Risks of Birth Defects and Other Adverse Outcomes Associated With Assisted Reproductive Technology

Approximately 1 million children world-wide have been born through assisted reproductive technology (ART),¹ which helps many motivated couples give birth to healthy infants. Children conceived through ART comprise as many as 1% to 2% of total births in some countries.^2,3 High rates of multiple births, with attendant complications of prematurity and low birth weight, are well documented. Concerns are now emerging about associated increased risks for congenital anomalies. Use of newer techniques may bring additional hazards, especially those requiring more biologic manipulation than artificial insemination and other, older ART methods. Outcomes data through ART registries permit risk estimates, although some data ascertainment is incomplete, especially in the United States. This report reviews ART outcomes, with focus on the potential risks of birth defects and their possible mechanisms, as well as limitations of current risk assessments. Moreover, it suggests ways to improve ART tracking and outcomes.

ART is broadly defined as conception through any procedure or medication assisting in achieving pregnancy, including ovulation induction and intrauterine insemination. The Centers for Disease Control and Prevention (CDC) defines ART more narrowly as “any procedure that entails the handling of both eggs and sperm or of embryos for the purpose of establishing a pregnancy.”⁴ These procedures include in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). In IVF, fertilization is achieved by mixing eggs and sperm together in the laboratory. In ICSI, fertilization consists of direct microinjection of 1 sperm into 1 egg. In both, fertilized eggs are implanted after several days of ex vivo cell growth. Techniques of surgical embryo transfer include gamete intrafallopian transfer and zygote intrafallopian transfer. Emerging techniques involve additional gamete and embryo manipulation such as in vitro oocyte maturation.¹

Complete data for the numbers of ART-related births, specific ART methods used, and birth …