Acupuncture on the Conception Vessel for Diminished ovarian reserve: A Multi-Center Randomized Controlled Trial Protocol

Acupuncture on the Conception Vessel for Diminished ovarian reserve: A Multi-Center Randomized Controlled Trial Protocol | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Study protocol Acupuncture on the Conception Vessel for Diminished ovarian reserve: A Multi-Center Randomized Controlled Trial Protocol Xiaoyu Zhang, Yujie Li, Zhengao Sun, Jun Wang, Xingjun Han, Zhibin Dong, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6134147/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Diminished ovarian reserve (DOR) is characterized by a decrease in the number and/or quality of oocytes, leading to insufficient ovarian reserve function. Currently, there is no unified treatment protocol for DOR either domestically or internationally. However, acupuncture, as a non-pharmacological therapy, has been shown in several studies to significantly improve ovarian function in patients with DOR and to maintain the balance of serum and endocrine hormones. This study aims to explore the effects of acupuncture on the Conception Vessel in improving clinical symptoms in patients with DOR, with the goal of providing higher-level evidence-based support. Methods : From November 2024 to October 2025, four hospitals in China will recruit 252 patients diagnosed with DOR to undergo acupuncture treatment. Eligible patients must meet the diagnostic criteria for DOR, be between the ages of 20 and 45, and provide informed consent. Participants will be randomly assigned in a 1:1:1 ratio to one of three groups: the Conception Vessel acupuncture group, the non-Conception Vessel acupoint group, or the Non-acupoint sham-acupuncture group, with 84 patients in each group. All patients will receive treatment three times per week for a total of 12 weeks, with a 4-week follow-up period after treatment completion. No treatment will be administered during menstruation. The primary outcome measure is the baseline antral follicle count (AFC), with comparisons made between the changes in bilateral ovarian AFC from baseline to 12 weeks after treatment, assessed via gynecological ultrasound on days 2-4 of the menstrual cycle. Expected Results and Conclusion: This study aims to further investigate an optimized treatment protocol through a prospective, sham-controlled, multicenter randomized controlled trial (RCT) design, based on real-world clinical settings. The goal is to provide new clinical insights and high-level evidence for the use of Conception Vessel acupuncture in treating DOR. Trial Registration: International Traditional Medicine Clinical Trial Registry, ITMCTR2024000882 Registered on 28 December 2024. Acupuncture Conception Vessel Diminished ovarian reserve Randomized controlled trial Study protocol Figures Figure 1 Figure 2 Figure 3 Background Diminished ovarian reserve (DOR) results from various factors that lead to a decline in oocyte quality and a reduction in follicle number within the ovaries. This condition causes decreased levels of female sex hormones and reduced fertility. It is also associated with a lower antral follicle count (AFC), elevated follicle-stimulating hormone (FSH) levels [1, 2]. In recent years, the incidence of DOR has been increasing. According to data from the American Society for Reproductive Medicine, 31.6% of infertility patients undergoing assisted reproductive technologies (ART) are diagnosed with DOR [3]. If timely and effective interventions are not implemented, women with DOR may progress to premature ovarian failure within 1 to 6 years [4]. Currently, there is no standardized treatment protocol for DOR either domestically or internationally. For patients with DOR who seek to conceive, ART and coenzyme Q10 (CoQ10) supplementation are commonly used approaches to enhance fertility [5-7]. For DOR patients with menstrual dysfunction, treatment often involves hormone-based therapies such as contraceptive pills, estrogen, and progesterone. However, due to the numerous contraindications and side effects associated with these medications, long-term efficacy is often unsatisfactory[8, 9]. Therefore, there is still a need for effective treatments for DOR to improve women's reproductive health and quality of life. In recent years, acupuncture has garnered widespread attention as a non-pharmacological therapy in the field of reproductive disorders[10, 11]. Studies have found that after 1 to 3 menstrual cycles of acupuncture treatment, there can be a significant improvement in the number of eggs retrieved and embryo quality, as well as an increase in embryo implantation rates and clinical pregnancy rates[12]. A meta-analysis combining the results of 13 randomized controlled trials on acupuncture for DOR found that acupuncture therapy demonstrates good clinical efficacy in improving sex hormone levels and increasing AFC in DOR patients[10]. Currently, acupuncture for treating DOR is still in the exploratory stage, with practitioners commonly using points such as CV4, SP6, BL23, EX-CA1, ST36, and LR3. A study on acupuncture point selection patterns for women of childbearing age with DOR found that the Conception Vessel is the most frequently chosen meridian in clinical treatments for DOR[13]. The Conception Vessel, which originates in the lower abdomen near the uterus, plays a role in regulating menstruation and enhancing female reproductive function. Acupuncture targeting the Conception Vessel points may prove to be an effective approach for treating DOR. However, at this stage, evidence from clinical practice regarding the optimization of acupuncture point selection for DOR is still insufficient. This study aims to further investigate the therapeutic effects of acupuncture on the Conception Vessel in DOR patients through a prospective, placebo-controlled, multi-center RCT design, providing new clinical treatment insights and high-level evidence for acupuncture targeting the Conception Vessel in treating DOR. Objectives Explore the clinical efficacy of acupuncture on the Conception Vessel with an optimized point selection for treating DOR through a prospective, placebo-controlled, multi-center randomized controlled trial, and validate the effectiveness of this optimized acupuncture approach for DOR treatment. Methods Study design A multi-center, placebo-controlled, blinded, randomized trial will be conducted from November 2024 to October 2025 at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Dongzhimen Hospital of Beijing University of Chinese Medicine, and Weifang Maternal and Child Health Care Hospital, to evaluate acupuncture treatment for DOR. This study has been approved by the Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, and all three sub-centers have received approval from their local institutions. The Institutional Review Boards at the local research centers have approved the trial protocol, and all patients will be provided written informed consent prior to their inclusion in the study. The study protocol has been approved by the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (Approval No: 2024KY-144) and registered with the International Traditional Medicine Clinical Trial Registry (Registration No: ITMCTR2024000882). In addition, informed consent will be obtained from all patients before the trial begins. All DOR patients will receive acupuncture treatment while awaiting the results of their routine examinations. The study flowchart and schedule are presented in Figure 1 and Table 1, respectively. Table.1 Study schedule of enrolment, intervention, and assessments Detection time Target Screening period Treatment period Follow-up period Pregnancy follow-up (only for pregnant patients) 0-30 days 4 weeks 8 weeks 12 weeks 16 weeks Primary outcome measures Antral follicle count (AFC) (On the 2nd to 4th day of the menstrual cycle, before and after treatment) √ √ Secondary outcome measures Patients in the outpatient clinic Modified Kupperman scale (at the end of each menstrual cycle) √ √ √ √ √ AMH (day 2-4 of each menstrual cycle) √ √ FSH, LH levels, FSH/LH ratio (days 2-4 of each menstrual cycle) √ √ Positive pregnancy (urine HCG test at 7-8 days after menstruation, blood HCG test after positive) √ Clinical pregnancy (gestational sac detected by transvaginal ultrasound 14-21 days after menopause) √ Early spontaneous abortion (within 12 weeks of gestation) √ Set of pregnancy indicators for IVF-ET patients Ongoing pregnancy (pregnancy lasting 12 weeks or later) √ Number of oocytes retrieved (day of oocyte retrieval) √ Number of normal fertilization (day 2 or 3 after oocyte retrieval) √ Number of embryos available for transfer and number of high-quality embryos, such as cleavage and blastocyst (3 and 5 days after oocyte retrieval) √ Participants The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Weifang Maternal and Child Health Hospital, and Dongzhimen Hospital of Beijing University of Chinese Medicine recruited a total of 252 patients diagnosed with DOR through posters, WeChat, media platforms, and online advertisements. At each hospital, two recruitment staff conducted informed consent consultations in dedicated office spaces. Participants were thoroughly informed about the study, including its objectives, intervention measures, potential benefits, and risks. Upon agreeing to participate, they were required to sign an informed consent form. Diagnostic criteria DOR is a condition characterized by diminished ovarian function due to a decrease in the quantity and/or quality of oocytes, leading to reduced fertility. It is often accompanied by decreased levels of anti-Müllerian hormone (AMH), reduced AFC, or elevated levels of basal FSH. Currently, there is no gold standard for the diagnosis of DOR in clinical medicine. This study follows the diagnostic criteria established by the Reproductive Endocrinology and Fertility Preservation Subcommittee of the Chinese Preventive Medicine Association, as outlined in the "Clinical Diagnosis and Treatment Expert Consensus on Ovarian Reserve Decline" published in the April 2022 issue (Volume 31, Issue 4) of the Journal of Reproductive Medicine. The study adopts the following standards: (1) AMH<1.1 ng/ml； (2) basal AFC number < 5-7; (3) 10 IU/L≤FSH≤25 IU/L； Note: AFC and FSH should be measured on days 2 to 4 of the menstrual cycle. Inclusion criteria (1) Meets the diagnostic criteria for DOR. (2) Age between 20 and 45 years. (3) Signed informed consent form. Exclusion criteria (1) Patients with endocrine-related disorders affecting ovulation, such as hyperprolactinemia, polycystic ovary syndrome, diabetes, thyroid disorders, or adrenal diseases. (2) Pelvic conditions such as uterine fibroids, adenomyosis, ovarian tumors, or unilateral or bilateral oophorectomy. (3) Diagnosed autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and antiphospholipid syndrome. (4) Use of hormonal or metabolic medications within the past three months that may affect results. (5) Presence of cardiovascular, neurological, hepatic, renal dysfunction, or severe mental health disorders. (6) Participants currently involved in or who have participated in another clinical trial within the past month. Note: Any participant meeting one or more of the above criteria will be excluded. Abort and fall off criteria (1) Participants who request to withdraw from the study on their own. (2) Participants deemed unsuitable for continued participation by the researcher, such as in cases of severe adverse events, serious complications, or disease progression requiring a change in treatment. (3) Participants who exit the study or are lost to follow-up for other reasons. After a participant drops out, researchers should attempt to contact them via phone or in person to inquire about the reason, record the last treatment date, and complete any remaining assessments. Dropout cases should be carefully documented, and their final primary efficacy endpoints should be transferred for statistical analysis as final results. Sample size calculation This study estimates the improvement in each research group and sets up a two-sided test with α = 0.05. With an equal sample size ratio of 1:1:1 across the three groups, β = 0.1, and a power of 1-β = 90%, the estimated sample size per group is N = 67, as determined using PASS 15 software. Considering a 20% dropout rate, the final sample size per group is calculated to be 84, with a total of 252 participants across all three groups. The calculation formula is as follows: Randomization and Allocation This trial employs a block randomization method to generate random group sequences. The randomization sequences are programmed and generated by an independent statistician using SAS (SAS Institute, Cary, North Carolina, USA) software. These sequences are entered into the Research Electronic Data Capture (Redcap) central randomization system at Peking University Third Hospital. Participants are randomly assigned to one of three groups—Conception Vessel acupoints group, Non - Conception Vessel acupoints group, or Non-acupoint sham-acupuncture group (Figure.2)—in a 1:1:1 ratio, with 84 participants in each group. After obtaining informed consent from eligible patients, the clinical coordinator uses the Redcap central randomization system to determine each patient's corresponding random number and group code. This information is recorded on the participant's Case Report Form (CRF), and backup records are maintained for the participant's random number, group assignment, enrollment date, and basic information. This process ensures the implementation of randomization and allocation concealment. Blinding In this trial, blinding is implemented for participants, outcome assessors, and statistical analysts. These individuals are only aware of group designations labeled as A, B, or C, and blinding is revealed only after the statistical analysis is completed. Due to the inherent nature of acupuncture, the acupuncturists are not blinded. The roles of acupuncturists, outcome assessors, and statistical analysts are assigned to different individuals to ensure separation of these roles. Interventions In this trial, various specifications of disposable acupuncture needles (0.30x25mm, 0.30x40mm, and 0.30x75mm) from Hua Tuo and the SDZ-III electroacupuncture device (Suzhou Medical Instruments, Jiangsu, China) will be used. To enhance patient adherence to the intervention, both groups will receive their interventions from the same experienced physician, who holds a licensed acupuncturist certification and has over three years of clinical acupuncture experience. Before the study begins, the acupuncturist will undergo training on the study protocol and standard acupuncture procedures. The acupuncture points, needle insertion angles, and depths will be determined based on the "Meridian and Acupoint Study" from the National Traditional Chinese Medicine Higher Education "14th Five-Year Plan" textbook and the WHO international acupuncture point location standards, as illustrated in Figure 3 and Table 2. All patients will receive treatments three times a week for a total of 12 weeks, with a 4-week follow-up period after treatment ends. Treatments will be paused during menstruation. Conception Vessel acupoints group Acupuncture treatment will follow a semi-standardized approach. Based on the treatment patterns for Conception Vessel acupuncture identified in a prior real-world study, the acupoints selected for treating DOR in the Conception Vessel group are CV12, CV4, SP6, CV6 (Bilateral), and ST36 (Bilateral). Additionally, one supplementary point will be chosen according to the specific syndrome differentiation: KI3 for Kidney deficiency, LR3 for Hepatic depression, CV12 for Phlegmatic hygrosis, and SP10 for Blood stasis. Non- Conception Vessel acupoints group Select non-therapeutic acupoints from the same nerve segments as those used in the Conception Vessel group, but which are not part of the Conception Vessel. These include GB28, SP14, GB39, and GB34 on one side. Non-acupoint sham-acupuncture group Select four non-acupoint, non-meridian sites close to the locations of the four acupoints in the Conception Vessel group, naming them Non-Acupoint 1, Non-Acupoint 2, Non-Acupoint 3, Non-Acupoint 4 and Non-Acupoint 5. Table.2 Locations and depths of the selected acupoints for the Conception Vessel Acupoints Group, Non-Conception Vessel Acupoints Group, and Non-acupoint sham-acupuncture group. Group Acupoint Location Insertion depth Conception Vessel acupoints CV12 (Zhongwan) On the anterior midline of the abdomen, 4 cun above the umbilicus. 1-1.5 cun CV4 (Guanyuan) On the mid-line of the abdomen, 3/5 of the way down from the umbilicus to the superior edge of the pubic bone. 3-3.5 cun SP6 (Sanyinjiao) 3 cun directly above the tip of the medial malleolus, on the posterior border of the tibia. 1-1.5 cun CV6 (Qihai) On the anterior midline of the lower abdomen, 1.5 cun below the umbilicus. 1-1.5 cun ST36 (Zusanli) 3 cun below ST35, one finger-breadth from the anterior crest of the tibia. 1-2 cun Non-Conception Vessel acupoints GB28 (Weidao) 0.5 cun anterior and inferior to GB27. 0.8-1 cun SP14 (Fujie) 3 cun below SP15, 4 cun lateral to the midline. 1-2 cun GB39 (Xuanzhong) 3 cun above the tip of the external malleolus, on the posterior border of the fibula. 1-1.5 cun GB34 (Yanglingquan) In the depression anterior and inferior to the head of the fibual. 1-1.5 cun Non-acupoint sham-acupuncture group Non-Acupoint 1 On the abdomen, 3 cun above the umbilicus, 1 cun lateral to the anterior midline (between the Kidney and stomach meridian) NA Non-Acupoint 2 On the abdomen, 2.5 cun below the umbilicus, 1 cun lateral to the anterior midline (between the Kidney and stomach meridian) NA Non-Acupoint 3 On the abdomen, 3.5 cun below the umbilicus, 1 cun lateral to the anterior midline (between the Kidney and stomach meridian) NA Non-Acupoint 4 On the lower leg, 2 cun above the medial malleolus, in the middle of the tibia's inner side (between the Liver and spleen meridian) NA Non-Acupoint 5 3 cun below GB34 (between the gallbladder and bladder meridian) NA Outcome measures The total observation period is 20 weeks, comprising a 4-week screening phase (Weeks -4 to 0), a 12-week intervention phase (Weeks 0 to 12), and a 4-week follow-up phase (Weeks 12 to 16). Assessments will be conducted at baseline, Week 12, and Week 16. Primary outcome measures Baseline AFC: Compare the changes in bilateral ovarian AFC from baseline to 12 weeks, assessed via gynecological ultrasound during days 2-4 of the menstrual cycle. AFC directly reflects ovarian reserve and is negatively correlated with age and baseline FSH, making it a reliable indicator for predicting ovarian reserve. Secondary outcome measures (1) Serum Anti-Müllerian Hormone Compare the average changes in serum AMH levels from baseline to Weeks 12 and 16 between groups, as measured by chemiluminescence. AMH is a biomarker that accurately reflects ovarian aging. Compared to other hormones, it can more promptly indicate the decline in ovarian reserve with age. Its levels are not influenced by the menstrual cycle, hormonal contraceptives, or pregnancy, making it a reliable and rapid measure for evaluating ovarian reserve function. (2) Serum Hormone Levels Compare the average changes in serum FSH, LH, and E2 levels from baseline to Weeks 12 and 16 between groups, as measured by chemiluminescence during days 2-4 of the menstrual cycle. As ovarian reserve decreases, the number of FSH receptors released by ovarian granulosa cells diminishes, leading to reduced ovarian responsiveness to FSH. This results in increased secretion of GnRH by the hypothalamus and pituitary, which elevates baseline FSH levels. Therefore, baseline FSH levels can partially reflect ovarian reserve function. (3) Compare the average change in AFC from baseline to Week 16 and perform intergroup comparisons. (4) Modified Kupperman score. (5) Clinical pregnancy rate, live birth rate, and miscarriage rate: Clinical pregnancy rate = (Number of clinical pregnancies / Total number of patients) × 100% Live birth rate = (Number of live births / Total number of patients) × 100% Miscarriage rate = (Number of miscarriages / Total number of patients) × 100% Note: All pregnancy outcomes will be followed up until November 30, 2025. Safety assessment Safety assessments and adverse events (AEs) related to interventions, such as needle-induced syncope, needle retention, subcutaneous bleeding, and hematomas, will be monitored and recorded by research assistants in the CRF. Severe adverse events will be managed by emergency physicians or acupuncturists and reported to the Ethics Committee of Shandong University of Traditional Chinese Medicine. Data collection and quality control Researchers must accurately and comprehensively record the required information in the CRF and store physician prescription data in a structured clinical information collection system. To ensure data accuracy, two data entry personnel will independently enter and verify the data using the web-based Clinical REDCap system. Once data entry and verification are complete, the CRFs will be archived in numerical order with a retrieval index for reference. Electronic data files, including databases, checking programs, analysis programs, results, coding books, and documentation, should be categorized, backed up on multiple disks or storage media, and securely stored to prevent damage. All test results and research records must be retained for at least five years to ensure data traceability. Statistical analysis Data analysis for this study will strictly adhere to the Intention-to-Treat (ITT) principle. Once randomization is assigned, subjects become part of the study cohort regardless of subsequent treatment or completeness of treatment and follow-up. All dropouts after randomization will be included in the ITT analysis at the end of the trial. Data management and statistical analysis will be performed using SPSS 25.0 software. Categorical data will be expressed as frequencies and percentages, while continuous data will be presented as means ± standard deviations (±SD) or means with 95% confidence intervals (95% CI). All statistical tests will be two-sided, with a significance level set at p<0.05. For clinical efficacy indicators and other repeated measures data, analysis will be based on whether the data meet normality and sphericity conditions, using repeated measures ANOVA or generalized estimation equations (GEE) as appropriate. Compliance analysis: Mann-Whitney U tests will be used to compare acupuncture compliance between the two acupuncture groups. Dropout details, including time and reasons, will be listed and analyzed using chi-square tests to compare dropout rates among the three groups. Safety analysis: Details of adverse events, including occurrence time, event name, and related actions, will be listed. Chi-square tests will be used to analyze the incidence of adverse events and safety grading evaluations. Discussion DOR leads to a decline in embryo quality and adversely affects reproductive outcomes, making it one of the primary causes of female infertility[14]. In recent years, the prevalence of DOR has increased and shows a trend toward affecting younger women, with a prevalence rate of 6.3% among women under 35 years old. Moreover, DOR patients experience significantly lower clinical pregnancy rates, live birth rates, and singleton live birth rates[15]. Current treatment options include hormone replacement therapy, ovarian stimulation, assisted reproductive technologies, stem cell therapy, and in vitro activation of follicles. However, these methods are associated with numerous contraindications and adverse effects, and their long-term efficacy remains unsatisfactory[16]. In recent years, research on Traditional Chinese Medicine (TCM) treatments for DOR has been increasing annually[9], with acupuncture showing significant clinical efficacy in treating DOR. Numerous clinical trials and basic research studies have demonstrated the multi-target advantages of acupuncture for DOR. Acupuncture can inhibit granulosa cell apoptosis, promote follicle development and maturation, reduce follicle atresia, regulate the reproductive endocrine system, and improve sex hormone levels[12]. It can also modulate the expression levels of signaling molecules in various signaling pathways, enhancing ovarian secretion and synthesis functions[17]. It can also modulate the expression levels of signaling molecules in various signaling pathways, enhancing ovarian secretion and synthesis functions. The Conception Vessel is directly and closely related to the uterus and pregnancy in terms of its origin, path, and functions. Its connection to the uterus is a key component of the traditional "meridian-organ relationship" theory. However, there is currently limited research on acupuncture of the Conception Vessel for DOR, and there is a lack of high-quality clinical evidence supporting this approach. In current clinical practice, evidence for optimizing acupuncture point selection for DOR is still insufficient. Our preliminary research on real-world clinical data for DOR has confirmed the close relationship between the Conception Vessel and uterine diseases, and has led to an optimized acupuncture point selection scheme for treating DOR. Therefore, this study aims to further investigate this optimized scheme through a prospective, placebo-controlled, multi-center RCT design. The goal is to provide new clinical treatment insights and higher-level evidence-based medical evidence for acupuncture on the Conception Vessel in treating DOR. Declarations Clinical Trial Number: ITMCTR2024000882 Trial status This study was registered in the International Traditional Medicine Clinical Trial Registry (ITMCTR) in 2024. The platform is jointly managed by the China Academy of Chinese Medical Sciences and the China Traditional Chinese Medicine Evidence-Based Center, and is a non-profit organization. It is recognized by the World Health Organization (WHO) as a primary registration platform and regularly provides data to the WHO International Clinical Trials Registry Platform (WHO ICTRP). The actual start date of the study is November 1, 2024, with an anticipated completion date of October 1, 2025. Recruitment began on November 30, 2024, and is expected to end by July 1, 2025. Acknowledgements: We appreciate the DeepL platform for helping to polish English language and grammatical check in my manuscript. Authors’ contributions: All authors have read and approved the manuscript. Xiaoyu Zhang and Yujie Li are responsible for planning and writing the protocol. Zhengao Sun, Jun Wang and Xingjun Han are overseeing the implementation and coordination of the research. Zhibin Dong is in charge of participant allocation and, together with Hao Sun and Zhihao Diao, is responsible for the statistical planning and analysis. Dongqing Du and Na Zhang are responsible for planning the process evaluation as well as reviewing and editing the protocol. Yuxia Ma is responsible for coordinating the progress across all centers and serves as the overall principal investigator of the study. Fundings: The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Key Research and Development Program Funding Project (2022YFC3500403) and NATCM's Project of High-level Construction of Key TCM Disciplines (zyyzdxk-2023116). Availability of data and materials: Not applicable. Ethics approval and consent to participate: This study will be conducted in accordance with the Declaration of Helsinki. The entire project has been approved by the Ethics Committee of Shandong University of Traditional Chinese Medicine Affiliated Hospital (Approval ID: 2024KY-144) and registered with the International Traditional Medicine Clinical Trial Registry (Registration Number: ITMCTR2024000882). Prior to randomization, patients will be required to sign an informed consent form. Participants' personal information will be kept confidential, and participation in the study is entirely voluntary. They have the right to withdraw at any stage of the study, at any time. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. References Neves AR, Montoya-Botero P, Polyzos NP: Androgens and diminished ovarian reserve: the long road from basic science to clinical implementation. A comprehensive and systematic review with meta-analysis . Am J Obstet Gynecol 2022, 227 (3):401-413.e418. Tal R, Seifer DB: Ovarian reserve testing: a user's guide . American journal of obstetrics and gynecology 2017, 217 (2):129-140. Kawwass JF, Chang J, Boulet SL, Nangia A, Mehta A, Kissin DM: Surgically acquired sperm use for assisted reproductive technology: trends and perinatal outcomes, USA, 2004-2015 . Journal of assisted reproduction and genetics 2018, 35 (7):1229-1237. Pastore LM, Christianson MS, Stelling J, Kearns WG, Segars JH: Reproductive ovarian testing and the alphabet soup of diagnoses: DOR, POI, POF, POR, and FOR . 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Xin Du HW, Xu Han, Yingying Qin: The patterns of acupuncture point selection for treating ovarian function decline in reproductive-aged women and its effects on the reproductive axis . Lishizhen Medicine and Materia Medica 2019, 11 :2784-2786. Moolhuijsen LME, Visser JA: Anti-Müllerian Hormone and Ovarian Reserve: Update on Assessing Ovarian Function . The Journal of clinical endocrinology and metabolism 2020, 105 (11):3361-3373. Harris BS, Jukic AM, Truong T, Nagle CT, Erkanli A, Steiner AZ: Markers of ovarian reserve as predictors of future fertility . Fertil Steril 2023, 119 (1):99-106. Morin SJ, Patounakis G, Juneau CR, Neal SA, Scott RT, Seli E: Diminished ovarian reserve and poor response to stimulation in patients <38 years old: a quantitative but not qualitative reduction in performance . Human reproduction (Oxford, England) 2018, 33 (8):1489-1498. Lu G, Zhu YY, Li HX, Yin YL, Shen J, Shen MH: Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats . Frontiers in genetics 2022, 13 :968711. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6134147","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Study protocol","associatedPublications":[],"authors":[{"id":428028658,"identity":"bdc4b3cc-9e01-4b85-b04d-5e8797f7a622","order_by":0,"name":"Xiaoyu Zhang","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyu","middleName":"","lastName":"Zhang","suffix":""},{"id":428028659,"identity":"eaf55f3c-dc84-4d24-8196-14f237c51d7e","order_by":1,"name":"Yujie Li","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yujie","middleName":"","lastName":"Li","suffix":""},{"id":428028660,"identity":"fc294ca3-58e7-4929-bcf1-b674e8c63180","order_by":2,"name":"Zhengao Sun","email":"","orcid":"","institution":"Affiliated Hospital of Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhengao","middleName":"","lastName":"Sun","suffix":""},{"id":428028661,"identity":"d3750209-1479-4c01-9b59-2ca091b1d234","order_by":3,"name":"Jun Wang","email":"","orcid":"","institution":"Dongzhimen Hospital Beijing University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Wang","suffix":""},{"id":428028662,"identity":"b515f0f2-d51e-4029-993f-b7826090d351","order_by":4,"name":"Xingjun Han","email":"","orcid":"","institution":"Second Affiliated hospital of Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Xingjun","middleName":"","lastName":"Han","suffix":""},{"id":428028663,"identity":"484db2e9-4623-4139-8e92-29d379949d5e","order_by":5,"name":"Zhibin Dong","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhibin","middleName":"","lastName":"Dong","suffix":""},{"id":428028664,"identity":"f6886fd8-3b17-41ba-9bc1-19935b9418a0","order_by":6,"name":"Hao Sun","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Sun","suffix":""},{"id":428028665,"identity":"dfe30df0-3358-4266-b13d-e78dc29e75c6","order_by":7,"name":"Zhihao Diao","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhihao","middleName":"","lastName":"Diao","suffix":""},{"id":428028666,"identity":"036526ff-b7fa-43c7-9f12-5f2826a1b6cd","order_by":8,"name":"Na Zhang","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Na","middleName":"","lastName":"Zhang","suffix":""},{"id":428028667,"identity":"5b8eeb33-c11c-479d-8dbf-102a49ee00e2","order_by":9,"name":"Dongqing Du","email":"","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Dongqing","middleName":"","lastName":"Du","suffix":""},{"id":428028670,"identity":"28aa195f-2236-4070-89fa-ba0460773dfc","order_by":10,"name":"Yuxia Ma","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYBAC+xkMBhAWe2Pjww/EaDG4AdYCxDyHm40lSNMikd4mwEOUltvNWzfztv2R1535sI1BgsFOTreBgBb7OcfKbvOcMTDcdjux7UEBQ7Kx2QFCtkjkmN3mqTBIMLud2G4gwXAgcRtxWgyAWm4ebJPgIV4LyJYbjERrSSu7OeeMseG2M4nAQDYgyi/J2268bZOTNzt+/OHDDxV2cgS1gAATIjoMiFAOAow/iFQ4CkbBKBgFIxQAAKiQRPOfPGiFAAAAAElFTkSuQmCC","orcid":"","institution":"Shandong University of Traditional Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Yuxia","middleName":"","lastName":"Ma","suffix":""}],"badges":[],"createdAt":"2025-03-01 10:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6134147/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6134147/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78690752,"identity":"32a02ee7-3129-48b7-a4c9-671e7467ad63","added_by":"auto","created_at":"2025-03-17 16:14:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":978900,"visible":true,"origin":"","legend":"\u003cp\u003eTrial flow chart.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6134147/v1/50a92c2cfe5df04d732413c7.png"},{"id":78690758,"identity":"0b263ec8-48f2-4fec-a880-731028090928","added_by":"auto","created_at":"2025-03-17 16:14:49","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":364356,"visible":true,"origin":"","legend":"\u003cp\u003eIllustration of Acupuncture and Non-penetrating Sham Needle\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6134147/v1/4f840294516e86e3fa1e52a5.jpg"},{"id":78690763,"identity":"8e5f330a-8af3-47ad-b6cd-aa822cd83234","added_by":"auto","created_at":"2025-03-17 16:14:49","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1442432,"visible":true,"origin":"","legend":"\u003cp\u003eDiagrams of the Conception Vessel Acupoints Group, Non-Conception Vessel Acupoints Group and Non-acupoint sham-acupuncture group.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6134147/v1/0b585bffd0ff107519cd23b4.png"},{"id":85458547,"identity":"facfa979-354c-4e40-a268-b1de61c7da51","added_by":"auto","created_at":"2025-06-26 07:01:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4173575,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6134147/v1/a2bf9376-592c-40a4-afd3-8d53cbac3c8f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Acupuncture on the Conception Vessel for Diminished ovarian reserve: A Multi-Center Randomized Controlled Trial Protocol","fulltext":[{"header":"Background","content":"\u003cp\u003eDiminished ovarian reserve (DOR) results from various factors that lead to a decline in oocyte quality and a reduction in follicle number within the ovaries. This condition causes decreased levels of female sex hormones and reduced fertility. It is also associated with a lower antral follicle count (AFC), elevated follicle-stimulating hormone (FSH) levels [1, 2]. In recent years, the incidence of DOR has been increasing. According to data from the American Society for Reproductive Medicine, 31.6% of infertility patients undergoing assisted reproductive technologies (ART) are diagnosed with DOR [3]. If timely and effective interventions are not implemented, women with DOR may progress to premature ovarian failure within 1 to 6 years [4]. Currently, there is no standardized treatment protocol for DOR either domestically or internationally. For patients with DOR who seek to conceive, ART and coenzyme Q10 (CoQ10) supplementation are commonly used approaches to enhance fertility [5-7]. For DOR patients with menstrual dysfunction, treatment often involves hormone-based therapies such as contraceptive pills, estrogen, and progesterone. However, due to the numerous contraindications and side effects associated with these medications, long-term efficacy is often unsatisfactory[8, 9]. Therefore, there is still a need for effective treatments for DOR to improve women\u0026apos;s reproductive health and quality of life.\u003c/p\u003e\n\u003cp\u003eIn recent years, acupuncture has garnered widespread attention as a non-pharmacological therapy in the field of reproductive disorders[10, 11]. Studies have found that after 1 to 3 menstrual cycles of acupuncture treatment, there can be a significant improvement in the number of eggs retrieved and embryo quality, as well as an increase in embryo implantation rates and clinical pregnancy rates[12]. A meta-analysis combining the results of 13 randomized controlled trials on acupuncture for DOR found that acupuncture therapy demonstrates good clinical efficacy in improving sex hormone levels and increasing AFC in DOR patients[10]. Currently, acupuncture for treating DOR is still in the exploratory stage, with practitioners commonly using points such as CV4, SP6, BL23, EX-CA1, ST36, and LR3. A study on acupuncture point selection patterns for women of childbearing age with DOR found that the Conception Vessel is the most frequently chosen meridian in clinical treatments for DOR[13]. The Conception Vessel, which originates in the lower abdomen near the uterus, plays a role in regulating menstruation and enhancing female reproductive function. Acupuncture targeting the Conception Vessel points may prove to be an effective approach for treating DOR. However, at this stage, evidence from clinical practice regarding the optimization of acupuncture point selection for DOR is still insufficient. This study aims to further investigate the therapeutic effects of acupuncture on the Conception Vessel in DOR patients through a prospective, placebo-controlled, multi-center RCT design, providing new clinical treatment insights and high-level evidence for acupuncture targeting the Conception Vessel in treating DOR.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eExplore the clinical efficacy of acupuncture on the Conception Vessel with an optimized point selection for treating DOR through a prospective, placebo-controlled, multi-center randomized controlled trial, and validate the effectiveness of this optimized acupuncture approach for DOR treatment.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA multi-center, placebo-controlled, blinded, randomized trial will be conducted from November 2024 to October 2025 at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Dongzhimen Hospital of Beijing University of Chinese Medicine, and Weifang Maternal and Child Health Care Hospital, to evaluate acupuncture treatment for DOR. This study has been approved by the Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, and all three sub-centers have received approval from their local institutions. The Institutional Review Boards at the local research centers have approved the trial protocol, and all patients will be provided written informed consent prior to their inclusion in the study. The study protocol has been approved by the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (Approval No: 2024KY-144) and registered with the International Traditional Medicine Clinical Trial Registry (Registration No: ITMCTR2024000882). In addition, informed consent will be obtained from all patients before the trial begins. All DOR patients will receive acupuncture treatment while awaiting the results of their routine examinations. The study flowchart and schedule are presented in Figure 1 and Table 1, respectively.\u003c/p\u003e\n\u003cp\u003eTable.1 Study schedule\u0026nbsp;of enrolment, intervention, and assessments\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Detection time\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eTarget \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003eScreening period\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 195px;\"\u003e\n \u003cp\u003eTreatment period\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eFollow-up period\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003ePregnancy follow-up (only for pregnant patients)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e0-30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e4 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e8 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e12 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e16 weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 474px;\"\u003e\n \u003cp\u003ePrimary outcome measures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAntral follicle count (AFC) (On the 2nd to 4th day of the menstrual cycle, before and after treatment)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"6\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 474px;\"\u003e\n \u003cp\u003eSecondary outcome measures\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 474px;\"\u003e\n \u003cp\u003ePatients in the outpatient clinic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eModified Kupperman scale (at the end of each menstrual cycle)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAMH (day 2-4 of each menstrual cycle)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" rowspan=\"2\" style=\"width: 195px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eFSH, LH levels, FSH/LH ratio (days 2-4 of each menstrual cycle)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003ePositive pregnancy (urine HCG test at 7-8 days after menstruation, blood HCG test after positive)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" rowspan=\"3\" style=\"width: 324px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eClinical pregnancy (gestational sac detected by transvaginal ultrasound 14-21 days after menopause)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eEarly spontaneous abortion (within 12 weeks of gestation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" valign=\"top\" style=\"width: 568px;\"\u003e\n \u003cp\u003eSet of pregnancy indicators for IVF-ET patients\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003eOngoing pregnancy (pregnancy lasting 12 weeks or later)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" rowspan=\"4\" style=\"width: 324px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003eNumber of oocytes retrieved (day of oocyte retrieval)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003eNumber of normal fertilization (day 2 or 3 after oocyte retrieval)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003eNumber of embryos available for transfer and number of high-quality embryos, such as cleavage and blastocyst (3 and 5 days after oocyte retrieval)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026radic;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Affiliated Hospital of Shandong University of Traditional Chinese Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Weifang Maternal and Child Health Hospital, and Dongzhimen Hospital of Beijing University of Chinese Medicine recruited a total of 252 patients diagnosed with DOR through posters, WeChat, media platforms, and online advertisements. At each hospital, two recruitment staff conducted informed consent consultations in dedicated office spaces. Participants were thoroughly informed about the study, including its objectives, intervention measures, potential benefits, and risks. Upon agreeing to participate, they were required to sign an informed consent form.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDOR is a condition characterized by diminished ovarian function due to a decrease in the quantity and/or quality of oocytes, leading to reduced fertility. It is often accompanied by decreased levels of anti-M\u0026uuml;llerian hormone (AMH), reduced AFC, or elevated levels of basal FSH.\u003c/p\u003e\n\u003cp\u003eCurrently, there is no gold standard for the diagnosis of DOR in clinical medicine. This study follows the diagnostic criteria established by the Reproductive Endocrinology and Fertility Preservation Subcommittee of the Chinese Preventive Medicine Association, as outlined in the \u0026quot;Clinical Diagnosis and Treatment Expert Consensus on Ovarian Reserve Decline\u0026quot; published in the April 2022 issue (Volume 31, Issue 4) of the Journal of Reproductive Medicine. The study adopts the following standards:\u003c/p\u003e\n\u003cp\u003e(1) AMH\u0026lt;1.1 ng/ml；\u003c/p\u003e\n\u003cp\u003e(2) basal AFC number \u0026lt; 5-7;\u003c/p\u003e\n\u003cp\u003e(3) 10 IU/L\u0026le;FSH\u0026le;25 IU/L；\u003c/p\u003e\n\u003cp\u003eNote: AFC and FSH should be measured on days 2 to 4 of the menstrual cycle. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1) Meets the diagnostic criteria for DOR.\u003c/p\u003e\n\u003cp\u003e(2) Age between 20 and 45 years.\u003c/p\u003e\n\u003cp\u003e(3) Signed informed consent form.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExclusion criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1) Patients with endocrine-related disorders affecting ovulation, such as hyperprolactinemia, polycystic ovary syndrome, diabetes, thyroid disorders, or adrenal diseases.\u003c/p\u003e\n\u003cp\u003e(2) Pelvic conditions such as uterine fibroids, adenomyosis, ovarian tumors, or unilateral or bilateral oophorectomy.\u003c/p\u003e\n\u003cp\u003e(3) Diagnosed autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and antiphospholipid syndrome.\u003c/p\u003e\n\u003cp\u003e(4) Use of hormonal or metabolic medications within the past three months that may affect results.\u003c/p\u003e\n\u003cp\u003e(5) Presence of cardiovascular, neurological, hepatic, renal dysfunction, or severe mental health disorders.\u003c/p\u003e\n\u003cp\u003e(6) Participants currently involved in or who have participated in another clinical trial within the past month.\u003c/p\u003e\n\u003cp\u003eNote: Any participant meeting one or more of the above criteria will be excluded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAbort and fall off criteria\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1) Participants who request to withdraw from the study on their own.\u003c/p\u003e\n\u003cp\u003e(2) Participants deemed unsuitable for continued participation by the researcher, such as in cases of severe adverse events, serious complications, or disease progression requiring a change in treatment.\u003c/p\u003e\n\u003cp\u003e(3) Participants who exit the study or are lost to follow-up for other reasons.\u003c/p\u003e\n\u003cp\u003eAfter a participant drops out, researchers should attempt to contact them via phone or in person to inquire about the reason, record the last treatment date, and complete any remaining assessments. Dropout cases should be carefully documented, and their final primary efficacy endpoints should be transferred for statistical analysis as final results.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size calculation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study estimates the improvement in each research group and sets up a two-sided test with \u0026alpha; = 0.05. With an equal sample size ratio of 1:1:1 across the three groups, \u0026beta; = 0.1, and a power of 1-\u0026beta; = 90%, the estimated sample size per group is N = 67, as determined using PASS 15 software. Considering a 20% dropout rate, the final sample size per group is calculated to be 84, with a total of 252 participants across all three groups. The calculation formula is as follows:\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAWsAAABYCAYAAAAz39bPAAAAAXNSR0IArs4c6QAAAARnQU1BAACxjwv8YQUAAAAJcEhZcwAADsMAAA7DAcdvqGQAAA/wSURBVHhe7Z3Ly93EG8fT3x8gXnbaVV8FRUXxUkWt0C6sFheCSFVcCILFuvLW2urOVq1KBcHbzl29bFx4qQoVWhWttigiCtoiIq5erbV/wGs+88v37bwxOUnOOTnn5OT7gTlzMpkkk5lnnkyeuWTVUkpijDFmpvlf5htjjJlhrKyNMaYDWFkbY0wHsLI2xpgOYGVtjDEdwMraGGM6gJW1MTPEm2++mZx//vnJqlWrkptvvjkLNcbK2swYr7/+enL22WdnW9X8+eefQcGh2FBwHF/FZ599VlsZHj9+PMR77rnnspDm1E0j6Tp48GDy1VdfJYcOHUo++uij5IMPPsj2mt7DpBhjps233367tHHjRiZoBVeHVKEtLSwshOPef//9pcXFxWxPOcThGK7BcYPYs2fP0llnnRXi8n8Yhkmj4NrDXtfMH25Zm6lDq3X9+vXJmWeemYVUQ0t13bp1yU033ZTs378/2bRpU3LOOedke8vZu3dvkirBbKuY7777Lrn66quTAwcONGrl5xk2jWLt2rXZP2NsBjFTBoV28uTJ5Oeffw7/64Ay3bp1a5K2VpNXXnklC60GM8Orr76aPPLII1lIMdu3b09efPHFoGDvv//+LLQZw6bRmDKsrM1UufPOO5Pdu3c3anGiTE+cONFICWI3vvfee5NnnnkmWb16dRZaDEr6hhtuyLaGY5g0xpDew4cPZ1vGWFmbjkGLlY63zZs3J2vWrMlCq3nwwQfDKIstW7ZkIe0xbBpjSC/K3hhhZW06BUoQsHFjNsG2zAgLje5AUeZhRMVbb72V7NmzJwtpl2HSGKP0GhNjZW06BZ1+8Pzzzye//fZbMFksLS2FoW6YDVCQDLcTmBPuueeeoKgvu+yyLLRdmqYxRum96qqrgr3bGGFlbTrJrl27km3bti3burExP/7448F08MILL4QwwJywsLAQ4paB3ZzOx3FTN40xMn/QwWlMjJW16SRFnYTXXXdd8NVqxdyAOeGbb75ZNkPgGE4HmCvYbsvkUCeNMTJ/7Ny5c+QOTjN/WFmbuQWzB+aHvMMcAZgZFDZt5SjzB2PAH3744eUwY4SVtekUGl3xzz//BH8WGSaNMn8w1E9mE94IjBFW1qZT3H333cF/7733gh/z4YcfBp/x1JOC2ZeYUuK1Q5qmUeYPWvrYz40pwsrazAzxokVlw9swVzzwwANhJmK8IBL/n3766TCKokrhqcVbZWZgv0Z2HD16NPh1aJJGmT8gP7QQ5f3rr7+GOAz5s1mk5ywZM2VSpbS8YFLstABSESxwpAWZcKkCrLXoEYspxddKlWq25zT79u0L51Oc2JEe9guuSXjRteukcfPmzWFfUTpee+215Wuy0JXpN6v4SQXCGGPMDGMziDHGdAAra2OM6QBW1sYY0wGsrI0xpgNYWRtjTAewsjbGmA4wtLJm0gID+5m9xaLuGrDPTC6+W0f4E088EcKMMcaMxlDKGsXM55F27NiR7Nu3Lzl27Fj4fD6zrFhV7K+//gqztJitVbXQukC5N3VtLGtpjDGzyFDKmoVm+AJGvJj7Sy+9FKbLavUyvugMp06dCn4VzM1p6ryMpDGmN6RKbySYJstp8tNomSI7htOPBNe3s7Ozm4Rrm5Gnm/N9OZZyXFxcXPGFaswUmEK+/vrrLMQYY8ywjDQaBNs1ijptRa9Q1Fo9TaaQOuTt0XWcbdbGmL4wkrKmUxE2bNgQfPH5558H//rrrw9+HWjgN3W2WRtj+sJIylpKWd+VE0eOHAn+NddcE3xjjDGjMZKyllK+6KKLgl8EC65v3bo12zLGGDMMIylrvg5NJ2JsrwZ9suiCCy5ITp48mTz11FNh28wuRX0CXXNm8hSVQxdcF/HHB0zoqOUB+8svv2QhxlRjuZksI7WszXzAR1ybjNwxBiw3k6WXylrrmnR17RKGTNIPwPT+cfDxxx8nt956a7Zl5hXkHpmJv8Q+Cl2WG+o/dej48eNZyOzTO2WNoK5fvz657bbbkt27d2eh3QAlTfqpcHw5exxorLxH7swvKCQU0+233x76mcZB1+VGy2XQ58b/QfCQo2HHBEDZvFm8jrpIPkwMbNZ9YefOneHL1uP4UrS+Sj3Jr07zZW59WZvp/LhR0Ze8zWRA/nCThK+kHzp0KPxHZou+xN6UeZEb6i/lEX+xPoZ8I8+Iozw8duzY8tfvx1EH69IbZa1MLyuUpkyj0sWMS1mztss4Kq+pBsWADPKgnxbjUtbzJDc8zMiXooaX9IYUtUBhE47j/yTojRlk165dycLCQrBVjQOWgcV1HeyO+UlNph147U7rXOVrdxeYJ7nZsmVL0A3bt2/PQk7DLGnKLD9bes2aNdm/JPnjjz+yf+3SC2WNzQlb3WOPPZaFzAbYvOKxn0VuXJ1BRWDLZC1yT9vvFvRZFMlK7NpcN2ce5SZ92wk6ou76+zHnnntu9q9deqGs33777eBffPHFwS8DAdfXb+SoGMzCFPG+uEKweJU6INR616gNwvh6Tr5FtW3btvDUHuSI0xaffPJJENI8Gi1Duv0VoMGQN+QL+US+KM/IP400QE60DxcTHys506gNnSuvQPbv318oK7FrU5GWyc0wdWBWuOWWW4JftwNWi9Vt3LhxRSu7VdKCnXuw7VbdqmxQ2OIWFxdDmGxZsW2OfYTF58PWhR2SfVrfmzCuy3l1zDht3OOwWZNm7jGGtBJO+rHvk246NrmW7HbsJ3xc9v8uQ3mXdT7FkIeExWVG3ku20tfwsI88lQzqGPJ7XHC+UW3NRXJTpw5wj4SzPWuojtatU5Qx5T7Je+mFsqYQqhQlAky8fEcChUeliRlUqKq8ElxRVIGHBQHhGgj/KMLCOahQZUhZcy9xPHW6MLqm7xTJAvmTHymhPCtTlJQlxyA/oqkCqSJW/rFsNqVKblQH9NARqmP5+jQrkDbKoQrknrh5XdE2vVHWVQIvxRRXliIQUuINqnRFBVknDVWowhe5pnAuKtQgJJT5VpTSQaXvCnFe1XV1KiPlXaW8QG9pRefkgcs+zhMrN+XzqC1hKcm8G0Ye68iNGib5PFE68vI0KyhfBiE9MY23yl7OYCwCG1sqZGGyCXa3sg6aL7/8MviXXHJJ8GOwz6UVL5wnthnqXFdeeWXwh4VzpmVW6JryxRdfLNsVy6DHP62Yobc85ocffgj+FVdcEfwuUJRnVa6O3Zdvj544cSK5/PLLg/1Z9v08n376afCLVqj86aefgp82FFYsikYZQZGsNaGsbwTbd1Oq5Ib7Z7JM+iBf8Y1WOHr0aPCr+o6agC28zU74GOztd911V/hIeFXdaQMr6wg+QZY+/YPCXbduXWEnmipd0cwtfYzhjjvuCL5gDQVo8jGGtnnnnXeSG2+8MdsqhkpXtPaDOrxGVSLzwKZNm5K0BRk6mhj6hVwUjSjgwcdDPL9CJWhdeHVyCcoIZmmWYJXc/Pjjj8FnlnAe5AkGLancBDWCJiGHlCkdpenb5lQUdSB9ws493GaTW+W1tOxVjldA9hVRZsvSuUaxE44T2UIH2bvLXsE5ljyoY9vrGzJ15M1DMp2V2fglHzEqozJZmwZ15EamjnwdkDxVmRmnCekrkmvum/Bpm/160bKm1TOIvNmDoThqHZ86dSr4wNOVV17iF0HrCfKvz7Qo0kpX2KpqA15FeWVj2FfRQjW8AZCeQUOO9AqeZ+/evSEPmGQkeAPhdVT5oiF+OIY4kR5aI4qTNxWwTauF+MRh2BpOw6OAvOd+iKOyUlhZebQJaSONMTIX/f3338EXMp1deumlwY+R2SAvo2qhTnJVu3HIzYEDB7J/K3nooYeC/+ijjwafa2l4IvIjGWBb16d8KVvC2BejY+MyIO2SO45HTjgX8apMJVwfiJ8HmWcC3Msvv5yFnIbzxnLaKpnSnmuqem/Zl1aW5RaDWtZlHT6cj3CetHHLm31FLSGFcwwtizY7J+hppxXA/XDdopYM6S9r5QnujePVmiDtajXF5+RecBppQBzdH+ngvolPnipOXA6clzg45b+uHectYYqr/yozpXGSKC/islTLOv82orjcP/ek9EMsUzFxuORR+dMG45Ib6gzHqxNR5UNYnFech7zA55rEYZv4xGWbfeQTPmExhBOm9HAcaVY4ea5t/PzxeWL5jVF6lDexo0zYV6ZXxk0vlHVZhQAVsjIeh8BJePJQSMQhflxIg64hYaHAY4FtA+4HAcWp4vA/hnQgnIPgWO5VFU33XHacFFXc08914gee8ijOVyky0i0I47gi2Md5SVd8zKShHMkf5bHyJ1/ZgXSSZuLk0637z+creSaZ5DptK4RxyA3lynH5+lRWl0Dypf2kg23uWRTJA2kjXj49SgPnFaSHtA9CD4R8OlU+g1zbZSN6oayBwqoqsHlDAhgrEFWGfEWMUZwixVMGlSOfv/lzSPBjqIRUphg9JIqQwm/7oddnhpUbyoQ4TZRXvvxVvvE5kIdYeQNKmnikK0aNhjicB0eZPAnSkb/GrNGb0SBvvPFGGOURTx2fd+67777gP/vss8s2ucOHDwf76CD7OXGgSS+7hmsJ2ZW5lsCeGW+rDyAeXUA6mfJbNJoAfv/99+CfccYZwTfjZ1i5OXjwYPDrjvbArkz5xx8woK8kVZwr+n2Qhw0bNmRb/4cRNGnj4D/2c2QqDucayGaZPAF2Z9Lx5JNPZiGzSW+UNYWfthiSHTt2hALtAwhs2moJgsh6DvDuu+/+R/DzfP/998E/77zzgl8FFYIHYdyBpg7KeKxtvtKp83b16tXBBzpzoGgsLuWGQkBpaLibGT/Dyg1DX1G0dTvS1Si48MILgw880NeuXZttnX7o51f4O3LkSOjszEMnf9wp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width=\"363\" height=\"88\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRandomization and Allocation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis trial employs a block randomization method to generate random group sequences. The randomization sequences are programmed and generated by an independent statistician using SAS (SAS Institute, Cary, North Carolina, USA) software. These sequences are entered into the Research Electronic Data Capture (Redcap) central randomization system at Peking University Third Hospital. Participants are randomly assigned to one of three groups\u0026mdash;Conception Vessel acupoints group, Non - Conception Vessel acupoints group, or\u0026nbsp;Non-acupoint sham-acupuncture\u0026nbsp;group (Figure.2)\u0026mdash;in a 1:1:1 ratio, with 84 participants in each group.\u003c/p\u003e\n\u003cp\u003eAfter obtaining informed consent from eligible patients, the clinical coordinator uses the Redcap central randomization system to determine each patient\u0026apos;s corresponding random number and group code. This information is recorded on the participant\u0026apos;s Case Report Form (CRF), and backup records are maintained for the participant\u0026apos;s random number, group assignment, enrollment date, and basic information. This process ensures the implementation of randomization and allocation concealment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBlinding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this trial, blinding is implemented for participants, outcome assessors, and statistical analysts. These individuals are only aware of group designations labeled as A, B, or C, and blinding is revealed only after the statistical analysis is completed. Due to the inherent nature of acupuncture, the acupuncturists are not blinded. The roles of acupuncturists, outcome assessors, and statistical analysts are assigned to different individuals to ensure separation of these roles.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this trial, various specifications of disposable acupuncture needles (0.30x25mm, 0.30x40mm, and 0.30x75mm) from Hua Tuo and the SDZ-III electroacupuncture device (Suzhou Medical Instruments, Jiangsu, China) will be used. To enhance patient adherence to the intervention, both groups will receive their interventions from the same experienced physician, who holds a licensed acupuncturist certification and has over three years of clinical acupuncture experience. Before the study begins, the acupuncturist will undergo training on the study protocol and standard acupuncture procedures.\u003c/p\u003e\n\u003cp\u003eThe acupuncture points, needle insertion angles, and depths will be determined based on the \u0026quot;Meridian and Acupoint Study\u0026quot; from the National Traditional Chinese Medicine Higher Education \u0026quot;14th Five-Year Plan\u0026quot; textbook and the WHO international acupuncture point location standards, as illustrated in Figure 3 and Table 2. All patients will receive treatments three times a week for a total of 12 weeks, with a 4-week follow-up period after treatment ends. Treatments will be paused during menstruation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConception Vessel acupoints group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcupuncture treatment will follow a semi-standardized approach. Based on the treatment patterns for Conception Vessel acupuncture identified in a prior real-world study, the acupoints selected for treating DOR in the Conception Vessel group are CV12, CV4, SP6, CV6 (Bilateral), and ST36 (Bilateral). Additionally, one supplementary point will be chosen according to the specific syndrome differentiation: KI3 for Kidney deficiency, LR3 for Hepatic depression, CV12 for Phlegmatic hygrosis, and SP10 for Blood stasis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNon- Conception Vessel acupoints group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSelect non-therapeutic acupoints from the same nerve segments as those used in the Conception Vessel group, but which are not part of the Conception Vessel. These include GB28, SP14, GB39, and GB34 on one side.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNon-acupoint sham-acupuncture group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSelect four non-acupoint, non-meridian sites close to the locations of the four acupoints in the Conception Vessel group, naming them Non-Acupoint 1, Non-Acupoint 2, Non-Acupoint 3, Non-Acupoint 4 and Non-Acupoint\u0026nbsp;5.\u003c/p\u003e\n\u003cp\u003eTable.2 Locations and depths of the selected acupoints for the Conception Vessel Acupoints Group, Non-Conception Vessel Acupoints Group, and Non-acupoint sham-acupuncture group.\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eGroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eAcupoint\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003eLocation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eInsertion\u003c/p\u003e\n \u003cp\u003edepth\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eConception Vessel acupoints\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eCV12 (Zhongwan)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003eOn the anterior midline of the abdomen, 4 cun above the umbilicus.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1-1.5 cun\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eCV4 (Guanyuan)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003eOn the mid-line of the abdomen, 3/5 of the way down from the umbilicus to the superior edge of the pubic bone.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e3-3.5 cun\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eSP6 (Sanyinjiao)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003e3 cun directly above the tip of the medial malleolus, on the posterior border of the tibia.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1-1.5 cun\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eCV6 (Qihai)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003eOn the anterior midline of the lower abdomen, 1.5 cun below the umbilicus.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1-1.5 cun\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eST36 (Zusanli)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003e3 cun below ST35, one finger-breadth from the anterior crest of the tibia.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1-2 cun\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eNon-Conception Vessel acupoints\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eGB28 (Weidao)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003e0.5 cun anterior and inferior to GB27.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e0.8-1 cun\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eSP14 (Fujie)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003e3 cun below SP15, 4 cun lateral to the midline.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1-2 cun\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eGB39 (Xuanzhong)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003e3 cun above the tip of the external malleolus, on the posterior border of the fibula.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1-1.5 cun\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eGB34 (Yanglingquan)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 275px;\"\u003e\n \u003cp\u003eIn the depression anterior and inferior to the head of the fibual.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1-1.5 cun\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" valign=\"top\" style=\"width: 106px;\"\u003e\n \u003cp\u003eNon-acupoint sham-acupuncture group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eNon-Acupoint 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 275px;\"\u003e\n \u003cp\u003eOn the abdomen, 3 cun above the umbilicus, 1 cun lateral to the anterior midline (between the Kidney and stomach meridian)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eNon-Acupoint 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 275px;\"\u003e\n \u003cp\u003eOn the abdomen, 2.5 cun below the umbilicus, 1 cun lateral to the anterior midline (between the Kidney and stomach meridian)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eNon-Acupoint 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 275px;\"\u003e\n \u003cp\u003eOn the abdomen, 3.5 cun below the umbilicus, 1 cun lateral to the anterior midline (between the Kidney and stomach meridian)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eNon-Acupoint 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 275px;\"\u003e\n \u003cp\u003eOn the lower leg, 2 cun above the medial malleolus, in the middle of the tibia\u0026apos;s inner side (between the Liver and spleen meridian)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 106px;\"\u003e\n \u003cp\u003eNon-Acupoint 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 275px;\"\u003e\n \u003cp\u003e3 cun below GB34 (between the gallbladder and bladder meridian)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe total observation period is 20 weeks, comprising a 4-week screening phase (Weeks -4 to 0), a 12-week intervention phase (Weeks 0 to 12), and a 4-week follow-up phase (Weeks 12 to 16). Assessments will be conducted at baseline, Week 12, and Week 16.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBaseline AFC: Compare the changes in bilateral ovarian AFC from baseline to 12 weeks, assessed via gynecological ultrasound during days 2-4 of the menstrual cycle. AFC directly reflects ovarian reserve and is negatively correlated with age and baseline FSH, making it a reliable indicator for predicting ovarian reserve.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(1) Serum Anti-M\u0026uuml;llerian Hormone\u003c/p\u003e\n\u003cp\u003eCompare the average changes in serum AMH levels from baseline to Weeks 12 and 16 between groups, as measured by chemiluminescence. AMH is a biomarker that accurately reflects ovarian aging. Compared to other hormones, it can more promptly indicate the decline in ovarian reserve with age. Its levels are not influenced by the menstrual cycle, hormonal contraceptives, or pregnancy, making it a reliable and rapid measure for evaluating ovarian reserve function.\u003c/p\u003e\n\u003cp\u003e(2) Serum Hormone Levels\u003c/p\u003e\n\u003cp\u003eCompare the average changes in serum FSH, LH, and E2 levels from baseline to Weeks 12 and 16 between groups, as measured by chemiluminescence during days 2-4 of the menstrual cycle. As ovarian reserve decreases, the number of FSH receptors released by ovarian granulosa cells diminishes, leading to reduced ovarian responsiveness to FSH. This results in increased secretion of GnRH by the hypothalamus and pituitary, which elevates baseline FSH levels. Therefore, baseline FSH levels can partially reflect ovarian reserve function.\u003c/p\u003e\n\u003cp\u003e(3) Compare the average change in AFC from baseline to Week 16 and perform intergroup comparisons.\u003c/p\u003e\n\u003cp\u003e(4) Modified Kupperman score.\u003c/p\u003e\n\u003cp\u003e(5) Clinical pregnancy rate, live birth rate, and miscarriage rate:\u003c/p\u003e\n\u003cp\u003eClinical pregnancy rate = (Number of clinical pregnancies / Total number of patients) \u0026times; 100%\u003c/p\u003e\n\u003cp\u003eLive birth rate = (Number of live births / Total number of patients) \u0026times; 100%\u003c/p\u003e\n\u003cp\u003eMiscarriage rate = (Number of miscarriages / Total number of patients) \u0026times; 100%\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNote: All pregnancy outcomes will be followed up until November 30, 2025.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSafety assessments and adverse events (AEs) related to interventions, such as needle-induced syncope, needle retention, subcutaneous bleeding, and hematomas, will be monitored and recorded by research assistants in the CRF. Severe adverse events will be managed by emergency physicians or acupuncturists and reported to the Ethics Committee of Shandong University of Traditional Chinese Medicine.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and quality control\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResearchers must accurately and comprehensively record the required information in the CRF and store physician prescription data in a structured clinical information collection system. To ensure data accuracy, two data entry personnel will independently enter and verify the data using the web-based Clinical REDCap system.\u003c/p\u003e\n\u003cp\u003eOnce data entry and verification are complete, the CRFs will be archived in numerical order with a retrieval index for reference. Electronic data files, including databases, checking programs, analysis programs, results, coding books, and documentation, should be categorized, backed up on multiple disks or storage media, and securely stored to prevent damage. All test results and research records must be retained for at least five years to ensure data traceability.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData analysis for this study will strictly adhere to the Intention-to-Treat (ITT) principle. Once randomization is assigned, subjects become part of the study cohort regardless of subsequent treatment or completeness of treatment and follow-up. All dropouts after randomization will be included in the ITT analysis at the end of the trial. Data management and statistical analysis will be performed using SPSS 25.0 software. Categorical data will be expressed as frequencies and percentages, while continuous data will be presented as means \u0026plusmn; standard deviations (\u0026plusmn;SD) or means with 95% confidence intervals (95% CI). All statistical tests will be two-sided, with a significance level set at p\u0026lt;0.05.\u003c/p\u003e\n\u003cp\u003eFor clinical efficacy indicators and other repeated measures data, analysis will be based on whether the data meet normality and sphericity conditions, using repeated measures ANOVA or generalized estimation equations (GEE) as appropriate.\u003c/p\u003e\n\u003cp\u003eCompliance analysis: Mann-Whitney U tests will be used to compare acupuncture compliance between the two acupuncture groups. Dropout details, including time and reasons, will be listed and analyzed using chi-square tests to compare dropout rates among the three groups.\u003c/p\u003e\n\u003cp\u003eSafety analysis: Details of adverse events, including occurrence time, event name, and related actions, will be listed. Chi-square tests will be used to analyze the incidence of adverse events and safety grading evaluations.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDOR leads to a decline in embryo quality and adversely affects reproductive outcomes, making it one of the primary causes of female infertility[14]. In recent years, the prevalence of DOR has increased and shows a trend toward affecting younger women, with a prevalence rate of 6.3% among women under 35 years old. Moreover, DOR patients experience significantly lower clinical pregnancy rates, live birth rates, and singleton live birth rates[15]. Current treatment options include hormone replacement therapy, ovarian stimulation, assisted reproductive technologies, stem cell therapy, and in vitro activation of follicles. However, these methods are associated with numerous contraindications and adverse effects, and their long-term efficacy remains unsatisfactory[16].\u003c/p\u003e\n\u003cp\u003eIn recent years, research on Traditional Chinese Medicine (TCM) treatments for DOR has been increasing annually[9], with acupuncture showing significant clinical efficacy in treating DOR. Numerous clinical trials and basic research studies have demonstrated the multi-target advantages of acupuncture for DOR. Acupuncture can inhibit granulosa cell apoptosis, promote follicle development and maturation, reduce follicle atresia, regulate the reproductive endocrine system, and improve sex hormone levels[12]. It can also modulate the expression levels of signaling molecules in various signaling pathways, enhancing ovarian secretion and synthesis functions[17]. It can also modulate the expression levels of signaling molecules in various signaling pathways, enhancing ovarian secretion and synthesis functions.\u003c/p\u003e\n\u003cp\u003eThe Conception Vessel is directly and closely related to the uterus and pregnancy in terms of its origin, path, and functions. Its connection to the uterus is a key component of the traditional \u0026quot;meridian-organ relationship\u0026quot; theory. However, there is currently limited research on acupuncture of the Conception Vessel for DOR, and there is a lack of high-quality clinical evidence supporting this approach. In current clinical practice, evidence for optimizing acupuncture point selection for DOR is still insufficient. Our preliminary research on real-world clinical data for DOR has confirmed the close relationship between the Conception Vessel and uterine diseases, and has led to an optimized acupuncture point selection scheme for treating DOR. Therefore, this study aims to further investigate this optimized scheme through a prospective, placebo-controlled, multi-center RCT design. The goal is to provide new clinical treatment insights and higher-level evidence-based medical evidence for acupuncture on the Conception Vessel in treating DOR.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eClinical Trial Number:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eITMCTR2024000882\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial status\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was registered in the International Traditional Medicine Clinical Trial Registry (ITMCTR) in 2024. The platform is jointly managed by the China Academy of Chinese Medical Sciences and the China Traditional Chinese Medicine Evidence-Based Center, and is a non-profit organization. It is recognized by the World Health Organization (WHO) as a primary registration platform and regularly provides data to the WHO International Clinical Trials Registry Platform (WHO ICTRP). The actual start date of the study is November 1, 2024, with an anticipated completion date of October 1, 2025. Recruitment began on November 30, 2024, and is expected to end by July 1, 2025.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe appreciate the DeepL platform for helping to polish English language and grammatical check in my manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read and approved the manuscript. Xiaoyu Zhang and Yujie Li are responsible for planning and writing the protocol. Zhengao Sun, Jun Wang and Xingjun Han are overseeing the implementation and coordination of the research. Zhibin Dong is in charge of participant allocation and, together with Hao Sun and Zhihao Diao, is responsible for the statistical planning and analysis. Dongqing Du and Na Zhang are responsible for planning the process evaluation as well as reviewing and editing the protocol. Yuxia Ma is responsible for coordinating the progress across all centers and serves as the overall principal investigator of the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFundings: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Key Research and Development Program Funding Project (2022YFC3500403) and NATCM\u0026apos;s Project of High-level Construction of Key TCM Disciplines (zyyzdxk-2023116).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study will be conducted in accordance with the Declaration of Helsinki. The entire project has been approved by the Ethics Committee of Shandong University of Traditional Chinese Medicine Affiliated Hospital (Approval ID: 2024KY-144) and registered with the International Traditional Medicine Clinical Trial Registry (Registration Number: ITMCTR2024000882). Prior to randomization, patients will be required to sign an informed consent form. Participants\u0026apos; personal information will be kept confidential, and participation in the study is entirely voluntary. They have the right to withdraw at any stage of the study, at any time.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNeves AR, Montoya-Botero P, Polyzos NP: \u003cstrong\u003eAndrogens and diminished ovarian reserve: the long road from basic science to clinical implementation. 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\u003cstrong\u003e119\u003c/strong\u003e(1):99-106.\u003c/li\u003e\n\u003cli\u003eMorin SJ, Patounakis G, Juneau CR, Neal SA, Scott RT, Seli E: \u003cstrong\u003eDiminished ovarian reserve and poor response to stimulation in patients \u0026lt;38 years old: a quantitative but not qualitative reduction in performance\u003c/strong\u003e. \u003cem\u003eHuman reproduction (Oxford, England) \u003c/em\u003e2018, \u003cstrong\u003e33\u003c/strong\u003e(8):1489-1498.\u003c/li\u003e\n\u003cli\u003eLu G, Zhu YY, Li HX, Yin YL, Shen J, Shen MH: \u003cstrong\u003eEffects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats\u003c/strong\u003e. \u003cem\u003eFrontiers in genetics \u003c/em\u003e2022, \u003cstrong\u003e13\u003c/strong\u003e:968711.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acupuncture, Conception Vessel, Diminished ovarian reserve, Randomized controlled trial, Study protocol","lastPublishedDoi":"10.21203/rs.3.rs-6134147/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6134147/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Diminished ovarian reserve (DOR) is characterized by a decrease in the number and/or quality of oocytes, leading to insufficient ovarian reserve function. Currently, there is no unified treatment protocol for DOR either domestically or internationally. However, acupuncture, as a non-pharmacological therapy, has been shown in several studies to significantly improve ovarian function in patients with DOR and to maintain the balance of serum and endocrine hormones. This study aims to explore the effects of acupuncture on the Conception Vessel in improving clinical symptoms in patients with DOR, with the goal of providing higher-level evidence-based support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: From November 2024 to October 2025, four hospitals in China will recruit 252 patients diagnosed with DOR to undergo acupuncture treatment. Eligible patients must meet the diagnostic criteria for DOR, be between the ages of 20 and 45, and provide informed consent. Participants will be randomly assigned in a 1:1:1 ratio to one of three groups: the Conception Vessel acupuncture group, the non-Conception Vessel acupoint group, or the Non-acupoint sham-acupuncture group, with 84 patients in each group. All patients will receive treatment three times per week for a total of 12 weeks, with a 4-week follow-up period after treatment completion. No treatment will be administered during menstruation. The primary outcome measure is the baseline antral follicle count (AFC), with comparisons made between the changes in bilateral ovarian AFC from baseline to 12 weeks after treatment, assessed via gynecological ultrasound on days 2-4 of the menstrual cycle.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExpected Results and Conclusion:\u003c/strong\u003e This study aims to further investigate an optimized treatment protocol through a prospective, sham-controlled, multicenter randomized controlled trial (RCT) design, based on real-world clinical settings. The goal is to provide new clinical insights and high-level evidence for the use of Conception Vessel acupuncture in treating DOR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration:\u003c/strong\u003e International Traditional Medicine Clinical Trial Registry, ITMCTR2024000882 Registered on 28 December 2024.\u003c/p\u003e","manuscriptTitle":"Acupuncture on the Conception Vessel for Diminished ovarian reserve: A Multi-Center Randomized Controlled Trial Protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-17 16:14:35","doi":"10.21203/rs.3.rs-6134147/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"27141035-dac6-4321-af09-ec8fb80d7404","owner":[],"postedDate":"March 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-26T06:53:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-17 16:14:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6134147","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6134147","identity":"rs-6134147","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}