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.
    Full-text · Article · Jan 2014 · Asian Journal of Andrology
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    • "The only cohort study in which a significant positive association between IVF and ASDs has been found [odds ratio (OR): 1.68, 95% confidence interval (CI): 1.11 –2.53] was based on a Finnish cohort (Klemetti et al., 2006) but the definition of the outcome was even less precise than in the previously mentioned studies. In addition to ASDs, practically all childhood developmental and psychiatric disorders were included (Klemetti et al., 2006). "
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    ABSTRACT: STUDY QUESTION: Does IVF increase the risk of autism spectrum disorders (ASDs)? SUMMARY ANSWER: No association between IVF and ASDs or any of its subtypes was found in this sample. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by Autism Speaks, NIMH 1K02-MH65422 and NIEHS 1R01ES019004. There are no competing interests.
    Preview · Article · Jan 2013 · Human Reproduction
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    • "According with Klemetti et al., stillbirths are significantly more frequent among IVF-conceived children (7.2 cases per 1000 births), who also presented worse indicators of perinatal health; curiously, perinatal health of IVF multiples was comparable to that of naturally conceived multiples (Klemetti et al., 2006 "
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    ABSTRACT: From the first birth of a child conceived by in vitro fertilization (IVF), much has been developed in assisted reproduction techniques (ART). However, the evolution of knowledge and therapeutic options, and progressively better results, were not followed by a proper control of risks and complications, which are still considerably frequent. The aim of this chapter is to deeply discuss undesirable outcomes such as ovarian hyperstimulation syndrome, ectopic and multiple pregnancies, and the higher rates of miscarriage among patients submitted to ART. In addition, birth defects, epigenetic inheritance and perinatal outcomes will be discussed, with the aim to offer clinicians an updated reference for daily practice.
    Full-text · Article · Jan 2013
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