Back to resultsEffect of Lifestyle and/or Metformin Intervention on Pregnancy Outcome, A Pilot Randomized Controlled Trial
Primary Purpose
Infertility, Female, Obesity, Insulin Resistance
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
weight loss intervention
metformin intervention
Sponsored by
About this trial
This is an interventional treatment trial for Infertility, Female
Eligibility Criteria
Inclusion Criteria:
- Women ages 18 to 36 years.
- Women BMI at least 25kg/m2.
- Women who are non-pcos patient(2003 Rotterdam criteria).
- Women with insulin resistance (HOMA criteria).
- Women who are participating in their first or second fresh embryo cycle of in- vitro fertilization(IVF) or intracytoplasmic sperm injection (ICSI).
- Women who are indicated IVF or ICSI.
Exclusion Criteria:
- Women with endometriosis.
- Women with untreated hydrosalpinx.
- Women with a uterine cavity abnormality, such as a uterine congenital malformation; untreated uterine septum(except shallow uterine septum), adenomyosis, submucous myoma, or intrauterine adhesions.
- Women who are indicated and planned to undergo preimplantation genetic diagnosis(PGD)/preimplantation genetic screening(PGS).
- Women with endocrine abnormalities, such as Cushing syndrome, congenital adrenal hyperplasia, pituitary amenorrhea, thyroid dysfunction etc.
- Women who had participated in other treatments known to affect diet or weight (such as diet drugs and dietitian intervention) for past 3 months.
- Women who are unable to follow verbal and written instructions.
- Women who use donated oocytes to achieve pregnancy.
- Women with poor ovarian response(Bologna criteria).
- Women with diabetes mellitus, abnormal glycosylated hemoglobin.
- Women who has a history of recurrent spontaneous abortion.
Sites / Locations
- Reproductive & Genetic Hospital of CITIC-XIANGYA
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
No Intervention
Arm Label
lifestyle intervention group
metformin intervention group
lifestyle combined with metformin intervention group
routine clinical education group
Arm Description
Subjects will receive weight loss intervention under the guidance of a dietitian after assigned to lifestyle intervention group, including: restricted energy balanced diet, aerobic exercise, etc. Subjects will come to the hospital to measure their height, weight, waist circumference, hip circumference, body fat rate, BMI and test oral glucose tolerance test (OGTT)/insulin resistance test(IRT)/HOMA, blood routine, liver and kidney function on the day of grouping and in the 4th week, the 8th week, the 12th week after grouping. The aim is to lose 5-10% of the initial body weight. If the target was reached within 3 months, subjects will receive ovarian stimulation treatment in advance, otherwise treatment starts after 3 months. All subjects are treated with the same procedures，including a long ovarian stimulation regimen, oocyte retrieval, and fertilization, followed by a planned transfer of two day-3 embryos. The pregnancy and perinatal outcomes after transfer were followed up.
Subjects will be given metformin intervention with a starting dose of 0.5g bid after assigned to metformin intervention group, and the dose will be adjusted by doctors according to the insulin level and adverse events. Subjects will come to the hospital to measure their height, weight, waist circumference, hip circumference, body fat rate, BMI and test OGTT/IRT/HOMA, blood routine, liver and kidney function on the day of grouping and the 4th week, the 8th week, the 12th week after grouping. The aim is to adjust insulin level to normal within 3 months. If the target was reached within 3 months, subjects will start to receive ovarian stimulation treatment in advance, Otherwise treatment starts after 3 months. All subjects are treated with the same procedures, including a long ovarian stimulation regimen, oocyte retrieval, and fertilization, followed by a planned transfer of two day-3 embryos etc. The pregnancy and perinatal outcomes after transfer were followed up.
Subjects will receive weight loss intervention and metformin intervention after assigned to lifestyle combined with metformin intervention group. Subjects will come to the hospital to measure their height, weight, waist circumference, hip circumference, body fat rate, BMI and test OGTT/IRT/HOMA, blood routine, liver and kidney function on the day of grouping and in the 4th week, the 8th week, the 12th week after grouping. The aim is to lose 5-10% of the initial body weight and adjust insulin level to normal within 3 months. If the target was reached within 3 months, subjects will receive ovarian stimulation treatment in advance, otherwise treatment starts after 3 months. All subjects are treated with the same procedures，including a long ovarian stimulation regimen, oocyte retrieval, and fertilization, followed by a planned transfer of two day-3 embryos etc. The pregnancy and perinatal outcomes after transfer were followed up.
Subjects will only accept clinical routine education after assigned to routine clinical education group. Subjects will measure their height, weight, waist circumference, hip circumference, body fat rate, BMI and test OGTT/IRT/HOMA, blood routine, liver and kidney function on the day of grouping and will start induced ovulation therapy after completing routine clinical examination. All subjects are treated with the same procedures，including a long ovarian stimulation regimen, oocyte retrieval, and fertilization, followed by a planned transfer of two day-3 embryos etc. The pregnancy and perinatal outcomes after transfer were followed up.
Outcomes
Primary Outcome Measures
recruitment rate
the proportion of eligible patients randomised
Secondary Outcome Measures
mean numbers of randomised participants per month
numbers of randomised participants / the duration of recruitment
the proportion of participants with good intervention compliance
numbers of participants with good intervention compliance / numbers of participants who received the intervention
the proportion of participants who crossed over from one allocated group to the other
numbers of participants who crossed over from one allocated group to the other / numbers of participants who received the intervention
Proportion of subjects who initiated infertility treatment according to the schedule
numbers of participants who initiated infertility treatment according to the schedule/ numbers of participants who received the intervention
the proportion of participants who completed follow-up
numbers of participants who completed follow-up/ numbers of participants who received the intervention
Biochemical Pregnancy Rate
Number of women with Biochemical pregnancy /number of women who received the intervention Biochemical pregnancy was defined as a human chorionic gonadotropin level of more than 10 milli-International unit（mIU）per milliliter（ml）, as measured at about 14 days after embryo transfer.
Clinical Pregnancy Rate
Number of women with clinical pregnancies /number of women who received the intervention. Clinical pregnancy was defined as the presence of a gestational sac in the uterine cavity at about 28 days after embryo transfer, as detected on ultrasonography.
Live Birth Rate
Numbers of Live birth /number of women who received the intervention.Live birth defined as the delivery of any viable infant at 28 weeks or more of gestation.
Birth weight
Weight of newborns at delivery.
Pregnancy Loss Rate
Number of pregnancy losses / number of clinical pregnancies. Pregnancy loss refers to a complete spontaneous abortion or a nonviable pregnancy before 28 weeks of gestation.
Incidence of moderate to severe ovarian hyperstimulation syndrome(OHSS)
Number of cycles of moderate to severe OHSS/total number of fresh stimulation cycle.
Cumulative incidence of maternal and neonatal complications during whole gestation and prenatal stage
Number of pregnancies with complications / number of pregnancies; Number of live births with neonatal complications / number of live births；
Full Information
NCT ID
NCT03898037
First Posted
March 29, 2019
Last Updated
August 18, 2022
Sponsor
Reproductive & Genetic Hospital of CITIC-Xiangya
1. Study Identification
Unique Protocol Identification Number
NCT03898037
Brief Title
Effect of Lifestyle and/or Metformin Intervention on Pregnancy Outcome, A Pilot Randomized Controlled Trial
Official Title
Effect of Lifestyle and/or Metformin Intervention on Pregnancy Outcome in Overweight/Obese Non-pcos Infertility Women With Insulin Resistance , A Pilot Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
June 13, 2019 (Actual)
Primary Completion Date
June 30, 2021 (Actual)
Study Completion Date
June 30, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Reproductive & Genetic Hospital of CITIC-Xiangya
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of pilot trial is to compare the efficacy of lifestyle intervention, metformin intervention, lifestyle combined with metformin intervention in improving assisted reproductive technology in non-polycystic ovary syndrome(pcos) patients with overweight/obesity and insulin resistance compared with conventional clinical education. Subjects who meet the inclusion criteria will be randomized to four groups: lifestyle intervention group, metformin intervention group, lifestyle combined with metformin intervention group, and routine clinical education group. Subjects of above three intervention group will start ovulation stimulation treatment after reach the aim or duration of intervention and routine clinical education group has no intervention. All subjects are treated with the same procedures, including a long ovarian stimulation regimen, oocyte retrieval, and fertilization, followed by a planned transfer of two day-3 embryos. The primary outcome is ongoing pregnancy rate.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Female, Obesity, Insulin Resistance
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
lifestyle intervention group
Arm Type
Experimental
Arm Description
Subjects will receive weight loss intervention under the guidance of a dietitian after assigned to lifestyle intervention group, including: restricted energy balanced diet, aerobic exercise, etc. Subjects will come to the hospital to measure their height, weight, waist circumference, hip circumference, body fat rate, BMI and test oral glucose tolerance test (OGTT)/insulin resistance test(IRT)/HOMA, blood routine, liver and kidney function on the day of grouping and in the 4th week, the 8th week, the 12th week after grouping.
The aim is to lose 5-10% of the initial body weight. If the target was reached within 3 months, subjects will receive ovarian stimulation treatment in advance, otherwise treatment starts after 3 months. All subjects are treated with the same procedures，including a long ovarian stimulation regimen, oocyte retrieval, and fertilization, followed by a planned transfer of two day-3 embryos. The pregnancy and perinatal outcomes after transfer were followed up.
Arm Title
metformin intervention group
Arm Type
Experimental
Arm Description
Subjects will be given metformin intervention with a starting dose of 0.5g bid after assigned to metformin intervention group, and the dose will be adjusted by doctors according to the insulin level and adverse events. Subjects will come to the hospital to measure their height, weight, waist circumference, hip circumference, body fat rate, BMI and test OGTT/IRT/HOMA, blood routine, liver and kidney function on the day of grouping and the 4th week, the 8th week, the 12th week after grouping.
The aim is to adjust insulin level to normal within 3 months. If the target was reached within 3 months, subjects will start to receive ovarian stimulation treatment in advance, Otherwise treatment starts after 3 months. All subjects are treated with the same procedures, including a long ovarian stimulation regimen, oocyte retrieval, and fertilization, followed by a planned transfer of two day-3 embryos etc. The pregnancy and perinatal outcomes after transfer were followed up.
Arm Title
lifestyle combined with metformin intervention group
Arm Type
Experimental
Arm Description
Subjects will receive weight loss intervention and metformin intervention after assigned to lifestyle combined with metformin intervention group. Subjects will come to the hospital to measure their height, weight, waist circumference, hip circumference, body fat rate, BMI and test OGTT/IRT/HOMA, blood routine, liver and kidney function on the day of grouping and in the 4th week, the 8th week, the 12th week after grouping.
The aim is to lose 5-10% of the initial body weight and adjust insulin level to normal within 3 months. If the target was reached within 3 months, subjects will receive ovarian stimulation treatment in advance, otherwise treatment starts after 3 months. All subjects are treated with the same procedures，including a long ovarian stimulation regimen, oocyte retrieval, and fertilization, followed by a planned transfer of two day-3 embryos etc. The pregnancy and perinatal outcomes after transfer were followed up.
Arm Title
routine clinical education group
Arm Type
No Intervention
Arm Description
Subjects will only accept clinical routine education after assigned to routine clinical education group. Subjects will measure their height, weight, waist circumference, hip circumference, body fat rate, BMI and test OGTT/IRT/HOMA, blood routine, liver and kidney function on the day of grouping and will start induced ovulation therapy after completing routine clinical examination. All subjects are treated with the same procedures，including a long ovarian stimulation regimen, oocyte retrieval, and fertilization, followed by a planned transfer of two day-3 embryos etc. The pregnancy and perinatal outcomes after transfer were followed up.
Intervention Type
Behavioral
Intervention Name(s)
weight loss intervention
Intervention Description
weight loss intervention under the guidance of a dietitian, including: restricted energy balanced diet, aerobic exercise, etc.
Intervention Type
Drug
Intervention Name(s)
metformin intervention
Intervention Description
metformin intervention with a starting dose of 0.5g bid, and the dose will be adjusted by doctors according to the patient's insulin level and adverse events.
Primary Outcome Measure Information:
Title
recruitment rate
Description
the proportion of eligible patients randomised
Time Frame
10 months
Secondary Outcome Measure Information:
Title
mean numbers of randomised participants per month
Description
numbers of randomised participants / the duration of recruitment
Time Frame
10 months
Title
the proportion of participants with good intervention compliance
Description
numbers of participants with good intervention compliance / numbers of participants who received the intervention
Time Frame
16 months
Title
the proportion of participants who crossed over from one allocated group to the other
Description
numbers of participants who crossed over from one allocated group to the other / numbers of participants who received the intervention
Time Frame
16 months
Title
Proportion of subjects who initiated infertility treatment according to the schedule
Description
numbers of participants who initiated infertility treatment according to the schedule/ numbers of participants who received the intervention
Time Frame
16 months
Title
the proportion of participants who completed follow-up
Description
numbers of participants who completed follow-up/ numbers of participants who received the intervention
Time Frame
26 months
Title
Biochemical Pregnancy Rate
Description
Number of women with Biochemical pregnancy /number of women who received the intervention Biochemical pregnancy was defined as a human chorionic gonadotropin level of more than 10 milli-International unit（mIU）per milliliter（ml）, as measured at about 14 days after embryo transfer.
Time Frame
16 months
Title
Clinical Pregnancy Rate
Description
Number of women with clinical pregnancies /number of women who received the intervention. Clinical pregnancy was defined as the presence of a gestational sac in the uterine cavity at about 28 days after embryo transfer, as detected on ultrasonography.
Time Frame
18 months
Title
Live Birth Rate
Description
Numbers of Live birth /number of women who received the intervention.Live birth defined as the delivery of any viable infant at 28 weeks or more of gestation.
Time Frame
26 months
Title
Birth weight
Description
Weight of newborns at delivery.
Time Frame
26 months
Title
Pregnancy Loss Rate
Description
Number of pregnancy losses / number of clinical pregnancies. Pregnancy loss refers to a complete spontaneous abortion or a nonviable pregnancy before 28 weeks of gestation.
Time Frame
26 months
Title
Incidence of moderate to severe ovarian hyperstimulation syndrome(OHSS)
Description
Number of cycles of moderate to severe OHSS/total number of fresh stimulation cycle.
Time Frame
16 months
Title
Cumulative incidence of maternal and neonatal complications during whole gestation and prenatal stage
Description
Number of pregnancies with complications / number of pregnancies; Number of live births with neonatal complications / number of live births；
Time Frame
26 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
36 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women ages 18 to 36 years.
Women BMI at least 25kg/m2.
Women who are non-pcos patient(2003 Rotterdam criteria).
Women with insulin resistance (HOMA criteria).
Women who are participating in their first or second fresh embryo cycle of in- vitro fertilization(IVF) or intracytoplasmic sperm injection (ICSI).
Women who are indicated IVF or ICSI.
Exclusion Criteria:
Women with endometriosis.
Women with untreated hydrosalpinx.
Women with a uterine cavity abnormality, such as a uterine congenital malformation; untreated uterine septum(except shallow uterine septum), adenomyosis, submucous myoma, or intrauterine adhesions.
Women who are indicated and planned to undergo preimplantation genetic diagnosis(PGD)/preimplantation genetic screening(PGS).
Women with endocrine abnormalities, such as Cushing syndrome, congenital adrenal hyperplasia, pituitary amenorrhea, thyroid dysfunction etc.
Women who had participated in other treatments known to affect diet or weight (such as diet drugs and dietitian intervention) for past 3 months.
Women who are unable to follow verbal and written instructions.
Women who use donated oocytes to achieve pregnancy.
Women with poor ovarian response(Bologna criteria).
Women with diabetes mellitus, abnormal glycosylated hemoglobin.
Women who has a history of recurrent spontaneous abortion.
Facility Information:
Facility Name
Reproductive & Genetic Hospital of CITIC-XIANGYA
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410008
Country
China
12. IPD Sharing Statement
Learn more about this trial
Effect of Lifestyle and/or Metformin Intervention on Pregnancy Outcome, A Pilot Randomized Controlled Trial
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