Integrating Yangjing Zhongyu Decoction into IVF/ICSI-ET Cycles in Patients with Diminished Ovarian Reserve

Summary

This study demonstrates that Yangjing Zhongyu decoction enhances assisted reproduction outcomes in women with diminished ovarian reserve by improving oocyte and embryo quality. In a rat model of premature ovarian failure, the decoction restored hormone balance, promoted follicle development, and modulated autophagy and lipid metabolism.

Abstract

Yangjing Zhongyu Decoction (YZD), a traditional Chinese herbal formula, has been suggested to improve ovarian function and fertility outcomes, but standardized clinical evidence remains limited. This study evaluated the effects of YZD in women with diminished ovarian reserve (DOR) undergoing IVF/ICSI-ET, alongside mechanistic validation in a rat model of premature ovarian failure (POF). In the clinical trial, DOR patients received either the standard GnRH antagonist protocol alone or in combination with YZD. Baseline characteristics between groups were comparable, and the YZD group showed higher numbers of retrieved oocytes and high-quality embryos, as well as improved traditional Chinese medicine syndrome scores. In parallel, POF was induced in rats, and animals treated with YZD exhibited improved estrous cyclicity, restoration of serum estradiol levels, reduction of follicle-stimulating hormone, and healthier ovarian histology. Electron microscopy revealed that YZD reduced excessive autophagosome formation and lipid accumulation in ovarian cells, suggesting regulation of the autophagy-lipid metabolism axis. Together, these findings indicate that YZD enhances ovarian reserve function, improves embryo development, and may increase pregnancy potential in women with DOR. This standardized protocol provides a reproducible framework for integrating YZD into assisted reproductive technology cycles, supporting its translational potential in clinical reproductive medicine.

Introduction

Diminished ovarian reserve (DOR) is a clinical condition that compromises female reproductive health and is characterized by a reduction in the number or quality of ovarian follicles¹. Clinically, it is reflected by decreased antral follicle count, reduced anti-Müllerian hormone (AMH) levels, or elevated follicle-stimulating hormone (FSH) concentrations². DOR accounts for approximately 10% of infertility cases and represents a major barrier to successful conception³. In the context of assisted reproductive technology (ART), the prevalence of DOR is estimated at 19%-26% in the United States

Protocol

All clinical procedures were conducted in accordance with the Declaration of Helsinki and were approved by the Ethics Committee of Shanghai Changhai Hospital (Approval No. CHEC2022-156). Written informed consent was obtained from all participants. Animal experiments were approved by the Ethics Committee of Changhai Medical College (Approval No. CHEC2022-156) and complied with national laboratory animal care standards.

Clinical features

Patient recruitment and grouping
From August 2022 to March 2023, 78 infertility patients diagnosed with kidney-yin deficiency

Results

Clinical features

During the study, 3 patients in the control group withdrew due to COVID-19 infection, and 1 was excluded because of abnormal liver function, leaving 35 patients. In the treatment group, 4 withdrew due to COVID-19, and 35 patients completed the study. Thus, a total of 70 subjects were included in the final analysis. There were no significant differences between groups in age, body mass index (BM.......

Discussion

In this study, we investigated the potential role of Yangjing Zhongyu Decoction (YZD) as an adjunct therapy for diminished ovarian reserve (DOR) in assisted reproductive technology (ART). Clinical findings demonstrated that patients receiving YZD in addition to the standard antagonist protocol achieved significantly higher numbers of retrieved oocytes and high-quality embryos. Although pregnancy rates did not differ significantly between groups, a favorable trend was observed. These results suggest that YZD may enhance f.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Centrifuge	Serum separation (1000 x g, 15 min, 4 °C)	Eppendorf 5810R	5811 000.012
Cotton swabs (sterile)	Collection of vaginal cytology samples	Jiangsu Kangjian Medical Supplies	KJ-MW-01
ELISA Kit for E2	Serum estradiol quantification (rat)	Elabscience Biotechnology Inc.	E-EL-0152
ELISA Kit for FSH	Serum FSH quantification (rat)	Elabscience Biotechnology Inc.	E-EL-R0391
Ethanol (70–100%)	Graded dehydration for histology	Sinopharm Chemical Reagent Co., China	100092683
Glass slides & coverslips	Sample mounting	Citotest Scientific, China	7101/1812
Hematoxylin & Eosin	Staining solution for histology	Beyotime Biotechnology, China	C0105S
Optical Microscope	Histology and cytology observation	Olympus (generic, no trademark)	CX23
Paraffin	Embedding medium	Leica Biosystems	39601095
Paraformaldehyde (4%)	Fixative for tissue preparation	Sigma-Aldrich	P6148
Saline solution (0.9%)	Vaginal smear preparation	Sinopharm Chemical Reagent Co., China	10019318
Sprague–Dawley rats	Experimental animals (female, 8 weeks, 160–200 g)	Beijing Weitong Lihua Experimental Animal Tech Co., Ltd.	SCXK(Beijing)2024-0011
SPSS Software	Statistical analysis (ver. 26.0)	IBM Corp.	RRID:SCR_002865
Transmission Electron Microscope	Ultrastructural observation	JEOL Ltd.	JEM-1400Plus
Tripterygium glycosides	Induction of DOR rat model	Generic supplier (no trademark)	TG-001
Xylene	Clearing reagent for histology	Sinopharm Chemical Reagent Co., China	10023418