Recent studies have given conflicting results regarding growth in children born following assisted reproductive treatments up to the age of 18years. It has been suggested that children conceived via IVF may be taller than naturally conceived children and that this may due to subtle epigenetic alteration of imprinted genes as a result of the IVF process. A prospective match-controlled study was performed to investigate the growth of children born in the UK following standard IVF and intracytoplasmic sperm injection (ICSI) up to the age of 12years. The study assessed 143 IVF and 166 ICSI children with 173 matched naturally conceived controls. Primary end-points were height and weight at various time points: birth, 5 years, 7–9 years and 10–12 years. In addition, head circumference was assessed at birth. No significant differences were observed regarding head circumference, height and weight between the three groups at any of the time points. In conclusion, this preliminary study provides reassuring information regarding the growth of IVF and ICSI children up to 12 years. Further studies must continue to investigate the growth and other outcomes in assisted-conception children as they develop through puberty into early adulthood.
Introduction
Assisted reproduction treatments, namely in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), have become widely used in the treatment of human infertility. At present, 1–3% of children born in developed countries are conceived via assisted reproduction treatments (Andersen et al., 2008, Wright et al., 2008). It is well established that assisted reproduction is associated with adverse perinatal outcomes, including increased risks of preterm delivery, low birthweight and neonatal mortality (Helmerhorst et al., 2004, Jackson et al., 2004, McDonald et al., 2005). In recent years there has been considerable work investigating health outcomes in IVF and ICSI children beyond the neonatal period (Basatemur and Sutcliffe, 2008, Sutcliffe and Ludwig, 2007).
A number of well-designed case control studies have investigated the growth of assisted-conception children up to the age of 18 years. The majority of these have not found any differences between children conceived via assisted reproduction treatments and naturally conceived children. The height, weight and head circumference of IVF and ICSI children at the ages of 6–12 months (Wennerholm et al., 1998), 1–3 years (Brandes et al., 1992), 5 years (Bonduelle et al., 2005, Ludwig et al., 2008) and 8 years (Belva et al., 2007, Knoester et al., 2008) have been reported to be the same as naturally conceived controls. Recently, a Dutch group reported no difference in growth between IVF children and naturally conceived controls aged between 8 and 18 years (Ceelen et al., 2008). Similar findings have recently been reported in children aged from 3 months to 4 years conceived after preimplantation genetic diagnosis (Banerjee et al., 2008).
In contrast to these reassuring findings, two studies have reported differences in growth between assisted-conception children and naturally conceived controls (Koivurova et al., 2003, Miles et al., 2007). A study in Finland (Koivurova et al., 2003) reported that their cohort of 299 IVF children were significantly lighter in weight than 558 naturally conceived controls up to the age of 3, although at the age of 3 no significant difference in weight remained. Recently, a New Zealand study (Miles et al., 2007) found that a cohort of 69 IVF and ICSI children aged between 4 and 10 years (mean age of 5.9 years) were significantly taller than 71 naturally conceived controls, after adjustment for age and parental height. They also reported higher serum concentrations of insulin-like growth factors I and II in the assisted-conception children and concluded that the observed differences in stature and growth factors may be due to subtle epigenetic alteration of imprinted genes as a result of the IVF process.
In response to the conflicting outcomes of previous studies, a prospective cohort study was designed to compare the growth of IVF and ICSI children up to the age of 12 years with naturally conceived controls. As far as is known, this is the first match controlled cohort study to investigate the growth of ICSI children above the age of 10 years.
Section snippets
Subjects
Children were recruited from an established cohort in the UK as part of a longitudinal study into outcomes in assisted-conception children (Bonduelle et al., 2005, Fisher-Jeffes et al., 2006, Ponjaert-Kristoffersen et al., 2005, Sutcliffe et al., 2001, Sutcliffe et al., 2003). Twins and higher order births were excluded from the study, and all children were born at 32 weeks of gestation or later. ICSI children were originally recruited from 22 participating fertility clinics in the UK, whilst
Results
In total, 482 children were enrolled in the study. The participants were from three conception groups: IVF, ICSI and natural. The study groups consisted of 143 singleton children conceived after conventional IVF (69 male and 74 female) and 166 singleton children conceived after ICSI (92 male and 74 female). The control group consisted of 173 naturally conceived singletons (94 male and 79 female).
Details of parental characteristics across the three conception groups are presented in Table 1.
Discussion
The majority of previous well designed cohort studies investigating the growth of children born following assisted reproductive techniques have not found any differences in the growth of IVF and ICSI children when compared with naturally conceived controls (Belva et al., 2007, Bonduelle et al., 2005, Brandes et al., 1992, Ceelen et al., 2008, Knoester et al., 2008, Ludwig et al., 2008, Wennerholm et al., 1998). However, the study by Ceelen et al. (2008) suggested that IVF children may exhibit
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Dr Alastair Sutcliffe is a paediatrician who has conducted a series of studies from 1993 looking at the health of children born after interventions in early life. These include the first on embryo cryopreservation outcome and twin–twin transfusion syndrome. He has collaborated with researchers in Belgium, Denmark, Sweden, Greece, Australia and Germany on ICSI outcome studies and is currently working on a study of oocyte cryopreservation outcome with Italian collaborators. He is author of over 40 papers and two books. His work has resulted in the ESHRE-established clinician award (1999) and the Donald Patterson prize (2003) from the Royal College of Paediatrics.
