Infant outcomes of assisted reproduction Carrie Williams 1 , Alastair Sutcliffe ⁎ Institute of Child Health, UCL, General Paediatric & Adolescent Unit, 30 Guilford Road, London, WC1N 1EH, UK abstract article info Keywords: Reproductive techniques Assisted Fertilization in vitro Infant Follow-up studies Assisted reproductive technologies (ART) have become widely used in the treatment of subfertility over the last 30 years. Currently 1.7% of all births in the UK occur after assisted conception. This review summarises work that has been undertaken to investigate health outcomes of these children and summarises areas where uncertainty continues to exist. Much of the adverse health outcomes of children born after ART are related to higher order birth; however evidence suggests adverse perinatal outcomes in singletons as well as twins and triplets. The cause of adverse health outcomes in ART conceived children is as yet unclear and studies investigating causal factors such as underlying subfertility are discussed. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The number and proportion of children born after assisted conception are increasing. There have already been over 3,500,000 births after Assisted Reproductive Technologies (ART) worldwide and with falling fertility rates in some countries this is likely to rise [1]. 1.7% of all children born in the UK in 2006 were conceived after ART, compared to 0.5% in 1992 [2]. Assisted reproductive techniques have developed rapidly since the birth of the first IVF conceived infant, Louise Brown, in 1978. The diverse range of techniques available includes gamete intra-fallopian tube transfer (GIFT), oocyte donation, embryo cryopreservation techniques, intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis (PGD) and blastocyst culture (extended embryo culture) as well as standard IVF. Whilst the development and use of these techniques have progressed rapidly, the same cannot be said for research into the safety outcomes of such treatments. The reason for this is not clear; however a contributing factor may be that institutions which provide ART are not usually responsible for providing care in pregnancy. Therefore they often have little direct contact with the family after the initial treatment period, making follow-up data difficult to collect. In addition some of the potential adverse outcomes are rare events and therefore very large cohorts are required. Currently there are no surveillance systems specifically developed for studying outcomes of ART and thus research has generally used registries and databases set up for other purposes. This often results in essential data not being available, such as information on confounding factors [3]. Despite these problems there is an emerging literature reporting infant outcomes of ART. Some of these outcomes have been studied empirically and some as the result of theoretical concerns and animal models. Potential risks of ART include multiple births, low birth weight and prematurity in singleton births, congenital abnormalities, imprinting disorders, neurodevelopmental risks, childhood cancers and growth disorders. This review aims to present much of this data including positive and negative outcomes, in the context of the methodology difficulties of many of the studies. 2. Perinatal outcomes 2.1. Multiple births The most well documented risk of ART is multiple births. Assisted conceptions account for 21% of all multiple births in the UK although they only account for 1.7% of all births (Table 1). The majority of multiple ART births are dizygotic twins, resulting from multiple embryo transfer. However interestingly there are also higher rates of monozygotic twins in ART pregnancies (1–5% of all ART pregnancies compared to 0.4% in the general population) [4,5]. Assisted hatching and blastocyst culture appear to be particular risk factors for monozygosity. This is thought to be due to potential manipulation of the zona pellucida [6,7]. Multiple pregnancies in general are associated with several adverse outcomes including preterm birth, low birth weight, neonatal mortality, congenital malformations and disability amongst survivors. [8] Delivery before 37weeks, for example, was reported to occur in 44% of all twin pregnancies compared to in 6% of all singleton pregnancies. [9] Twins have a 6 fold increased risk of mortality compared to singletons. [9] They also have a high risk of morbidity, predominantly associated with preterm birth, resulting in a 1 in 13 risk of permanent handicap in twins. [10]. Early Human Development 85 (2009) 673–677 ⁎ Corresponding author. Tel.: + 44 0207 905 2367; fax: + 44 20 7905 2834. E-mail addresses: carrie.williams@ucl.ac.uk (C. Williams), a.sutcliffe@ich.ucl.ac.uk (A. Sutcliffe). 1 Tel.: +44 08451 555 000x3394; fax: +44 0207 3809064. 0378-3782/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.earlhumdev.2009.08.055 Contents lists available at ScienceDirect Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev