Effect of the Glycemic Index of Diet on Metabolic and Reproductive Parameters in Overweight and Obese Infertile Women

Study Overview
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Brief Summary
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Infertility has been currently recognized as a disorder related to obesity. Among several metabolic changes associated with obesity, insulin resistance appears to be linked to hormonal disorders that affect reproductive system. Leptin and ghrelin are hormones involved in energy balance regulation and are also associated with reproductive system regulation, but its relationship with infertility is scarce. The aim of this study is to determine the effect of a hypocaloric diet with different glycemic indexes on ghrelin and leptin levels, hormonal, metabolic and reproductive parameters in infertile overweight or obese women candidates to in vitro fertilization. The patients who meet the inclusion criteria and accept to participate in the study, will be allocated in one of the following groups: Hypocaloric Low Glycemic Index diet group; Hypocaloric Conventional diet group or Control group (maintenance of usual diet) and follow the study protocol for 12 week. Immediately after the end of the diet protocol, the patients will be submitted to the in vitro fertilization treatment.

Detailed Description
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Infertility has been currently recognized as a disorder related to obesity. Among several metabolic changes associated with obesity, insulin resistance appears to be linked to hormonal disorders that affect reproductive system. Leptin and ghrelin are hormones involved in energy balance regulation and are also associated with reproductive system regulation, but its relationship with infertility is scarce. The aim of this study is to determine the effect of a hypocaloric diet with different glycemic indexes on ghrelin and leptin levels, hormonal, metabolic and reproductive parameters in infertile overweight or obese women candidates to in vitro fertilization. Infertile women with grade I and II obesity, or pre-obesity with increased waist circumference will be recruited. Patients will be assigned to Hypocaloric Low Glycemic Index diet group; Hypocaloric Conventional diet group or Control group (maintenance of usual diet), and will follow the protocol for 12 weeks. The two intervention diets will be similar in terms of caloric intake and macronutrient distribution and different in terms of carbohydrates quality (index and glycemic load). Immediately after the end of the diet protocol, the patients will be submitted to the in vitro fertilization treatment. Before and after the intervention anthropometric measurements (weight, height, body mass index, waist and hip circumference) and body composition (body fat percentage determined by the measurement of seven skinfolds) will be evaluated as well as biochemical parameters: leptin, acylated ghrelin, glucose, insulin, serum lipids (total cholesterol and lipoproteins, and triglycerides), sex hormones - follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, prolactin, testosterone and sex hormone binding globulin (SHBG). Primary outcome: clinical pregnancy rate. Secondary outcomes: HOMA-IR (Homeostasis Model Assessment), acylated ghrelin and leptin levels, body fat percentage, number of oocytes retrieved, percentage of fertilized oocytes and embryo quality.

Official Title
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Effect of a Hypocaloric Diet With Different Glycemic Indexes on Ghrelin and Leptin Levels, Metabolic Parameters, and Reproductive Outcomes in Overweight and Obese Infertile Women: A Randomized Clinical Trial

Conditions
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Female Infertility, Obesity

Intervention / Treatment
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* Other: Low Glycemic Index Diet Group
* Other: Conventional Diet Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnose of female infertility and indication for treatment with in vitro fertilization Body Mass Index (BMI) equal or greater than 30 kg/m² or BMI > 25 kg/m² with increased waist circumference (> 80 cm); Being not treated (diet) for weight loss/gain and maintaining stable body weight in the three months prior to the study; Not having stomach/digestive problems Not having the knowledge of cardiovascular disease history; Non-smokers; Not using any medication. Exclusion Criteria: Patients with BMI equal or higher than 40 kg/m² (morbid obesity) Patients who are already receiving some type of nutritional intervention Patients with co-morbidities that may interfere with reproductive capacity (genetic and/or endocrine disorders, diabetes mellitus, cancer, liver or kidney failure), alcoholics, individuals who have contact (work) with heavy metals or chemicals (exposure to solvents and pesticides) Lack of adherence to the proposed dietary treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Glycemic Index Diet Group<br>Patients will follow a treatment with a hypocaloric diet with low glycemic index/load for 12 weeks, immediately before the in vitro fertilization cycle. | Other: Low Glycemic Index Diet Group<br>* This diet will be designed as a moderate reduced-energy, moderate-to-high ﬁber, low glycemic index/load diet.<br>|
| Active Comparator: Conventional Diet Group<br>Patients will follow a treatment with a hypocaloric diet with high glycemic index/load for 12 weeks, immediately before the in vitro fertilization cycle. | Other: Conventional Diet Group<br>* This diet will be designed as a moderate reduced-energy, moderate-to-high ﬁber, high glycemic index/load diet.<br>|
| No Intervention: Control Group<br>Patients will follow their usual diet for 12 weeks, immediately before the in vitro fertilization cycle. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Pregnancy Rate | Clinical Pregnancy will be considered as pregnancy diagnosed by ultrasound visualization of one or more gestational sacs or definitive clinical signs of pregnancy. | up to 18 weeks - in average, two weeks after the end of the in vitro fertilization cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HOMA-IR index (Homeostasis Model Assessment) | The HOMA-IR index will be obtained by the following formula: fasting glucose (mg/dl/18) x fasting insulin (U/mL)/22.5. | baseline and 12 weeks | 
| Acylated Ghrelin Levels (pg/dL) | The levels of acylated ghrelin will be determined by enzyme immunoassay (SPI BIO, Montigny le Bretonneux, France) using a plate reader (Biochrom Anthos MultiRead 400, Biochrom Ltd., Cambridge, UK). | baseline and 12 weeks | 
| Leptin Levels (ng/mL) | The levels of leptin will be determined by enzyme immunoassay (SPI BIO, Montigny le Bretonneux, France) using a plate reader (Biochrom Anthos MultiRead 400, Biochrom Ltd., Cambridge, UK). | baseline and 12 weeks | 
| Body Fat Percentage (%) | The body fat percentage will be determined measuring the skinfolds at seven sites (triceps, subscapular, suprailiac, axillary, pectoral, abdomen and thigh) using a standardized technique of measurement and determination. | baseline and 12 weeks | 
| Number of Oocytes Retrieved | Women will follow a pre-established protocol of ovarian stimulation as part of the preparation for the in vitro fertilization cycle. The evolution of oocytes development will be accompanied by the medical team using the ultrasound technique and when at least one oocyte reach the average size of 17 mm the puncture of oocytes by aspiration will be held. | between 12 and 16 weeks, during the in vitro fertilization cycle | 
| Percentage of Fertilized Oocytes (%) | The percentage of fertilized oocytes will be obtained using the following formula: number of embryos/ total number of oocytes x 100. | between 12 and 16 weeks, during the in vitro fertilization cycle | 
| Embryo Quality | Embryo quality will be determined by the Embryonic Score Calculation - ESC, where embryos with score 4, are considered the best quality. | between 12 and 16 weeks, during the in vitro fertilization cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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female infertility, glycemic index, leptin, ghrelin, overweight, obesity, in vitro fertilization