The Effect of a Liraglutide on IVF in Obese PCOS

Study Overview
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Brief Summary
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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
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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

Official Title
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The Effect of Liraglutide on Pregnancy Rates in Obese Women With PCOS Undergoing in Vitro Fertilization: a Pilot Randomized Study

Conditions
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Polycystic Ovary Syndrome, Obesity, Infertility, Female

Intervention / Treatment
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* Drug: MET
* Drug: COMBI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 37 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metfrormin group (MET)<br>Drug: Metformin | Drug: MET<br>* 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.<br>* Other names: Glucophage tbl;|
| Active Comparator: COMBI group (COMBI)<br>Drug: liraglutide | Drug: COMBI<br>* 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.<br>* Other names: Victoza 6 mg/ml solution for injection in pre-filled pen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IVF pregnancy rates | Clinical pregnancy rate defined as the presence of a fetal heart beat by ultrasound | 14 days | 
| BMI | Patient's BMI was defined as the patient's body mass in kilograms divided by the square of their height in meters. | Patient's BMI was measured at the beginning and every four weeks during 12 weeks of clinical trial. ] | 
| Cumulative pregnancy rates | Number of all pregnancies (IVF pregnancies and spontaneous pregnancies) per patient | The pregnancies were collected by phone interview after one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oocyte nuclear maturation | The number of metaphase 2 oocytes, metaphase 1 oocytes, and germinal vesicles | 2 days | 
| Embryo quality | 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 | 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polycystic Ovary Syndrome, Obesity, Infertility, IVF