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CLINICAL TRIAL article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1552581
Clinical efficacy and pharmacological mechanism of Er Zhi Tian Gui Formula in enhancing IVF-ET outcomes for diminished ovarian reserve
Provisionally accepted- 1 Shandong University of Traditional Chinese Medicine, Jinan, China
- 2 Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
Objective: To investigate the efficacy of the Er Zhi Tian Gui Formula (EZTGF) in diminished ovarian reserve (DOR) patients undergoing in vitro fertilization-embryo transfer (IVF-ET); to examine the pharmacological mechanism of EZTGF in inhibiting oocyte-granulosa cell (OGC) apoptosis.Methods: A total of 120 DOR patients undergoing IVF-ET in the Affiliated Hospital of Shandong University of TCM from March to December 2021 were randomly assigned to the EZTGF (n=60) or Placebo (n=60) groups. All participants followed a gonadotropin-releasing hormone antagonist protocol for controlled ovarian stimulation, with interventions starting on days 2-3 of the preceding menstrual cycle and continuing until the trigger day. IVF-ET outcomes measured included the number of oocytes retrieved, embryo quality, and pregnancy rates. NEAT1, miR-10b-3p, and FOXO3a OGCs expression was analyzed via qRT-PCR. Mechanistic studies were conducted using KGN cells, with dual-luciferase reporter assays confirming regulatory relationship between NEAT1, miR-10b-3p, and FOXO3a.Results: A total of 116 patients completed the trial (58 in each group). The EZTGF group showed a significant increase in both the number (especially at the cleavage stage) and rate of high-quality embryos, compared with the Placebo group (P < 0.05). No statistically significant differences in pregnancy outcomes were observed (P > 0.05). Cellular experiments showed that miR-10b-3p inhibits proliferation and promotes apoptosis in oocyte granulosa cells (OGCs). Dual luciferase reporter gene assay confirms target-regulatory relationship of NEAT1 with miR-10b-3p, miR-10b-3p and FOXO3a. EZTGF treatment partially reversed the low expression of NEAT1 and FOXO3a, and the high expression of miR-10b-3p in OGCs from DOR patients.Treatment with EZTGF enhances embryo quality in women with DOR undergoing IVF-ET, which can be partially attributed to modulation of the NEAT1/miR-10b-3p/FOXO3a pathway. Trial registration: ChiCTR2100052522.This trial was registered in the China Clinical Trial Registry (ChiCTR2100052522). FromMarch 2021 to December 2021, a total of 120 DOR participants undergoing IVF-ET were recruited for this study at the Reproduction and Genetics Centre of the Affiliated Hospital of Shandong University of TCM. A randomized controlled Placebo trial was conducted by random number table
Keywords: diminished ovarian reserve, Er Zhi Tian Gui Formula, Reproductive Health, Traditional Chinese Medicine, Oocyte quality, Granulosa cell apoptosis
Received: 28 Dec 2024; Accepted: 12 Mar 2025.
Copyright: © 2025 Chen, Lian, Song, Yu, Ding and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Sheng-Yong Ding, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
Haicui Wu, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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