Increased risk of blastogenesis birth defects, arising in the first 4 weeks of pregnancy, after assisted reproductive technologies.

BACKGROUND The reasons for increased birth defect prevalence following in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are largely unknown. Classification of birth defects by pathology rather than organ system, and examination of the role of embryo freezing and thawing may provide clues to the mechanisms involved. This study aimed to investigate these two factors. METHOD Data on 6946 IVF or ICSI singleton pregnancies were linked to perinatal outcomes obtained from population-based data sets on births and birth defects occurring between 1991 and 2004 in Victoria, Australia. These were compared with 20,838 outcomes for singleton births in the same population, conceived without IVF or ICSI. Birth defects were classified according to pathogenesis. RESULTS Overall, birth defects were increased after IVF or ICSI [adjusted odds ratio (OR) 1.36; 95% CI: 1.19-1.55] relative to controls. There was no strong evidence of risk differences between IVF and ICSI or between fresh and thawed embryo transfer. However, a specific group, blastogenesis birth defects, were markedly increased [adjusted OR 2.80, 95% CI: 1.63-4.81], with the increase relative to the controls being significant for fresh embryo transfer (adjusted OR 3.65; 95% CI: 2.02-6.59) but not for thawed embryo transfer (adjusted OR 1.60; 95% CI: 0.69-3.69). CONCLUSION Our findings suggest that there is a specific risk of blastogenesis birth defects arising very early in pregnancy after IVF or ICSI and that this risk may be lower with use of frozen-thawed embryo transfer.

[1]  A. Selbing,et al.  Children born after cryopreservation of embryos or oocytes: a systematic review of outcome data. , 2009, Human reproduction.

[2]  O. Ishihara,et al.  World collaborative report on Assisted Reproductive Technology, 2002. , 2009, Human reproduction.

[3]  R. Dobson Number of babies born by assisted reproduction rises by 12% , 2009, BMJ : British Medical Journal.

[4]  D. Amor,et al.  Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome. , 2009, Human reproduction.

[5]  S. Rasmussen,et al.  Assisted reproductive technology and major structural birth defects in the United States. , 2009, Human reproduction.

[6]  D. Amor,et al.  A review of known imprinting syndromes and their association with assisted reproduction technologies. , 2008, Human reproduction.

[7]  C. Peterson,et al.  Monozygotic twinning associated with assisted reproductive technologies: a review. , 2008, Reproduction.

[8]  P. Haentjens,et al.  Neonatal outcome of 937 children born after transfer of cryopreserved embryos obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF cycles. , 2008, Human reproduction.

[9]  H. Baker,et al.  Factors affecting low birthweight after assisted reproduction technology: difference between transfer of fresh and cryopreserved embryos suggests an adverse effect of oocyte collection. , 2008, Human reproduction.

[10]  Jeani Chang,et al.  Assisted reproductive technology surveillance--United States, 2005. , 2008, Morbidity and mortality weekly report. Surveillance summaries.

[11]  V. Goossens,et al.  Assisted reproductive technology in Europe, 2004: results generated from European registers by ESHRE. , 2008, Human reproduction.

[12]  A. Pinborg,et al.  Vanishing twins: a predictor of small-for-gestational age in IVF singletons. , 2007, Human reproduction.

[13]  B. Fisch,et al.  Risk of major congenital malformations associated with infertility and its treatment by extent of iatrogenic intervention. , 2007, Pediatric endocrinology reviews : PER.

[14]  Y. Yamazaki,et al.  Assisted reproductive technologies do not alter mutation frequency or spectrum , 2007, Proceedings of the National Academy of Sciences.

[15]  Jean Cohen Infertile couples, assisted reproduction and increased risks to the children. , 2007, Reproductive biomedicine online.

[16]  J. Olsen,et al.  Infertility, infertility treatment, and congenital malformations: Danish national birth cohort , 2006, BMJ : British Medical Journal.

[17]  I. Blickstein,et al.  Effect of the mode of assisted reproductive technology conception on obstetric outcomes for survivors of the vanishing twin syndrome. , 2006, Fertility and sterility.

[18]  S. Rasmussen,et al.  Risk of birth defects among children conceived with assisted reproductive technology: providing an epidemiologic context to the data. , 2005, Fertility and sterility.

[19]  B. V. Van Voorhis,et al.  In vitro fertilization is associated with an increase in major birth defects. , 2005, Fertility and sterility.

[20]  E. Kuipers,et al.  Multiplicity in polyp count and extracolonic manifestations in 40 Dutch patients with MYH associated polyposis coli (MAP) , 2005, Journal of Medical Genetics.

[21]  B. Källén,et al.  In vitro fertilization (IVF) in Sweden: risk for congenital malformations after different IVF methods. , 2005, Birth defects research. Part A, Clinical and molecular teratology.

[22]  Elizabeth Milne,et al.  Assisted reproductive technologies and the risk of birth defects--a systematic review. , 2005, Human reproduction.

[23]  P. Boyd,et al.  An aetiological classification of birth defects for epidemiological research , 2005, Journal of Medical Genetics.

[24]  P. Nayudu,et al.  Cryopreservation of Human Embryos , 2005, Cell and Tissue Banking.

[25]  A. Rimm,et al.  A Meta-Analysis of Controlled Studies Comparing Major Malformation Rates in IVF and ICSI Infants with Naturally Conceived Children , 2004, Journal of Assisted Reproduction and Genetics.

[26]  M. Riley,et al.  Validation study of the Victorian Birth Defects Register , 2004, Journal of paediatrics and child health.

[27]  A. Katalinic,et al.  Pregnancy course and outcome after intracytoplasmic sperm injection: a controlled, prospective cohort study. , 2004, Fertility and sterility.

[28]  J. Hanley,et al.  Statistical analysis of correlated data using generalized estimating equations: an orientation. , 2003, American journal of epidemiology.

[29]  P. Devroey,et al.  Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. , 2002, Human reproduction.

[30]  J. Kurinczuk,et al.  The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. , 2002, The New England journal of medicine.

[31]  M. Riley,et al.  Validating notifications of pregnancy terminations for birth defects before 20 weeks gestation. , 2002, Health information management : journal of the Health Information Management Association of Australia.

[32]  A. Sutcliffe,et al.  Minor congenital anomalies, major congenital malformations and development in children conceived from cryopreserved embryos. , 1995, Human reproduction.

[33]  J. Opitz,et al.  Blastogenesis and the "primary field" in human development. , 1993, Birth defects original article series.