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In vitro fertilisation
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===Birth defects=== A review in 2013 came to the result that infants resulting from IVF (with or without ICSI) have a [[relative risk]] of birth defects of 1.32 (95% [[confidence interval]] 1.24β1.42) compared to naturally conceived infants.<ref name="pmid23449641">{{cite journal |vauthors=Hansen M, Kurinczuk JJ, Milne E, de Klerk N, Bower C |year=2013 |title=Assisted reproductive technology and birth defects: a systematic review and meta-analysis |journal=Human Reproduction Update |volume=19 |issue=4 |pages=330β353 |doi=10.1093/humupd/dmt006 |pmid=23449641 |doi-access=free}}</ref> In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in infants conceived through IVF, notably [[septal heart defect]]s, [[cleft lip]] with or without [[cleft palate]], [[esophageal atresia]], and [[anorectal atresia]]; the mechanism of causality is unclear.<ref>{{cite journal |vauthors=Reefhuis J, Honein MA, Schieve LA, Correa A, Hobbs CA, Rasmussen SA |date=February 2009 |title=Assisted reproductive technology and major structural birth defects in the United States |journal=Human Reproduction |volume=24 |issue=2 |pages=360β366 |doi=10.1093/humrep/den387 |pmid=19010807 |doi-access=free}}</ref> However, in a population-wide cohort study of 308,974 births (with 6,163 using assisted reproductive technology and following children from birth to age five) researchers found: "The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors."<ref name="Davies">{{cite journal |display-authors=6 |vauthors=Davies MJ, Moore VM, Willson KJ, Van Essen P, Priest K, Scott H, Haan EA, Chan A |date=May 2012 |title=Reproductive technologies and the risk of birth defects |journal=The New England Journal of Medicine |volume=366 |issue=19 |pages=1803β1813 |doi=10.1056/NEJMoa1008095 |pmid=22559061 |s2cid=12552533 |doi-access=free}}</ref> Parental factors included known independent risks for birth defects such as maternal age, smoking status, etc. Multivariate correction did not remove the significance of the association of birth defects and ICSI (corrected odds ratio 1.57), although the authors speculate that underlying male infertility factors (which would be associated with the use of ICSI) may contribute to this observation and were not able to correct for these confounders. The authors also found that a history of infertility elevated risk itself in the absence of any treatment (odds ratio 1.29), consistent with a Danish national registry study<ref name="Zhu">{{cite journal |vauthors=Zhu JL, Basso O, Obel C, Bille C, Olsen J |date=September 2006 |title=Infertility, infertility treatment, and congenital malformations: Danish national birth cohort |journal=BMJ |volume=333 |issue=7570 |pages=679 |doi=10.1136/bmj.38919.495718.AE |pmc=1584372 |pmid=16893903}}</ref> and "implicates patient factors in this increased risk."<ref name="Davies"/> The authors of the Danish national registry study speculate: "our results suggest that the reported increased prevalence of congenital malformations seen in singletons born after assisted reproductive technology is partly due to the underlying infertility or its determinants."<ref name="Zhu"/> {| class="wikitable" style="float:right;" |+ Risk in singleton pregnancies resulting from IVF (with or without [[intracytoplasmic sperm injection|ICSI]])<ref name="Pandey2012">{{cite journal |vauthors=Pandey S, Shetty A, Hamilton M, Bhattacharya S, Maheshwari A |year=2012 |title=Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis |journal=Human Reproduction Update |volume=18 |issue=5 |pages=485β503 |doi=10.1093/humupd/dms018 |pmid=22611174 |doi-access=free}}</ref> |- ! Condition !! [[Relative risk|Relative<br /> risk]] !! 95% [[confidence interval|confidence<br /> interval]] |- | [[BeckwithβWiedemann syndrome]] || 3-4 || |- | [[congenital anomalies]] || 1.67 || 1.33β2.09 |- | [[ante-partum haemorrhage]] || 2.49 || 2.30β2.69 |- | [[hypertensive disorders of pregnancy]] || 1.49 || 1.39β1.59 |- | [[preterm rupture of membranes]] || 1.16 || 1.07β1.26 |- | [[Caesarean section]] || 1.56 || 1.51β1.60 |- | [[gestational diabetes]] || 1.48 || 1.33β1.66 |- | [[induction of labour]] || 1.18 || 1.10β1.28 |- | [[small for gestational age]] || 1.39 || 1.27β1.53 |- | [[preterm birth]] || 1.54 || 1.47β1.62 |- | [[low birthweight]] || 1.65 || 1.56β1.75 |- | [[perinatal mortality]] || 1.87 || 1.48β2.37 |}
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