title: Congenital anomalies in offspring of subfertile couples: a registry-based study in the northern Netherlands.
abstract: OBJECTIVE
  To study whether specific congenital anomalies occur more often with a history of subfertility and/or the use of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI).
  
  
  METHODS
  Case-only analyses.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  We included live births, stillbirths, and terminated pregnancies with congenital anomalies without a known cause that had a birth year between 1997 and 2010 (n = 4,525). A total of 4,185 malformed cases were born to fertile couples and 340 to subfertile couples, of whom 139 had conceived after IVF/ICSI and 201 had conceived naturally after >12 months.
  
  
  METHODS
  None.
  
  
  METHODS
  The contribution, expressed in odds ratios (ORs), of a history of subfertility and IVF/ICSI to each specific type of congenital anomaly, imprinting disorder, and syndromal disorder.
  
  
  RESULTS
  We found subfertility to be associated with an increase in abdominal wall defects (adjusted OR [aOR] 2.43, 95% CI 1.05-5.62), penoscrotal hypospadia (aOR 9.83, 95% CI 3.58-27.04), right ventricular outflow tract obstruction (aOR 1.77, 95% CI 1.06-2.97), and methylation defects causing imprinting disorders (aOR 13.49, 95% CI 2.93-62.06). In vitro fertilization/ICSI was associated with an increased risk of polydactyly (OR 4.83, 95% CI 1.39-16.77) and more specifically polydactyly of the hands (OR 5.02, 95% CI 1.43-17.65).
  
  
  CONCLUSIONS
  In our registry-based study, parental subfertility was associated with an increase in abdominal wall defects, penoscrotal hypospadia, right ventricular outflow tract obstruction, and methylation defects causing imprinting disorders. In vitro fertilization/ICSI was associated with an increase in polydactyly, mainly of the hands.
authors.affiliation: Division of Developmental Neurology, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. Electronic address: jorienseggers@gmail.com.
authors.forename: Jorien
authors.initials: J
authors.lastname: Seggers
authors.affiliation: Division of Eurocat Northern Netherlands, Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Hermien E K
authors.initials: HE
authors.lastname: de Walle
authors.affiliation: Division of Eurocat Northern Netherlands, Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Jorieke E H
authors.initials: JE
authors.lastname: Bergman
authors.affiliation: Division of Eurocat Northern Netherlands, Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Groen
authors.affiliation: Division of Developmental Neurology, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Mijna
authors.initials: M
authors.lastname: Hadders-Algra
authors.affiliation: Division of Eurocat Northern Netherlands, Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Marly E
authors.initials: ME
authors.lastname: Bos
authors.affiliation: Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Hoek
authors.affiliation: Division of Eurocat Northern Netherlands, Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Maaike L
authors.initials: ML
authors.lastname: Haadsma
mesh_terms: D000293:Adolescent; D000328:Adult; D000013:Congenital Abnormalities / Q000453:epidemiology* / Q000209:etiology; D005191:Family Characteristics; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects / Q000706:statistics & numerical data; D006228:Hand Deformities, Congenital / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D007246:Infertility / Q000453:epidemiology* / Q000628:therapy; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D017689:Polydactyly / Q000453:epidemiology; D011247:Pregnancy; D012042:Registries / Q000706:statistics & numerical data; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects / Q000706:statistics & numerical data; D055815:Young Adult
keywords: In vitro fertilization; assisted reproductive technology; birth defects; congenital anomalies; subfertility