Effect of Lifestyle and/or Metformin Intervention on Pregnancy Outcome, A Pilot Randomized Controlled Trial

• ClinicalTrials.gov Identifier: NCT03898037
• Recruitment Status: Completed
• First Posted: April 1, 2019
• Last Update Posted: January 11, 2022
• Sponsor: Reproductive & Genetic Hospital of CITIC-Xiangya
• Information provided by (Responsible Party): Reproductive & Genetic Hospital of CITIC-Xiangya

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.

Condition or disease	Intervention/treatment	Phase
Infertility, Female; Obesity; Insulin Resistance	Behavioral: weight loss intervention; Drug: metformin intervention	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 13, 2019
• Actual Primary Completion Date: September 24, 2020
• Actual Study Completion Date: June 30, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: lifestyle intervention group; 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.	Behavioral: weight loss intervention; weight loss intervention under the guidance of a dietitian, including: restricted energy balanced diet, aerobic exercise, etc.
Experimental: metformin intervention group; 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.	Drug: metformin intervention; 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.
Experimental: lifestyle combined with metformin intervention group; 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.	Behavioral: weight loss intervention; weight loss intervention under the guidance of a dietitian, including: restricted energy balanced diet, aerobic exercise, etc.; Drug: metformin intervention; 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.
No Intervention: routine clinical education group; 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.

Outcome Measures

Primary Outcome Measures :

1. Ongoing Pregnancy Rate [ Time Frame: 8 months ]

   Number of women with ongoing pregnancy / number of women randomized to the specific group.

   Ongoing pregnancy was defined as the presence of a fetus with heart motion at 10 to 12 weeks of gestation.

Secondary Outcome Measures :

1. Number of eggs obtained [ Time Frame: 5 months ]
   The total number of oocytes obtained after one treatment cycle
2. Biochemical Pregnancy Rate [ Time Frame: 5 months ]

   Number of women with Biochemical pregnancy /number of women randomized to the specific group.

   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.

3. Clinical Pregnancy Rate [ Time Frame: 6 months ]
   Number of women with clinical pregnancies /number of women randomized to the specific group. 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.
4. Live birth rate [ Time Frame: 16 months ]

   Number of women with live births / number of women randomized to the specific group.

   Live birth is defined as the delivery of any viable infant at 28 weeks or more of gestation after our interventions.

5. Duration of pregnancy [ Time Frame: 16 months ]
   The time from the first day of last menstrual period to the day of delivery.
6. Birth weight [ Time Frame: 16 months ]
   Weight of newborns at delivery.
7. Pregnancy Loss Rate [ Time Frame: 12 months ]
   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.
8. Incidence of moderate to severe ovarian hyperstimulation syndrome(OHSS) [ Time Frame: 6 months ]
   Number of cycles of moderate to severe OHSS/total number of fresh stimulation cycle.
9. Cumulative incidence of maternal and neonatal complications during whole gestation and prenatal stage [ Time Frame: 16 months ]
   Number of pregnancies with complications / number of pregnancies; Number of live births with neonatal complications / number of live births；

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 36 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Women ages 18 to 36 years.
2. Women BMI at least 25kg/m2.
3. Women who are non-pcos patient(2003 Rotterdam criteria).
4. Women with insulin resistance (HOMA criteria).
5. Women who are participating in their first or second fresh embryo cycle of in- vitro fertilization(IVF) or intracytoplasmic sperm injection (ICSI).
6. Women who are indicated IVF or ICSI.

Exclusion Criteria:

1. Women with endometriosis.
2. Women with untreated hydrosalpinx.
3. 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.
4. Women who are indicated and planned to undergo preimplantation genetic diagnosis(PGD)/preimplantation genetic screening(PGS).
5. Women with endocrine abnormalities, such as Cushing syndrome, congenital adrenal hyperplasia, pituitary amenorrhea, thyroid dysfunction etc.
6. Women who had participated in other treatments known to affect diet or weight (such as diet drugs and dietitian intervention) for past 3 months.
7. Women who are unable to follow verbal and written instructions.
8. Women who use donated oocytes to achieve pregnancy.
9. Women with poor ovarian response(Bologna criteria).
10. Women with diabetes mellitus, abnormal glycosylated hemoglobin.
11. Women who has a history of recurrent spontaneous abortion.

Contacts and Locations

Locations

China, Hunan

Reproductive & Genetic Hospital of CITIC-XIANGYA

Changsha, Hunan, China, 410008

Sponsors and Collaborators

Reproductive & Genetic Hospital of CITIC-Xiangya

More Information

• Responsible Party: Reproductive & Genetic Hospital of CITIC-Xiangya
• ClinicalTrials.gov Identifier: NCT03898037
• Other Study ID Numbers: P2019001
• First Posted: April 1, 2019
• Last Update Posted: January 11, 2022
• Last Verified: January 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infertility; Infertility, Female; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs