Yulinzhu for Women With Diminished Ovarian Reserve (DOR)

Yulinzhu for Women With Diminished Ovarian Reserve: a Randomized, Waiting-list Controlled, Crossover Trial

This is a randomized waiting-list controlled crossover trial carried out to investigate the efficacy of traditional Chinese medicine (TCM) for DOR and its potential beneficial effects on fertility. Subjects' (1) Ovarian function (AMH, FSH), (2) Bilateral AFC as shown in pelvic ultrasound, and (3) Traditional Chinese Medicine Symptom Score (TCMSS) will be recorded. It is hypothesized that a 12-week course (5 days medication per week) of TCM herbal therapy for DOR patients will improve one or more of the above aspects when compared to the waiting-list control group.

Study Overview

• Status: Not yet recruiting
• Conditions: Diminished Ovarian Reserve (DOR)
• Intervention / Treatment: Drug: Yulinzhu (a Chinese Medicinal Formulae)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kwai Ching Lo, Dr; Phone Number: 852-3917 6462; Email: angelos@hku.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Women aged 18-40, with regular menstruation (cycle from 21 to 35 days) and reduced fertility (infertility, early miscarriage, recurrent pregnancy loss, recurrent implantation failure, etc.) ;

2. Tests of ovarian reserve within 6 months:

   1. AMH < 1.1 ng/ml or (any day in cycle, refer to laboratory standards);
   2. AFC < 7 follicles or (any day in cycle);
   3. Received <3 cycles of IVF in public sector;
3. Subject has no history of allergy to TCM;
4. Subjects agree to receive IVF treatment upon the completion of this research within 12 weeks if they are not pregnant spontaneously; and
5. As diagnosed by Chinese Medicine practitioner through four diagnostic methods, suitable to receive Yulinzhu.

Exclusion Criteria:

1. Previous history of a unilateral or bilateral oophorectomy;
2. Recent administration of TCM for DOR within 3 months;
3. Diagnosis of pregnancy, premature ovarian failure, residual follicles, cysts or space-occupying lesions in the ovary, pelvic inflammatory disease or polycystic ovary syndrome; and
4. Cancer, untreated thyroid dysfunction, severe cardiovascular/cerebrovascular diseases, severe liver/kidney diseases or hematopoietic system diseases.
5. Subjects are allowed to withdraw from the trial for one of the following reasons:

(1) The patient fails to complete treatment due to safety or medical reasons; (2) The patient fails to follow treatment guidelines; (3) The patient is unwilling to continue treatment for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chinese Medicine herbal treatment group; After completing the screening process, Chinese Medicine herbal treatment group will start to receive the Chinese medicine treatment for 12 weeks, during which the TCMSS will be repeated once for every 2 weeks of oral Chinese medicine treatment, for a total of 5 times. At the end of the treatment period, subjects will repeat the same examinations they received before enrollment and enter a waiting list control period for 12 weeks. At the end of the waiting list control period, subjects will repeat the above tests again and undergo IVF treatment after 12 weeks.	Drug: Yulinzhu (a Chinese Medicinal Formulae); Yulinzhu (毓麟珠) originally published in The Complete Compendium of [Zhang] Jingyue (景岳全書), the mechanisms of action are nourishing kidney essence, qi and blood . The Composition includes: Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Poria, Paeoniae Radix Alba, Chuanxiong Rhizoma, Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Rehmanniae Radix, Cuscutae Semen, Eucommiae Cortex, CervusnipponTemminck, Zanthoxyli Pericarpium. Both groups will receive Chinese Medicine treatment in form of ready-to-drink packaged Chinese medicine decoction during their treatment period. Subjects will receive Yulinzhu (毓麟珠) with variations allowed. Eight variations can be chosen. The prescription can be edited by applying 2 variations at most every two weeks after TCM consultation.
Other: waiting-list control group; After completing the screening process, waiting-list control group will enter a 12-week waiting list control period. At the end of the waiting list control period, the subjects will repeat the screening procedures they have undergone before enrollment. Upon completion of the screening process, the subject will start to receive Chinese medicine treatment for a period of 12 weeks, during which the TCMSS will be repeated once for every 2 sessions of oral Chinese medicine treatment, making a total of 5 sessions. At the end of the treatment, subjects in Group B will repeat the above tests and receive IVF treatment. The effect of the intervention will be evaluated by comparing the test data between groups and within groups.	Drug: Yulinzhu (a Chinese Medicinal Formulae); Yulinzhu (毓麟珠) originally published in The Complete Compendium of [Zhang] Jingyue (景岳全書), the mechanisms of action are nourishing kidney essence, qi and blood . The Composition includes: Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Poria, Paeoniae Radix Alba, Chuanxiong Rhizoma, Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Rehmanniae Radix, Cuscutae Semen, Eucommiae Cortex, CervusnipponTemminck, Zanthoxyli Pericarpium. Both groups will receive Chinese Medicine treatment in form of ready-to-drink packaged Chinese medicine decoction during their treatment period. Subjects will receive Yulinzhu (毓麟珠) with variations allowed. Eight variations can be chosen. The prescription can be edited by applying 2 variations at most every two weeks after TCM consultation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum anti-Mullerian hormone (AMH)	For all subjects, on the 2nd to 5th days of the menstrual cycle, 3-5 mL of blood will be collected from the arm-cubital vein once. ELISA (enzyme-linked immunosorbent assay) will be adopted to evaluate the level of AMH.	will be performed on the first menstrual cycle before treatment, and then at week 12 and 24.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Follicle stimulating hormone (FSH)	For all subjects, on the 2nd to 5th days of the menstrual cycle, 3-5 mL of blood will be collected from the arm-cubital vein once. Electrochemiluminescence will be used to detect the level of serum FSH.	will be performed on the first menstrual cycle before treatment, and then at week 12 and 24.
Pelvic ultrasound	For all subjects, pelvic ultrasound will be performed on the 2nd to 5th days of the menstrual cycle (on the same day with blood taking) for bilateral ovarian antral follicle count (AFC).	This assessment will be carried out at baseline, week 12 and week 24.
Traditional Chinese Medicine Symptom Score (TCMSS)	The revised Blatt-Kupperman Menopausal Index will be adopted: (i) Weighting factor: sweating/hot flushes (4 points); paresthesia, sleeplessness, melancholia (categorized as psychological symptoms), dyspareunia, nervousness, urinary tract symptoms (2 points); vertigo, arthralgia/myalgia (categorized as somatic symptoms), fatigue, palpitations, headache, dysesthesia (1 point). (ii) Severity score: asymptomatic (0 point); occasional symptoms (1 point); frequent symptoms (2 points); often and severe symptoms (3 points). (iii) Symptom score = weighting factor × severity score, and the total score is the sum of all symptom scores. (iv)Degree of menopause: mild = 7-15 points; moderate = 16-30 points; severe ≥ 30 points.	Up to 18 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: Queen Mary Hospital, Hong Kong; Kwong Wah Hospital
• Investigators: Principal Investigator: Kwai Ching Lo, Dr, The Univerisity of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): April 24, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: April 14, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Chinese Medicine; diminished ovarian reserve; Yulinzhu
• Other Study ID Numbers: DOR20241209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No