Effect of Electro-acupuncture on Women With Diminished Ovarian Reserve

Effect of Electro-acupuncture on Ovarian Function and Outcome of IVF-ET of Women With Diminished Ovarian Reserve：a Randomized Controlled Clinical Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Diminished Ovarian Reserve
• Intervention / Treatment: Other: Treatment group protocol; Other: Control group protocol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 338
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dongmei Huang, doctor; Phone Number: 02783663275 13971578190; Email: hdmjcr@qq.com
• Study Contact Backup: Name: Hanwang Zhang, doctor; Phone Number: 13386151967; Email: hwzhang605@126.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 027
      • Recruiting
      • Department of Integrated Traditional Chinese and Western Medicine Tongji hospital of Huazhong University of Science and Technology
      • Contact: Dongmei Huang; Phone Number: 13971578190; Email: hdmjcr@qq.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age < 40, will undergo IVF-ET;
2. 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;
3. Spouse' semen examination is normal, or after semen prewash can reach the standard of common IVF or Intracytoplasmic Sperm Injection(ICSI).

Exclusion Criteria:

1. Male with azoospermia;
2. Male/female's chromosome is abnormal;
3. Adenomyosis, uterine fibroids, endometrial polyps, scar uterine, reproductive system tuberculosis, oviduct effusion, pelvic lesions such as ovarian endometriosis cyst or tumor;
4. Female has other endocrine disease: thyroid diseases, hyperprolactinemia, insulin resistance, diabetes, adrenal diseases, etc.
5. Definitively diagnosed autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome;
6. Other pathogenesis that leads to recurrent miscarriage or agnogenic recurrent miscarriage;
7. A history of cancer and has received radiotherapy and chemotherapy;
8. Had acupuncture treatment in recent 3 months;
9. 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; 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; 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.
Sham Comparator: Control group; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology
• Collaborators: Wuhan Union Hospital, China; Wuhan No.1 Hospital; The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine; Edwatz Medical Research Institude; Wuhan Jinxin Gynecology and Obstetrics Hospital of Integrative Medicine
• Investigators: Principal Investigator: Dongmei Huang, doctor, Department of Integrated Traditional Chinese and Western Medicine Tongji hospital of Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2019
• Primary Completion (Anticipated): December 1, 2024
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: July 12, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 12, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Randomized controlled trial; In vitro fertilization-embryo transfer; Electro-acupuncture; Diminished ovarian reserve
• Other Study ID Numbers: TJ-IRB20190620

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, 2026, for 1 year
• IPD Sharing Access Criteria: only for research
• IPD Sharing Supporting Information Type: Clinical Study Report (CSR)

Drug and device information, study documents

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