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

Study Overview
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Brief Summary
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Using a multi-center, large sample, randomized, controlled and blind clinical trial to evaluate the effect of thumbtack needle on ovarian function of patients with diminished ovarian reserve (DOR).

Detailed Description
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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 function. Thumbtack needle, as a kind of acupuncture, has been found effective in treating DOR in our clinic. In this trial, the investigators Using a multi-center, large sample, randomized, controlled and blind clinical trial to evaluate the effect of thumbtack needle on ovarian 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 thumbtack needle for a total of 2 menstrual cycles. Last, the above baseline measurements will be taken again as soon as the treatment is finished and outcome measures will be recorded after the treatment.

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

Conditions
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Diminished Ovarian Reserve

Intervention / Treatment
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* Other: active thumbtack needle
* Other: sham thumbtack needle


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: treatment group<br>Active thumbtack needle will be used for the treatment group | Other: active thumbtack needle<br>* 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 points of CV4, CV3, SP6, ST36 and BL23 were treated by the sterile thumbtack needle for single use (Hangzhou Zhuomai Medical Technology Co., LTD., model: ZM2-6YDL), and four points of bilateral ovary acupoints and bilateral EX-B7 were treated by disposable sterile electro-thumbtack needle (Hangzhou Zhuomai Medical Technology Co., LTD., model: ZM3-ZY). The patients were receive a treatment of 2 menstrual cycles<br>|
| Sham Comparator: control group<br>Sham thumbtack needle will be used for the control group | Other: sham thumbtack needle<br>* 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 points of CV4, CV3, SP6, ST36 and BL23 were treated by the sterile sham thumbtack needle for single use (Hangzhou Zhuomai Medical Technology Co., LTD., model: ZM2-6YDL), and four points of bilateral ovary acupoints and bilateral EX-B7 were treated by disposable sterile sham electro-thumbtack needle (Hangzhou Zhuomai Medical Technology Co., LTD., model: ZM3-ZY). The patients were receive a treatment of 2 menstrual cycles<br>|

What is the study measuring?
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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 and immediately after treatment on the second day of menstruation. | 0 week and up to 4 weeks | 
| 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 and immediately after treatment. | 0 week and up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluating the serum levels of sex hormones | Evaluating the serum levels of sex hormones on the second day of menstruation at baseline and immediately after treatment | 0 week and up to 4 weeks | 
| Observing the sex hormones in follicular fluid collected from patients undergoing IVF/ICSI-ET cycle after treatment | Observing follicular fluid levels of sex hormones when patients undergoing IVF/ICSI -ET after the treatment. | through study completion, an average of 1 year | 
| 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. | through study completion, an average of 1 year | 
| 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. | through study completion, an average of 1 year | 
| 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. | through study completion, an average of 1 year | 
| 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. | through study completion, an average of 1 year | 
| Observing the ovum morphology (MII ovum ratio) during IVF-ET after treatment | Observing the MII ovum ratio during IVF-ET after treatment | through study completion, an average of 1 year | 
| Observing the embryo status | Observing the grade I embryo ratio, blastocyst formation rate and high quality blastocyst ratio when patients undergoing IVF/ICSI-ET after the treatment | through study completion, an average of 1 year | 
| Observing the pregnancy status | Observing the biochemical, clinical and ongoing pregnancy rate | through study completion, an average of 1 year | 
| 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 12 weeks | 
| Blood norepinephrine index examination | Observing the level of blood norepinephrine at baseline and immediately after treatment | 0 week and up to 12 weeks | 
| 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 12 weeks | 
| Blood beta-aminobutyric acidne (DA) examination | Observing the level of blood beta-aminobutyric acidne (DA) at baseline and immediately after treatment | 0 week and up to 12 weeks | 
| 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 12 weeks | 
| Blood dopamine (DA) examination | Observing the level of blood dopamine (DA) at baseline and immediately after treatment | 0 week and up to 12 weeks | 
| 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 12 weeks | 
| 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 | 
| 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 | 
| 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 | 
| 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 |