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Concin N, Matias-Guiu X, Cibula D, et al. ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma:update 2025[J]. Lancet Oncol, 2025, 26(8):e423-e435. DOI: 10.1016/S1470-2045(25)00167-6.
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Wu P, Shan W, Xue Y, et al. Impacts of ovarian reserve on conservative treatment for endometrial cancer and atypical hyperplasia[J]. Front Endocrinol(Lausanne), 2024, 14:1286724. DOI: 10.3389/fendo.2023.1286724.
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Meczekalski B, Czyzyk A, Kunicki M, et al. Fertility in women of late reproductive age:the role of serum anti-Mullerian hormone (AMH) levels in its assessment[J]. J Endocrinol Invest, 2016, 39(11):1259-1265. DOI: 10.1007/s40618-016-0497-6.
Fertility is referred to the capability for having offspring and can be evaluated by fertility rate. Women's fertility is strictly dependent on individual's age. The fertility peak occurs in the early 20s, and it starts to decline in the third and fourth decades of life (falling sharply after age 35).The aim of this work is to review the available data concerning fertility in women of late reproductive age, especially the role of serum anti-Müllerian hormone (AMH) levels.There are a lot of factors responsible for decrease of fertility in women of late reproductive age. These factors can be classified as oocyte-dependent (decrease in oocyte quantity and quality) and oocyte-independent (reproductive organs [uterus, oviducts] status and general health). Anti-Müllerian hormone (AMH) is a dimeric glycoprotein of the transforming growth factor-β (TGF-β) superfamily produced directly by the ovarian granulosa cells of secondary, preantral, and early antral follicles. It has been used as an ovarian reserve marker since 2002. Anti-Müllerian hormone seems to be the best endocrine marker for assessing the age-related decline of the ovarian pool in healthy women. Evaluation of AMH's predictive value in the naturally aging population is important for counseling women about reproductive planning as well as for treatment planning for women experiencing hormone-sensitive gynecological conditions such as endometriosis and fibroids.AMH can be considered as an indicator of fertility in late reproductive age women and pregnancy outcome in assisted reproductive technology cycles. AMH can strongly predict poor response in the controlled ovarian stimulation.
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Hsieh HC, Su JY, Wang S, et al. Age effect on in vitro fertilization pregnancy mediated by anti-Mullerian hormone (AMH) and modified by follicle stimulating hormone (FSH)[J]. BMC Pregnancy Childbirth, 2020, 20(1):209. DOI: 10.1186/s12884-020-02875-2.
Both follicle stimulating hormone (FSH) and anti-mullerian hormone (AMH) are widely used to assess the ovarian reserve in women for in vitro fertilization (IVF). However, studies also showed that both AMH and FSH are significantly associated with age: as age increases, AMH decreases and FSH increases. This study aims to investigate the mechanism of age effect on IVF live birth rate, particularly through mediation and interaction by AMH and FSH.
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Sonigo C, Beau I, Binart N, et al. The impact of chemotherapy on the ovaries:molecular aspects and the prevention of ovarian damage[J]. Int J Mol Sci, 2019, 20(21):5342. DOI: 10.3390/ijms20215342.
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Fukunaga H, Hamada N. Radiation‑induced impacts on female fertility and fecundity:perspectives from the viewpoint of radiation protection[J]. Int J Radiat Biol, 2026, 102(3):216-220. DOI: 10.1080/09553002.2025.2606997.
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Xu Z, Yang B, Shan W, et al. Comparison of the effect of levonorgestrel-intrauterine system with or without oral megestrol acetate on fertility-preserving treatment in patients with atypical endometrial hyperplasia:A prospective,open-label,randomized controlled phaseⅡstudy[J]. Gynecol Oncol, 2023, 174:133-141. DOI: 10.1016/j.ygyno.2023.05.001.
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Xu Z, Yang B, Guan J, et al. Comparison of the effect of oral megestrol acetate with or without levonorgestrel-intrauterine system on fertility-preserving treatment in patients with early-stage endometrial cancer:a prospective,open-label,randomized controlled phaseⅡtrial (ClinicalTrials.gov NCT03241914)[J]. J Gynecol Oncol, 2023, 34(1):e32. DOI: 10.3802/jgo.2023.34.e32.
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Tao M, Wu T, Zhou X, et al. Comparative effects of different treatments based on the levonorgestrel intrauterine system in endometrial carcinoma and endometrial hyperplasia patients:a network meta-analysis[J]. Arch Gynecol Obstet, 2024, 310(3):1315-1329. DOI: 10.1007/s00404-024-07608-w.
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Yang B, Xu Y, Zhu Q, et al. Treatment efficiency of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young women with endometrial atypical hyperplasia and endometrial cancer[J]. Gynecol Oncol, 2019, 153(1):55-62. DOI: 10.1016/j.ygyno.2019.01.014.
This study aimed to evaluate the efficacy of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young patients with endometrial atypical hyperplasia (EAH) and early stage endometrial cancer (EEC) who wished to preserve their fertility.Patients with EAH (n = 120) or well-differentiated EEC (n = 40, FIGO stage IA, without myometrial invasion) were retrospectively included. All patients received constant oral progestin combined with hysteroscopic evaluation every 3 months until achieving complete response (CR). The location, number and size of each suspected lesion or cluster were detailly recorded during the hysteroscopy.The median age was 32.0 year-old (range, 22-47 year-old). Totally 148 patients (97.4%) achieved CR while 3 EAH and 1 EEC patients presented with disease progression, and 8 patients were still in treatment. The mean treatment duration for achieving CR was 6.7 ± 0.3 months (range, 1-18 months). After adjusting for patient age, body mass index (BMI), history of pregnancy and type of conservative therapies, lesion size ≤2 cm (OR, 0.701; 95% CI, 0.496-0.991; P = 0.045) was significantly correlated with shorter treatment time to achieve CR. Among 60 patients attempted to conceive after achieving CR, 45.0% (15/60) had been pregnant, 25.0% (15/60) delivered live birth, 13.3% (8/60) are still in pregnancy, while 6.7% experienced spontaneous abortion.Comprehensive hysteroscopic evaluation and lesion resection plus progestin therapy seem to be an effective and safe fertility sparing therapy for patients with EAH or EEC. Endometrial lesion size ≤2 cm correlated with a shorter treatment period to achieve CR.Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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Peng S, Zheng Y, Liu J, et al. Molecular classification in fertility-sparing treatment of early-stage endometrial cancer:A potential tool for optimizing patient selection[J]. Gynecol Oncol, 2024, 191:240-248. DOI: 10.1016/j.ygyno.2024.10.012.
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Hu Z, Wu Z, Liu W, et al. Proteogenomic insights into early-onset endometrioid endometrial carcinoma:predictors for fertility-sparing therapy response[J]. Nat Genet, 2024, 56(4):637-651. DOI: 10.1038/s41588-024-01703-z.
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Zhou S, Xu Z, Yang B, et al. Characteristics of progestin-insensitive early stage endometrial cancer and atypical hyperplasia patients receiving second-line fertility-sparing treatment[J]. J Gynecol Oncol, 2021, 32(4):e57. DOI: 10.3802/jgo.2021.32.e57.
This study investigated the characteristics of progestin-insensitive endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) patients receiving fertility-sparing treatments and assessed the therapeutic effects of second-line fertility-preserving treatments.Three hundred and thirty-eight patients with EEC (n=75) or AEH (n=263) receiving fertility-preserving treatment were retrospectively analyzed. 'Progestin-insensitive' was defined as meeting one of the following criteria: 1) presented with progressed disease at any time during conservative treatment, 2) remained with stable disease after 7 months of treatment, and/or 3) did not achieve complete response (CR) after 10 months of treatment. Clinical characteristics and treatment results of progestin-insensitive patients receiving second-line treatment and those of progestin-sensitive patients were compared.Eight-two patients (59 AEH and 23 EEC) were defined as progestin-insensitive and 256 as progestin-sensitive. In multivariate analysis, body mass index ≥28.0 kg/m² (odds ratio [OR]=1.898) and lesion size >2 cm (OR=2.077) were independent predictors of progestin-insensitive status. Compared to AEH patients, progestin-insensitive EEC patients had poorer second-line treatment responses (28-week cumulative CR rate after changing second-line treatment, 56.3% vs. 85.4%, p=0.011). No statistical difference was found in CR rate among different second-line treatments.Obesity and larger lesion size were independent risk factors associated with progestin-insensitive status. In progestin-insensitive patients receiving second-line treatment, EEC patients had lower CR rate comparing with AEH patients. Further study with larger sample size is needed to evaluate efficacy of different second-line treatments for progestin insensitive patients.Copyright © 2021. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.
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Yang BY, Gulinazi Y, Du Y, et al. Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer:a randomised controlled trial[J]. BJOG, 2020, 127(7):848-857. DOI: 10.1111/1471-0528.16108.
To assess the efficacy of metformin in megestrol acetate (MA)‐based fertility‐sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC).
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| [19] |
Chen Y, Yang J, Wan Y, et al. DEAR model in overweight endometrial cancer patients undergoing fertility-sparing treatment:A randomized controlled trial[J]. Gynecol Oncol, 2024, 185:148-155. DOI: 10.1016/j.ygyno.2024.02.017.
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Yang X, Xue Y, Shao W, et al. Fertility-sparing treatment outcomes using immune checkpoint inhibitors in endometrial cancer patients with Lynch syndrome[J]. J Gynecol Oncol, 2025, 36(4):e59. DOI: 10.3802/jgo.2025.36.e59.
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Cao Y, Sun H, Zhu H, et al. Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion:a phase I clinical trial[J]. Stem Cell Res Ther, 2018, 9(1):192. DOI: 10.1186/s13287-018-0904-3.
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Gao J, Zhou X, Jiang N, et al. Meta-analysis of mesenchymal stem cell therapy for intrauterine adhesions:a comprehensive consideration of efficacy and safety[J]. Front Bioeng Biotechnol, 2025, 13:1619778. DOI: 10.3389/fbioe.2025.1619778.
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Yin M, Zhou HJ, Lin C, et al. CD34+KLF4+stromal stem cells contribute to endometrial regeneration and repair[J]. Cell Rep, 2019, 27:2709-2724e3. DOI: 10.1016/j.celrep.2019.04.088.
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Liu X, Qian C, Jiang X, et al. Efficacy of platelet-rich plasma in the treatment of thin endometrium:a meta-analysis of randomized controlled trials[J]. BMC Pregnancy Childbirth, 2024, 24(1):567. DOI: 10.1186/s12884-024-06741-3.
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Mao L, Wang X, Sun Y, et al. Platelet-rich fibrin improves repair and regeneration of damaged endometrium in rats. Front Endocrinol (Lausanne) 2023; 14:1154958. 10.3389/fendo.2023.1154958.
Intrauterine adhesion (IUA) is the most common cause of uterine infertility. This study aims to evaluate whether platelet-rich fibrin (PRF) treatment can stimulate damaged endometrium regeneration in rats.
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| [27] |
Yuan G, Li D, Du X, et al. Effects of platelet-rich fibrin on human endometrial stromal cells behavior in comparison to platelet-rich plasma[J]. Front Cell Dev Biol, 2024, 12:1445928. DOI: 10.3389/fcell.2024.1445928.
Intrauterine transfusion of platelet-rich plasma (PRP) has become a new treatment for thin endometrium (TE) in recent years, but its low efficacy due to rapid release of growth factors limits its clinical use. Platelet-rich fibrin (PRF) starts the coagulation cascade reaction immediately after the blood comes into contact with the test tube. The natural coagulation process results in stable platelet activation and the slow release of growth factors.
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| [29] |
Chen J, Cheng Y, Fu W, et al. PPOS protocol effectively improves the IVF outcome without increasing the recurrence rate in early endometrioid endometrial cancer and atypical endometrial hyperplasia patients after fertility preserving treatment[J]. Front Med (Lausanne), 2021, 8:581927. DOI: 10.3389/fmed.2021.581927.
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Zong X, Yu Y, Yang H, et al. Effects of gonadotropin-releasing hormone analogs on ovarian function against chemotherapy-induced gonadotoxic effects in premenopausal women with breast cancer in China:a randomized clinical trial[J]. JAMA Oncol, 2022, 8(2):252-258. DOI: 10.1001/jamaoncol.2021.6214.
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Kano M, Sosulski AE, Zhang L, et al. AMH/MIS as a contraceptive that protects the ovarian reserve during chemotherapy[J]. Proc Natl Acad Sci U S A, 2017, 114(9):E1688-E1697. DOI: 10.1073/pnas.1620729114.
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中华医学会妇科肿瘤学分会. 中国妇科肿瘤临床实践指南2025版(下卷):妇科肿瘤保留生育功能治疗管理指南[M]. 中华医学电子音像出版社, 2025.
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Varlas VN, Bors RG, Albu D, et al. Social freezing:pressing pause on fertility[J]. Int J Environ Res Public Health, 2021, 18(15):8088. DOI: 10.3390/ijerph18158088.
Increasing numbers of women are undergoing oocyte or tissue cryopreservation for medical or social reasons to increase their chances of having genetic children. Social egg freezing (SEF) allows women to preserve their fertility in anticipation of age-related fertility decline and ineffective fertility treatments at older ages. The purpose of this study was to summarize recent findings focusing on the challenges of elective egg freezing. We performed a systematic literature review on social egg freezing published during the last ten years. From the systematically screened literature, we identified and analyzed five main topics of interest during the last decade: (a) different fertility preservation techniques, (b) safety of freezing, (c) usage rate of frozen oocytes, (d) ethical considerations, and (e) cost-effectiveness of SEF. Fertility can be preserved for non-medical reasons through oocyte, embryos, or ovarian tissue cryopreservation, with oocyte vitrification being a new and optimal approach. Elective oocyte cryopreservation is better accepted, supports social gender equality, and enhances women’s reproductive autonomy. Despite controversies, planned oocyte cryopreservation appears as a chosen strategy against age-related infertility and may allow women to feel that they are more socially, psychologically, and financially stable before motherhood.
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| [36] |
Hu J, Wang L, Yang B, et al. Cholesterol desensitizes the response of endometrial cancer to progestin by attenuating progestin signaling[J]. Sci Transl Med, 2025, 17(818):eadp0064. DOI: 10.1126/scitranslmed.adp0064.
\n Progestin is the primary fertility-preserving treatment for patients with endometrial cancer (EC) and its precursor lesions, endometrial atypical hyperplasia (EAH); however, a subset of patients exhibits a poor response. In this study, through the analysis of serum lipid differences, we found that progestin-resistant patients with EC/EAH exhibited reduced serum apolipoprotein A-I concentrations and increased cholesterol accumulation in endometrial tissue. Mechanistically, molecular docking simulations and cellular models confirmed that cellular cholesterol interfered with progestin-driven signaling by competing with progestin for binding to progesterone receptor B (PRB), thereby impairing its phosphorylation, nuclear translocation, and downstream gene activation. Substitution of leucine\n 887\n with alanine\n 887\n in PRB disrupted cholesterol binding but preserved progestin responsiveness. Furthermore, cholesterol-lowering therapy with rosuvastatin calcium restored progestin sensitivity in animal models and in a single-arm, open-label phase 2 clinical trial. Our work shows that cholesterol accumulation contributes to progestin resistance and that combining progestin with statins may enhance therapeutic efficacy in EC.\n
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