Effect of Electro-acupuncture on Women With Diminished Ovarian Reserve

Study Overview
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Brief Summary
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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. In this trial, we hypothesize that electro-acupuncture is efficient for the ovarian function and the following outcome of IVF-ET in DOR patients.

Detailed Description
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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) will be taken. Third, each patient will receive 24 sessions of acupuncture in 2-3 months, twice or three times a week. 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 Electro-acupuncture on Ovarian Function and Outcome of IVF-ET of Women With Diminished Ovarian Reserve：a Randomized Controlled Clinical Trial

Conditions
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Diminished Ovarian Reserve

Intervention / Treatment
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* Other: Treatment group protocol
* Other: Control group protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 40, will undergo IVF-ET; Low ovarian reserve: Antral follicle count (AFC)<7, or AMH<1.1ng/ml; or has a history of poor ovarian response: in the last hyper stimulation cycle, the number of retrieved oocytes<3; Spouse' semen examination is normal, or after semen prewash can reach the standard of common IVF or Intracytoplasmic Sperm Injection(ICSI). Exclusion Criteria: Male with azoospermia; Male/female's chromosome is abnormal; Adenomyosis, uterine fibroids, endometrial polyps, scar uterine, reproductive system tuberculosis, oviduct effusion, pelvic lesions such as ovarian endometriosis cyst or tumor; Female has other endocrine disease: thyroid diseases, hyperprolactinemia, insulin resistance, diabetes, adrenal diseases, etc. Definitively diagnosed autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome; Other pathogenesis that leads to recurrent miscarriage or agnogenic recurrent miscarriage; A history of cancer and has received radiotherapy and chemotherapy; Had acupuncture treatment in recent 3 months; 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment group<br>Treatment group protocol：participants will receive electro-acupuncture twice or three times a week with a maximum of 24 times in 2-3 months. Each treatment session lasts for 30 minutes. | Other: Treatment group protocol<br>* For treatment group, two groups of acupoints will be used alternatively. The first group consists of some acupoints. The patients will be asked to stay in supine position. Disposable sterilized needles (Size: 0.25*40/50 mm) will be inserted into a depth of 15 35 mm and stimulated manually to evoke needle sensation. And then some acupoints will be thereafter connected to electrical stimulators and stimulated with low-frequency and the maximum tolerated intensity of the patients. The other needles without electrical stimulators will be manually stimulated to evoke Deqi every 10 minutes. The second group consists of other acupoints. Patients will be asked to stay in prone position. The stimulation will be in the same way as the first group.<br>|
| Sham Comparator: Control group<br>Control group protocol：participants will receive sham electro-acupuncture twice or three times a week with a maximum of 24 times in 2-3 months. Each treatment session lasts for 30 minutes. | Other: Control group protocol<br>* For control group, four pseudo-acupoints are used, with two points on each shoulder and the two on each upper arm, which are not located on any meridians. The patients will be asked to stay in supine position and keep the whole body relaxed and comfortable. Disposable sterilized needles (Size: 0.18*25 mm) will be inserted superficially to a depth of < 5 mm without any manual stimulus and the needle sensation (Deqi in TCM) should not be evoked. Electrodes are connected to the needles, but the stimulators should be turned on at an intensity of zero. Each intervention lasts for 30 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessing the change of ovarian reserve function | Assessing patients' ovarian reserve function before and after electro-acupuncture intervention, including: (1) The serum AMH, inhibin, and FSH and E2 levels on the third day of menstruation;(2) AFC. | 0 week and up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | the clinical pregnancy rate per cycle of IVF-ET after electro-acupuncture. | through study completion, an average of 1 year | 
| Outcomes of IVF | Gn dosage(U/d) and usage days; E2 level(pg/ml) and endometrial thickness(mm) on human chorionic gonadotropin (HCG) day; number of oocytes; MII oocytes; normal fertility rate; the number of available embryos; number of high-quality embryos; cycle cancellation rate (including cycle cancellation rate caused by various reasons); implantation rate: including fresh periodic implantation rate, per cycle implantation rate and cumulative implantation rate; fresh cycle clinical pregnancy rate and cycle cumulative clinical pregnancy rate; early, mid and late pregnancy abortion rate; risk of ovarian hypertrophy and incidence of obstetric complications; FSH(mIU/ml), LH(mIU/ml), E2(pg/ml) and AMH(ng/ml) in follicular fluid; Oxidative stress related indicators such as reactive oxygen species (ROS), superoxide dismutase (SOD) level, etc.; live rate: including fresh cycle live rate, cycle live rate and cumulative live rate. | through study completion, an average of 1 year | 
| Blood biochemical index examination | Testing the levels of blood corticotrophin-releasing hormone (CRH), norepinephrine, adrenaline, 5-hydroxytryptamine, beta-aminobutyric acid (GABA), dopamine (DA) and neuro-endorphin of the patients before and after treatment. | 0 week and up to 12 weeks | 
| Questionnaires | Evaluation of anxiety, depression, quality of life and sleep state is performed before and after treatment. Baker anxiety self-rating scale (BAI) and baker depression self-rating scale (BDI-Ⅱ) : higher score indicates higher degree of depression or anxiety [12-13]. Zung anxiety self-rating scale (Zung-SAS), Zung depression self-rating scale (Zung-SDS) [14-15]. Quality of life measurement (QOL): Quality of life will be assessed by SF-36 and Chinese quality of life scale (CHQOL). Self-Rating Scale of Sleep (SRSS), sleep dysfunction rating scale (SDRS), Pittsburgh sleep quality index (PSQI). | 0 week and up to 4 weeks | 
| Follow-up detection | Pregnancy patients will be followed up to the end of pregnancy. Adverse pregnancy outcomes and live birth rates will be recorded. Non-pregnant patients will be followed up for 1 year after treatment, testing the ovarian reserve function, follow-up treatment and pregnancy status of the patients within 1 year. | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diminished ovarian reserve, In vitro fertilization-embryo transfer, Randomized controlled trial, Electro-acupuncture