Is in Vitro Fertilization Associated with Preeclampsia? A Propensity Score Matched Study

Background: Although an increased risk of preeclampsia in pregnancies conceived by in vitro fertilization (IVF) has been reported, it remains unknown whether IVF is associated with preeclampsia. In the present study, we sought to investigate whether IVF is associated with preeclampsia in pregnant women using propensity score matching analysis.

Methods: This study included 3,084 pregnant women who visited the National Center for Child Health and Development before 20 weeks of gestation without hypertension or renal disease and delivered a singleton after 22 weeks of gestation between 2009 and 2011. Of the 3084 patients, 474 (15.4%) conceived by IVF (IVF group) and 2,610 (84.6%) conceived without IVF (non-IVF group). The propensity score for receiving IVF was estimated using multiple logistic regression with 27 maternal and paternal variables. This model yielded a c-statistic of 0.852, indicating a strong ability to differentiate between those conceiving with and without IVF. The association between IVF and onset of preeclampsia was assessed by the propensity matched sample (pair of N = 474).

Results: There were 46 preeclampsia cases (1.5%) in the total study population, with a higher proportion of cases in the IVF group (15 cases, 3.2%) than the non-IVF group (31 cases, 1.2%). Before propensity score matching, the IVF group was 2.72 (95% confidence intervals [CI]: 1.46-5.08) times more likely to have preeclampsia when unadjusted, and 2.32 (95% CI: 1.08-4.99) times more likely to have preeclampsia when adjusted for maternal and paternal variables by logistic regression. After propensity score matching, the IVF group did not show a significantly greater association with preeclampsia compared to the non-IVF group (odds ratio: 2.50, 95% CI: 0.49-12.89), although point estimates showed a positive direction.

Conclusions: Propensity score matching analysis revealed that the association between IVF and preeclampsia became weaker than when conventional adjustments are made in multivariate logistic regression analysis, suggesting that the association between IVF and preeclampsia might be confounded by residual unmeasured factors.