ABSTRACT

Introduction “Subclinical stage” of premature ovarian insufficiency (POI) refers to menstrual disorders with FSH levels in the range of 15-25 U/L in women under 40 years old caused by diminished ovarian function. Early intervention of subclinical POI may be able to protect ovarian function more effectively and prevent further development to POI. Currently, no standard-of-care exists for subclinical POI. Previous studies have shown effectiveness of electroacupuncture (EA) on POI and transcutaneous electrical acupoint stimulation (TEAS) on diminished ovarian reserve, but no published studies focus on the treatment of subclinical POI. This study aims to assess whether EA or TEAS will be effective in improving ovarian function at the subclinical stage of POI and preventing the progression.

Methods 114 subclinical POI patients between 25 and 40 years will be randomly assigned to three groups (an EA group, a TEAS group and a waiting for treatment group) in this randomized, controlled, assessor-blinded trial. The treatment will last for three months and the follow-up will last for twelve months. The primary outcomes will be anti-Mullerian hormone (AMH) and follicle-stimulating hormone (FSH). Secondary outcomes will include serum estradiol (E2), luteinizing hormone (LH), FSH/LH ratio, the menstrual status assessment, and modified Kupperman Menopausal Index. We will also investigate the incidence of adverse events.

Trial registration Trial was registered in the Chinese Clinical Trail Registry (ChiCTR-2100045598); Pre-results.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

Trial was registered in the Chinese Clinical Trail Registry (ChiCTR-2100045598).

Funding Statement

Dr. Lifang Chen and Dr. Zhanglian Wang are initials of the authors who received the awards. Dr. Lifang Chen received fund from the Administration of Traditional Chinese Medicine of Zhejiang Province (NO. 2021ZB145) in 2020. Dr. Zhanglian Wang received fund from the Inheritance Studio Construction Project of National Famous Old Chinese Medicine Experts of Dr. Wang Zhanglian (Letter of the Department of Personnel and Education of the National Administration of Traditional Chinese Medicine, No.(2022)75) in 2022. The URL of the former funder is http://www.zjtcm.gov.cn/. The URL of the latter funder is http://www.satcm.gov.cn/. The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

the Ethics committees of the Third Affiliated Hospital of Zhejiang Chinese Medical University.Ethics approval numbers: ZSLL-KY-2021-004-01

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Footnotes

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AbbreviationsPOIPremature ovarian insufficiencyEAelectro-acupunctureTEAStranscutaneous electrical acupoint stimulationHRThormone replacement therapyFSHfollicle-stimulating hormoneAMHanti-Müllerian hormoneE2estradiolLHluteinizing hormoneCRFcase report formAEsadverse events