Elsevier

The Lancet

Volume 357, Issue 9274, 30 June 2001, Pages 2080-2084
The Lancet

Articles
Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: a UK case-control study

https://doi.org/10.1016/S0140-6736(00)05180-1Get rights and content

Summary

Background

There have been reports suggesting that children born after in-vitro fertilisation by intracytoplasmic sperm injection (ICSI) are at increased risk of neurodevelopmental delay. We have undertaken a case-control study of this issue.

Methods

We studied 208 singleton children conceived by ICSI and a control group of 221 normally conceived singleton children. Children were recruited from 22 fertility centres and local nurseries throughout the UK. Controls were selected to match cases as closely as possible for social class, maternal educational attainment, region, sex, and race. The primary outcome measure was neurodevelopmental scoring; secondary measures were perinatal outcomes, postnatal health, and congenital abnormalities. A single examiner assessed all the children.

Findings

A follow-up rate of 90% for the ICSI group was achieved at a mean age of 17 months. No difference between the study children and controls was found in mean neurodevelopmental scores (98–08 [SD 10–93] vs 98–69 [9–99]) or any subscales on the Griffiths' scales of mental development. Perinatal outcome was similar apart from a higher rate of caesarean section (73 [35·1%] vs 53 [24·0%], p=0·015) and a lower mean birthweight (3163 [SD 642] vs 3341 [606] g, p=0·013) in the study group. Rates of major congenital abnormality were also similar overall (ten [4·8%] study vs ten [4·5%] control), although there were significantly more congenital anomalies among children born to fathers with oligozoospermia than in other children.

Interpretation

This population study did not show any significant difference between children conceived after ICSI and their naturally conceived peers in terms of physical health and development.

Introduction

Intracytoplasmic sperm injection (ICSI) is a successful treatment for severe male-factor infertility. Since the first description of a successful human pregnancy,1 the technique has been widely applied, and more than 750 centres are now using the technique in Europe alone. With conventional in-vitro fertilisation, 50 000–100 0000 sperm are incubated with an oocyte in a Petri dish containing culture medium, whereas with ICSI a single sperm is injected directly into the vitellus of an oocyte in metaphase II. This procedure bypasses all natural sperm selection barriers. Concerns have been expressed about the use of ICSI per se and particularly with less mature epididymal or testicular sperm. Theoretically, the sperm used may carry genetic abnormalities or have structural defects. There is also potential for chemical or mechanical damage to the oocyte and for the introduction of foreign material. Reports of children conceived by this technique suggesting developmental or other problems2, 3 have reinforced these theoretical anxieties.

To date, neurodevelopmental follow-up studies of children born after ICSI have been limited by small sample sizes,2 unstandardised assessment systems,2 poor rates of follow-up,4 the absence of controls,5 or poorly matched controls and multiple observers.2 These limited studies left unresolved many concerns about children conceived after ICSI. We undertook a case-control study to investigate outcome. Our primary outcome measure was neurodevelopmental scoring, and our secondary measures were perinatal morbidity, postnatal health, and congenital abnormalities.

Section snippets

Participants

The study group consisted of 208 children aged 1–2 years, born after ICSI at 22 participating fertility clinics in the UK. Each clinic identified all children of appropriate age. The families were invited to join the study, and those who agreed were seen between January, 1997, and January, 1999.

The control group consisted of 221 children conceived naturally. They were recruited, over the same period, from local day nurseries or, in 15% of cases, as social peers of the study children. The groups

Results

The case and control groups were similar in terms of a range of sociodemographic factors. The mean maternal age was higher in the study group than in the control group, and study mothers were more likely to be having their first child (table 1). Paternal sociodemographic characteristics were also similar; the only significant differences between the study and control groups were in mean paternal age (37·93 vs 32·71 years, p=0·0088) and the proportion of fathers who were manual workers (25

Discussion

We assessed a population of children conceived after ICSI and born throughout the UK. The study started in early 1997, at which time there were 32 licensed centres in the UK. The popularity and success of ICSI are reflected by the increase to 70 licensed centres in the UK and more than 750 in Europe. Nevertheless, few outcome studies have been done. Although most of the reports on perinatal outcome have been reassuring,4, 5, 7, 8, 9, 10, 11 some follow-up studies have been less so.2, 3

The

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