Objective:

Risk factors for metabolic syndrome may be increased in children conceived by IVF, but the metabolic consequences of hormonal stimulation versus embryo culture on later health have not been well studied to date. To dissect this, we metabolically phenotyped adult C57BL/6J female mice conceived by natural conception (NC), by ovarian stimulation alone (OS) or by IVF.

Methods:

Blastocysts from uteri of adult cycling mice or generated by ovarian stimulation followed by either natural conception or IVF were transferred to pseudopregnant mice. Pups were weighed weekly from birth and weaned at 3-weeks of age onto chow (20% kcals fat) or high fat diet (60% kcals fat) for 8 weeks. An intraperitoneal glucose tolerance test (2g/kg) or insulin tolerance test (0.75U/kg) was performed at 11 weeks of age. At 12 weeks of age, inguinal fat, epididymal fat and liver were dissected and weighed.

Results:

There were no differences in litter size between groups (4-10 pups/litter). Birth weight of IVF (n=29) and OS (n=24) was lower than NC females (n=29) (p≤0.001); however, body weight gain was not different between groups on either diet. Fasting glucose was higher in IVF versus the other groups (p≤0.01), irrespective of diet. In response to high fat diet, the percentage of inguinal and parametrial fat and glucose area under the curve was higher in OS and IVF versus NC (p≤0.02). Following high fat diet, a reduced glucose response to insulin was observed in IVF versus NC (p<0.001).

Conclusions:

Ovarian stimulation resulted in reduced fetal growth, and increased susceptibility to high fat diet as evidenced by increased adiposity and impaired glucose tolerance. Embryo culture increased adult fasting glucose irrespective of diet, and reduced insulin sensitivity following high fat diet. Thus both ovarian stimulation and embryo culture may contribute to metabolic consequences later in life. IVF in particular may increase the risk of developing type 2 diabetes.