Article

A meta-analysis of controlled studies comparing major malformation rates in IVF and ICSI infants with naturally conceived children.

Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Journal of Assisted Reproduction and Genetics (Impact Factor: 1.77). 01/2005; 21(12):437-43. DOI: 10.1007/s10815-004-8760-8
Source: PubMed

ABSTRACT To estimate the risk of major malformations in IVF and ICSI infants.
Forty-four studies published in English since 1990 where the major malformation rate for IVF or ICSI cases was compared to an appropriate control group were reviewed. Nineteen studies met all selection criteria. In addition, a quality score was developed to assess each study based on sample size, timing of diagnosis, appropriateness of control group and other factors.
In 19 studies, the major malformation rates ranged from 0-9.5% for IVF; 1.1-9.7 for ICSI; and 0-6.9% in the control groups. When ICSI was compared to IVF, and multiple births compared to singleton, there were no statistically significant differences. When data from 16 studies involving 28,524 IVF infants and 2,520,988 spontaneously conceived controls and 7 studies involving 7234 ICSI infants and 978,078 controls were pooled, we found an overall odds ratio for the 19 studies of 1.29 (95% CI 1.01-1.67).
The overall odds ratio of 1.29 was statistically significant at the 5% level. These results may be useful for counseling ART patients and properly designing the consent forms used for ART procedures. It is not clear whether this risk is due to the procedures used in ART. We found that some of these studies have design flaws. All of them lacked an appropriate control group, i.e. infertile patients conceiving spontaneously. These flaws may create biases that would in almost all instances increase the risk of major malformations in the study group. Further research with better designed studies will likely result in a better estimate of the risk of major malformations associated with IVF and ICSI.

0 Followers
 · 
144 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We, and others, have demonstrated previously that there are differences in DNA methylation and transcript levels of a number of genes in cord blood and placenta between children conceived using assisted reproductive technologies (ART) and children conceived in vivo. The source of these differences (the effect of ART versus the underlying infertility) has never been determined in humans. In this study, we have attempted to resolve this issue by comparing placental DNA methylation levels at 37 CpG sites in 16 previously identified candidate genes in independent populations of children conceived in vivo ('fertile control' group) with ART children conceived from two groups: either autologous oocytes with infertility in one or both parents ('infertile ART' group) or donor oocytes (obtained from young fertile donors) without male infertility ('donor oocyte ART' group). Of the 37 CpG sites analyzed, significant differences between the three groups were found in 11 CpGs (29.73 %), using ANOVA. Tukey's post hoc test on the significant results indicated that seven (63.63 %) of these differences were significant between the donor oocyte ART and fertile control groups. In addition, 20 of the 37 CpGs analyzed had been identified as differentially methylated between ART and fertile control groups in an independent population in a prior study. Of these 20 CpG sites, 9 also showed significant differences in the present population. An additional 9 CpGs were found to be significantly different between the two groups. Of these 18 candidate CpGs, 12 CpGs (in seven candidate genes) also showed significant differences in placental DNA methylation levels between the donor oocyte ART and fertile control groups. These data suggest strongly that the DNA methylation differences observed between ART and in vivo conceptions are associated with some aspect of ART protocols, not simply the underlying infertility.
    04/2015; 7(1):41. DOI:10.1186/s13148-015-0071-7
  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate, in men presenting with recurrent pregnancy loss (RPL), the prevalence of sperm autosome and sex chromosome aneuploidy. Retrospective study. Male infertility clinic. A total of 140 men with RPL provided semen samples, and five normozoospermic controls provided 140 semen samples for comparison. Recurrent pregnancy loss, documented in the female partners, was defined as a prior miscarriage and/or recurrent IVF/intracytoplasmic sperm injection failure. Fluorescence in situ hybridization (FISH) was used to detect numerical abnormalities in sex chromosomes (X, Y) and autosomes (13, 18, 21) in ejaculated sperm. Sperm aneuploidy in men with RPL and normozoospermic controls. Men with RPL had a greater percentage of sperm aneuploidy within the sex chromosomes and chromosomes 18 and 13/21 (1.04% vs. 0.38%; 0.18% vs. 0.03%; 0.26% vs. 0.08%). In total, 40% of men with normal sperm density and motility had abnormal sperm aneuploidy in all the chromosomes analyzed. Men with abnormal sperm density and motility had a higher proportion of sperm sex chromosome aneuploidy than men with normal density/motility (62% vs. 45%). Men with normal strict morphology (>4%) had lower rates of sex chromosome and sperm aneuploidy than men with abnormal strict morphology (28% vs. 57%). There was no association between sperm DNA fragmentation and sperm aneuploidy. Men with RPL have increased sperm aneuploidy compared with controls. A total of 40% of men with RPL and normal sperm density/motility had abnormal sperm aneuploidy. Men with oligoasthenozoospermia and abnormal strict morphology had a greater percentage of sperm aneuploidy compared with men with normal semen parameters. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    Fertility and Sterility 02/2015; 193(4). DOI:10.1016/j.fertnstert.2015.01.029 · 4.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To assess the association between assisted reproductive technology (ART) and risk of congenital malformations (CM) by conducting a meta-analysis of cohort studies. PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through August 2014 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. Fifty-seven studies involving 119,874 infants conceived following ART and 1,212,320 infants conceived naturally were included in the analysis. The ART-conceived infants were associated with a higher risk of CM [relative risk (RR) = 1.33; 95 % confidence interval (CI) 1.24-1.43] when compared with those conceived naturally. When data were restricted to singleton births (RR = 1.38; 95 % CI 1.30-1.47), major CM (RR = 1.47; 95 % CI 1.29-1.68), matched/adjusted studies (RR = 1.37; 95 % CI 1.27-1.47) or high quality studies (RR = 1.40; 95 % CI 1.27-1.55), the increased risk of CM still existed in ART pregnancies. Additionally, an increased risk of CM was also found when the ART twin (RR = 1.18; 95 % CI 1.06-1.32) or multiple births (RR = 1.16; 95 % CI 1.05-1.27) were separately compared with spontaneously conceived twin or multiple births. Substantial heterogeneity was observed across studies (I (2) = 68, 44, 39, and 33 % for all infants, singletons, twins and multiples, respectively). Whether confounding factors were matched or adjusted, study quality and sample size as the first three of the most relevant heterogeneity moderators have been identified. No evidence of publication bias was observed (P > 0.10). The ART-conceived infants have a higher risk of CM compared with those conceived naturally. However, these estimates have to be viewed with caution because of heterogeneity.
    Archives of Gynecology 04/2015; DOI:10.1007/s00404-015-3707-0 · 1.28 Impact Factor

Preview

Download
1 Download
Available from