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The goal of this clinical trial is to evaluate whether the complementary intervention of auricular point sticking therapy (APST) can improve pregnancy outcomes by ameliorating psychological distress and sleep quality in female patients aged 20-45 years undergoing in-vitro fertilization and embryo transfer (IVF-ET) who also present with anxiety and/or insomnia.
The main questions it aims to answer are:
Does the addition of APST to standard luteal phase support improve key IVF-ET pregnancy outcomes (embryo implantation rate, clinical pregnancy rate, ongoing pregnancy rate)? Does APST effectively reduce anxiety and depression scores (measured by GAD-7 and PHQ-9) and improve sleep quality (measured by PSQI and actigraphy) in this patient population? Are the observed clinical improvements associated with modulation of stress-related biomarkers (e.g., serum cortisol, 5-HT)? Researchers will compare the intervention group (standard care + APST) to the control group (standard care only) to see if the combined therapy leads to superior outcomes in psychological well-being, sleep parameters, and ultimately, reproductive success.
Participants will be randomly assigned to either the control group or the intervention group.
In the control group, receive standard luteal phase support medication (e.g., progesterone injections or oral dydrogesterone) for 4 weeks post-embryo transfer.
In the intervention group, receive the same standard medication plus auricular point sticking therapy. This involves: 1.Having vaccaria seeds attached to specific ear acupoints (Heart, Liver, Endocrine, Shenmen, Subcortex, Sympathetic). 2.Performing self-acupressure on the seeds 3 times daily for 3 minutes each session. 3.Replacing the seeds at a new site every 3 days. 4.Complete psychological (GAD-7, PHQ-9) and sleep quality (PSQI) questionnaires at baseline and 12 weeks post-transfer. 5.Wear an actigraphy device on the wrist for 7 consecutive days to objectively monitor sleep patterns. 6.Provide blood samples for biomarker analysis (cortisol, 5-HT) on specific days post-transfer. 7.Undergo follow-up assessments to determine pregnancy status (β-hCG test, ultrasound).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Conventional Artificial Cycle Therapy | Active Comparator | Patients in the control group will receive artificial cycle therapy post-IVF-ET: progesterone injection 40 mg/day, or oral dydrogesterone tablets (Duphaston) 20 mg/day, or progesterone soft capsules 200 mg/day. |
|
| Conventional artificial cycle therapy will be supplemented with auricular point sticking therapy | Experimental | Patients in the intervention group will receive the same artificial cycle therapy as the control group, combined with Auricular Point Sticking Therapy (APST).Auricular Point Sticking Therapy Procedure: Unilateral ear acupoints-Heart (CO15), Liver (CO12), Endocrine (CO18), Shenmen (TF4), Subcortex (AT4), and Sympathetic (AH6a)-are selected. The auricle is disinfected using an alcohol-saturated cotton swab. After the alcohol evaporates, a Vaccaria segetalis seed patch is applied to each designated acupoint using forceps and secured. Following application, appropriate digital pressure is applied to each point until a local sensation of warmth, soreness, numbness, distension, or pain (Deqi sensation) is achieved. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| auricular point sticking therapy | Other | Patients in the intervention group will receive the same artificial cycle therapy as the control group, combined with Auricular Point Sticking Therapy (APST).Auricular Point Sticking Therapy Procedure: Unilateral ear acupoints-Heart (CO15), Liver (CO12), Endocrine (CO18), Shenmen (TF4), Subcortex (AT4), and Sympathetic (AH6a)-are selected. The auricle is disinfected using an alcohol-saturated cotton swab. After the alcohol evaporates, a Vaccaria segetalis seed patch is applied to each designated acupoint using forceps and secured. Following application, appropriate digital pressure is applied to each point until a local sensation of warmth, soreness, numbness, distension, or pain (Deqi sensation) is achieved. |
| Measure | Description | Time Frame |
|---|---|---|
| Embryo implantation rate | defined as serum β-hCG ≥ 50 IU/L on day 12 after embryo transfer | 12 days after embryo transfer |
| Clinical pregnancy rate | confirmed by the presence of at least one intrauterine gestational sac on transvaginal ultrasound | 28 days after embryo transfer |
| Generalized Anxiety Disorder 7-item scale | The Generalized Anxiety Disorder 7-item (GAD-7) scale is a self-reported questionnaire for assessing anxiety severity. It consists of 7 items, each scored from 0 to 3. The total score ranges from 0 to 21, with higher scores indicating worse outcomes (more severe anxiety symptoms). | Baseline and 4 weeks after embryo transfer |
| Patient Health Questionnaire-9 Score | The Patient Health Questionnaire-9 (PHQ-9) is a self-reported depression screening tool. It consists of 9 items, each scored from 0 to 3. The total score ranges from 0 to 27, with higher scores indicating worse outcomes (more severe depressive symptoms). | Baseline and 4 weeks after embryo transfer |
| Pittsburgh Sleep Quality Index | The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that assesses sleep quality and disturbances over a 1-month time interval. The measure consists of 19 individual items, generating 7 "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. Each component is weighted on a 0-3 scale. The global PSQI score is the sum of these 7 component scores, ranging from 0 to 21. A higher total score indicates a worse outcome (poorer sleep quality). | Baseline and 4 weeks after embryo transfer |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Pregnancy Outcomes | Includes ectopic pregnancy, molar pregnancy, threatened abortion, embryonic/fetal demise, and other abnormal pregnancy conditions occurring during the study period. All outcomes will be confirmed by clinical assessment and ultrasound. | From embryo transfer up to 12 weeks of gestation |
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1.Diagnostic Criteria for Infertility
The diagnosis is established in accordance with *Obstetrics and Gynecology (10th Edition)* and the *Guidelines for Diagnosis and Treatment of Infertility (2019)*. To be eligible, patients must meet the following criteria:
Furthermore, the indication for IVF-ET must be met by satisfying at least one of the following conditions:
2. Diagnostic Criteria for Anxiety State
Diagnosis is based on the diagnostic criteria for anxiety disorders as outlined in the *Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)* and the *International Classification of Diseases, Eleventh Revision (ICD-11)*. Eligible patients must meet the following criteria:
3 Diagnostic Criteria for Insomnia Disorder Diagnosis is based on the diagnostic criteria for insomnia disorder as outlined in the *Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the International Classification of Diseases, Eleventh Revision (ICD-11) 3. Eligible patients must meet the following criteria:
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jing Ma | Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hangzhou Hospital of Traditional Chinese Medicine | Hangzhou | Zhejiang | 310007 | China |
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| Conventional Artificial Cycle Therapy | Drug | Patients in the control group will receive artificial cycle therapy post-IVF-ET: progesterone injection 40 mg/day, or oral dydrogesterone tablets (Duphaston) 20 mg/day, or progesterone soft capsules 200 mg/day. |
|
| Change in objective sleep parameters measured by actigraphy | Objective sleep parameters are measured using the Actigraph wGT3X-BT monitor (ActiGraph, USA). Participants wear the device on the non-dominant wrist (left hand) continuously for 7 days and nights. The device is worn daily from 21:00 until 09:00 the following morning. A standardized sleep diary is used concurrently to record lights-off time and wake time. Data are collected at a sampling frequency of 30 Hz and analyzed using ActiLife software (version 7.0.0) to derive parameters such as total sleep time (TST), sleep efficiency (SE), wake after sleep onset (WASO), and sleep latency. | Baseline and 4 weeks after embryo transfer |
| serum cortisol levels | Serum cortisol concentration is measured in venous blood samples collected in the morning under fasting conditions. Cortisol is a key hormone of the hypothalamic-pituitary-adrenal (HPA) axis, and its level reflects stress response and HPA axis activity. The unit of measurement is nmol/L | Fasting morning venous blood samples are collected at 2 days (baseline) and 12 days after embryo transfer for analysis. |
| Serum serotonin (5-HT) levels | Serum serotonin (5-HT) concentration is measured in venous blood samples. Serotonin is a key neurotransmitter involved in mood regulation, and its peripheral level is considered a potential biomarker related to psychological stress and emotional states. The unit of measurement is ng/mL. | Fasting morning venous blood samples are collected at 2 days (baseline) and 12 days after embryo transfer for analysis. |
| Local discomfort at auricular acupressure sites assessed by Visual Analogue Scale (VAS) |
Discomfort level at the site of auricular acupressure patches is assessed using a 100-mm Visual Analogue Scale. Participants mark a point on the line between 0 mm ("no discomfort at all") and 100 mm ("the worst discomfort imaginable"). Higher scores indicate worse local tolerance. |
| From the start of intervention up to 4 weeks |
| Incidence of local skin reactions related to auricular acupressure | Includes ulceration, rash, pruritus, or other dermatological adverse events at the site of auricular acupressure patch application. Assessed by visual inspection and participant report. | From the start of intervention up to 4 weeks |
| ID | Term |
|---|---|
| D007247 | Infertility, Female |
| D001008 | Anxiety Disorders |
| D020920 | Dyssomnias |
| D003863 | Depression |
| ID | Term |
|---|---|
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D007246 | Infertility |
| D001523 | Mental Disorders |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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