Abstract
Purpose: To estimate the risk of major malformations in IVF and ICSI infants.
Methods: Forty-four studies published in English since 1990 where the major malformation rate for IVF or ICSI cases was compared to an appropriate control group were reviewed. Nineteen studies met all selection criteria. In addition, a quality score was developed to assess each study based on sample size, timing of diagnosis, appropriateness of control group and other factors.
Results: In 19 studies, the major malformation rates ranged from 0–9.5% for IVF; 1.1–9.7 for ICSI; and 0–6.9% in the control groups. When ICSI was compared to IVF, and multiple births compared to singleton, there were no statistically significant differences. When data from 16 studies involving 28,524 IVF infants and 2,520,988 spontaneously conceived controls and 7 studies involving 7234 ICSI infants and 978,078 controls were pooled, we found an overall odds ratio for the 19 studies of 1.29 (95% CI 1.01–1.67).
Conclusions: The overall odds ratio of 1.29 was statistically significant at the 5% level. These results may be useful for counseling ART patients and properly designing the consent forms used for ART procedures. It is not clear whether this risk is due to the procedures used in ART. We found that some of these studies have design flaws. All of them lacked an appropriate control group, i.e. infertile patients conceiving spontaneously. These flaws may create biases that would in almost all instances increase the risk of major malformations in the study group. Further research with better designed studies will likely result in a better estimate of the risk of major malformations associated with IVF and ICSI.
References
Saunders DM, Mathews M, Lancaster PAL: The Australian Register: Current Research and Future Role. Ann NY Acad Sci 1988;541:7–21
Van Steirteghem A, Borduelle M, Devroey P, Liebars I: Follow up of children born after ICSI. Hum Reprod Update 2002;8:111–116
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB: Meta-analysis of observational studies in epidemiology: A proposal for reporting. JAMA 2000;283:2008–2012
Testart J: Safety of embryo cryopreservation: statistical facts and artefacts: episcientific aspects of the epigenetic factors in artifical procreation(Debate). Hum Reprod 1998;13:783–785
Devroey P, Van Steirteghem A: A review of ten years experience of ICSI. Hum. Reprod. Update. 2004;10/1:19–28
Palermo GD, Colombero LT, Schattman GL, Davis OK, Rosenwaks Z: Evolution of pregnancies and initial follow-up of newborns delivered after intra cytoplasmic sperm injection. JAMA 1996;276:1893–1897
Bowen JR, Gibson FL, Leslie GI, Saunders DM: Medical and developmental outcome at 1 year for children conceived by intracytoplasmic sperm injection. Lancet 1998;351:1529–1534
Sutcliffe AG, Taylor B, Saunders K, Thornton S, Lieberman BA, Grudzinskas JG: Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: A UK case-control study. Lancet 2001;357:2080–2084
Palermo GD, Neri QV, Hariprashad JJ, Davis OK, Veeck LL, Rosenwaks Z: ICSI and its outcome. Semin Reprod Med 2000;18:161–169
Wennerholm UB, Bergh C, Hamberger L, Lundin K, Nilsson L, Wikland M, Källén B: Incidence of congenital malformations in children born after ICSI. Hum Reprod 2000;15:944–948
Ericson A, Källén B: Congenital malformations in infants born after IVF: A population-based study. Hum Reprod 2001;16:504–509
Anthony S, Buitendijk SE, Dorrepaal CA, Lindner K, Braat DDM, den Ouden AL: Congential malformations in 4224 children conceived after IVF. Hum Reprod 2002;17:2089–2095
Hansen M, Kurinczuk JJ, Bower C, Webb S: The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med 2002;346:725–730
Isaksson R, Gissler M, Tiitinen A: Obstetric outcome among women with unexplained infertility after IVF: a matched case-control study. Hum Reprod 2002;17:1755–1761
Ludwig M, Katalinic A: Pregnancy course and health of children born after ICSI depending on parameters of male factor infertility. Hum Reprod 2003;18:351–357
Merlob P, Fisch B: Neonatal outcome and congenital malformations in children born after IVF. Hum Reprod 2002;17:3004–3005
MRC Working Party: Rose G, Beral V, Davis JA, Edwards RG, Harper PS, O Loudon JD: Births in Great Britain resulting from assisted conception. BMJ 1990;300:1229–1233
Westergaard HB, Tranberg Johansen AM, Erb K, Nyboe Andersen A: Danish national in-vitro fertilization registry 1994 and 1995: A controlled study of births, malformations and cytogenetic findings. Hum Reprod 1999;14:1896–1902
D Souza SW, Rivlin E, Cadman J, Richards B, Buck P, Lieberman BA: Children conceived by in vitro fertilisation after fresh embryo transfer. Arch Dis Child 1997;76: F70–F74
Verlaenen H, Cammu H, Derde MP, Amy JJ: Singleton pregnancy after in vitro fertilization: expectations and outcome. Obstet Gynecol 1995;86:906–910
Sutcliffe AG, D Souza SW, Cadman J, Richards B, McKinlay IA, Lieberman B: Minor congenital anomalies, major congenital malformations and development in children conceived from cryopreserved embryos. Hum Reprod 1995;10:3332–3337
Zádori J, Kozinszky Z, Orvos H, Katona M, Kaáli SG, Pál A: The incidence of major birth defects following in vitro fertilization. J Assist Reprod Genet 2003;20:131–132
Pinborg A, Loft A, Rasmussen S, Schmidt L, Langhoff-Ross J, Greisen G, Andersen AN: Neonatal outcome in a Danish national cohort of 3438 IVF/ICSI and 10362 non-IVF/ICSI twins born between 1995 and 2000. Hum Reprod 2004;19:435–441
Place I, Englert Y: A prospective longitudinal study of the physical, psychomotor and intellectual development of singleton children up to 5 years who were conceived by intracytoplasmic sperm injection compared with children conceived spontaneously and by in vitro fertilization. Fertil Steril. 2003;80:1388–1397
Wennerholm UB, Albertsson-Wikland K, Bergh C, Hamberger L, Niklasson A, Nilsson L, Thiringer K, Wennergren M, Wikland M, Borres MP: Postnatal growth and health in children born after cryopreservation as embryos. Lancet 1998;351:1085–1090
Society for Assisted Reproductive Technology/American Society for Reproductive Medicine: Assisted reproductive technology in the United States: 1998 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry. Fertil Steril 2002;77:18–31
Tarlatzis B, Bili H: Survey on intracytoplasmic sperm injection: Report from the ESHRE ICSI Task Force. Hum Reprod 1998;13(suppl 1): 165–177
DerSimonian R, Laird NM: Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188
New York State Department of Health: Congenital Malformations Registry Annual Report: Statistical Summary of Children Born in 1990 and Diagnosed through 1992. Albany, NY, 1995
Draper ES, Kurinczuk JJ, Abrams KR, Clarke M: Assessment of separate contributions to perinatal mortality of infertility history and treatment: a case-control analysis. Lancet 1999;353:1746–49
Khoury MJ, Erickson JD: Recurrent pregnancy loss as an indicator for increased risk of birth defects: a population-based case-control study. Paediatr Perinat Epidemiol 1993;7(4):404–416
Ghazi HA, Spielberger C, Källën B. Delivery outcome after infertility—a registry study. Fertil Steril 1991;55:726–732
Basso O, Baird DD: Infertility and preterm delivery, birthweight and Caesarean section: A study within the Danish National Birth Cohort. Human Reprod 2003;18:2478–2484
Schreurs A, Legius E, Meuleman C, Fryns JP, D’Hooghe TM: Increased frequency of chromosomal abnormalities in female partners of couples undergoing in vitro fertilization or intracytoplasmic sperm injection. Fertil Steril 2000;74:94–96
Lange JG, Engel W: Chromosome studies in in-vitro fertilization patients. Hum Reprod 1993;8:572–574
Legius E, Matthijs G, Cuppens H, Vanderschueren D, D’Hooghe TM, Ombelet W, Gordts S, Fryns JP: Genetic aspects and intracytoplasmic sperm injection: an update on non Y-chromosomal genetic defects. Studies in Profertility Series 1998;8:123–9
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Rimm, A.A., Katayama, A.C., Diaz, M. et al. A Meta-Analysis of Controlled Studies Comparing Major Malformation Rates in IVF and ICSI Infants with Naturally Conceived Children. J Assist Reprod Genet 21, 437–443 (2004). https://doi.org/10.1007/s10815-004-8760-8
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DOI: https://doi.org/10.1007/s10815-004-8760-8