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

Acupuncture and Chinese Herbal Medicine to Improve Live Birth Rate of in Vitro Fertilization - A Randomized Controlled Trial (IVFAct)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: In Vitro Fertilization
• Intervention / Treatment: Other: Acupuncture and Chinese Herbal Medicine

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 Type: Interventional
• Enrollment (Anticipated): 2728
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiaoke Wu, Ph.D; Phone Number: 13796025599; Email: xiaokewu2002@vip.sina.com

Study Locations

• China
  • Hong Kong, China
    • The Chinese University of Hong Kong
    • Contact: Ronald Wang; Email: ccwang@cuhk.edu.hk
    • Principal Investigator: Ronald Wang
  • Anhui
    • Hefei, Anhui, China
      • The First Affiliated Hospital of Anhui Medical University
      • Contact: Yunxia Cao; Phone Number: 13605605972
      • Principal Investigator: Yunxia Cao
  • Gansu
    • Lanzhou, Gansu, China
      • The First Hospital of Lanzhou University
      • Contact: Xuehong Zhang; Phone Number: 13893215266
      • Principal Investigator: Xuehong Zhang
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Yingpu Sun; Phone Number: 13503841888
      • Principal Investigator: Yingpu Sun
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital, Tongji Medical College Huazhong University of Science ＆ Technology
      • Contact: Hanwang Zhang; Email: Hwzhang605@126.com
      • Principal Investigator: Hanwang Zhang
  • Jiangsu
    • Huai'an, Jiangsu, China
      • Huaian Maternal and Child Health Hospital
      • Contact: Huiying Xue
      • Principal Investigator: Huiying Xue
    • Nanjing, Jiangsu, China
      • The First Affiliated Hospital of Nanjing University Medical School (Nanjing Drum Tower Hospital)
      • Contact: Haixiang Sun; Phone Number: 13851622008
      • Principal Investigator: Haixiang Sun
    • Xuzhou, Jiangsu, China
      • Xuzhou Central Hospital
      • Contact: Yijuan Cao; Phone Number: 18952171922
      • Principal Investigator: Yijuan Cao
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Maternal and Child Health Hospital
      • Contact: Qiongfang Wu
      • Principal Investigator: Qiongfang Wu
  • Liaoning
    • Dalian, Liaoning, China
      • Dalian Municipal Women and Children's Medical Center
      • Contact: Xiaoguang Shao; Phone Number: 13804086511; Email: shaoxiaoguang03@sohu.com
      • Principal Investigator: Xiaoguang Shao
    • Shenyang, Liaoning, China
      • Shengjing Hospital of China Medical University
      • Contact: Jichun Tan; Phone Number: 18940251868
      • Principal Investigator: Jichun Tan
  • Shanxi
    • Xi'an, Shanxi, China
      • Xibei Women and Children's Hospital
      • Contact: Juanzi Shi
      • Principal Investigator: Juanzi Shi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth	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	≥20 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Embryo quality: embryo scoring standard	Embryo quality is judged by embryo scoring standard	On the third day after egg retrieval and before embryo transfer
Miscarriage rate	Cumulative miscarriage rate	≤42 weeks of gestation
Implantation rate	Cumulative implantation rate	2 weeks after embryo transfer
Positive serum human chorionic gonadotropin (hCG) level	Positive serum hCG level 2 weeks after embryo transfer	2 weeks after embryo transfer
Ongoing pregnancy rate	Cumulative ongoing pregnancy rate	≥8 weeks
Multiple pregnancy rate	Cumulative multiple pregnancy rate	≥2 weeks after embryo transfer
Ectopic pregnancy rate	Cumulative ectopic pregnancy rate	≥2 weeks after embryo transfer
Cumulative live birth rate	Cumulative live birth rate	within 6 months after randomization
Changes in markers of stress, anxiety	To elucidate the anxiety level as measured with serum cortisol concentration and Stait-Trait Anxiety Inventory (STAI)	≤8 weeks of gestation
Health related quality of life(HRQoL)	To determine women's health related quality of life (HRQoL) by short-form 36 (SF36)	≤8 weeks of gestation
Patient acceptability: acupuncture trust score	Patient acceptability of acupuncture to be measured by acupuncture trust score	On the day of embryo transfer
Side effects	Side effects	≤ 8 weeks of gestation
Congenital abnormalities	Judging by prenatal ultrasound and postnatal physical examination	at 6 weeks postpartum
Pregnancy complications	Complications of Pregnancy	≤42 weeks of gestation

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: May 18, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): May 29, 2020

Study Record Updates

• Last Update Posted (Actual): September 23, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Acupuncture; In Vitro Fertilization; Chinese Herbal Medicine; Live Birth
• Other Study ID Numbers: IVFAct

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Subject's privacy is protected undoubtedly at the time of the informed consent signing

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