Cardiovascular and Metabolic Profiles in Pre-pubertal Singletons Aged 6-8 Years of Age Conceived After Frozen Embryo Transfer Compared to Singletons Conceived After Fresh Embryo Transfer and After Natural Conception

The investigators aim to conduct a clinical follow-up study of three groups of children: Exposed children conceived by ART(assisted reproductive technology) after frozen embryo transfer (FET) and two unexposed control groups; (1) Children conceived by ART after fresh embryo transfer and (2) Naturally conceived children. All children will be identified via their mother's CPR number in the in-vitro fertilization (IVF) and medical birth registry. Only singletons 6-8 years of age (birth year 2009-2011) born in hospitals in the Capital Region will be included. Access to maternal postal addresses will be retrieved through the CPR registry. The investigators will contact the mothers by an invitation letter by post including the patient information and the information for the child. The invitation letter and patient information will be similar for study and control groups. The mothers can reply via sms, email or telephone. If they do not reply within 2 weeks, the investigators will send them one postal reminder. In case they respond, the investigators will schedule the visit. The investigators will start contacting and examining the oldest children. Children of mothers with preexisting diabetes (type 1 or type 2) or gestational diabetes will be excluded the study.

Subjects:

• Singletons conceived by ART after FET (N=200)
• Singletons conceived by ART after fresh embryo transfer (N=200). (N~1000 mothers will be contacted, 40% of eligible ART subjects are expected to participate).
• Singletons born after natural conception (N=200). A random sample of naturally conceived children matched with FET children on month and year of birth and child sex (N~ 670, 30% of eligible subjects are expected to participate).

Clinical examinations:

The clinical examinations of the children will be carried out in the Clinic of Growth and Reproduction and Clinic of Cardiology at Rigshospitalet. The investigators aim that each child attends all examinations at the same day and the full examination will last no longer than 30-40 minutes. The participants meet fasting in the morning and a fasting blood sample will be collected. Local anesthetic cream will be sent to all participants prior to the examination. The fasting blood sample will be analyzed for: Glucose profile: glucose, insulin, c-peptid (calculation of HOMA-IR), HbA1c - Lipid profile: Total cholesterol, LDL, HDL, Triglycerides - Growth factors: IGF-I and IGFBP-3 - Androgen status and Anti Müllerian Hormone (AMH) - Lipids and cytokines (CRP, IL-6, adiponectin, leptin, inkretin) - Biobank sampling The clinical examination includes determination of: Height, weight, waist and hip circumference - Skinfold measurements (Harpenden Skinfold Caliper) - Pubertal staging (Tanner) - Blood pressure (systolic, diastolic) measured by FINA press device (valid continuous measurements)