Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (7): 42-49.doi: 10.6040/j.issn.1671-7554.0.2025.0602

• Clinical Medicine • Previous Articles     Next Articles

Changes in endometrial microenvironment and its impact on pregnancy outcomes after frozen embryo transfer in patients with recurrent implantation failure

ZHAO Jianhua, FAN Yanling, FENG Chengwen   

  1. Department of Reproductive Genetics, Tangshan Maternal and Child Health Hospital, Tangshan 063014, Hebei, China
  • Online:2026-07-10 Published:2026-07-21

Abstract: Objective To investigate the dynamic changes in the endometrial microenvironment before and after frozen embryo transfer(FET)in patients with recurrent implantation failure(RIF), analyze their impact on pregnancy outcomes. Methods This prospective study enrolled 80 patients with RIF(RIF group)and 80 patients undergoing their first FET without RIF(control group)from March 2022 to April 2024. Serum levelsfollicle-stimulating hormone(FSH)and anti-Müllerian hormone(AMH)were measured upon admission. Changes in endometrial microenvironment were evaluated by quantifying cytokines, including vascular endothelial growth factor(VEGF), interleukin-1β(IL-1β), transforming growth factor-β1(TGF-β1), and interferon-γ(IFN-γ), in uterine cavity fluid before and after embryo transfer. Pregnancy outcomes, including biochemical pregnancy, clinical pregnancy, miscarriage rate, and live birth rate, were compared between the two groups. Univariate and multivariate analyses were conducted to identify independent risk factors influencing clinical pregnancy in RIF patients. Results Prior to embryo transfer, levels of IL-1β, TGF-β1, and IFN-γ were significantly higher in the RIF group than in the control group(P<0.05). Post-transfer, VEGF and TGF-β1 levels in the RIF group were significantly lower than those in the control group(P<0.05), whereas IL-1β and IFN-γ levels were significantly elevated(P<0.05). The RIF group also exhibited significantly lower clinical pregnancy and live birth rates compared to the control group(P<0.05). Both univariate and multivariate regression analyses indicated that FSH, AMH, post-transplantation IL-1β, and IFN-γ were significant independent risk factors affecting clinical pregnancy in RIF patients(P<0.05). Conclusion Patients with RIF demonstrate an immune-inflammatory imbalance in the endometrial microenvironment. Serum FSH and AMH levels, as well as post-transfer IL-1β and IFN-γ levels, serve as independent predictors of FET pregnancy outcomes.

Key words: Recurrent implantation failure, Frozen embryo transfer, Endometrial microenvironment, Pregnancy outcome

CLC Number: 

  • R711.6
[1] 胡奕芳, 杨宇欣, 王灿, 等. 反复种植失败与复发性流产的病因比较[J]. 新医学, 2024, 55(9): 693-700. Hu Yifang, Yang Yuxin, Wang Can, et al. Comparison of the etiological composition between recurrent implantation failure and recurrent pregnancy loss[J]. New Medicine, 2024, 55(9): 693-700.
[2] 赵圣蕊, 曲慧灵, 许鑫鑫, 等. 体外受精/卵胞浆内单精子注射-胚胎移植后稽留流产采用药物流产和清宫术效果比较[J]. 山东大学学报(医学版), 2024, 62(2): 69-74. Zhao Shengrui, Qu Huiling, Xu Xinxin, et al. Comparison of medical abortion and surgical abortion in the management of missed abortion after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer[J]. Journal of Shandong University(Health Science), 2024, 62(2): 69-74.
[3] 刘思佳, 乔岩岩. 宫腔灌注治疗反复种植失败的研究进展[J]. 济宁医学院学报, 2024, 47(4): 342-345. Liu Sijia, Qiao Yanyan. Research progress on intrauterine infusion therapy for recurrent implant failure[J]. Journal of Jining Medical University, 2024, 47(4): 342-345.
[4] 孙利静, 孟月茹, 张召义, 等. 反复种植失败患者焦虑抑郁症状与情绪调节策略的相关性研究[J]. 山东大学学报(医学版), 2025, 63(10): 89-97. Sun Lijing, Meng Yueru, Zhang Zhaoyi, et al. Emotion regulation strategies and psychological distress in recurrent implantation failure patients: a correlational study[J]. Journal of Shandong University(Health Sciences), 2025, 63(10): 89-97.
[5] Hanevik H I, Hessen D O. IVF and human evolution[J]. Hum Reprod Update, 2022, 28(4): 457-479.
[6] Lawrenz B, Coughlan C, Melado L, et al. The ART of frozen embryo transfer: back to nature![J]. Gynecol Endocrinol, 2020, 36(6): 479-483.
[7] 戚丹, 张曦, 于倩, 等. 子宫内膜增生症及早期子宫内膜癌保留生育功能后冻胚移植妊娠结局[J]. 山东大学学报(医学版), 2023, 61(4): 56-63. Qi Dan, Zhang Xi, Yu Qian, et al. Pregnancy outcomes of frozen embryo transfer in 112 patients of endometrial hyperplasia and early-stage endometrial cancer after ferti-lity preserving treatment[J]. Journal of Shandong University(Health Science), 2023, 61(4): 56-63.
[8] 刘浩然, 杨爱军, 李泽武, 等. 冻胚移植前子宫内膜准备方案的研究进展[J]. 中国医药科学, 2024, 14(23): 48-51. Liu Haoran, Yang Aijun, Li Zewu, et al. Research progress of endometrial preparation before frozenthawed embryo transfer[J]. China Medicine and Pharmacy, 2024, 14(23): 48-51.
[9] Lin J Y, Wang Z, Huang J L, et al. Microenvironment-protected exosome-hydrogel for facilitating endometrial regeneration, fertility restoration, and live birth of offspring[J]. Small, 2021, 17(11): e2007235. DOI:10.1002/smll.202007235
[10] Li F F, Gao W X, Li Y M, et al. Potential biomarkers and endometrial immune microenvironment in recurrent implantation failure[J]. Biomolecules, 2023, 13(3):406.
[11] Shi J L, Xu Q H, Yu S Y, et al. Perturbations of the endometrial immune microenvironment in endometriosis and adenomyosis: their impact on reproduction and pregnancy[J]. Semin Immunopathol, 2025, 47(1): 16. DOI:10.1007/s00281-025-01040-1
[12] Mukherjee N, Sharma R, Modi D. Immune alterations in recurrent implantation failure[J]. Am J Reprod Immunol, 2023, 89(2): e13563. DOI:10.1111/aji.13563
[13] Wiener-Megnazi Z, Reznick A Z, Lahav-Baratz S, et al. Oxidation and female reproduction: the good, the bad and whats between[J]. Harefuah, 2011, 150(3): 255-259.
[14] Tang Y, Li Y N. Evaluation of serum AMH, INHB combined with basic FSH on ovarian reserve function after laparoscopic ovarian endometriosis cystectomy[J]. Front Surg, 2022, 9: 906020. DOI:10.3389/fsurg.2022.906020
[15] 卵巢储备功能减退临床诊治专家共识专家组, 中华预防医学会生育力保护分会生殖内分泌生育保护学组. 卵巢储备功能减退临床诊治专家共识[J]. 生殖医学杂志, 2022, 31(4): 425-434. Expert Group of Consensus on Clinical Diagnosis & Management of Diminished Ovarian Reserve; Reproductive Endocrinology & Fertility Preservation Section of Chinese Society on Fertility Preservation under Chinese Preventive Medicine Association. Consensus on clinical diagnosis and management of diminished ovarian reserve[J]. Journal of Reproductive Medicine, 2022, 31(4): 425-434.
[16] 程萌, 孔令伶俐, 许良智, 等. 卵巢储备功能减退临床诊治专家共识解读[J]. 实用妇产科杂志, 2022, 38(10): 743-745.
[17] Ishikawa H, Goto Y, Hirooka C, et al. Role of inflammation and immune response in the pathogenesis of ute-rine fibroids: Including their negative impact on reproductive outcomes[J]. J Reprod Immunol, 2024, 165: 104317. DOI:10.1016/j.jri.2024.104317
[18] Yao Y, Chen R, Wang G W, et al. Exosomes derived from mesenchymal stem cells reverse EMT via TGF-β1/Smad pathway and promote repair of damaged endometrium[J]. Stem Cell Res Ther, 2019, 10(1): 225. DOI:10.1186/s13287-019-1332-8
[19] Zhou Z L, Wu X M, Chen T W, et al. Restoration of functional endometrium in an intrauterine adhesion rat model with endometrial stromal cells transplantation[J]. Stem Cell Res Ther, 2024, 15(1): 181. DOI:10.1186/s13287-024-03788-z
[20] Oliveira C R, Polonini H, Marcucci M C, et al. Miodesin(TM)positively modulates the immune response in endometrial and vaginal cells[J]. Molecules, 2022, 27(3): 782. DOI:10.3390/molecules27030782
[21] Degos C, Heinemann M, Barrou J, et al. Endometrial tumor microenvironment alters human NK cell recruitment, and resident NK cell phenotype and function[J]. Front Immunol, 2019, 10: 877. DOI:10.3389/fimmu.2019.00877
[22] Eigenbrod T, Bode K A, Dalpke A H. Early inhibition of IL-1β expression by IFN-γ is mediated by impaired binding of NF-κB to the IL-1β promoter but is indepen-dent of nitric oxide[J]. J Immunol, 2013, 190(12): 6533-6541.
[23] 臧朝雯, 代彩凤, 高景悦, 等. 胚胎反复种植失败的子宫内膜免疫因素及其研究进展[J]. 国际生殖健康/计划生育杂志, 2022, 41(1): 68-73. Zang Zhaowen, Dai Caifeng, Gao Jingyue, et al. Research progress on endometrial immune factors of recurrent implantation failure[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(1): 68-73.
[24] Di Nicuolo F, Specchia M, Trentavizi L, et al. An emerging role of endometrial inflammasome in reproduction: new therapeutic approaches[J]. Protein Pept Lett, 2018, 25(5): 455-462.
[25] Rossi M, Sharkey A M, Viganò P, et al. Identification of genes regulated by interleukin-1beta in human endo-metrial stromal cells[J]. Reproduction, 2005, 130(5): 721-729.
[26] Levine L D, Holland T L, Kim K, et al. The role of aspirin and inflammation on reproduction: the EAGeR trial(1)[J]. Can J Physiol Pharmacol, 2019, 97(3): 187-192.
[27] 王丽媛, 甄秀梅, 王丽娜, 等. 卵巢储备功能减退患者辅助生殖技术前预处理的研究进展[J]. 生殖医学杂志, 2022, 31(11): 1601-1606. Wang Liyuan, Zhen Xiumei, Wang Lina, et al. Research progress of pretreatment before assisted reproductive technology in patients with diminished ovarian reserve[J]. Journal of Reproductive Medicine, 2022, 31(11): 1601-1606.
[28] Zhang Y, Sun X Y, Zhang Y Y, et al. Immune dys-regulation and endometrial receptivity impairment in women with repeated implantation failure and dyslipidemia[J]. J Clin Endocrinol Metab, 2025, 110(11): 3230-3242. DOI:10.1210/clinem/dgaf100
[29] Yang J, Wang L L, Ma J W, et al. Endometrial proteomic profile of patients with repeated implantation failure[J]. Front Endocrinol, 2023, 14: 1144393. DOI:10.3389/fendo.2023.1144393
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