The Influence of Obesity on Oocyte, Cumulus and Granulosa Functioning

NCT01945671 | Unknown DMC

• 1 other identifier: HYMC 0070-13
• Study Type: observational
• Target: 80
• Locations: 0 countries
• Sites: N/A

Brief Summary

Obese women have a higher prevalence of infertility than their lean counterparts. Obesity is a risk factor for anovulation , including in response to gonadotropin treatment .Further, even in women who are cycling regularly, obesity is associated with increased time-to-pregnancy and decreased chance of natural pregnancy. During obesity or periods of overnutrition, lipid accumulates in nonadipose tissues, notably skeletal muscle, liver, heart, and pancreas due to cellular uptake of exogenous fatty acids, triglycerides, and cholesterol as well as de novo lipogenesis in response to elevated glucose. The accumulation of intracellular lipid leads to high levels of free fatty acids that are subject to oxidative damage and the formation of cytotoxic and highly reactive lipid peroxides, which ultimately are detrimental to intracellular organelles, particularly the endoplasmic reticulum (ER) and mitochondria. Exposure of the ER to high levels of free fatty acids and lipid peroxides causes structural alterations that perturb ER function and lead to accumulation of unfolded proteins and calcium release. Failure of the UPR to reestablish ER homeostasis can lead to apoptosis .When mitochondria are exposed to high levels of free fatty acids, these can become oxidized by mitochondrial reactive oxygen species, forming lipid peroxides that damage essential proteins and uncouple mitochondrial function. This results in mitochondrial damage, which can cause further accumulation of lipids that cannot be catabolized, disrupted cellular homeostasis, and ultimately apoptosis . The cellular mechanisms by which obesity causes decreased conception rates are not known. Based on extensive evidence of obesity-induced lipotoxicity in other cells, it was hypothesized that obesity results in the activation of lipotoxicity pathways in the ovary. It was shown that lipid accumulation, ER stress, mitochondrial dysfunction, and apoptosis occur in ovarian cells and the oocyte in response to a high-fat diet. The aim of our study was to evaluate the influence of high BMI on oocytes, granulose cells and metabolites in the follicular fluid.

Conditions

BMI; Lipid Profile

Outcome Measures

Primary Outcomes (1)

• pregnancy rate

  1 year

Secondary Outcomes (1)

• lipid profile in different BMI

  1 year

Eligibility Criteria

• Age: 20 Years - 42 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

All patients undergo IVF treatments

You may qualify if:

• All patients

Sponsors & Collaborators

• Hillel Yaffe Medical Center: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

1\. triglycerides, free fatty acid, cholesterol (HDl, LDL), insulin, glucose, lactate, IGF-1, Leptin E2, Progessterone, IL-1, Il-6 and TNF-2. α.blood free fluid from the leading follicle will be collected in a container for further evaluation of metabolic markers including triglycerides, free fatty acid, cholesterol (HDl, LDL), insulin, glucose, lactate, IGF-1, Leptin E2, Progessterone, IL-1, Il-6 and TNF-α , ROS. 3\. Cumulus cells 4. Oocytes diameter 5. GV oocytes, M1 and M2 that fail to fertilize 6. GDF-9, BMP-15, BMP-6, TNF-α, SMAD family will be analyzed by western blott as marker for oocytes quality.

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2013
• First Posted: September 18, 2013
• Study Start: November 1, 2013
• Primary Completion: January 1, 2015
• Study Completion: May 1, 2015
• Last Updated: September 18, 2013

Record last verified: 2013-08