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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    • "Furthermore, sperm DNA damage appears to be linked to the most important checkpoints of fertility such as reduced fertilization rates, lower embryo quality and pregnancy rates, higher miscarriage rates, malformations, and childhood dis- eases[22]. Evidence continues to suggest that ART does increase risk of higher order pregnancy (with its inherent pre-and perinatal risks), prematurity and low birth weight, congenital malformations , in particular of the male urogenital system, and imprinting disorders23242526. Paternal sperm DNA damage has negative effects on the integrity of early embryonic development as the percentage of good quality embryos as well as implantation rates was significantly reduced in patients exhibiting high DNA damage[27]and it appears that the second and third mitoses are the sensitive periods[28].Ghaleno et al. (2014)showed that the intracellular levels of hydrogen peroxide (H 2 O 2 ) and superoxide (O 2 −@BULLET ) correlate negatively with impaired sperm mitochondrial membrane potential leading to poor-quality pronuclear embryos[29]. "

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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.
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    • "This is particularly true in cases of assisted reproductive techniques, such as intracytoplasmic sperm injection (ICSI), that have improved the chances of achieving pregnancy also for patients with severe seminal anomalies (Van Steirteghem et al. 1993 , 1996 ), despite an increased incidence of embryo aneuploidies (Verpoest and Tournaye 2006 ; Tesarik and Mendoza 2007 ). In particular, it appears that men with severe factor infertility treated by ICSI have an increased risk of generating offspring with unbalanced chromosomal constitution (Rimm et al. 2004 ; Wen et al. 2012 ). "
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    ABSTRACT: Chromosomal abnormalities are relevant causes of human infertility, affecting 2 –14 % of infertile males. Patients with seminal anomalies could be affected by improper meiotic recombination and increased sperm chromosome aneuploidy. Since the transmission of a haploid chromosomal asset is fundamental for embryo vitality and development, the study of sperm chromosomes has become fundamental because intracytoplasmic sperm injection allows fertilization in cases of severe male infertility. In this chapter we summarize the data on the incidence of sperm aneuploidy, detected by fluorescence in situ hybridization (FISH), in infertile men with normal or abnormal karyotype. The possibility of reducing sperm chromosomal imbalance is also reported. Among control males, the lowest aneuploidy rate was detected (range: 0.09 –0.14 % for autosomes; 0.04 –0.10 % for gonosomes). In infertile patients with normal karyotype, the severity of semen alteration is correlated with the frequency of aneuploidy, particularly for X and Y chromosomes. Among patients with abnormal karyotype, 47,XXY and 47,XYY carriers showed a high variability of sperm aneuploidy both for gonosomes and autosomes. In Robertsonian translocation carriers, the increase in aneuploidy rate was particularly evident for total sex disomy, and resulted mainly from interchromosomal effect (ICE). In reciprocal translocation carriers, a high percentage of unbalanced sperm (approximately 50 %) was detected, perhaps mostly related to ICE. Sperm chromosomal constitution could be analyzed to obtain more accurate information about the causes of male infertility. It would be worthwhile to evaluate the benefits of a therapy with recombinant Follicle Stimulating Hormone (rFSH) on sperm chromosome segregation in selected infertile males.
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