; 35(3):e27; doi: 10.3802/jgo.2024.35.e27
21.
PengS, ZhengY, LiuJ, et al.Molecular classification in fertility-sparing treatment of early-stage endometrial cancer: A potential tool for optimizing patient selection. Gynecol Oncol, 2024; 191:240–248; doi: 10.1016/j.ygyno.2024.10.012
22.
AgustiN, KanbergsA, NiteckiR. Potential of molecular classification to guide fertility-sparing management among young patients with endometrial cancer. Gynecol Oncol, 2024; 185:121–127; doi: 10.1016/j.ygyno.2024.02.020
23.
Centers for Disease Control and Prevention. Vital Statistics Rapid Release – Births: Provisional Data for 2024. National Center for Health Statistics. Published April 2025. Available from: https://www.cdc.gov/nchs/data/vsrr/vsrr038.pdf
24.
Herrera CappellettiE, HumannJ, TorrejónR, et al.Chances of pregnancy and live birth among women undergoing conservative management of early-stage endometrial cancer: A systematic review and meta-analysis. Hum Reprod Update, 2022; 28(2):282–295; doi: 10.1093/humupd/dmab041
25.
Practice Committee of the American Society for Reproductive Medicine. Fertility evaluation of infertile women: A committee opinion. Fertil Steril, 2021; 116(5):1255–1265; doi: 10.1016/j.fertnstert.2021.08.038
26.
FaderAN, ArribaLN, FrasureHE, et al.Endometrial cancer and obesity: Epidemiology, biomarkers, prevention and survivorship. Gynecol Oncol, 2009; 114(1):121–127; doi: 10.1016/j.ygyno.2009.03.039
27.
CarlsonMJ, ThielKW, YangS, et al.Catch it before it kills: Progesterone, obesity, and the prevention of endometrial cancer. Discov Med, 2012; 14(76):215–222.
28.
KlugeL, KällénK, Thurin-KjellbergA, et al.The association between body mass index and live birth and maternal and perinatal outcomes after in-vitro fertilization: A national cohort study. Front Endocrinol (Lausanne), 2023; 14:1239702; doi: 10.3389/fendo.2023.1239702
29.
Practice Committee of the American Society for Reproductive Medicine. Obesity and reproduction: A committee opinion. Fertil Steril, 2021; 116(5):1266–1285.
30.
ParkJY, NamJH. Progestins in the fertility-sparing treatment and retreatment of patients with primary and recurrent endometrial cancer. Oncologist, 2015; 20(3):270–278; doi: 10.1634/theoncologist.2013-0445
31.
ParkJY, KimDY, KimJH, et al.Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer, 2013; 49(4):868–874; doi: 10.1016/j.ejca.2012.09.017
32.
BaxterE, BrennanDJ, McAlpineJN, et al.Improving response to progestin treatment of low-grade endometrial cancer. Int J Gynecol Cancer, 2020; 30(11):1811–1823.
33.
Leone Roberti MaggioreU, Khamisy-FarahR, BragazziNL, et al.Fertility-Sparing treatment of patients with endometrial cancer: A review of the literature. J Clin Med, 2021; 10(20):4784; doi: 10.3390/jcm10204784
34.
ChenJ, CaoD, YangJ, et al.Fertility-Sparing treatment for endometrial cancer or atypical endometrial hyperplasia patients with obesity. Front Oncol, 2022; 12:812346; doi: 10.3389/fonc.2022.812346
35.
JandaM, RobledoKP, GebskiV, et al.Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: Results of a randomized clinical trial. Gynecol Oncol, 2021; 161(1):143–151.
36.
WestinSN, FellmanB, SunCC, et al.Prospective phase II trial of levonorgestrel intrauterine device: Nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer. Am J Obstet Gynecol, 2021; 224(2):191.e1–191.e15; doi: 10.1016/j.ajog.2020.08.032
37.
SuzukiY, FerrisJS, ChenL, et al.Fertility-preserving treatment for stage IA endometrial cancer: A systematic review and meta-analysis. Am J Obstet Gynecol, 2024; 231(6):599–610.e17; doi: 10.1016/j.ajog.2024.07.018
38.
FangF, XuH, WuL, et al.LNG-IUS combined with progesterone ameliorates endometrial thickness and pregnancy outcomes of patients with early-stage endometrial cancer or atypical hyperplasia. Am J Transl Res, 2021; 13(5):5412–5419.
39.
EmonsG, GründkerC. The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer. Cells, 2021; 10(2):292; doi: 10.3390/cells10020292
40.
van WeeldenWJ, MassugerLFAG, PijnenborgJMA, RomanoA, ENITEC. Anti-estrogen Treatment in Endometrial Cancer: A Systematic Review. Front Oncol, 2019; 9:359; doi: 10.3389/fonc.2019.00359
41.
ShaoF, LiY, ZhaoY. Progestin plus metformin improves outcomes in patients with endometrial hyperplasia and early endometrial cancer more than progestin alone: A meta-analysis. Front Endocrinol (Lausanne), 2023; 14:1139858; doi: 10.3389/fendo.2023.1139858
42.
MitsuhashiA, SatoY, KiyokawaT, et al.Phase II study of medroxyprogesterone acetate plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer. Ann Oncol, 2016; 27(2):262–266; doi: 10.1093/annonc/mdv539
43.
MitsuhashiA, HabuY, KobayashiT, et al.Long-term outcomes of progestin plus metformin as a fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer patients. J Gynecol Oncol, 2019; 30(6):e90; doi: 10.3802/jgo.2019.30.e90
44.
BourouMZ, MatsasA, ValsamakisG, et al.The potential role of glucagon-like peptide-1 (glp-1) receptor agonists as a type of conservative treatment of endometrial cancer in women of reproductive age: A review of the literature and a call for study. Cureus, 2024; 16(9):e69678; doi: 10.7759/cureus.69678
45.
ZhangY, XuF, LiangH, et al.Exenatide inhibits the growth of endometrial cancer Ishikawa xenografts in nude mice. Oncol Rep, 2016; 35(3):1340–1348; doi: 10.3892/or.2015.4476
46.
LiW, GuY, LiuS, et al.GLP1R inhibits the progression of endometrial carcinoma through activation of cAMP/PKA pathway. J Clin Lab Anal, 2022; 36(10):e24604; doi: 10.1002/jcla.24604
47.
LinA, DingY, LiZ, et al.Glucagon-like peptide 1 receptor agonists and cancer risk: Advancing precision medicine through mechanistic understanding and clinical evidence. Biomark Res, 2025; 13(1):50; doi: 10.1186/s40364-025-00765-3
48.
HagemannAR, HagemannIS, MutchDG, et al.Enhancing progestin therapy with a glucagon-like peptide 1 agonist for the conservative management of endometrial cancer. Cancers (Basel), 2025; 17(4):598; doi: 10.3390/cancers17040598
49.
YeX, LiT. Effects of hysteroscopic surgery combined with progesterone therapy on fertility and prognosis in patients with early endometrial cancer and atypical endometrial hyperplasia or endometrial intraepithelial neoplasia: A meta-analysis. Arch Gynecol Obstet, 2024; 309(1):259–268; doi: 10.1007/s00404-023-07173-8
50.
XiY, LiuG, LiuD, et al.Efficacy and pregnancy outcomes of hysteroscopic surgery combined with progestin as fertility-sparing therapy in patients with early stage endometrial cancer and atypical hyperplasia. Arch Gynecol Obstet, 2023; 307(2):583–590; doi: 10.1007/s00404-022-06626-w
51.
BilirE, Kahramanoğluİ. The role of hysteroscopy in fertility preservation in endometrial cancer and atypical endometrial hyperplasia: A semi-systematic literature review. Arch Gynecol Obstet, 2023; 308(4):1113–1126; doi: 10.1007/s00404-023-06960-7
52.
XuZ, TianY, FuJ, et al.Efficacy and prognosis of fertility-preserved hysteroscopic surgery combined with progesterone in the treatment of complex endometrial hyperplasia and early endometrial carcinoma. J BUON, 2020; 25(3):1525–1533.
53.
ZhangQ, QiG, KanisMJ, et al.Comparison among fertility-sparing therapies for well differentiated early-stage endometrial carcinoma and complex atypical hyperplasia. Oncotarget, 2017; 8(34):57642–57653; doi: 10.18632/oncotarget.17588
54.
TörökP, MolnárS, LampéR, et al.The use of hysteroscopy in endometrial cancer: Old questions and novel challenges. Climacteric, 2020; 23(4):330–335; doi: 10.1080/13697137.2020.1732914
55.
ChangYN, ZhangY, WangYJ, et al.Effect of hysteroscopy on the peritoneal dissemination of endometrial cancer cells: A meta-analysis. Fertil Steril, 2011; 96(4):957–961; doi: 10.1016/j.fertnstert.2011.07.1146
56.
RossRC, AkindeYM, SchauerPR, et al.The role of bariatric and metabolic surgery in the development, diagnosis, and treatment of endometrial cancer. Front Surg, 2022; 9:943544; doi: 10.3389/fsurg.2022.943544
57.
MacKintoshML, DerbyshireAE, McVeyRJ, et al.The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk. Int J Cancer, 2019; 144(3):641–650; doi: 10.1002/ijc.31913
58.
FloydJL, CampbellS, Rauh-HainJA, et al.Fertility preservation in women with early-stage gynecologic cancer: Optimizing oncologic and reproductive outcomes. Int J Gynecol Cancer, 2021; 31(3):345–351; doi: 10.1136/ijgc-2020-001328
59.
GalloA, CatenaU, SacconeG, et al.Conservative surgery in endometrial cancer. J Clin Med, 2021; 11(1):183; doi: 10.3390/jcm11010183
60.
ShimSH, ChaeSH, SoKA, et al.Optimal duration of fertility-sparing hormonal treatment for early-stage endometrioid endometrial cancer. Gynecol Oncol, 2021; 161(3):810–816; doi: 10.1016/j.ygyno.2021.03.032
61.
WeiJ, ZhangW, FengL, et al.Comparison of fertility-sparing treatments in patients with early endometrial cancer and atypical complex hyperplasia: A meta-analysis and systematic review. Medicine (Baltimore), 2017; 96(37):e8034; doi: 10.1097/MD.0000000000008034
62.
FalconeF, LaurelliG, LositoS, et al.Fertility preserving treatment with hysteroscopic resection followed by progestin therapy in young women with early endometrial cancer. J Gynecol Oncol, 2017; 28(1):e2; doi: 10.3802/jgo.2017.28.e2
63.
FanY, LiX, WangJ, et al.Analysis of pregnancy-associated factors after fertility-sparing therapy in young women with early stage endometrial cancer or atypical endometrial hyperplasia. Reprod Biol Endocrinol, 2021; 19(1):118; doi: 10.1186/s12958-021-00808-y
64.
ParkJY, SeongSJ, KimTJ, et al.Pregnancy outcomes after fertility-sparing management in young women with early endometrial cancer. Obstet Gynecol, 2013; 121(1):136–142; doi: 10.1097/aog.0b013e31827a0643
65.
InoueO, HamataniT, SusumuN, et al.Factors affecting pregnancy outcomes in young women treated with fertility-preserving therapy for well-differentiated endometrial cancer or atypical endometrial hyperplasia. Reprod Biol Endocrinol, 2016; 14:2; doi: 10.1186/s12958-015-0136-7
66.
American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice; Committee on Genetics; U.S. Food and Drug Administration. Committee Opinion No 671: Perinatal Risks Associated With Assisted Reproductive Technology. Obstet Gynecol, 2016; 128(3):e61–e68; doi: 10.1097/AOG.0000000000001643
67.
LeeAJ, ShimSH, KimNR, et al.Retreatment with progestin for recurrence after complete response with fertility-sparing treatment in patients with endometrial cancer. Int J Gynecol Cancer, 2022; 32(8):1001–1008; doi: 10.1136/ijgc-2022-003546
68.
JangEB, LeeAJ, SoKA, et al.Risk factors for the recurrence in patients with early endometrioid endometrial cancer achieving complete remission for fertility-sparing hormonal treatment. Gynecol Oncol, 2024; 191:19–24; doi: 10.1016/j.ygyno.2024.09.015
69.
MutluL, ManavellaDD, GulloG, et al.Endometrial cancer in reproductive age: Fertility-sparing approach and reproductive outcomes. Cancers (Basel), 2022; 14(21):5187; doi: 10.3390/cancers14215187
70.
MatsuoK, MandelbaumRS, MatsuzakiS, et al.Ovarian conservation for young women with early-stage, low-grade endometrial cancer: A 2-step schema. Am J Obstet Gynecol, 2021; 224(6):574–584; doi: 10.1016/j.ajog.2020.12.1213
71.
VioletteCJ, AgarwalR, MandelbaumRS, et al.The potential role of GLP-1 receptor agonist targeting in fertility-sparing treatment in obese patients with endometrial malignant pathology: A call for research. Expert Rev Anticancer Ther, 2023; 23(4):385–395; doi: 10.1080/14737140.2023.2194636
72.
Anderson Cancer CenterMD. Levonorgestrel-Releasing Intrauterine System With or Without Everolimus in Treating Patients With Atypical Hyperplasia or Stage IA Grade 1 Endometrial Cancer (LEVER). ClinicalTrials.gov identifier: NCT02397083. Updated February 25, 2025. Available from: https://clinicaltrials.gov/study/NCT02397083
73.
Washington University School of Medicine. Primary prevention and uterine preservation in premenopausal women with obesity and endometrial hyperplasia. ClinicalTrials.gov identifier: NCT05829460. Updated May 23, 2025. Available from: https://clinicaltrials.gov/study/NCT05829460
74.
WoodruffTK. The Oncofertility Consortium–addressing fertility in young people with cancer. Nat Rev Clin Oncol, 2010; 7(8):466–475; doi: 10.1038/nrclinonc.2010.81
