Reproductive Technologies and the Risk of Birth Defects

Robinson Institute, University of Adelaide, Adelaide, SA, Australia.
New England Journal of Medicine (Impact Factor: 55.87). 05/2012; 366(19):1803-13. DOI: 10.1056/NEJMoa1008095
Source: PubMed


The extent to which birth defects after infertility treatment may be explained by underlying parental factors is uncertain.
We linked a census of treatment with assisted reproductive technology in South Australia to a registry of births and terminations with a gestation period of at least 20 weeks or a birth weight of at least 400 g and registries of birth defects (including cerebral palsy and terminations for defects at any gestational period). We compared risks of birth defects (diagnosed before a child's fifth birthday) among pregnancies in women who received treatment with assisted reproductive technology, spontaneous pregnancies (i.e., without assisted conception) in women who had a previous birth with assisted conception, pregnancies in women with a record of infertility but no treatment with assisted reproductive technology, and pregnancies in women with no record of infertility.
Of the 308,974 births, 6163 resulted from assisted conception. The unadjusted odds ratio for any birth defect in pregnancies involving assisted conception (513 defects, 8.3%) as compared with pregnancies not involving assisted conception (17,546 defects, 5.8%) was 1.47 (95% confidence interval [CI], 1.33 to 1.62); the multivariate-adjusted odds ratio was 1.28 (95% CI, 1.16 to 1.41). The corresponding odds ratios with in vitro fertilization (IVF) (165 birth defects, 7.2%) were 1.26 (95% CI, 1.07 to 1.48) and 1.07 (95% CI, 0.90 to 1.26), and the odds ratios with intracytoplasmic sperm injection (ICSI) (139 defects, 9.9%) were 1.77 (95% CI, 1.47 to 2.12) and 1.57 (95% CI, 1.30 to 1.90). A history of infertility, either with or without assisted conception, was also significantly associated with birth defects.
The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors. The risk of birth defects associated with ICSI remained increased after multivariate adjustment, although the possibility of residual confounding cannot be excluded. (Funded by the National Health and Medical Research Council and the Australian Research Council.).

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Available from: Kevin Priest, Apr 16, 2014
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    • "Another explanation for the observed zygosity differences might be fertility treatments, which generally produce DZ twins. It has been reported that parents of twins conceived via fertility treatments are better educated and are better off financially than those of naturally conceived twins (Burt & Klump, 2012; Davies et al., 2012). Due to the expenses of fertility treatments in many countries, these treatments would be more accessible to parents of a better socio-economic status (SES), which is in turn associated "
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    ABSTRACT: A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
    Twin Research and Human Genetics 09/2015; DOI:10.1017/thg.2015.57 · 2.30 Impact Factor
    • "Indeed, in species such as the human and mouse, it has been shown that spermatozoa that are capable of binding to the zona pellucida have a significantly higher degree of DNA integrity than those gametes that are unable to interact with homologous oocytes (Liu and Baker, 2007; Kumar et al., 2013). Such findings are supported by large-scale epidemiological studies that have shown an elevated risk of birth defects in children conceived by techniques such as intracytoplasmic sperm injection that bypass this natural barrier to fertilization (Davies et al., 2012). It is therefore concerning that one of the most common lesions identified in the sperm of men attending IVF clinics is an idiopathic failure of sperm – oocyte recognition (Liu and Baker, 2000). "
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    ABSTRACT: While a large cohort of sperm surface receptors underpin sperm-oocyte adhesion processes, our recent work has revealed that the molecular chaperone Heat Shock Protein A2 (HSPA2) is a key regulator of zona pellucida-receptor complex assembly in our own species. Indeed, in the infertile population, spermatozoa that fail to interact with the zona pellucida of the oocyte consistently lack HSPA2 protein expression. While the mechanisms behind this protein deficiency are under consideration, BCL2-associated athanogene 6 (BAG6) has been identified as a key regulator of HSPA2 stability in mouse germ cells. However, in the human, the presence of BAG family proteins remains completely uncharacterized. Consequently, this study aimed to determine the presence of BAG6 in human sperm cells and to characterize its putative interaction with HSPA2 throughout sperm cell development. BAG6 was shown to co-localize with HSPA2 in human testicular germ cells and epididymal spermatozoa. Similarly, BAG6 was identified in the equatorial region of non-capacitated spermatozoa but underwent a marked relocation to the anterior region of the head upon the induction of capacitation in these cells. Protein-protein interaction assays revealed the stable interaction of BAG6 and HSPA2 proteins in mature spermatozoa. Furthermore, examination of the spermatozoa of infertile men with zona pellucida binding defects, related to a lack of HSPA2, revealed a concomitant deficiency in BAG6 protein expression. In view of the findings described in this study, we propose that BAG6 is likely a key regulator of HSPA2 stability/function in human germ cells. Moreover, its under-representation in spermatozoa with zona pellucida binding deficiency suggests that BAG6 may be an important candidate to study for a further understanding of male idiopathic infertility.
    Molecular Human Reproduction 07/2015; DOI:10.1093/molehr/gav041 · 3.75 Impact Factor
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    • "In the Western world, an estimated 1% of children born annually are conceived by ART (ICMART, 2012). The great majority of these children are healthy (Davies et al., 2012), although several reports have demonstrated the potential for adverse perinatal conditions in ART pregnancies (Templeton, 2000; Hansen et al., 2013). For example, there is an increased risk for several pregnancy complications, including pre-eclampsia (Chen et al., 2009), placenta praevia (Romundstad et al., 2006), placenta accreta (Esh-Broder et al., 2011), abnormal placental growth, perinatal mortality, preterm delivery, and most importantly, low birthweight (Schieve et al., 2002; Helmerhorst et al., 2004; Jackson et al., 2004; Ceelen et al., 2008; Rinaudo and Lamb, 2008; Haavaldsen et al., 2012). "
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    ABSTRACT: BACKGROUND The number of children conceived using assisted reproductive technologies (ART) has reached >5 million worldwide and continues to increase. Although the great majority of ART children are healthy, many reports suggest a forthcoming risk of metabolic complications, which is further supported by the Developmental Origins of Health and Disease hypothesis of suboptimal embryo/fetal conditions predisposing adult cardiometabolic pathologies. Accumulating evidence suggests that fetal and placental growth kinetics are important features predicting post-natal health, but the relationship between ART and intrauterine growth has not been systematically reviewed.
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