Multifaceted Benefits of Auricular Point Sticking for IVF Patients: Psychological Well-being, Sleep, and Treatment Outcomes

Official title

The Synergistic Ameliorative Effects of Auricular Point Sticking Therapy on the Psychological Well-being, Sleep Quality, and Pregnancy Outcomes of IVF Patients

Overview

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).

Interventions

• Other auricular point sticking therapy
  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 designate
• Drug Conventional Artificial Cycle Therapy
  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.

Primary outcome measures

• Embryo implantation rate [Time frame: 12 days after embryo transfer]
• Clinical pregnancy rate [Time frame: 28 days after embryo transfer]
• Generalized Anxiety Disorder 7-item scale [Time frame: Baseline and 4 weeks after embryo transfer]
• Patient Health Questionnaire-9 Score [Time frame: Baseline and 4 weeks after embryo transfer]
• Pittsburgh Sleep Quality Index [Time frame: Baseline and 4 weeks after embryo transfer]
• Change in objective sleep parameters measured by actigraphy [Time frame: Baseline and 4 weeks after embryo transfer]
• serum cortisol levels [Time frame: Fasting morning venous blood samples are collected at 2 days (baseline) and 12 days after embryo transfer for analysis.]
• Serum serotonin (5-HT) levels [Time frame: Fasting morning venous blood samples are collected at 2 days (baseline) and 12 days after embryo transfer for analysis.]

Secondary outcome measures (3)

• Adverse Pregnancy Outcomes [Time frame: From embryo transfer up to 12 weeks of gestation]
• Local discomfort at auricular acupressure sites assessed by Visual Analogue Scale (VAS) [Time frame: From the start of intervention up to 4 weeks]
• Incidence of local skin reactions related to auricular acupressure [Time frame: From the start of intervention up to 4 weeks]

Eligibility criteria

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:

• Be a woman of reproductive age, between 20 and 45 years old;
• Have failed to achieve a clinical pregnancy after ≥12 months of regular, unprotected intercourse (or ≥6 months for women aged ≥35).

Furthermore, the indication for IVF-ET must be met by satisfying at least one of the following conditions:

• Ovulatory factor infertility (e.g., hypothalamic amenorrhea or menstrual disorders, pituitary amenorrhea or menstrual disorders, ovarian amenorrhea or menstrual disorders, other endocrine disorders);
• Pelvic factor infertility (e.g., congenital anomalies of the reproductive system, cervical factors, uterine disorders, tubal and/or peritoneal factors, endometriosis);
• Male factor infertility (e.g., azoospermia, oligospermia, asthenospermia, teratospermia, isolated abnormal seminal plasma);
• Unexplained infertility.

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:

• Score ≥5 on the self-administered Generalized Anxiety Disorder 7-item (GAD-7) scale;
• Exhibit significant anxiety symptoms: excessive worry not confined to specific circumstances, or disproportionate worry about various aspects of life;
• Experience associated symptoms, such as: muscle tension or restlessness; symptoms of autonomic hyperactivity (e.g., frequent gastrointestinal symptoms like nausea or abdominal discomfort, palpitations, sweating, trembling, dry mouth); subjective feelings of tension, restlessness, difficulty concentrating, or irritability;
• Symptoms persist for at least one month and are present most of the time;
• The symptoms are not better explained by another mental disorder, are not attributable to the physiological effects of a substance or medication (or its withdrawal), and are not a manifestation of another medical condition;
• The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

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:

• Score ≥8 on the self-administered Pittsburgh Sleep Quality Index (PSQI);
• Report dissatisfaction with sleep quantity or quality, accompanied by one or more of the following symptoms: ① Difficulty initiating sleep (sleep latency >30 minutes); ② Difficulty maintaining sleep, characterized by frequent awakenings or difficulty returning to sleep after awakenings (wake after sleep onset >30 minutes); ③ Early morning awakening (waking >30 minutes earlier than desired) with inability to return to sleep;
• The sleep disturbance causes clinically significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning;
• The sleep difficulty occurs at least three nights per week and has been present for at least one month;
• The insomnia is not better explained by and does not occur exclusively during the course of another sleep-wake disorder, mental disorder, or medical condition, and is not attributable to the physiological effects of a substance.

Inclusion criteria

• (1) Patients who meet the above diagnostic criteria and have undergone IVF-ET; (2) Female patients aged 20-45 years, with a BMI of 18-28 kg/m²; (3)The embryo to be transferred is a high-quality frozen-thawed embryo (either a Day-3 embryo with ≥8 cells, uniform blastomere size, and fragmentation rate <10%, or a blastocyst with a grade of ≥3BB); (4) Willing to provide written informed consent and comply with luteal support therapy and follow-up.

Exclusion criteria

• (1) Unauthorized use of sedatives or anxiolytics during the treatment period; (2) Adherence to auricular point sticking therapy less than 80% (based on patient diary records); (3) Cancellation of the frozen embryo transfer cycle (e.g., due to endometrial transformation failure or sudden onset of ovarian hyperstimulation syndrome); (4) The participant voluntarily requests to withdraw from the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Hangzhou Hospital of Traditional Chinese Medicine — Hangzhou

Identifiers

NCT: NCT07409792 · 2025KLL180

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗