Effect of Thumbtack Needle (TN) on Ovarian Reserve Function of Women With Diminished Ovarian Reserve (DOR) (TN-DOR)

Effect of Thumbtack Needle (TN) on Ovarian Reserve Function of Women With Diminished Ovarian Reserve (DOR): A Randomized Controlled Clinical Trial

Using a multi-center, large sample, randomized, patient-assessor blinded, sham-controlled clinical trial to evaluate the effect of thumbtack needle (TN) on ovarian function of patients with diminished ovarian reserve (DOR).

Study Overview

• Status: Completed
• Conditions: Diminished Ovarian Reserve
• Intervention / Treatment: Other: active TN and ETN treatment; Other: sham TN and sham ETN treatment

Detailed Description

Diminished ovarian reserve (DOR) is the precursor state of ovarian failure, and can cause the decline of women's reproductive function. Some studies have demonstrated that acupuncture can improve ovarian reserve function. Thumbtack needle (TN), as a kind of acupuncture, is a form of long-term indwelling intradermal needle therapy. TN has been found effective in treating DOR in our clinic. In this study, a multi-center, large sample, randomized, patient-assessor blinded, sham-controlled clinical trial was used to evaluate the effect of TN on ovarian reserve function of patients with diminished ovarian reserve (DOR).

First, patients will be recruited according to the inclusion criteria and exclusion criteria.

Second, baseline measurements (including ovarian reserve function, blood biochemical index, scores from the self-rating anxiety and depression scale, quality of life, sleep status) will be taken.

Third, each patient will receive the treatment of TN or sham TN for a total of 2 menstrual cycles.

Fourth, the above baseline measurements will be taken again as soon as the treatment is finished and outcome measures will be recorded after the treatment.

Last, Natural pregnancy outcomes includes natural pregnancy rate (including biochemical pregnancy rate, clinical pregnancy rate) and miscarriage rate during the treatment period and within 6 months after treatment completion will be followed up. Pregnancy outcome Includes number of oocytes retrieved, fertilization rate, embryo formation rate, blastocyst formation rate, biochemical pregnancy rate, clinical pregnancy rate and miscarriage rate during IVF-ET within 6 months after treatment completion will also be followed up.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with age between 18 and 40 years;
• Low ovarian reserve: AMH<1.1ng/ml; or AFC<7; or 10 U/L<FSH<25U/L or FSH/LH>3.6; or has a history of poor ovarian response, that is, in the last controlled hyperstimulation cycle, the number of retrieved oocytes<3. Any 2 of the above 4 conditions are met.
• Sign informed consent voluntarily.

Exclusion Criteria:

• Patient's chromosome is abnormal.
• Patients with previous ovarian surgery because of such as ovarian teratoma or chocolate cyst and so on.
• Patients with uncorrected endocrine disease, such as: Simple hyperthyroidism or hypothyroidism, hyperprolactinemia, insulin resistance, diabetes, adrenal diseases, etc.
• Patients with definitively diagnosed autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, Sjogren's syndrome, Hashimoto's thyroiditis.
• Patients with a history of cancer and has received radiotherapy or chemotherapy.
• Patients had the treatment of acupuncture or thumbtack needle in recent 3 months.
• Patients who take Chinese medicine decoction or granule during the treatment;
• Patients unwilling to sign the informed consent of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: treatment group; Active thumbtack needle (TN) and electro-thumbtack needle (ETN) will be used in the treatment group	Other: active TN and ETN treatment; The following 12 acupoints including conception vessel (CV) 4, CV3, bilateral ovary acupoints, bilateral spleen (SP) 6, bilateral stomach (ST) 36, bilateral bladder (BL) 23 and bilateral EX-B7 will be used. Eight acupoints of CV4, CV3, SP6, ST36 and BL23 will be treated by disposable sterile thumbtack needle (TN) for single use (Hangzhou Zhuomai Medical Technology Co., LTD., model: ZM2-6YDL), and four acupoints of bilateral ovary acupoints and bilateral EX-B7 will be treated by disposable sterile electro-thumbtack needle (ETN) (Hangzhou Zhuomai Medical Technology Co., LTD., model: ZM3-ZY) with pulsed electrical stimulation. The patients will receive a treatment of 2 menstrual cycles.
Sham Comparator: control group; Sham thumbtack needle (TN) and sham electro-thumbtack needle (ETN) will be used in the control group	Other: sham TN and sham ETN treatment; The acupoints used in the control group are the same as those in the treatment group. Eight points of CV4, CV3, SP6, ST36 and BL23 will be treated by the sterile sham thumbtack needle (TN) for single use (Hangzhou Zhuomai Medical Technology Co., LTD.), and four points of bilateral ovary acupoints and bilateral EX-B7 will be treated by disposable sterile sham electro-thumbtack needle (ETN) (Hangzhou Zhuomai Medical Technology Co., LTD.) with sham pulsed electrical stimulation. The sham TN and ETN used in this group are identical in appearance, shape, and color to the active TN and ETN but lack the needle body, thus lacking the needle-penetrating effect. The stimulation method and frequency for the sham ETN are the same as those of the ETN group. The only difference is that the electrode pads used in the sham ETN group are specially designed as insulated controls. The patients will receive a treatment of 2 menstrual cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluating the change of serum AMH level	Assessing patients' serum level of AMH in ng/ml at baseline (0 week) and immediately (up to 4 weeks) after treatment completion.	0 week and up to 4 weeks after treatment completion
Evaluating the change of the ovarian antral follicle count (AFC)	Counting the number of ovarian antral follicle count (AFC) on the second day of menstruation at baseline (0 week) and immediately (up to 4 weeks) after treatment completion.	0 week and up to 4 weeks after treatment completion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluating the serum levels of sex hormones	Evaluating the serum levels of sex hormones (FSH, LH, E2, P, T, and PRL) on the second day of menstruation at baseline and immediately (up to 4 weeks) after treatment completion.	0 week and up to 4 weeks after treatment completion
Natural pregnancy outcomes include natural pregnancy rate and miscarriage rate	Natural pregnancy outcomes include natural pregnancy rate (including biochemical pregnancy rate, and clinical pregnancy rate) and miscarriage rate during the treatment period and within 6 months after treatment completion.	0 week and within 6 months after treatment completion
Pregnancy outcomes of IVF-ET within 6 Months after Treatment Completion	Pregnancy outcomes Include number of oocytes retrieved, fertilization rate, embryo formation rate, blastocyst formation rate, biochemical pregnancy rate, clinical pregnancy rate, and miscarriage rate during IVF-ET within 6 months after treatment completion.	0 week and within 6 months after treatment completion
Observing the level of transforming growth factor β (TGF β) in follicular fluid	Observing follicular fluid level of transforming growth factor β (TGF β) when patients undergoing IVF/ICSI -ET after the treatment.	within 6 months after treatment completion
Observing the level of tumor necrosis factor-α (TNF-α) in follicular fluid	Observing follicular fluid level of TNF-α when patients undergoing IVF/ICSI -ET after the treatment.	within 6 months after treatment completion
Observing the level of reactive oxygen species (ROS) in follicular fluid	Observing follicular fluid level of ROS when patients undergoing IVF/ICSI -ET after the treatment.	within 6 months after treatment completion
Observing the level of superoxide dismutase (SOD) in follicular fluid	Observing follicular fluid level of SOD when patients undergoing IVF/ICSI -ET after the treatment.	within 6 months after treatment completion
Blood corticotropin-releasing hormone (CRH) examination	Observing the level of blood corticotropin-releasing hormone (CRH) at baseline and immediately after treatment	0 week and up to 4 weeks after treatment completion
Blood norepinephrine index examination	Observing the level of blood norepinephrine at baseline and immediately after treatment	0 week and up to 4 weeks after treatment completion
Blood 5-hydroxytryptamine (5-HT) index examination	Observing the level of blood 5-hydroxytryptamine (5-HT) at baseline and immediately after treatment	0 week and up to 4 weeks after treatment completion
Blood beta-aminobutyric acid (GABA) examination	Observing the level of blood beta-aminobutyric acid (GABA) at baseline and immediately after treatment	0 week and up to 4 weeks after treatment completion
Blood dopamine (DA) examination	Observing the level of blood dopamine (DA) at baseline and immediately after treatment	0 week and up to 4 weeks after treatment completion
Blood neuro-endorphin (β-ET) examination	Observing the level of blood neuro-endorphin (β-ET) at baseline and immediately after treatment	0 week and up to 4 weeks after treatment completion
Evaluation of anxiety status	Anxiety status will be assessed using Zung anxiety self-rating scale (Zung-SAS) at baseline and immediately after treatment.	0 week and up to 4 weeks after treatment completion
Evaluation of depression status	Depression status will be assessed using Zung depression self-rating scale (Zung-SDS) at baseline and immediately after treatment.	0 week and up to 4 weeks after treatment completion
Evaluation of quality of life	Quality of life will be assessed by SF-36 at baseline and immediately after treatment..	0 week and up to 4 weeks after treatment completion
Evaluation of sleep state	Sleep status will be evaluated using Pittsburgh sleep quality index (PSQI) at baseline and immediately after treatment.	0 week and up to 4 weeks after treatment completion
Untargeted metabolomics levels in serum	Untargeted metabolomics levels in patient serum before and after treatment.	0 week and up to 4 weeks after treatment completion
Untargeted metabolomics levels in follicular fluid	Observing untargeted metabolomics levels in follicular fluid collected from patients undergoing IVF/ICSI-ET cycle after treatment completion	During IVF-ET within 6 months after study completion
Proteomic analysis of granulosa cells	Proteomic analysis of granulosa cells collected during IVF-ET cycles after treatment.	During IVF-ET within 6 months after study completion

Collaborators and Investigators

• Sponsor: Dongmei Huang
• Investigators: Principal Investigator: Hanwang Zhang, Huazhong University of Science Tech

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2021
• Primary Completion (Actual): November 28, 2025
• Study Completion (Actual): December 6, 2025

Study Registration Dates

• First Submitted: December 22, 2021
• First Submitted That Met QC Criteria: March 3, 2022
• First Posted (Actual): March 14, 2022

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 22, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: diminished ovarian reserve; thumbtack needle; ovarian reserve function
• Other Study ID Numbers: Effect of TN on DOR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: we use the Clinical Trial Management Public Platform to manage and share our date
• IPD Sharing Time Frame: January, 2027, for 1 year
• IPD Sharing Access Criteria: only for research
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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