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

Reproductive & Genetic Hospital of CITIC-Xiangya

Status: Completed

Conditions: Insulin Resistance; Obesity; Infertility, Female

Treatments: Behavioral: weight loss intervention; Drug: metformin intervention

Study type: Interventional

Funder types: Other

Identifiers

NCT03898037

P2019001

Details and patient eligibility

About

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.

Enrollment: 80 patients

Sex: Female

Ages: 18 to 36 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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80 participants in 4 patient groups

lifestyle intervention group

Experimental group

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.

Treatment:

Behavioral: weight loss intervention

metformin intervention group

Experimental group

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.

Treatment:

Drug: metformin intervention

lifestyle combined with metformin intervention group

Experimental group

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.

Treatment:

Behavioral: weight loss intervention

Drug: metformin intervention

routine clinical education group

No Intervention group

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.