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

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02416960
• Other study ID #: 11-0326
• Status: Completed
• Phase: N/A
• First received: April 7, 2015
• Last updated: April 14, 2015
• Start date: January 2012
• Est. completion date: December 2013

Study information

• Verified date: April 2015
• Source: Hospital de Clinicas de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 35 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Female Infertility
• Infertility
• Infertility, Female
• Obesity
• Overweight

Intervention

Other:
• Low Glycemic Index Diet Group
This diet will be designed as a moderate reduced-energy, moderate-to-high ?ber, low glycemic index/load diet.
• Conventional Diet Group
This diet will be designed as a moderate reduced-energy, moderate-to-high ?ber, high glycemic index/load diet.

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	RS

Sponsors (3)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre	Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Country where clinical trial is conducted

Brazil, 

References & Publications (10)

Cummings DE, Foster-Schubert KE, Overduin J. Ghrelin and energy balance: focus on current controversies. Curr Drug Targets. 2005 Mar;6(2):153-69. Review. — View Citation

Jackson AS, Pollock ML. Generalized equations for predicting body density of men. Br J Nutr. 1978 Nov;40(3):497-504. — View Citation

Loret de Mola JR. Obesity and its relationship to infertility in men and women. Obstet Gynecol Clin North Am. 2009 Jun;36(2):333-46, ix. doi: 10.1016/j.ogc.2009.03.002. Review. — View Citation

Marfell-Jones, M., Olds, T., Stewart, A., and Carter, J.E.L. 2006. International standards for anthropometric assessment. North-West University, Potchefstroom, RSA.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412-9. — View Citation

Metwally M, Ledger WL, Li TC. Reproductive endocrinology and clinical aspects of obesity in women. Ann N Y Acad Sci. 2008 Apr;1127:140-6. doi: 10.1196/annals.1434.000. Review. — View Citation

Singla P, Bardoloi A, Parkash AA. Metabolic effects of obesity: A review. World J Diabetes. 2010 Jul 15;1(3):76-88. doi: 10.4239/wjd.v1.i3.76. — View Citation

Sliwowska JH, Fergani C, Gawalek M, Skowronska B, Fichna P, Lehman MN. Insulin: its role in the central control of reproduction. Physiol Behav. 2014 Jun 22;133:197-206. doi: 10.1016/j.physbeh.2014.05.021. Epub 2014 May 27. Review. — View Citation

Terriou P, Sapin C, Giorgetti C, Hans E, Spach JL, Roulier R. Embryo score is a better predictor of pregnancy than the number of transferred embryos or female age. Fertil Steril. 2001 Mar;75(3):525-31. — View Citation

Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, Sullivan E, Vanderpoel S; International Committee for Monitoring Assisted Reproductive Technology; World Health Organization. International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) revised glossary of ART terminology, 2009. Fertil Steril. 2009 Nov;92(5):1520-4. doi: 10.1016/j.fertnstert.2009.09.009. Epub 2009 Oct 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No