Risk of stillbirth in low-risk singleton term pregnancies following fertility treatment: a national cohort study

BJOG. 2019 Jan;126(2):253-260. doi: 10.1111/1471-0528.15509. Epub 2018 Nov 16.

Abstract

Objective: To assess the risk of stillbirth in low-risk in vitro fertilisation (IVF) pregnancies.

Design: Register-based national cohort study.

Setting: Denmark 2003-2013.

Population: Cohort of 425 732 singleton pregnancies including 10 235 conceived following IVF/intracytoplasmic sperm injection (ICSI), 4521 conceived following intrauterine insemination (IUI), and 410 976 spontaneously conceived.

Methods: Information on pregnancy, obstetrical risk factors, stillbirth, and fertility treatment was obtained from the Danish national health registers for all pregnancies after gestational week 21+6 . We estimated the overall and gestational age-specific risk of stillbirth in low-risk term pregnancies following IVF, ICSI, and IUI. Further, we estimated the association between stillbirth and IVF and ICSI respectively as well as fresh or frozen-thawed embryo transfer.

Main outcome measures: Risk of stillbirth.

Results: The number of stillbirths in spontaneously conceived and IVF/ICSI low-risk term pregnancies was 525 (0.1%) and 35 (0.3%), respectively. In multivariate analysis, the risk of stillbirth in pregnancies following IVF/ICSI was increased (odds ratio 2.1, 95% CI 1.4-3.1). The risk of stillbirth was correspondingly increased in time-to-event analyses taking risk time for each fetus into account from gestational week 37 and onwards (hazard ratio 2.4, 95% CI 1.6-3.6). In sub-analyses, the risk of stillbirth was increased for pregnancies following ICSI (odds ratio 2.2, 95% CI 1.2-3.1), but not IVF (odds ratio 1.7, 95% CI 0.9-3.1).

Conclusion: We found a systematically increased risk of stillbirth in low-risk term pregnancies following IVF/ICSI. Whether the risk was related to the treatment or to underlying subfertility is uncertain. The results may indicate a need for obstetrical surveillance for these pregnancies when reaching term.

Tweetable abstract: Increased risk of stillbirth in low-risk term pregnancies following fresh cycle IVF/ICSI.

Keywords: Fertility treatment; in vitro fertilisation; intracytoplasmic sperm injection; stillbirth.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cohort Studies
  • Denmark
  • Female
  • Fertilization in Vitro / adverse effects
  • Fertilization in Vitro / statistics & numerical data
  • Gestational Age
  • Humans
  • Insemination, Artificial / adverse effects
  • Insemination, Artificial / statistics & numerical data
  • Male
  • Middle Aged
  • Odds Ratio
  • Pregnancy
  • Registries
  • Risk Assessment
  • Sperm Injections, Intracytoplasmic / adverse effects*
  • Sperm Injections, Intracytoplasmic / statistics & numerical data
  • Stillbirth / epidemiology*
  • Term Birth