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: 1.72). 01/2005; 21(12):437-43. DOI: 10.1007/s10815-004-8760-8
Source: PubMed


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.

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    • "In agreement with the present study, Rimm et al reported the insignificant differences between ART (IVF and ICSI) protocols with the pregnancy outcomes (38). The other investigations also were showed a lower chance of successful conception in ICSI protocol (39). "
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    ABSTRACT: Background: Frozen embryo transfer (FET) is one of the most important supplementary procedures in the treatment of infertile couples. While general information concerning the outcome of fresh embryo transfer has been documented, paucity of investigations has addressed the clinical factors influenced on pregnancy rates in FET. Objective: In this study, we performed a retrospective analysis of clinical factors that potentially influence the outcome of FET. Materials and Methods: We reviewed the data from 372 women who were subjected to FET registered from April 2009-2011 at the Research and clinical center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Baseline data and pregnancy rate were collected. The data were analyzed statistically using the Kolmogorov-Smirnov, and Mann-Whitney tests. Results: The clinical pregnancy rate was 57.7 and 29.2% in women <35 years old, and women >35 years old, respectively (p<0.0001). Clinical pregnancy rates in women with FSH <10 IU/ml, and FSH >10 IU/ml were 56.3% and 17.5 %, respectively (p<0.0001). Whereas the other clinical parameters consist of reason of fetus freezing, primary IVF protocol, IVF procedure, endometrial thickness, treatment duration to fetal transfer found to be unrelated to FET outcomes (p>0.05). Conclusion: Female age and basal FSH level are the most important factors influencing the clinical pregnancy rate following FET.
    Iranian Journal of Reproductive Medicine 07/2014; 12(7):513-518. · 0.19 Impact Factor
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    • "Studies of perinatal outcomes of ART singletons appear to show even stronger differences between ART and non-ART singletons compared to ART and non-ART twins (Ceelen, van Weissenbruch, Vermeiden, van Leeuwen, & Delemarre-van de Waal, 2008; Helmerhorst, Perquin, Donker, & Keirse, 2004; McDonald, Murphy, Beyene, & Ohlsson, 2005). ART singletons, when compared with naturally conceived singletons, are at significantly increased risk of placental abnormalities, low birth weight, preterm birth, small for gestational age, perinatal mortality, and congenital malformations (Hansen, Bower, Milne, de Klerk, & Kurinczuk, 2005; Jackson, Gibson, Wu, & Croughan, 2004; McDonald, Han, Mulla, & Beyene, 2010; Rimm et al., 2004). Preterm birth is associated with increased morbidity, mortality, and diminished long-term survival and reproduction (McIntire & Leveno, 2008; Swamy, Ostbye, & Skjaerven, 2008), while low birth weight is associated with chronic diseases expressed later in life such as cardiovascular disease, hypertension, and type 2 diabetes (Barker, 2004). "
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    ABSTRACT: Since the early twentieth century, inheritance was seen as the inheritance of genes. Concurrent with the acceptance of the genetic theory of inheritance was the rejection of the idea that the cytoplasm of the oocyte could also play a role in inheritance and a corresponding devaluation of embryology as a discipline critical for understanding human development. Development, and variation in development, came to be viewed solely as matters of genetic inheritance and genetic variation. We now know that inheritance is a matter of both genetic and cytoplasmic inheritance. A growing awareness of the centrality of the cytoplasm in explaining both human development and phenotypic variation has been promoted by two contemporaneous developments: the continuing elaboration of the molecular mechanisms of epigenetics and the global rise of artificial reproductive technologies. I review recent developments in the ongoing elaboration of the role of the cytoplasm in human inheritance and development.
    Advances in child development and behavior 07/2013; 44:225-55. DOI:10.1016/B978-0-12-397947-6.00008-8 · 0.95 Impact Factor
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    • "for ICSI, after multivariate adjustment; as compared with ICSI, IVF was associated with a reduced risk of birth defect (OR 0.68, 95% CI 0.53–0.87). However, in other recent large studies and meta-analyses, no significant differences were found between ICSI and IVF children (Sutcliffe et al., 2003; Rimm et al., 2004; Lie et al., 2005; Tararbit et al., 2011; Wen et al., 2012). Whether it is ART procedures or the infertility situation that results in the increased risk of birth defects still remains in debate. "
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    ABSTRACT: Children conceived via assisted reproductive technologies (ART) are nowadays a substantial proportion of the population. It is important to follow up these children and evaluate whether they have elevated health risks compared to naturally conceived (NC) children. In recent years there has been a lot of work in this field. This review will summarize what is known about the health of ART-conceived children, encompassing neonatal outcomes, birth defects, growth and gonadal developments, physical health, neurological and neurodevelopmental outcomes, psychosocial developments, risk for cancer, and epigenetic abnormalities. Most of the children conceived after ART are normal. However, there is increasing evidence that ART-conceived children are at higher risk of poor perinatal outcome, birth defects, and epigenetic disorders, and the mechanism(s) leading to these changes have not been elucidated. Continuous follow-up of children after ART is of great importance as they progress through adolescence into adulthood, and new ART techniques are constantly being introduced.
    Journal of Zhejiang University SCIENCE B 05/2013; 14(5):359-71. DOI:10.1631/jzus.B1200348 · 1.28 Impact Factor
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