Congenital anomalies in offspring of subfertile couples: a registry-based study in the northern Netherlands

Jorien Seggers*, Hermien E. K. de Walle, Jorieke E. H. Bergman, Henk Groen, Mijna Hadders-Algra, Marly E. Bos, Annemieke Hoek, Maaike L. Haadsma

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)

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).

Design: Case-only analyses.

Setting: Not applicable.

Patient(s): 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.

Intervention(s): None.

Main Outcome Measure(s): 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.

Result(s): 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).

Conclusion(s): 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. (C) 2015 by American Society for Reproductive Medicine.

Original languageEnglish
Pages (from-to)1001-1010.e3
Number of pages13
JournalFertility and sterility
Volume103
Issue number4
DOIs
Publication statusPublished - Apr-2015

Keywords

  • In vitro fertilization
  • assisted reproductive technology
  • subfertility
  • congenital anomalies
  • birth defects
  • IN-VITRO FERTILIZATION
  • ASSISTED REPRODUCTIVE TECHNOLOGY
  • INTRACYTOPLASMIC SPERM INJECTION
  • MAJOR BIRTH-DEFECTS
  • HEART-DEFECTS
  • INCREASED RISK
  • INFANTS BORN
  • MALFORMATIONS
  • COHORT
  • METAANALYSIS

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