title: Assisted reproductive techniques and risk of exstrophy-epispadias complex: a German case-control study.
abstract: OBJECTIVE
  We assessed the risk of exstrophy-epispadias complex in children conceived by in vitro fertilization or intracytoplasmic sperm injection.
  
  
  METHODS
  Data from the German Network for Congenital Uro-REctal malformations were compared to nationwide data from the German In Vitro Fertilization Register and the German Federal Statistical Office. Odds ratios (95% CI) were determined to quantify associations using logistic regression.
  
  
  RESULTS
  A total of 123 patients with exstrophy-epispadias complex born in Germany between 1997 and 2011 were recruited through participating departments of pediatric urology and pediatric surgery throughout the country as well as the German self-help organizations Blasenekstrophie/Epispadie e.V. and Kloakenekstrophie. All German live births (10,069,986) between 1997 and 2010 comprised the controls. Overall, 12 subjects (10%) and 129,982 controls (1%) were conceived by in vitro fertilization or intracytoplasmic sperm injection. Conception by assisted reproductive technique was associated with a more than eightfold increased risk of exstrophy-epispadias complex compared to spontaneous conception (OR 8.3, 95% CI 4.6-15.0, p <0.001). Separate analyses showed a significantly increased risk of exstrophy-epispadias complex in children conceived by in vitro fertilization (OR 14.0, 95% CI 6.5-30.0, p <0.0001) or intracytoplasmic sperm injection (OR 5.3, 95% CI 2.2-12.9, p <0.0001).
  
  
  CONCLUSIONS
  This study provides evidence that assisted reproductive techniques such as in vitro fertilization and intracytoplasmic sperm injection are associated with a markedly increased risk of having a child born with exstrophy-epispadias complex. However, it remains unclear whether this finding may be due to assisted reproduction per se and/or underlying infertility/subfertility etiology or parent characteristics.
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. n.zwink@dkfz.de
authors.forename: Nadine
authors.initials: N
authors.lastname: Zwink
authors.forename: Ekkehart
authors.initials: E
authors.lastname: Jenetzky
authors.forename: Karin
authors.initials: K
authors.lastname: Hirsch
authors.forename: Peter
authors.initials: P
authors.lastname: Reifferscheid
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schmiedeke
authors.forename: Dominik
authors.initials: D
authors.lastname: Schmidt
authors.forename: Sabrina
authors.initials: S
authors.lastname: Reckin
authors.forename: Florian
authors.initials: F
authors.lastname: Obermayr
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Boemers
authors.forename: Raimund
authors.initials: R
authors.lastname: Stein
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Rösch
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.forename: Anne-Karoline
authors.initials: AK
authors.lastname: Ebert
mesh_terms: D001746:Bladder Exstrophy / Q000453:epidemiology* / Q000209:etiology*; D016022:Case-Control Studies; D004842:Epispadias / Q000453:epidemiology* / Q000209:etiology*; D005307:Fertilization in Vitro / Q000009:adverse effects*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects; D018570:Risk Assessment; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects*