The Feasibility of taVNS on Pregnancy Outcomes of Infertility Patients Undergoing IVF

The Feasibility of Transcutaneous Auricular Vagus Nerve Stimulation on Pregnancy Outcomes of Infertility Patients Undergoing in Vitro Fertilization: Study Protocol for a Pilot Randomized Controlled Trial

To assess the feasibility of taVNS on pregnancy outcomes of infertility subjects undergoing IVF, the primary aim of this trial will focus on encompassing recruitment, compliance, and preliminary engagement outcomes.

The exploratory aim is to carry out clinical research, which entails evaluating the preliminary effects of the intervention in order to ascertain its potential benefits.

The main question it aims to answer is: Does the taVNS is feasible and tolerated in the context of IVF?

What medical problems do participants have when using the taVNS device? Researchers will compare the taVNS to the sham transcutaneous auricular vagus nerve stimulation (a look-alike device that produces a sub-threshold therapeutic stimulus and functions as a sham stimulus) and blank control to see if the taVNS device works to enhance outcomes of IVF.

Participants will:

Use the device a total of 1.5 hours daily, with the sessions divided into three parts, each lasting 30 minutes. At least one of these periods occur within 2 hours before bedtime.

Visit the clinic according to the scheduled treatment time points of IVF. Keep a diary of their adverse events and the number of times they use the device.

Study Overview

• Status: Recruiting
• Conditions: Infertility Assisted Reproductive Technology
• Intervention / Treatment: Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS); Device: sham transcutaneous auricular vagus nerve stimulation (staVNS)

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaofei Fei; Phone Number: +8613822311264; Email: feixiaofeixzyz@126.com
• Study Contact Backup: Name: Yonghong Liu; Phone Number: +8629-84771377; Email: liuyhong@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hospital
      • Contact: Yonghong Liu; Phone Number: +8629-84771377; Email: liuyhong@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects aged 20 to 40 years, diagnosed with infertility, and preparing to undergo IVF treatment;
2. Female subjects with anti-Müllerian hormone (AMH) > 1.2 ng/mL;
3. Scoring at mild-to-moderate levels of impairment on anxiety, and depression scales;
4. Both the subject and their family sign the informed consent form.

Exclusion Criteria:

1. The subject had been treated with taVNS in the past;
2. Subjects preparing to undergo frozen embryo transfer;
3. Subjects with a history of mental disorder or who score at a severe level of impairment on anxiety and depression scales;
4. Taking sedatives, anxiety, depression, or psychiatric medications;
5. Comorbidities including arrhythmia, hypertension, diabetes, chronic heart and kidney diseases;
6. Ineligibility for enrollment assessed by a gynecologist or neurologist;
7. Metallic implants or devices contraindicating taVNS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: the IVF control group; The IVF control group refers to receiving only in vitro fertilization (IVF) treatment without any additional Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) treatment.
Experimental: the taVNS group; The taVNS group receives Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) along with In Vitro Fertilization (IVF) treatment. The taVNS protocol is configured with a pulse width of 500 µs, a frequency of 25 Hz, and a current intensity titrated to each patient's pain tolerance threshold (range: 0.5-2.0 mA). The stimulation is to be carried out for a total of 1.5 hours daily, with the sessions divided into three parts, each lasting 30 minutes. At least one of these periods occur within 2 hours before bedtime.	Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS); Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) is an emerging, non-invasive adjunctive therapy. The taVNS protocol is configured with a pulse width of 500 µs, a frequency of 25 Hz, and a current intensity titrated to each patient's pain tolerance threshold (range: 0.5-2.0 mA). The stimulation is to be carried out for a total of 1.5 hours daily, with the sessions divided into three parts, each lasting 30 minutes. At least one of these periods occur within 2 hours before bedtime. The study will use the Chinese National Institutes for Food and Drug Control certificated taVNS device TVNS-100 (Xinzhile Medical Technology Co., Jiangxi, China). The study includes an intervening period of 4 weeks.
Sham Comparator: the staVNS group; The staVNS group receives sham transcutaneous auricular vagus nerve stimulation, along with In Vitro Fertilization (IVF) treatment. The staVNS protocol is set at a pulse width of 500 µs and a frequency of 25 Hz, with an intensity value of 0.1 mA.The stimulation of 0.1 mA acts as a therapeutic signal below the threshold level and functions as a sham stimulus. The stimulation is to be carried out for a total of 1.5 hours daily, with the sessions divided into three parts, each lasting 30 minutes. At least one of these periods occur within 2 hours before bedtime.	Device: sham transcutaneous auricular vagus nerve stimulation (staVNS); The sham transcutaneous auricular vagus nerve stimulation (staVNS) serves as a sub-threshold therapeutic stimulus functions as a sham stimulus. The staVNS protocol is set at a pulse width of 500 µs and a frequency of 25 Hz, with an intensity value of 0.1 mA. The stimulation is to be carried out for a total of 1.5 hours daily, with the sessions divided into three parts, each lasting 30 minutes. At least one of these periods occur within 2 hours before bedtime. The study will use the Chinese National Institutes for Food and Drug Control certificated taVNS device TVNS-100 (Xinzhile Medical Technology Co., Jiangxi, China). The study includes an intervening period of 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the recruitment rate	The recruitment rate refers to the number of eligible individuals screened.	The time frame for the recruitment rate is 12 months after the intervention begins.
the enrollment rate	The the enrollment rate refers to the proportion of eligible patients who consent to participate.	The time frame for the enrollment rate is 12 months after the intervention begins.
the retention rate	The retention rate refers to the proportion of enrolled individuals who do not withdraw from the intervention.	The time frame for the retention rate spans from baseline to 4 weeks after ET.
the patient adherence	The patient adherence refers to the proportion of patients who complete the intervention.	The time frame for patient adherence spans from baseline to 4 weeks after ET.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the total number of oocytes retrieved		On the day of oocyte retrieval
the positive rate of hCG	The hCG level, specifically defined as >10 mIU/mL, is an important indicator of pregnancy success.	The positive rate of hCG will also be observed two weeks after ET
high-quality embryo rate		On the day of embryo transfer (day 14)
The Fertility Quality of Life Scale (FertiQoL, Simplified Chinese version)	The Fertility Quality of Life Scale yields six subscale and three total scores with a range of 0 to 100. Higher scores mean higher quality of life and a better outcome.	The scale will be observed at baseline, the day of embryo transfer (day 14) and 2 weeks after embryo transfer.
Pittsburgh Sleep Quality Index (PSQI)	The total score range of the Pittsburgh Sleep Quality Index (PSQI) is from 0 to 21. Higher scores mean poorer sleep quality and a worse outcome.	The scale and questionnaire measurement will be observed at baseline, the day of embryo transfer (day 14) and 2 weeks after embryo transfer.
14-item Hamilton Anxiety Rating Scale (HAMA-14)	The total score range of the 14-item Hamilton Anxiety Rating Scale (HAMA-14) is from 0 to 56. Higher scores mean more severe anxiety and a worse outcome.	The scale and questionnaire measurement will be observed at baseline, the day of embryo transfer (day 14) and 2 weeks after embryo transfer.
17-item Hamilton Depression Rating Scale (HAMD-17)	The total score range of the 17-item Hamilton Depression Rating Scale (HAMD-17) is from 0 to 68. Higher scores mean more severe depression and a worse outcome.	The scale and questionnaire measurement will be observed at baseline, the day of embryo transfer (day 14) and 2 weeks after embryo transfer.
Clinical Pregnancy Rate	Description: The clinical pregnancy rate (CPR) is a measure used in reproductive medicine to evaluate the success of in vitro fertilization (IVF) treatment. It is defined as the percentage of women who achieve a clinical pregnancy from the first fresh or frozen embryo transfer cycle. A clinical pregnancy is confirmed by ultrasound and is characterized by the presence of a gestational sac within the uterine cavity, as observed 4 weeks after the embryo transfer has taken place.	The primary efficacy outcome of the study is to measure and compare the difference in CPR among three groups 4 weeks after ET.

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Yonghong Liu, Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2025
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: December 13, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Actual): July 2, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Infertility; Transcutaneous Auricular Vagus Nerve Stimulation; Assisted Reproductive Techniques
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility
• Other Study ID Numbers: KY20242351liuyonghong

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No