Health of Children Born as a Result of In Vitro Fertilization

Health Services Research, National Research and Development Centre for Welfare and Health, Helsinki, Finland.
PEDIATRICS (Impact Factor: 5.47). 12/2006; 118(5):1819-27. DOI: 10.1542/peds.2006-0735
Source: PubMed


The purpose of this study was to use nationwide registries to examine the health of children up to 4 years of age who were born as a result of in vitro fertilization.
Children born after in vitro fertilization (N = 4559) from 1996 to 1999 were monitored until 2003. Two control groups were selected from the Finnish Medical Birth Register as follows: all other children (excluding children born after ovulation induction) from the same period (N = 190,398, for study of perinatal health and hospitalizations) and a random sample of those children (n = 26,877, for study of health-related benefits). Mortality rates and odds ratios for perinatal outcomes, hospitalizations, health-related benefits, and long-term medication use were calculated.
Although the health of most in vitro fertilization children was good, such children had more health problems than other children. A total of 35.7% of in vitro fertilization children and 2.2% of control children were multiple births, and the health of multiple births was worse than that of singletons. Perinatal outcomes of in vitro fertilization children were worse and hospital episodes were more common than among control children. Risks for cerebral palsy and psychological and developmental disorders were increased. Among in vitro fertilization singletons, worse results for perinatal outcomes and hospitalizations, but no increased risk for specific diseases, were found. The health of in vitro fertilization multiple births was comparable to the health of control multiple births.
Reducing the number of transferred embryos would improve the health of in vitro fertilization children. Additional studies are needed to explain the poorer health of in vitro fertilization singletons, as well as follow-up studies to examine the health of in vitro fertilization children from 4 years onward.

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Available from: Reija Klemetti, Jan 08, 2015
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    • "Infants produced by ART are also significantly more likely to be admitted to a neonatal intensive care unit, to be hospitalized and to stay in hospital longer than their naturally conceived counterparts.19 Recent studies have also shown an increase in the hospitalization of ART offspring in infancy and early childhood compared with spontaneously conceived children, as well as abnormal patterns of retinal vascularization and an increase in the incidence of undescended testicles in boys conceived by ICSI.7374757677 "
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    ABSTRACT: One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane. The origins of such oxidative stress appear to involve the sperm mitochondria, which have a tendency to generate high levels of superoxide anion as a prelude to entering the intrinsic apoptotic cascade. Unfortunately, these cells have very little capacity to respond to such an attack because they only possess the first enzyme in the base excision repair (BER) pathway, 8-oxoguanine glycosylase 1 (OGG1). The latter successfully creates an abasic site, but the spermatozoa cannot process the oxidative lesion further because they lack the downstream proteins (APE1, XRCC1) needed to complete the repair process. It is the responsibility of the oocyte to continue the BER pathway prior to initiation of S-phase of the first mitotic division. If a mistake is made by the oocyte at this stage of development, a mutation will be created that will be represented in every cell in the body. Such mechanisms may explain the increase in childhood cancers and other diseases observed in the offspring of males who have suffered oxidative stress in their germ line as a consequence of age, environmental or lifestyle factors. The high prevalence of oxidative DNA damage in the spermatozoa of male infertility patients may have implications for the health of children conceivedin vitro and serves as a driver for current research into the origins of free radical generation in the germ line.
    Asian Journal of Andrology 01/2014; 16(1):31-8. DOI:10.4103/1008-682X.122203 · 2.60 Impact Factor
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    • "A recent, large registry-based study of Swedish children concluded that those born after assisted reproduction techniques (ART), such as IVF, were more likely to be prescribed anti-asthmatic medication compared with naturally conceived children but the underlying duration of subfertility appeared to be the putative risk factor rather than an effect of treatment (Kallen et al., 2012). Others analysing Scandinavian registry data have also reported a significant increase in the use of asthma medications and hospitalization among children conceived after infertility treatment (Ericson et al., 2002; Koivurova et al., 2007; Finnstrom et al., 2011), though some researchers have found no effect (Pinborg et al., 2003; Klemetti et al., 2006). Smaller clinic-based studies in Turkish and American populations have found no increased risk of asthma after infertility treatment (Cetinkaya et al., 2009; Sicignano et al., 2010). "
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    ABSTRACT: STUDY QUESTION: Is asthma more common in children born after subfertility and assisted reproduction technologies (ART)? SUMMARY ANSWER: Yes. Asthma, wheezing in the last year and anti-asthmatic medication were all more common in children born after a prolonged time to conception (TTC). This was driven specifically by an increase in children born after ART. WHAT IS KNOWN ALREADY: Few studies have investigated any association between ART and asthma in subsequent children, and findings to date have been mixed. A large registry-based study found an increase in asthma medication in ART children but suggests underlying infertility is the putative risk factor. Little is known about asthma in children after unplanned or mistimed conceptions. STUDY DESIGN, SIZE, DURATION: The Millennium Cohort Study is a UK-wide, prospective study of 18 818 children recruited at 9 months of age. Follow-up is ongoing. This study analyses data from follow-up surveys at 5 and 7 years of age (response rates of 79 and 70%, respectively). PARTICIPANTS/MATERIALS, SETTING, METHODS: Singleton children whose natural mothers provided follow-up data were included. Mothers reported whether their pregnancy was planned; planners provided TTC and details of any ART. The population was divided into 'unplanned' (unplanned and unhappy), 'mistimed' (unplanned but happy), 'planned' (planned, TTC < 12 months), 'untreated subfertile' (planned, TTC >12 months), 'ovulation induced' (received clomiphene citrate) and 'ART' (IVF or ICSI). The primary analysis used the planned children as the comparison group; secondary analysis compared the treatment groups to the children born to untreated subfertile parents. Outcomes were parent report of asthma and wheezing at 5 and 7 years, derived from validated questions in the International Study of Asthma and Allergies in Childhood, plus use of anti-asthmatic medications. A total of 13 041 (72%) children with full data on asthma and confounders were included at 5 years of age, and 11 585 (64%) at 7 years. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with planned children, those born to subfertile parents were significantly more likely to experience asthma, wheezing and to be taking anti-asthmatics at 5 years of age [adjusted odds ratio (OR): 1.39 (95% confidence interval (CI): 1.07, 1.80), OR: 1.27 (1.00, 1.63) and OR: 1.90 (1.32,2.74), respectively]. This association was mainly related to an increase among children born after ART (adjusted OR: 2.65 (1.48, 4.76), OR: 1.97, (1.10, 3.53) and OR: 4.67 (2.20, 9.94) for asthma, wheezing and taking anti-asthmatics, respectively). The association was also present, though reduced, at the age of 7 years. LIMITATIONS, REASONS FOR CAUTION: The number of singletons born after ART was relatively small (n = 104), and as such the findings should be interpreted with caution. However, data on a wide range of possible confounding and mediating factors were available and analysed. The data were weighted for non-response to minimize selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The findings add to the growing body of evidence suggesting an association between subfertility, ART and asthma in children. Further work is needed to establish causality and elucidate the underlying mechanism. These findings are generalizable to singletons only, and further work on multiples is needed. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a Medical Research Council project grant. No competing interests.
    Human Reproduction 12/2012; 28(2). DOI:10.1093/humrep/des398 · 4.57 Impact Factor
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    • "Several studies have found an increased risk of cerebral palsy (CP) or neurological abnormalities among the ART population (Ericson et al., 2002; Strö mberg et al., 2002; Pinborg et al., 2004; Källén et al., 2005; Lidegaard et al., 2005; Hvidtjørn et al., 2006, 2010; Klemetti et al., 2006; Romundstad et al., 2008). However, the authors concluded that these outcomes were generally explained by higher rates of multiple pregnancies, prematurity and low birthweight among ART offspring. "
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    ABSTRACT: There is a large population of children conceived via assisted reproductive technology (ART), which continues to increase worldwide, without a clear understanding of associated long-term outcomes. ART children are more likely to be the result of multiple pregnancies, and thus to be born prematurely or low birthweight. There is growing evidence that ART children are phenotypically and biochemically different from naturally conceived children, but the mechanism(s) leading to these changes have not been elucidated. There is a possible increased risk of rare imprinted gene disorders in these children. However, it remains unclear whether more subtle changes in DNA methylation occur commonly, leading to differences in gene expression and phenotype in ART children. Although an increased risk of cancer among ART children has been reported, the role of ART in the development of cancer has not been demonstrated. Further research and ongoing surveillance of ART children is essential to better understand the possible effects of ART on the long-term health of this population.
    Human Reproduction 06/2011; 26(9):2392-400. DOI:10.1093/humrep/der212 · 4.57 Impact Factor
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