Polycystic Ovary Syndrome, Obesity, Infertility, Female
Conditions
Keywords
Polycystic Ovary Syndrome, Obesity, Infertility, IVF
Brief summary
The aim of this study was to evaluate the impact of low dose liraglutide in combination with metformin compared to metformin alone on IVF pregnancy rate (PR) and cumulatively PR (IVF and spontaneous) in infertile obese women with PCOS who had been previously poor responders regarding weight reduction with lifestyle modification and resistant to first line reproductive treatments.
Detailed description
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, in particular when PCOS is linked to obesity. Obese PCOS has poor IVF outcomes associated with impaired oocyte and embryo parameters and morphology. The purpose of this pilot prospective study was to investigate the effect of the novel medical therapy (combination of metformin and liraglutide (COMBI)) in the specific infertile obese PCOS population. GLP-1 has been investigated in regulation of reproductive system in animal models. Current observations suggest that it directly regulates kisspeptin and GnRH expression and that ovaries express GLP-1 mRNA. In obese PCOS, GLP-1 receptor agonist liraglutide provided positive effects on weight reduction and glucose homeostasis
Interventions
DRUGMET
In the MET group metformin was initiated at a dose of 500 mg once per day and increased by 500 mg every 3 days up to 1000 mg BID per os for 12 weeks. After 1 month IVF was done.
DRUGCOMBI
In the COMBI group the initial dose of MET was 500 mg for at least 2 wk and gradually increased to a final dose of 1000 mg BID. Liraglutide 1.2 mg QD s.c. was added after first two weeks of monotherapy with MET. After 1 month IVF was done.
Sponsors
University Medical Centre Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 37 Years
Healthy volunteers
No
Inclusion criteria
* 18 years old to 38 years old * polycystic ovary syndrome (rotterdam criteria) * BMI of 30 kg/m² or higher * Infertility * Before IVF
Exclusion criteria
* type 1 or type 2 diabetes mellitus * history of carcinoma * Cushing's syndrome or congenital (non-classic) adrenal hyperplasia * personal or family history of MEN 2 * significant cardiovascular, kidney or hepatic disease * the use of medications known or suspected to affect reproductive or metabolic functions * the use of statins, within 90 days prior to study entry no other ovarian pathology normal male semen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IVF pregnancy rates | 14 days | Clinical pregnancy rate defined as the presence of a fetal heart beat by ultrasound |
| Cumulative pregnancy rates | The pregnancies were collected by phone interview after one year | Number of all pregnancies (IVF pregnancies and spontaneous pregnancies) per patient |
| BMI | Patient's BMI was measured at the beginning and every four weeks during 12 weeks of clinical trial. ] | Patient's BMI was defined as the patient's body mass in kilograms divided by the square of their height in meters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oocyte nuclear maturation | 2 days | The number of metaphase 2 oocytes, metaphase 1 oocytes, and germinal vesicles |
| Embryo quality | 6 days | The embryo quality assessed by standard cleavage stage embryo grading system on day 3 of embryo culture. For any embryos grown to day 5, the embryo quality assessed by standard blastocyst grading system on day 5 of embryo culture |
Other
| Measure | Time frame | Description |
|---|---|---|
| The other outcomes was changes changes in fasting concentrations of glucose | Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial. | Patient's blood was drawn between 8 and 9 a.m. Concentrations of fasting glucose was measured in mmol/L. |
| The other outcomes was changes changes in fasting concentrations of insulin | Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial. | Patient's blood was drawn between 8 and 9 a.m. Fasting concentrations of insulin was measured in mU/L. |
| Other outcome was change in blood concentration in androstenedione. | Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial. | Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of androstenedione was measured in nmol/L. |
| Other outcome was change in blood concentration of testosterone | Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial. ] | Patient's blood was drawn between 8 and 9 a.m. Blood concentration was measured in nmol/L. |
| Other outcome was change in blood concentrations of SHBG (sex hormone-binding globulin). | Patient's fasting blood was drawn at the beginning and every four weeks during the 12 weeks of clinical trial. ] | Patient's blood was drawn between 8 and 9 a.m. Blood concentrations of SHBG was measured in nmol/L. |
Outcome results
None listed