Plain English Summary
Background and study aims
Approximately 10% to 35% of women may experience a premature diminished ovarian reserve (DOR) due to various reasons, and the incidence of DOR significantly increases with age. For DOR patients with infertility, in vitro fertilization and embryo transfer (IVF-ET) can shorten treatment duration and increase pregnancy rates. In IVF-ET, poor egg quality directly affects embryo quality and is one of the crucial factors influencing pregnancy rates. Acupuncture, as a non-pharmacological treatment, can improve ovarian function and egg quality, thereby enhancing pregnancy rates. This study aims to evaluate the effect of acupuncture on ovarian function and the pregnancy outcomes of IVF-ET in patients with DOR.
Who can participate?
Women aged between 20 and 42 years old with infertility due to DOR
What does the study involve?
Eligible patients will be randomly allocated to either the acupuncture group (AG) or the sham acupuncture group (SAG). Based on conventional treatment, patients in AG will receive acupuncture therapy, while the SAG will receive sham acupuncture treatment. Both groups will receive 8 weeks of acupuncture treatments.
What are the possible benefits and risks of participating?
Both groups will receive basic treatment and symptomatic treatment. Participants' symptoms may be relieved in this study. Acupuncture may cause some slight side effects, including bleeding, hematoma, serious pain, and dizziness. These side effects are generally mild and rarely cause serious harm.
Where is the study run from?
Luohu District Hospital of Traditional Chinese Medicine (China)
When is the study starting and how long is it expected to run for?
October 2023 to October 2026
Who is funding the study?
1. Sanming Project of Medicine in Shenzhen (No. SZZYSM 202101007)
2. 2021 Luohu District (First Batch) Soft Science Research Programme Project (No. LX20210102)
Who is the main contact?
Prof. Hong Zhao, hongzhao2005@aliyun.com
Study website
Contact information
Type
Public, Scientific, Principal Investigator
Contact name
Prof Zhao Hong
ORCID ID
http://orcid.org/0000-0001-8211-9483
Contact details
No.16 Xiantong Road
Luohu District
Shenzhen
518004
China
+86 (0)755 25160866
hongzhao2005@aliyun.com
Additional identifiers
EudraCT/CTIS number
Nil known
IRAS number
ClinicalTrials.gov number
Nil known
Secondary identifying numbers
Nil known
Study information
Scientific title
Effect of acupuncture on ovarian function and pregnancy outcomes in patients with diminished ovarian reserve: a prospective randomized controlled trial
Acronym
Study hypothesis
Acupuncture therapy has better efficacy than sham acupuncture in improving ovarian function in women with diminished ovarian reserve (DOR) and improving pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET).
Ethics approval(s)
Approved 06/12/2023, Medical Ethics Committee of Luohu District Hospital of Traditional Chinese Medicine (16 Xiantan Road, Luohu District, Shenzhen, Guangdong Province, 518004, China; +86 (0)755 82311699; lhzyykjk@163.com), ref: 2023-LHQZYYYXLL-KY-147
Study design
Single-center interventional two-armed single-blinded prospective randomized controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment, Efficacy
Patient information sheet
See study outputs table
Condition
Women with infertility due to diminished ovarian reserve including those with or without transferable embryos
Intervention
Eligible patients will be randomly allocated to either the acupuncture group (AG) or the sham acupuncture group (SAG). The SPSS software version 26.0 will be used to generate a random number table at a 1:1 ratio. The concealment of the random allocation scheme will be ensured through sequentially numbered, opaque, sealed envelopes. Blinding will be employed for participants, outcome evaluators, and statistical analysts.
Based on conventional treatment, patients in AG will receive acupuncture therapy, while the SAG will receive sham acupuncture with acupoints located approximately 1 cm adjacent to those used in AG, involving superficial needle insertion of 1-2 mm into the skin. The acupoints for both groups will include Liangmen (ST 21), Huangshu (KI 16), Guanyuan (CV 4), Zhongji (CV 3), Zigong (EX-CA 1), Zusanli (ST 36), and Sanyinjiao (SP 6). Baihui (GV 20) and Shenting (GV 24) will be added for those with insomnia or anxiety.
Acupuncture treatment will be conducted for a continuous 8 weeks before entering the ovulation induction or transplantation cycle, with 3 sessions per week in the 1 to 3 weeks and 2 sessions per week in the following 4 to 8 weeks. Patients without transferable embryos receive acupuncture treatment once a week until the day of hCG injection during ovulation induction based on 8 weeks of acupuncture treatment.
After routine disinfection of the skin at the acupoints, appropriate-length filiform needles will be used. ST 21 and KI 16 will be punctured perpendicularly at a depth of 20-30 mm; CV 4, CV 3, and EX-CA 1 will be punctured perpendicularly or obliquely at a depth of 25-40 mm; ST 36 and SP 6 will be punctured perpendicularly at a depth of 25-50 mm; GV 20 and GV 24 will be punctured horizontally or obliquely at a depth of 10-20 mm. Each treatment will last for 30 minutes.
Intervention type
Procedure/Surgery
Primary outcome measure
Clinical pregnancy rate measured using data collection about on-site visits, telephone calls, or WeChat communications at 4 to 7 weeks after embryo transfer
Secondary outcome measures
1. Biochemical pregnancy rate measured using data collection about on-site visits, telephone calls, and WeChat communications at 2 weeks after embryo transfer
2. Live birth rate measured using data collection about on-site visits, telephone calls and WeChat communications monthly until the end of pregnancy
3. Miscarriage rate measured using data collection about on-site visits, telephone calls and WeChat communications monthly until the end of pregnancy
4. Anti-Müllerian hormone measured using blood samples at baseline and after 8 weeks of treatment
5. Basic hormone levels (follicle-stimulating Hormone, estradiol, luteinizing hormone, FSH/LH ratio) measured using blood samples at baseline and after 8 weeks of treatment
6. Antral follicle count measured using ultrasound at baseline and after 8 weeks of treatment
7. Anxiety assessment measured using the self-rating anxiety scale (SAS) at baseline and after 8 weeks of treatment
8. Endometrial thickness and morphology measured using ultrasound on the day of embryo transfer
9. Patients undergoing ovulation induction cycles measured using data collection about the following indicators within 1 to 7 days after ovulation:
9.1. Gonadotropin (Gn) usage
9.2. Oocyte retrieval
9.3. Fertilization rate
9.4. Cleavage rate
9.5. Morphological assessment of oocytes
9.6. Day 3 high-quality embryo rate
9.7. Day 3 utilizable embryo rate
9.8. Blastocyst formation rate
9.9. High-quality blastocyst rate
Overall study start date
06/10/2023
Overall study end date
30/10/2026
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Women aged 20 to 42 years
2. Conforming to the clinical diagnostic criteria for DOR
3. Voluntary and written informed consent
Participant type(s)
Patient
Age group
Adult
Lower age limit
20 Years
Upper age limit
42 Years
Sex
Female
Target number of participants
164
Participant exclusion criteria
1. Male factor infertility characterized by severe oligospermia, asthenospermia, necrospermia, teratospermia, or azoospermia
2. Conditions such as severe hydrosalpinx, significant tubal or pelvic adhesions, and myomas invading the endometrium, which adversely affect the outcome of IVF pregnancies
3. Immune system disorders such as immune nephritis and systemic lupus erythematosus, which may lead to infertility
4. Endocrinopathies such as hyperprolactinemia, hyperandrogenemia, chronic adrenal insufficiency, and marked thyroid dysfunction
5. Infertility attributable to congenital malformations of the reproductive system, chromosomal anomalies, or other genetic etiologies
6. Coexistence of severe cardiovascular, cerebrovascular, hepatic, renal, or hematopoietic disorders, malignant neoplasms, or psychiatric conditions.
7. Contraindications to pregnancy or uterine non-viability for gestation
8. Received DOR-related interventions (ie. drugs, acupuncture, herbs, etc.) within 4 weeks
9. Subjects considered ineligible for trial participation based on researcher evaluation
Recruitment start date
30/01/2024
Recruitment end date
30/06/2026
Locations
Countries of recruitment
China
Study participating centre
Luohu District Hospital of Traditional Chinese Medicine
16 Xiantan Road, Luohu District
Shenzhen
518004
China
Sponsor information
Organisation
Shenzhen Municipal People's Government
Sponsor details
Shenzhen Municipal Health Commission
East Block
New Town Building
No. 1025 Shennan Middle Road
Futian District
Shenzhen
518031
China
+86 (0)755-88113731
zyc@wjw.sz.gov.cn
Sponsor type
Government
Website
ROR
Organisation
Shenzhen Luohu District Science and Technology Innovation Bureau
Sponsor details
17/F
Luohu Business Centre
No. 2028 Shennan Road East
Luohu District
Shenzhen
518001
China
+86 (0)755-25666780
lh_kcj@szlh.gov.cn
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Sanming Project of Medicine in Shenzen Municipality
Alternative name(s)
'sanming' project of medicine in Shenzhen, Sanming Project of Medicine in Shenzhen, San-Ming Project of Medicine in Shenzhen, Sanming Project of Medicine in Shenzen Municipal
Funding Body Type
government organisation
Funding Body Subtype
Local government
Location
China
Funder name
Soft science Research Program of Luohu District
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
The researchers plan to publish the protocol before February 2024. They plan to publish results before October 2027.
Intention to publish date
30/10/2027
Individual participant data (IPD) Intention to share
Yes
IPD sharing plan
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.
IPD sharing plan summary
Published as a supplement to the results publication
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 09/01/2024 | No | Yes |