Infertility, Obesity, PCOS
Conditions
Keywords
polycystic ovary syndrome, liraglutide, infertile, obesity
Brief summary
Liraglutide, a hypoglycemic drug, can reduce weight and improve insulin resistance while stabilizing blood glucose metabolism without increasing the risk of hypoglycemia, and has been approved by the State Food and Drug Administration of China and the US Food and Drug Administration for the treatment of obesity. Polycystic ovary syndrome (PCOS) is the main cause of female anovulatory infertility, and it is also a high-risk group of obesity. Previous studies have suggested that liraglutide improves glucose metabolism, body weight, and inflammation levels in obese women with PCOS, and improves sex hormone profiles and menstrual cycles, possibly contributing to increased fertility. Therefore, this project intends to test the following hypothesis through a large sample randomized controlled trial in obese and infertile PCOS women who are assisted by in vitro fertilization-frozen embryo transfer (IVF-FET), using liraglutide before transplantation to reduce weight can improve the live birth rate of assisted reproduction.
Interventions
DRUGMetformin
Metformin 1500 mg/day until pregnancy
DRUGLiraglutide and metformin
Liraglutide 3.0 mg or maximum tolerable dose/day × 12 weeks and metformin 1500 mg/day until pregnancy.
Sponsors
Peking University Third Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Women with polycystic ovary syndrome (PCOS) who meet the Rotterdam diagnostic criteria. * Aged 20-40 years; * 25 kg/m2 ≤ BMI ≤ 35 kg/m2; * Have not used any anti-diabetes or weight-loss medications (metformin excluded) within the past 3 months; * Have at least 1 transplantable frozen embryo available at the research center; * Able to follow the study's contraceptive requirements.
Exclusion criteria
* Diabetic ketoacidosis or other acute complications of diabetes; * HbA1c ≥ 9.0% before enrollment; * Using drugs that affect appetite or nutrient absorption within the past 2 months (metformin excluded); * Uncontrolled hyperthyroidism or hypothyroidism, hypertension, systemic autoimmune diseases, etc. that may affect pregnancy and fetal development; * 17 hydroxyprogesterone in follicualr phase \> 2.0 ng/ml; * Serious cardiovascular, digestive, liver, or kidney diseases, HBsAg-positive chronic hepatitis B, active pulmonary tuberculosis, or AIDS, etc. that are infectious or hereditary diseases; * Any psychiatric or psychological disorders requiring drug treatment; * Poor pregnancy and delivery history: recurrent failed implantations ≥3 times, spontaneous abortions ≥2 times; history of stillbirth, dystocia, or birth defects; previous pregnancies with preeclampsia, eclampsia, or HELLP syndrome; * Uncontrolled metabolic, autoimmune, or hereditary disease in the husband; * A contraindication or relative contraindication to using GLP-1 receptor agonists (history of medullary thyroid carcinoma or family history of medullary thyroid carcinoma, acute cholecystitis or pancreatitis in the acute phase or history of previous attacks, GLP-1 receptor agonist allergy, etc.); * Failure to comply with the contraceptive requirements of the study design; * Failure to take medication regularly and follow up; * Current smokers, drug addicts, alcoholics, or individuals with substance abuse; * Participants who have participated in any clinical trial within the past 3 months prior to screening; * Individuals with other conditions deemed unsuitable for participation in this clinical trial by the investigator;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Live birth rate associated with single cycle frozen embryo transfer | At delivery | The rate of live birth of intervention and control groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of newly diagnosed diabetes or gestational diabetes during pregnancy | At 28 weeks of pregnancy | Newly diagnosed diabetes or gestational diabetes at 28 weeks of pregnancy confirmed by 75 g oral glucose tolerance test。 |
| Pregnancy outcome and complications | From baseline to delivery | Rate of miscarriage, multiple pregnancies, pregnancy induced hypertension, preeclampsia, HELLP syndrome, prematurity (\< 37 weeks), macrosomia (birth weight \> 4 kg), induction of labour, prolonged duration of labour, caesarean section, assisted delivery, peripartum increased blood loss (≥ 800 ml). |
| Birth weight for gestational age | At delivery | Birth weight percentile for gestational age for neonatal sex |
| Clinical pregnancy rate of single cycle frozen embryo transfer | Thirty days after the embryo transplantation | Viable intrauterine pregnancy confirmed by ultrasound |
| Other perinatal outcomes | At delivery | Rate of major birth defects, stillbirth, neonatal complications, and neonatal admission to a neonatal intensive care unit. |
| Accumulated live birth rate | At delivery | Accumulated liver birth rate associated with the pregnancy achieved during the first 6 months of the study |
| Accumulated clinical pregnancy rate | At month 6 | Accumulated clinical pregnancy rate achieved during the first 6 months of the study |
| Apgar scores | At delivery | Apgar scores (0\ 10) of the newborns at delivery |
Other
| Measure | Time frame | Description |
|---|---|---|
| Quality of life specifically for PCOS individuals | Baseline and week 12 | Measured by Modified Polycystic ovary syndrome Quality of life, with each item scores from 1 (maximum impairment) to 7 (no impairment) |
| Weight | At baseline, and week 12 | Measured by the same weight scale |
| Costs | At delivery | The cost per live birth for the different intervention groups, considering both direct medical and non-medical costs, as well as indirect costs. |
| Major congenital malformations | Six weeks after live birth | Identified in the Birth Defects Prevention and Control Plan (2023-2027) issued by the National Health Commission of the People's Republic of China |
| Oral glucose tolerance test | At baseline, week 12, 28 weeks of pregnant, six weeks after delivery | oral glucose tolerance test was conducted to test glucose metabolism |
| HbA1c | At baseline and week12 | Glycosylated hemoglobin |
| Rate of insulin usage during pregancy | Throughout pregnancy | — |
| Number of menstrual cycles | From to 12 weeks | — |
| Free testosterone index | At baseline, week 12 | Free testosterone index |
| Drug-related adverse reactions | During the treatment with liraglutide or metformin | Drug-related adverse reactions, including but not limited to, nausea, diarrhea, vomiting, decreased appetite, dyspepsia, constipation, drug allergy, hypoglycemia, acute pancreatitis, acute gallbladder disease. |
| Anxiety | Baseline and week 12 | Measured by Generalized Anxiety Disorder-7 scores, from 0 (no anxiety) to 21 (severe anxiety) |
| Depression | Baseline and week 12 | Measured by Patient Health Questionnaire-9 score from 0 (no depression) to 27 (severe depression) |
Countries
China
Contacts
Primary ContactHaining Wang, Professor
Backup ContactYe Liu, Associate Professor
Outcome results
None listed