Diminished Ovarian Reserve
Conditions
Keywords
diminished ovarian reserve, thumbtack needle, ovarian reserve function
Brief summary
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).
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.
Interventions
OTHERactive 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.
OTHERsham 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
Sponsors
Dongmei Huang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluating the change of serum AMH level | 0 week and up to 4 weeks after treatment completion | Assessing patients' serum level of AMH in ng/ml at baseline (0 week) and immediately (up to 4 weeks) after treatment completion. |
| Evaluating the change of the ovarian antral follicle count (AFC) | 0 week and up to 4 weeks after treatment completion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of anxiety status | 0 week and up to 4 weeks after treatment completion | Anxiety status will be assessed using Zung anxiety self-rating scale (Zung-SAS) at baseline and immediately after treatment. |
| Evaluation of depression status | 0 week and up to 4 weeks after treatment completion | Depression status will be assessed using Zung depression self-rating scale (Zung-SDS) at baseline and immediately after treatment. |
| Evaluation of quality of life | 0 week and up to 4 weeks after treatment completion | Quality of life will be assessed by SF-36 at baseline and immediately after treatment.. |
| Evaluation of sleep state | 0 week and up to 4 weeks after treatment completion | Sleep status will be evaluated using Pittsburgh sleep quality index (PSQI) at baseline and immediately after treatment. |
| Untargeted metabolomics levels in serum | 0 week and up to 4 weeks after treatment completion | Untargeted metabolomics levels in patient serum before and after treatment. |
| Untargeted metabolomics levels in follicular fluid | During IVF-ET within 6 months after study completion | Observing untargeted metabolomics levels in follicular fluid collected from patients undergoing IVF/ICSI-ET cycle after treatment completion |
| Proteomic analysis of granulosa cells | During IVF-ET within 6 months after study completion | Proteomic analysis of granulosa cells collected during IVF-ET cycles after treatment. |
| Blood norepinephrine index examination | 0 week and up to 4 weeks after treatment completion | Observing the level of blood norepinephrine at baseline and immediately after treatment |
| Blood 5-hydroxytryptamine (5-HT) index examination | 0 week and up to 4 weeks after treatment completion | Observing the level of blood 5-hydroxytryptamine (5-HT) at baseline and immediately after treatment |
| Blood beta-aminobutyric acid (GABA) examination | 0 week and up to 4 weeks after treatment completion | Observing the level of blood beta-aminobutyric acid (GABA) at baseline and immediately after treatment |
| Evaluating the serum levels of sex hormones | 0 week and up to 4 weeks after treatment completion | 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. |
| Natural pregnancy outcomes include natural pregnancy rate and miscarriage rate | 0 week and within 6 months after treatment completion | 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. |
| Pregnancy outcomes of IVF-ET within 6 Months after Treatment Completion | 0 week and 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. |
| Observing the level of transforming growth factor β (TGF β) in follicular fluid | within 6 months after treatment completion | Observing follicular fluid level of transforming growth factor β (TGF β) when patients undergoing IVF/ICSI -ET after the treatment. |
| Observing the level of tumor necrosis factor-α (TNF-α) in follicular fluid | within 6 months after treatment completion | Observing follicular fluid level of TNF-α when patients undergoing IVF/ICSI -ET after the treatment. |
| Observing the level of reactive oxygen species (ROS) in follicular fluid | within 6 months after treatment completion | Observing follicular fluid level of ROS when patients undergoing IVF/ICSI -ET after the treatment. |
| Observing the level of superoxide dismutase (SOD) in follicular fluid | within 6 months after treatment completion | Observing follicular fluid level of SOD when patients undergoing IVF/ICSI -ET after the treatment. |
| Blood dopamine (DA) examination | 0 week and up to 4 weeks after treatment completion | Observing the level of blood dopamine (DA) at baseline and immediately after treatment |
| Blood corticotropin-releasing hormone (CRH) examination | 0 week and up to 4 weeks after treatment completion | Observing the level of blood corticotropin-releasing hormone (CRH) at baseline and immediately after treatment |
| Blood neuro-endorphin (β-ET) examination | 0 week and up to 4 weeks after treatment completion | Observing the level of blood neuro-endorphin (β-ET) at baseline and immediately after treatment |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORHanwang Zhang
Huazhong University of Science Tech
Outcome results
None listed