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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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In Vitro Fertilization

Intervention / Treatment
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* Other: Acupuncture and Chinese Herbal Medicine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women ≥20 to ≤40 years of age Indications for IVF Duration of infertility >1 year Undergoing IVF with an intention of fresh ET on day 3 or 5. Exclusion Criteria: Women with an intention to replace frozen embryos only. Preimplantation genetic testing History of recurrent miscarriages defined as having three consecutive miscarriages. Having acupuncture or CHM for infertility within 3 months prior the IVF Women with abnormal liver or renal function tests

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: acupuncture and CHM<br>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<br>* 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.<br>|
| Placebo Comparator: acupuncture and placebo CHM<br>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<br>* 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.<br>|
| Placebo Comparator: control acupuncture and CHM<br>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<br>* 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.<br>|
| Placebo Comparator: control acupuncture and placebo CHM<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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In Vitro Fertilization, Chinese Herbal Medicine, Acupuncture, Live Birth