Hum. Reprod. Advance Access originally published online on November 26, 2004
Human Reproduction 2005 20(2):328-338; doi:10.1093/humrep/deh593
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
SYSTEMATIC REVIEW |
Assisted reproductive technologies and the risk of birth defectsa systematic review
1 Centre for Child Health Research, The University of Western Australia Telethon Institute for Child Health Research, West Perth, Western Australia 6872, Australia and 2 The National Perinatal Epidemiology Unit, University of Oxford, OX3 7LF, UK
3 To whom correspondence should be addressed at: Telethon Institute for Child Health Research, PO Box 855, West Perth, Western Australia 6872. Email: michele{at}ichr.uwa.edu.au
BACKGROUND: The risk of birth defects in infants born following assisted reproductive technology (ART) treatment is a controversial question. Most publications examining the prevalence of birth defects in ICSI and IVF infants compared to spontaneously conceived infants have serious methodological limitations; despite this, most researchers have concluded that there is no increased risk. METHODS: We carried out a systematic review to identify all papers published by March 2003 with data relating to the prevalence of birth defects in infants conceived following IVF and/or ICSI compared with spontaneously conceived infants. Independent expert reviewers used criteria defined a priori to determine whether studies were suitable for inclusion in a meta-analysis. Fixed effects meta-analysis was performed for all studies and reviewer-selected studies. RESULTS: Twenty-five studies were identified for review. Two-thirds of these showed a 25% or greater increased risk of birth defects in ART infants. The results of meta-analyses of the seven reviewer-selected studies and of all 25 studies suggest a statistically significant 3040% increased risk of birth defects associated with ART. CONCLUSIONS: Pooled results from all suitable published studies suggest that children born following ART are at increased risk of birth defects compared with spontaneous conceptions. This information should be made available to couples seeking ART treatment.
Key words: assisted reproductive technology/congenital malformations/IVF/meta-analysis/systematic review
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
L. A. Schieve, O. Devine, C. A. Boyle, J. R. Petrini, and L. Warner Estimation of the Contribution of Non-Assisted Reproductive Technology Ovulation Stimulation Fertility Treatments to US Singleton and Multiple Births Am. J. Epidemiol., October 23, 2009; (2009) kwp281v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. L. Halliday, O. C. Ukoumunne, H.W. G. Baker, S. Breheny, A. M. Jaques, C. Garrett, D. Healy, and D. Amor Increased risk of blastogenesis birth defects, arising in the first 4 weeks of pregnancy, after assisted reproductive technologies Hum. Reprod., October 22, 2009; (2009) dep364v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Katari, N. Turan, M. Bibikova, O. Erinle, R. Chalian, M. Foster, J. P. Gaughan, C. Coutifaris, and C. Sapienza DNA methylation and gene expression differences in children conceived in vitro or in vivo Hum. Mol. Genet., October 15, 2009; 18(20): 3769 - 3778. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. H. Shelton, J. Boivin, D. Hay, M. B.M. van den Bree, F. J. Rice, G. T. Harold, and A. Thapar Examining differences in psychological adjustment problems among children conceived by assisted reproductive technologies International Journal of Behavioral Development, September 1, 2009; 33(5): 385 - 392. [Abstract] [PDF] |
||||
![]() |
M. Hansen, L. Colvin, B. Petterson, J. J. Kurinczuk, N. de Klerk, and C. Bower Twins born following assisted reproductive technology: perinatal outcome and admission to hospital Hum. Reprod., September 1, 2009; 24(9): 2321 - 2331. [Abstract] [Full Text] [PDF] |
||||
![]() |
G.H. Woldringh, D.E. Besselink, A.H.J. Tillema, J.C.M. Hendriks, and J.A.M. Kremer Karyotyping, congenital anomalies and follow-up of children after intracytoplasmic sperm injection with non-ejaculated sperm: a systematic review Hum. Reprod. Update, August 21, 2009; (2009) dmp030v1. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Mitsiakos, E. Giougi, C. Tsakalidis, M. Kourti, H. Chatziionnidis, P. Karagianni, E. M. Kolibianakis, and N. Nikolaidis A case of Adams-Oliver syndrome following in vitro fertilization Hum. Reprod., June 1, 2009; 24(6): 1529 - 1530. [Full Text] [PDF] |
||||
![]() |
C. Blockeel, P. Mock, G. Verheyen, N. Bouche, Ph. Le Goff, Y. Heyman, C. Wrenzycki, K. Hoffmann, H. Niemann, P. Haentjens, et al. An in vivo culture system for human embryos using an encapsulation technology: a pilot study Hum. Reprod., April 1, 2009; 24(4): 790 - 796. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Reefhuis, M.A. Honein, L.A. Schieve, A. Correa, C.A. Hobbs, S.A. Rasmussen, and the National Birth Defects Prevention Study Assisted reproductive technology and major structural birth defects in the United States Hum. Reprod., February 1, 2009; 24(2): 360 - 366. [Abstract] [Full Text] [PDF] |
||||
![]() |
G.H. Woldringh, I.M. Janssen, J.Y. Hehir-Kwa, C. van den Elzen, J.A.M. Kremer, P. de Boer, and E.F.P.M. Schoenmakers Constitutional DNA copy number changes in ICSI children Hum. Reprod., January 1, 2009; 24(1): 233 - 240. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Horcajadas, P. Minguez, J. Dopazo, F. J. Esteban, F. Dominguez, L. C. Giudice, A. Pellicer, and C. Simon Controlled Ovarian Stimulation Induces a Functional Genomic Delay of the Endometrium with Potential Clinical Implications J. Clin. Endocrinol. Metab., November 1, 2008; 93(11): 4500 - 4510. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Nyboe Andersen, E. Carlsen, and A. Loft Trends in the use of intracytoplasmatic sperm injection marked variability between countries Hum. Reprod. Update, November 1, 2008; 14(6): 593 - 604. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. A. Abu-Musa, A. H. Nassar, and I. M. Usta Attitude of women with IVF and spontaneous pregnancies towards prenatal screening Hum. Reprod., November 1, 2008; 23(11): 2438 - 2443. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Griesinger, E.M. Kolibianakis, K. Diedrich, and M. Ludwig Ovarian stimulation for IVF has no quantitative association with birthweight: a registry study Hum. Reprod., November 1, 2008; 23(11): 2549 - 2554. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. L. Boulet, L. A. Schieve, A. Nannini, C. Ferre, O. Devine, B. Cohen, Z. Zhang, V. Wright, and M. Macaluso Perinatal outcomes of twin births conceived using assisted reproduction technology: a population-based study Hum. Reprod., August 1, 2008; 23(8): 1941 - 1948. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Hansen, L. Colvin, B. Petterson, J. J. Kurinczuk, N. de Klerk, and C. Bower Admission to hospital of singleton children born following assisted reproductive technology (ART) Hum. Reprod., June 1, 2008; 23(6): 1297 - 1305. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. J. Amor and C. Cameron PGD gender selection for non-Mendelian disorders with unequal sex incidence Hum. Reprod., April 1, 2008; 23(4): 729 - 734. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Fernandez-Gonzalez, P. N. Moreira, M. Perez-Crespo, M. Sanchez-Martin, M. A. Ramirez, E. Pericuesta, A. Bilbao, P. Bermejo-Alvarez, J. d. D. Hourcade, F. R. d. Fonseca, et al. Long-Term Effects of Mouse Intracytoplasmic Sperm Injection with DNA-Fragmented Sperm on Health and Behavior of Adult Offspring Biol Reprod, April 1, 2008; 78(4): 761 - 772. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. T. Carrell The Clinical Implementation of Sperm Chromosome Aneuploidy Testing: Pitfalls and Promises J Androl, March 1, 2008; 29(2): 124 - 133. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Knoester, F.M. Helmerhorst, L.A.J. van der Westerlaken, F.J. Walther, S. Veen, and on behalf of the Leiden Artificial Reproductive Te Matched follow-up study of 5 8-year-old ICSI singletons: child behaviour, parenting stress and child (health-related) quality of life Hum. Reprod., December 1, 2007; 22(12): 3098 - 3107. [Abstract] [Full Text] [PDF] |
||||
![]() |
The ESHRE Capri Workshop Group Intracytoplasmic sperm injection (ICSI) in 2006: Evidence and Evolution Hum. Reprod. Update, November 1, 2007; 13(6): 515 - 526. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Pinborg, O. Lidegaard, N. la Cour Freiesleben, and A. N. Andersen Vanishing twins: a predictor of small-for-gestational age in IVF singletons Hum. Reprod., October 1, 2007; 22(10): 2707 - 2714. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Larcher The health of children conceived by assisted reproduction technologies Arch. Dis. Child., August 1, 2007; 92(8): 668 - 669. [Full Text] [PDF] |
||||
![]() |
L. Lefievre, K. Bedu-Addo, S. J Conner, G. S M Machado-Oliveira, Y. Chen, J. C Kirkman-Brown, M. A Afnan, S. J Publicover, W C. L Ford, and C. L R Barratt Counting sperm does not add up any more: time for a new equation? Reproduction, April 1, 2007; 133(4): 675 - 684. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Fedder, A. Gabrielsen, P. Humaidan, K. Erb, E. Ernst, and A. Loft Malformation rate and sex ratio in 412 children conceived with epididymal or testicular sperm Hum. Reprod., April 1, 2007; 22(4): 1080 - 1085. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Poikkeus, M. Gissler, L. Unkila-Kallio, C. Hyden-Granskog, and A. Tiitinen Obstetric and neonatal outcome after single embryo transfer Hum. Reprod., April 1, 2007; 22(4): 1073 - 1079. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Belva, S. Henriet, I. Liebaers, A. Van Steirteghem, S. Celestin-Westreich, and M. Bonduelle Medical outcome of 8-year-old singleton ICSI children (born >=32 weeks' gestation) and a spontaneously conceived comparison group Hum. Reprod., February 1, 2007; 22(2): 506 - 515. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Bungum, P. Humaidan, A. Axmon, M. Spano, L. Bungum, J. Erenpreiss, and A. Giwercman Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome Hum. Reprod., January 1, 2007; 22(1): 174 - 179. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Sun, M. Vestergaard, J. Christensen, J. L. Zhu, B. H. Bech, and J. Olsen Epilepsy and febrile seizures in children of treated and untreated subfertile couples Hum. Reprod., January 1, 2007; 22(1): 215 - 220. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Mau Kai, K. M. Main, A. Nyboe Andersen, A. Loft, M. Chellakooty, N. E. Skakkebaek, and A. Juul Serum Insulin-Like Growth Factor-I (IGF-I) and Growth in Children Born after Assisted Reproduction J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4352 - 4360. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Klemetti, T. Sevon, M. Gissler, and E. Hemminki Health of Children Born as a Result of In Vitro Fertilization Pediatrics, November 1, 2006; 118(5): 1819 - 1827. [Abstract] [Full Text] [PDF] |
||||
![]() |
D Elsner Just another reproductive technology? The ethics of human reproductive cloning as an experimental medical procedure. J. Med. Ethics, October 1, 2006; 32(10): 596 - 600. [Abstract] [Full Text] [PDF] |
||||
![]() |
S.-M. Park, R. Mathur, and G. C S Smith Congenital anomalies after treatment for infertility. BMJ, September 30, 2006; 333(7570): 665 - 666. [Full Text] [PDF] |
||||
![]() |
J. L. Zhu, O. Basso, C. Obel, C. Bille, and J. Olsen Infertility, infertility treatment, and congenital malformations: Danish national birth cohort BMJ, September 30, 2006; 333(7570): 679. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Zini and J. Libman Sperm DNA damage: clinical significance in the era of assisted reproduction. Can. Med. Assoc. J., August 29, 2006; 175(5): 495 - 500. [Abstract] [Full Text] [PDF] |
||||
![]() |
U.-B. Wennerholm, M. Bonduelle, A. Sutcliffe, C. Bergh, A. Niklasson, B. Tarlatzis, C. M. Kai, C. Peters, A. V. Cederqvist, and A. Loft Paternal sperm concentration and growth and cognitive development in children born with a gestational age more than 32 weeks after assisted reproductive therapy Hum. Reprod., June 1, 2006; 21(6): 1514 - 1520. [Abstract] [Full Text] [PDF] |
||||
![]() |
A.K. Ludwig, A. Katalinic, V. Steinbicker, K. Diedrich, and M. Ludwig Antenatal care in singleton pregnancies after ICSI as compared to spontaneous conception: data from a prospective controlled cohort study in Germany Hum. Reprod., March 1, 2006; 21(3): 713 - 720. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Horsthemke and M. Ludwig Assisted reproduction: the epigenetic perspective Hum. Reprod. Update, September 1, 2005; 11(5): 473 - 482. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Ragni, A. Allegra, P. Anserini, F. Causio, A.P. Ferraretti, E. Greco, R. Palermo, E. Somigliana, and on behalf of the Societa Italiana della Riproduzio The 2004 Italian legislation regulating assisted reproduction technology: a multicentre survey on the results of IVF cycles Hum. Reprod., August 1, 2005; 20(8): 2224 - 2228. [Abstract] [Full Text] [PDF] |
||||
![]() |
Does In Vitro Fertilization Increase Risk for Birth Defects? Journal Watch (General), March 25, 2005; 2005(325): 4 - 4. [Full Text] |
||||














