One of the major concerns about ART is the risk of birth defects in children born after in vitro fertilization. We report on a cohort of consecutive children affected with anorectal malformation (ARM) requiring surgical correction in which we found a significantly high proportion (Odds ratio 13.31, 95% confidence limits 4.0-39.6) of children born after ART. Our data is in agreement with the result of a recent epidemiological study in Sweden. Further studies are necessary to define the risk and identify the causes, if any. At present, couples undergoing ART should be informed of the general risk of congenital anomalies, of which, ARM can be suggested as an example.
To investigate a proposed association between in vitro fertilisation (IVF) and child asthma.
The risk for asthma after IVF was estimated as ORs using Mantel-Haenszel analysis.
The Swedish Medical Birth Register.
Of the 2 628 728 children born in 1982-2007 and surviving the perinatal period, 31 918 were conceived by IVF. Presence of asthma was defined as at least five prescriptions of antiasthmatic drugs during the period 1 July 2005-31 December 2009 according to the Swedish Prescribed Drug Register (115 767 children, 2323 of whom were born after IVF).
A significantly increased risk for asthma, albeit small, was found in children conceived by IVF (aOR 1.28, 95% CI 1.23 to 1.34), increasing the absolute risk from 4.4% to 5.6%. The risk increase for asthma was the same in boys and girls, in singletons and twins, and after caesarean section and vaginal delivery. The risk was higher for preterm than term singletons. For children with a low Apgar score, respiratory diagnoses, mechanical ventilation, continuous positive airway pressure or neonatal sepsis, the effect of IVF on asthma risk was low and statistically non-significant. Adjustment for length of involuntary childlessness eliminated the effect, and removal of infants whose mothers had used antiasthmatics in early pregnancy reduced the risk.
This study verifies an association between IVF and asthma in children. This can be partly explained by neonatal morbidity and by maternal asthma acting as mediators, but the main risk factor is parental subfertility. The mechanism for this is unclear.
Does IVF increase the risk of autism spectrum disorders (ASDs)?
No association between IVF and ASDs or any of its subtypes was found in this sample.
Certain prenatal factors may increase the risk of ASDs. Studies on the association between IVF and ASDs have shown inconsistent results. IVF is known to increase the risk of perinatal problems but many of them are related to multiple pregnancies.
This case-control study included 4164 autistic cases and 16 582 matched controls born in Finland in 1991-2005. The cases were diagnosed with ASDs by the year 2007. The maximum age at diagnosis was 16 years.
Four controls were matched to each case. For singletons the matching criteria were date of birth, place of birth, sex and residency in Finland. For twins the birth order within a twin pair was included as well. In the whole sample, there were 63 cases (1.51%) and 229 controls (1.38%) born after IVF.
No significant association was found between IVF and ASDs (adjusted odds ratio (OR): 0.9, 95% confidence interval (CI): 0.7-1.3) or its subtypes childhood autism (OR: 0.8, 95% CI: 0.4-1.5), Asperger's syndrome (OR: 0.9, 95% CI: 0.5-1.6) or other pervasive developmental disorder (OR: 1.0,?95% CI: 0.6-1.6). When only singletons were included, there was an association between IVF and Asperger's syndrome in an unadjusted analysis (OR: 2.0, 95% CI: 1.1-3.5) but this was not significant when adjusted for mother's socioeconomic status or parity. When the analyses were conducted separately for boys and girls, there was a significant association between IVF and Asperger's syndrome for boys in an unadjusted analysis (OR: 2.1, 95% CI: 1.2-3.7) but this was not significant in the final adjusted model.
Information both on IVF and on ASDs was based on registers and it is possible that there is some misclassification. No information on different subtypes of IVF or other assisted reproduction techniques was available. Statistical power may have been insufficient.
This study showed no increased risk of ASDs in children born after IVF but studies with larger sample sizes and information on different subtypes of IVF are needed to confirm the finding.
The study was supported by Autism Speaks, NIMH 1K02-MH65422 and NIEHS 1R01ES019004. There are no competing interests.
To assess the existing evidence of associations between assisted conception and cerebral palsy (CP), autism spectrum disorders (ASD), and developmental delay.
Forty-one studies identified in a systematical PubMed and Excerpta Medica Database (EMBASE) search for articles published from January 1, 1996, to April 1, 2008.
Studies written in English comparing children born after assisted conception with children born after natural conception assessing CP, ASD, and developmental delay, based on original data with a follow-up of 1 year or more. Main Exposures In vitro fertilization (IVF) with or without intracytoplasmic sperm injection or ovulation induction with or without subsequent intrauterine insemination.
Cerebral palsy, ASD, and developmental delay.
Nine CP studies showed that children born after IVF had an increased risk of CP associated with preterm delivery. In our meta-analysis including 19 462 children exposed to IVF, we estimated a crude odds ratio of 2.18 (95% confidence interval, 1.71-2.77). Eight ASD studies and 30 studies on developmental delay showed inconsistent results. No studies assessed the risk of CP, ASD, or developmental delay in children born after ovulation induction exclusively.
Methodological problems were revealed in the identified studies, and the gaps in our knowledge about the long-term outcomes of children born after assisted conception are considerable, including a lack of information on the long-term consequences of ovulation induction. Possible associations with ASD and developmental delay need assessment in larger studies. Studies on assisted conception and CP from countries outside of Scandinavia are needed, including detailed information on time to pregnancy, underlying cause of infertility, and type of IVF treatment.
To study the occurrence of major congenital anomalies (CAs) among children born after IVF (IVF, microinjections, and frozen embryo transfers) and after ovulation inductions with or without insemination (other assisted reproductive technologies [ART]).
Data regarding CAs were obtained from the Register of Congenital Malformations.
Children from IVF (n = 4,559), children from other ART (n = 4,467), and controls (n = 27,078, a random sample of naturally conceived children) from the Medical Birth Register.
In vitro fertilization and other ART treatment in ordinary practice.
Rate of major CAs. Children from IVF and other ART were compared with control children, both overall and by plurality, controlling for confounding factors by logistic regression.
For IVF children, the adjusted odds ratio (OR) was 1.3 (95% confidence interval [CI], 1.1-1.6). Stratifying by gender and plurality showed that the risk was only increased for boys, and the risk was decreased for multiple IVF girls (OR = 0.5, 95% CI 0.2-0.9). The crude OR of major CA for other ART children was 1.3 (95% CI 1.1-1.5), but adjusted differences by gender and plurality were statistically insignificant.
In vitro fertilization was associated with an increased risk for major CAs among singleton boys and a decreased risk among multiple girls. The risk after other ART was only slightly increased.
The frequency and importance of complications of IVF and other ovulation induction (OI) are poorly known. We examined the occurrence of serious complications and miscarriages leading to hospitalization or operation after IVF (including microinjections and frozen embryo transfers) and OI treatment (with or without insemination).
Women who received IVF (n = 9175) or OI treatment (n = 10 254) 1996-1998 in Finland were followed by a register linkage study until 2000.
After the first IVF treatment cycle, 14 per 1000 women had a serious case of OHSS (ovarian hyperstimulation syndrome), with 23 per 1000 throughout the study period (mean of 3.3 treatments). The corresponding values after OI were very low. The rates of registered ectopic pregnancies and miscarriages after IVF were nine and 42 respectively per 1000 women, with corresponding rates after OI of eight and 42. Infections and bleeding were not common after IVF and even rarer after OI. Overall, 15% of IVF and 8% of OI women had at least one hospital episode during the study period.
Though there was a low risk of complications after each IVF treatment cycle, repeated attempts resulted in serious complications for many women, and these occurred much more often than after ovulation induction alone.
The aim of this study was to compare the prevalence at birth of birth defects in children born after intracytoplasmatic sperm injection (ICSI) and children born after traditional in vitro fertilisation (IVF). Altogether 553 children were born after ICSI treatment in Norway during the period 1996-1998 (351 singletons, 95 twins-pairs and 4 triplets) while 1731 were born after IVF treatment (1004 singletons, 344 sets of twins and 13 triplets). Birth defects were registered in 5.42% of children born after ICSI and in 5.14% of children born after IVF; 3,07% and 3.00% respectively were major birth defects. We conclude that intracytoplasmic sperm injection does not imply a significant increase in the prevalence at birth of birth defects compared to children conceived by traditional IVF.