Assisted reproductive techniques and the risk of anorectal malformations: a German case-control study

Abstract

BackgroundThe use of assisted reproductive techniques (ART) for treatment of infertility is increasing rapidly worldwide. However, various health effects have been reported including a higher risk of congenital malformations. Therefore, we assessed the risk of anorectal malformations (ARM) after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).MethodsData of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (95% confidence intervals) were determined to quantify associations using multivariable logistic regression accounting for potential confounding or interaction by plurality of births.ResultsIn total, 295 ARM patients born between 1997 and 2011 in Germany, who were recruited through participating pediatric surgeries from all over Germany and the German self-help organisation SoMA, were included. Controls were all German live-births (n = 10,069,986) born between 1997 and 2010. Overall, 30 cases (10%) and 129,982 controls (1%) were born after IVF or ICSI, which translates to an odds ratio (95% confidence interval) of 8.7 (5.9–12.6) between ART and ARM in bivariate analyses. Separate analyses showed a significantly increased risk for ARM after IVF (OR, 10.9; 95% CI, 6.2–19.0; P < 0.0001) as well as after ICSI (OR, 7.5; 95% CI, 4.6–12.2; P < 0.0001). Furthermore, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed strong associations with ART (ORs 4.9, 11.9 and 7.9, respectively). After stratification for plurality of birth, the corresponding odds ratios (95% confidence intervals) were 7.7 (4.6–12.7) for singletons and 4.9 (2.4–10.1) for multiple births.ConclusionsThere is a strongly increased risk for ARM among children born after ART. Elevations of risk were seen after both IVF and ICSI. Further, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed increased risks in each group. An increased risk of ARM was also seen among both singletons and multiple births.

Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000-2010

“…22 However, because we used a limited group of conditions, our prevalence estimates of 1% are lower than national estimates for all types of birth defects (approximately 3%). 27 In accordance with other studies, 3–5,7,28–32 we found that the risk of birth defects following ART varied by type of defect; the largest relative risks were observed for gastrointestinal and limb reduction defects. We also found an association between ART use and transposition of great vessels, which has been previously reported.…”

Genetic and nongenetic etiology of nonsyndromic anorectal malformations: A systematic review

“…Candidate genes were also selected based on the knowledge from animal studies, syndromic forms of ARM, or other congenital malformations of the colon. After screening the caudal type homeobox 1 ( CDX1 ) gene, four heterozygous mutations (c.213–214InsGAA, c.6G>C, c.27G>T, c.18A>C) were identified, and lower CDX1 expression levels were found in cases when compared with controls (Zhang et al, ). Although the ret proto‐oncogene ( RET ) is a major gene involved in Hirschsprung's disease, it was not associated with ARM (Wu et al, ).…”

“…In three studies, associations were investigated between ARM and common methods of contraception, including oral contraceptives, spermicides, male condoms, and intrauterine devices; however, no associations were found (Table ; Stoll et al, ; Gallaway et al, ; Waller et al, ). However, assisted reproduction seems to attribute to the occurrence of ARM in several studies, showing highly increased risk estimates ranging from 2.4 to 13.3 (Robert and Francannet, ; Källén et al, ; Midrio et al, ; Reefhuis et al, ; Zwink et al, ). The highest risks were observed in studies comparing personal interviews among case parents with register‐based control data (Midrio et al, ; Zwink et al, ).…”

An Unusual Case of Malrotation in a Baby Conceived by In vitro Fertilization

“…However, analysis of data from 2001-2007 by the same group found only oesophageal atresia to be significantly increased. A German study however, noted an increased risk of anorectal malformation with assisted reproduction [8]. A review of the literature does not suggest that malrotation has been identified as being more prevalent in babies conceived via assisted reproductive techniques.…”