Acupuncture and Chinese Herbal Medicine to Improve Live Birth Rate of in Vitro Fertilization (IVFAct)

• Sponsor: Heilongjiang University of Chinese Medicine (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT04407871
• Collaborator: (none)
• Enrollment: 2,728
• Locations: 12
• Arms: 4
• Anticipated Duration (Months): 14
• Patients Per Site: 227.3
• Patients Per Site Per Month: 16.3

Study Details

Study Description

Brief Summary

The most successful treatment for infertility is in vitro fertilization (IVF), but less than 10% of infertile couples undergo IVF because of the high cost and relatively low success rate. Many patients have tried complementary and alternative medical treatments as an adjuvant therapy to improve their IVF success. Acupuncture given 2-4 times around the day of embryo transfer has not been shown to improve the IVF live birth rate. Chinese Herbal Medicine (CHM) may improve the IVF pregnancy rates, but the evidence so far is inconclusive because of high risks of bias in these studies.

The objective of this multi-centre double blind randomized trial is to evaluate the efficacy of acupuncture with or without CHM on the live birth of IVF. The randomization process will be coordinated through a central mechanism. A total of 2,728 subjects will be randomized in 1:1:1:1 ratio in to one of the four treatment arms: 1) acupuncture and CHM, 2) acupuncture and placebo CHM, 3) control acupuncture and CHM or 4) control acupuncture and placebo CHM. Women will receive acupuncture or control acupuncture three times a week 4 weeks prior to IVF during ovarian stimulation, and before and after the embryo transfer. They will also take CHM or placebo CHM daily 4 weeks prior to IVF till a negative pregnancy test or till 8 weeks of gestation if pregnant.

Condition or Disease	Intervention/Treatment	Phase
In Vitro Fertilization	Other: Acupuncture and Chinese Herbal Medicine	N/A

Detailed Description

The objective of this multi-centre double blind randomized trial is to evaluate the efficacy of acupuncture with or without CHM on the live birth of IVF. The randomization process will be coordinated through a central mechanism. A total of 2,728 subjects will be randomized in 1:1:1:1 ratio in to one of the four treatment arms: 1) acupuncture and CHM, 2) acupuncture and placebo CHM, 3) control acupuncture and CHM or 4) control acupuncture and placebo CHM. Women will receive acupuncture or control acupuncture three times a week 4 weeks prior to IVF during ovarian stimulation, and before and after the embryo transfer. They will also take CHM or placebo CHM daily 4 weeks prior to IVF till a negative pregnancy test or till 8 weeks of gestation if pregnant.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 2728 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Acupuncture and Chinese Herbal Medicine to Improve Live Birth Rate of in Vitro Fertilization - A Randomized Controlled Trial (IVFAct)
• Anticipated Study Start Date: Nov 1, 2021
• Anticipated Primary Completion Date: Dec 31, 2022
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: acupuncture and CHM Women will receive acupuncture three times a week 4 weeks prior to ovarian stimulation for IVF and during ovarian stimulation, and before and after embryo transfer (ET). They will also take CHM daily 4 weeks prior to IVF till the day of serum hCG testing. If the hCG testing is positive and a viable pregnancy is confirmed by transvaginal ultrasound, CHM will be continued till 8 weeks of gestation. If the hCG testing is negative or spontaneous miscarriage is confirmed, the drug treatment will be stopped.	Other: Acupuncture and Chinese Herbal Medicine; 1) acupuncture and CHM, 2) acupuncture and placebo CHM, 3) control acupuncture and CHM or 4) control acupuncture and placebo CHM by an interactive online computer program in a central office. Using a 1:1:1:1 treatment ratio, there will be 682 women assigned to each treatment group.
Placebo Comparator: acupuncture and placebo CHM Women will receive acupuncture three times a week 4 weeks prior to ovarian stimulation for IVF and during ovarian stimulation, and before and after ET. They will also take placebo CHM daily 4 weeks prior to IVF till the day of serum hCG testing. If the hCG testing is positive and a viable pregnancy is confirmed by transvaginal ultrasound, placebo CHM will be continued till 8 weeks of gestation. If the hCG testing is negative or spontaneous miscarriage is confirmed, the drug treatment will be stopped.	Other: Acupuncture and Chinese Herbal Medicine; 1) acupuncture and CHM, 2) acupuncture and placebo CHM, 3) control acupuncture and CHM or 4) control acupuncture and placebo CHM by an interactive online computer program in a central office. Using a 1:1:1:1 treatment ratio, there will be 682 women assigned to each treatment group.
Placebo Comparator: control acupuncture and CHM Women will receive control acupuncture three times a week 4 weeks prior to ovarian stimulation for IVF and during ovarian stimulation, and before and after ET. They will also take CHM daily 4 weeks prior to IVF till the day of serum hCG testing. If the hCG testing is positive and a viable pregnancy is confirmed by transvaginal ultrasound, CHM will be continued till 8 weeks of gestation. If the hCG testing is negative or spontaneous miscarriage is confirmed, the drug treatment will be stopped.	Other: Acupuncture and Chinese Herbal Medicine; 1) acupuncture and CHM, 2) acupuncture and placebo CHM, 3) control acupuncture and CHM or 4) control acupuncture and placebo CHM by an interactive online computer program in a central office. Using a 1:1:1:1 treatment ratio, there will be 682 women assigned to each treatment group.
Placebo Comparator: control acupuncture and placebo CHM Women will receive control acupuncture three times a week 4 weeks prior to ovarian stimulation for IVF and during ovarian stimulation, and before and after ET. They will also take placebo CHM daily 4 weeks prior to IVF till the day of serum hCG testing. If the hCG testing is positive and a viable pregnancy is confirmed by transvaginal ultrasound, placebo CHM will be continued till 8 weeks of gestation. If the hCG testing is negative or spontaneous miscarriage is confirmed, the drug treatment will be stopped.	Other: Acupuncture and Chinese Herbal Medicine; 1) acupuncture and CHM, 2) acupuncture and placebo CHM, 3) control acupuncture and CHM or 4) control acupuncture and placebo CHM by an interactive online computer program in a central office. Using a 1:1:1:1 treatment ratio, there will be 682 women assigned to each treatment group.

Outcome Measures

Primary Outcome Measures

1. Live birth [≥20 weeks of gestation]

   Live birth defined as a delivery ≥20weeks gestation per transfer in the stimulated IVF cycles or in the first frozen-thawed embryo transfer cycle in those with elective freezing of all embryos

Secondary Outcome Measures

1. Embryo quality: embryo scoring standard [On the third day after egg retrieval and before embryo transfer]

   Embryo quality is judged by embryo scoring standard

2. Miscarriage rate [≤42 weeks of gestation]

   Cumulative miscarriage rate

3. Implantation rate [2 weeks after embryo transfer]

   Cumulative implantation rate

4. Positive serum human chorionic gonadotropin (hCG) level [2 weeks after embryo transfer]

   Positive serum hCG level 2 weeks after embryo transfer

5. Ongoing pregnancy rate [≥8 weeks]

   Cumulative ongoing pregnancy rate

6. Multiple pregnancy rate [≥2 weeks after embryo transfer]

   Cumulative multiple pregnancy rate

7. Ectopic pregnancy rate [≥2 weeks after embryo transfer]

   Cumulative ectopic pregnancy rate

8. Cumulative live birth rate [within 6 months after randomization]

   Cumulative live birth rate

9. Changes in markers of stress, anxiety [≤8 weeks of gestation]

   To elucidate the anxiety level as measured with serum cortisol concentration and Stait-Trait Anxiety Inventory (STAI)

10. Health related quality of life(HRQoL) [≤8 weeks of gestation]

    To determine women's health related quality of life (HRQoL) by short-form 36 (SF36)

11. Patient acceptability: acupuncture trust score [On the day of embryo transfer]

    Patient acceptability of acupuncture to be measured by acupuncture trust score

12. Side effects [≤ 8 weeks of gestation]

    Side effects

13. Congenital abnormalities [at 6 weeks postpartum]

    Judging by prenatal ultrasound and postnatal physical examination

14. Pregnancy complications [≤42 weeks of gestation]

    Complications of Pregnancy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Women ≥20 to ≤40 years of age

2. Indications for IVF

3. Duration of infertility >1 year

4. Undergoing IVF with an intention of fresh ET on day 3 or 5.

Exclusion Criteria:

1. Women with an intention to replace frozen embryos only.

2. Preimplantation genetic testing

3. History of recurrent miscarriages defined as having three consecutive miscarriages.

4. Having acupuncture or CHM for infertility within 3 months prior the IVF

5. Women with abnormal liver or renal function tests

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui	China
2	The First Hospital of Lanzhou University	Lanzhou	Gansu	China
3	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China
4	Tongji Hospital, Tongji Medical College Huazhong University of Science & Technology	Wuhan	Hubei	China
5	Huaian Maternal and Child Health Hospital	Huai'an	Jiangsu	China
6	The First Affiliated Hospital of Nanjing University Medical School (Nanjing Drum Tower Hospital)	Nanjing	Jiangsu	China
7	Xuzhou Central Hospital	Xuzhou	Jiangsu	China
8	Jiangxi Maternal and Child Health Hospital	Nanchang	Jiangxi	China
9	Dalian Municipal Women and Children's Medical Center	Dalian	Liaoning	China
10	Shengjing Hospital of China Medical University	Shenyang	Liaoning	China
11	Xibei Women and Children's Hospital	Xi'an	Shanxi	China
12	The Chinese University of Hong Kong	Hong Kong		China

Sponsors and Collaborators

• Heilongjiang University of Chinese Medicine

Investigators

• Study Chair: Xiaoke Wu, Ph.D, First Affiliated Hospital in Heilongjiang University of Chinese Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Xiaoke Wu, Professor and Director of Obstetrics and Gynecology Department, Heilongjiang University of Chinese Medicine
• ClinicalTrials.gov Identifier: NCT04407871
• Other Study ID Numbers: IVFAct
• First Posted: May 29, 2020
• Last Update Posted: Sep 23, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Xiaoke Wu, Professor and Director of Obstetrics and Gynecology Department, Heilongjiang University of Chinese Medicine: In Vitro Fertilization; Chinese Herbal Medicine; Acupuncture; Live Birth

Study Results

No Results Posted as of Sep 23, 2021