Assisted reproductive technologies and the risk of birth defects—a systematic review

Hansen, Michèle; Bower, Carol; Milne, Elizabeth; Klerk, Nicholas de; Kurinczuk, Jennifer J

doi:10.1093/humrep/deh593

Cited by 633 publications

(358 citation statements)

References 67 publications

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“…Most papers on the consequences of ART concentrated on short-term outcomes, such as perinatal mortality, multiple pregnancies, weight at birth and malformations (reviewed in Schieve et al, 2004 andHansen et al, 2005), while few studies have considered the long-term effects of these techniques. Now that several children born after ART have reached adolescence, it is useful to study the possible long-term consequences of this procedure, such as cancer incidence.…”

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confidence: 99%

Meta-analysis of cancer incidence in children born after assisted reproductive technologies

2005

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A meta-analysis was performed on 11 cohort studies of Assisted Reproductive Technologies (ART) and subsequent childhood cancer, published up to February 2005, which reported comparable, nonoverlapping data, and then restricted to eight studies which presented a similar research design. The overall Standardised Incidence Ratio was 1.33 (95% CI 0.62 -2.85), and 0.77 (95% CI 0.41 -1.42) when the analysis was restricted to eight studies. No evidence of publication bias was observed for the overall analysis. The data are consistent with a lack of increase in risk of childhood cancer, though the amount of data on ART and cancer is still limited; larger multicentric studies as well as a pooled analysis on the available data are warranted.

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confidence: 99%

Meta-analysis of cancer incidence in children born after assisted reproductive technologies

2005

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“…The rise in preterm births and long-term implications on growth and development and psych-behavioural health has raised concerns with potential widespread use of ART. 13 As is common in ART, there were cases of triplets and quadruplets reported in many studies, [6][7][8]11 A further research is wanted to refine ART to improve birth outcomes; especially reducing risk of LBW babies and multiple pregnancies. At our centre, the infertile women were treated with embryo reduction techniques, thus reducing the multiple pregnancies just to twins.…”

Section: Discussionmentioning

confidence: 99%

“…There has been an increased incidence of congenital malformations. 7,8 There is a higher propensity for multiple pregnancies in ART. 9 There have not been many studies done in the Indian context where the socioeconomic background is very different, and the reproductive morbidity among women is high.…”

Section: Introductionmentioning

confidence: 99%

Perinatal outcomes among children born by assisted reproductive techniques—a hospital-based case control study

Gupta¹,

Nayan

Sharma

2012

Medical Journal Armed Forces India

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“…We would like to raise some concerns about the methods used to 'adjust' for the effect of subfertility in the metaanalysis of ART and major birth defects in the recent paper by Rimm et al [1] Having also published a systematic review and meta-analysis of ART and birth defects (BDs) [2], we are concerned both by the methods used and some of the statements made in the Rimm et al paper.…”

Section: To the Editormentioning

confidence: 99%

“…All counselling should be based on the best available evidence; to date, that evidence suggests that an increased risk of major BDs exists in children born after ART (in the order of 30-40%). [2] Couples should also be told that an increased BD risk also appears to exist, and is biologically plausible, in subfertile patients who manage to conceive spontaneously.…”

Section: To the Editormentioning

confidence: 99%

ART, birth defects and subfertility—what should prospective patients be told?

Hansen

Milne

Klerk

et al. 2011

J Assist Reprod Genet

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To the EditorWe would like to raise some concerns about the methods used to 'adjust' for the effect of subfertility in the metaanalysis of ART and major birth defects in the recent paper by Rimm et al. [1] Having also published a systematic review and meta-analysis of ART and birth defects (BDs) [2], we are concerned both by the methods used and some of the statements made in the Rimm et al. paper.Assumptions underlying the adjustment method:In their recent meta-analysis, Rimm et al.[1] attempt to 'adjust' the study-specific estimates of BD risk for couples conceiving by ART for the proportion they estimate to be due to underlying subfertility, by subtracting the risk for couples who conceived naturally after more than 12 months (based on Zhu et al. [3]). In doing so, they have assumed that the underlying causes of infertility in couples who managed to conceive spontaneously after 12+ months of trying were the same (and of equal severity) as those in couples who required ART to conceive. We think this is unlikely since many couples who proceed to ART treatment, such as those where the female partner has blocked or absent fallopian tubes or is unable to ovulate, or where the male partner has very low or no sperm in his ejaculate, would have little or no chance of conceiving spontaneously.Meta-analysis is a statistical technique used to summarise the results from many different studies identified through systematic review on the premise that we should look at the body of evidence rather than any study in isolation. Rimm et al. have adjusted the results of the many ART studies they identified (with OR estimates ranging from 0.54 to 15.4) based on an estimate of subfertility derived from a single study, ignoring any of the uncertainty around the single estimate they use. The fact that there are limited data on subfertility and BD risk does not make this valid or appropriate.Inconsistencies in data presented: There appear to be errors in some of the adjustments made to the ORs in this meta-analysis.Although the OR estimates for individual studies are not listed in the original , the ORs presented in the forest plot increase in size from left to right. When these ORs are compared with those in the more recent paper, it is evident that the OR for Place et al. [5] is lower than the one included in the first meta-analysis. Using information in the Place et al. paper, we estimate the OR for major BDs among IVF and ICSI children combined to be 1.36, compared with the OR of 1.24 used in the second Rimm meta-analysis. It is not clear how this was calculated. Moreover, many of the adjusted ORs in Table 1 of the second meta-analysis appear to have been incorrectly calculated (eg MRC, Isaksson, Place, Sutcliffe 1995) so that the hierarchical position of the studies on the second forest plot has changed even further from the original. Some studies also appear to have been incorrectly labelled on the forest plot (eg the OR for Ludwig appears to have been labelled Zadori and vice-versa).Capsule Clinicians who counsel prospective...

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Assisted reproductive technologies and the risk of birth defects—a systematic review

Abstract: 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.

Cited by 633 publications

References 67 publications

Meta-analysis of cancer incidence in children born after assisted reproductive technologies

Meta-analysis of cancer incidence in children born after assisted reproductive technologies

Perinatal outcomes among children born by assisted reproductive techniques—a hospital-based case control study

ART, birth defects and subfertility—what should prospective patients be told?

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