Pregnancy complications following fertility treatment-disentangling the role of multiple gestation

Int J Epidemiol. 2018 Aug 1;47(4):1333-1342. doi: 10.1093/ije/dyy103.


Background: To assess the extent to which multiple gestations mediate risk of pregnancy complications from fertility treatment and to address possible confounding by the underlying infertility.

Methods: From the nearly 1.8 million pregnancies recorded in the Swedish Medical Birth Register between 1996 and 2013, we selected the 9.9% (N = 174 067) that occurred to couples with known trouble conceiving (clinical infertility). Fertility treatment was identified from self-reports, medical records and procedural information from fertility clinics. We used logistic regression to estimate odds ratios (ORs) and their 95% confidence intervals (CIs), and decomposed the total effect into direct and mediated effects to estimate the proportion mediated by multiple gestations.

Results: Compared with pregnancies achieved without any assistance, those having received some treatment had higher odds of all studied complications except gestational diabetes. Associations with placenta previa (OR 2.17, 95% CI 1.95-2.40) and placental abruption (OR 1.77, 95% CI 1.54-2.03) were almost entirely independent of multiple gestations. In contrast, the majority of the associations with preterm birth (OR 1.69, 95% CI 1.62-1.77), caesarean delivery (RR 1.15, 95% CI 1.13-1.17) and pre-eclampsia (OR 1.17, 95% CI 1.11-1.22) were mediated by multiple gestations (87%, 62% and 91% of the effect mediated, respectively). Both direct and mediated pathways contributed to the remaining positive associations with chorioamnionitis, labour induction and postpartum haemorrhage. Results were similar when considering primi- and multi-parous women separately, and after restriction to assisted reproductive technologies only.

Conclusion: Multiple gestations are responsible for a large proportion of pregnancy complications associated with fertility treatment, suggesting that interventions to restrict the occurrence of multiples could reduce excess risk of pre-eclampsia, preterm birth and caesarean delivery after fertility treatment. However, the elevated risk of serious placental complications after fertility treatment appears to be largely independent of multiple gestations.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cesarean Section / statistics & numerical data
  • Female
  • Humans
  • Infant, Newborn
  • Infertility / therapy*
  • Logistic Models
  • Male
  • Pre-Eclampsia / epidemiology
  • Pregnancy
  • Pregnancy Complications / epidemiology*
  • Pregnancy Outcome
  • Pregnancy, Multiple*
  • Premature Birth / epidemiology
  • Reproductive Techniques, Assisted / adverse effects
  • Reproductive Techniques, Assisted / statistics & numerical data*
  • Sweden / epidemiology