IJE Advance Access originally published online on November 23, 2004
International Journal of Epidemiology 2005 34(3):696-701; doi:10.1093/ije/dyh363
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Perinatal Epidemiology |
Birth defects in children conceived by ICSI compared with children conceived by other IVF-methods; a meta-analysis
1 Department of Public Health and Primary Health Care, University of Bergen and The Medical Birth Registry of Norway, Norway
2 The Norwegian Centre for Health Technology Assessment, Sintef Unimed,Oslo, Norway
3 Institute Group for Clinical Medicine, University of Oslo and Department of Medical Genetics, Rikshospitalet, Oslo, Norway
4 Institute of Public Health, University of Southern Denmark, Odense, Denmark
5 Department of Community Medicine and General Pratice, Norwegian University of Science and Technology, Trondheim, Norway
6 Department of Obstetrics and Gynaecology, Rikshospitalet, Oslo, Norway
* Corresponding author. Section for Epidemiology and Medical Statistics,Department of Public Health and Primary Health Care, University of Bergen, Kalfarveien 31, 5018 Bergen, Norway. E-mail: rolv.lie{at}smis.b.no
Background Intracytoplasmic sperm injection (ICSI) is a method of assisted reproductive technology that involves the selection of a single sperm cell and the manual injection of this cell into the egg. The lack of relevant experimental studies, the nature of the technology involving non-natural selection of the fertilizing sperm, and possible damage to the egg have caused concern that ICSI could increase the risk of birth defects. Data from available cohort studies comparing ICSI with standard in vitro fertilization (IVF) should be combined to evaluate the risks involved with ICSI.
Methods We reviewed more than 2500 titles and abstracts containing keywords related to ICSI and identified 22 scientific articles with data on birth defects among ICSI-births. A total of four peer-reviewed, non-overlapping prospective cohort studies provided reliable and comparable data on birth defects both for children conceived by ICSI and children conceived by standard IVF. These studies included a total of 5395 children born after ICSI.
Results The pooled estimate of the risk of a major birth defect was a 1.12-fold increase after ICSI when compared with standard IVF (risk ratio = 1.12, 95% confidence interval (CI): 0.97–1.28, P = 0.12). There was no marked heterogeneity of risk ratios between these studies (P = 0.10). We found no significantly increased risks after ICSI for any of the categories cardiovascular defects, musculoskeletal defects, hypospadias, neural tube defects, or oral clefts.
Conclusions Our analysis does not indicate that the ICSI-procedure represents significant additional risks of major birth defects in addition to the risk involved in standard IVF. The data was limited, particularly on risks of specific categories of defects.
Keywords Birth defects, in vitro fertilization, reproduction, meta-analysis
Accepted 15 September 2004
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