The major complication of in vitro fertilization (IVF) is the development of multiple births. This is directly related to the practice of placing multiple embryos at embryo transfer. Multiple births are related to increased pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict embryo transfer policies have been enacted to reduce this problem, but are not universally followed or accepted. Recent evidence suggest that singleton offspring after IVF is at higher risk for lower birth weight for unknown reasons.

The issue of birth defects remains a controversial topic in IVF. A majority of studies do not show a significant increase after use of IVF. Some studies suggest higher rates for intracytoplasmic sperm injection (ICSI), while others do not support this finding. Major birth defects include chromosomal abnormalities, genetic imprinting defects, and multiple organ abnormalities. Possible explanations for birth defects offered were the underlying cause of the infertility, factors associated with IVF/ICSI, culture conditions, and medications, however, the actual cause is not known.