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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    • "Indeed, ICSI seems to be 'oversized' as first therapeutic approach to idiopathic infertile couples, especially in cases of (mild) oligozoospermia in the male and absent female factors. Furthermore, ICSI may increase the risk for congenital defects and not to forget that the necessary hormonal treatment regimen puts the health risk burden solely on the female partner (Davies et al., 2012). On the other hand, although the recent Cochrane review points to a beneficial effect, FSH treatment is ineffective in unselected idiopathic infertile men (Kamischke et al., 1998) since response to FSH differs between individuals due to the variety of underlying unknown aetiologies subsumed under the term 'idiopathic infertility' (Foresta et al., 2000). "
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    ABSTRACT: Male infertility contributes to a substantial share to couple infertility. Despite scientific efforts, most cases of male infertility remain 'idiopathic' and male-specific therapeutic options are sparse. Given the crucial role of the follicle-stimulating hormone (FSH) for spermatogenesis, FSH is used empirically to improve semen parameters. Furthermore, a recently updated Cochrane review points to a beneficial effect of FSH treatment in idiopathic infertile men on spontaneous pregnancy rates. However, since response to FSH varies strongly even in selected patients and given the lack of powerful evidence of FSH treatment regimens, intra-cytoplasmic spermatozoa injection (ICSI) is widely used in idiopathic male infertility, though the treatment burden is high for the couple and it entails considerable costs and some risks. Single nucleotide polymorphisms (SNPs) within FSH ligand/receptor genes (FSHB/FSHR), significantly influencing reproductive parameters in men, represent promising candidates to serve as pharmacogenetic markers to improve prediction of response to FSH. However, there is an evident lack of information which patients should be treated and how many patients in an andrological outpatient clinic would be eligible for such a treatment, a crucial decision criterion for clinicians and also pharmaceutical industry to start such a pharmacogenetic intervention therapy. After screening our andrological patient cohort, we present a realistic scenario and a basis for further prospective studies using FSH in idiopathic infertile men.
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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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    • "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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