In vitro fertilization as an independent risk factor for placenta accreta spectrum: In vitro fertilization, an independent risk factor for placenta accreta.

Abstract Background Placenta accreta spectrum (PAS) is well known in its association with catastrophic maternal outcomes. However, the pathophysiology rendering PAS is not well-defined. There has been emerging data that in vitro fertilization (IVF) may be a risk factor for placenta accreta. Objectives We aimed to investigate the hypothesis that IVF is an independent risk factor predicting PAS. Study design A retrospective analysis of all deliveries in a prospective, population-based cohort (2012-2019) was performed in a tertiary academic center. Primary outcome variable was PAS disorder. Univariate analysis was performed on potential risk factors for prediction of PAS and multivariate model was designed to best fit the prediction of PAS adjusted for risk factors including Cesarean delivery, placenta previa, age and parity. Since history of previous cesarean delivery was known to act as a risk factor for both placenta previa and PAS, the interaction between ‘placenta previa’ and ‘previous cesarean delivery’ was included in the final model. Odds ratios were calculated as exponential of beta coefficients from the multivariate regression analysis. Results A total of 37,461 deliveries were included in this analysis. Among those, 5464 (15%) had history of cesarean delivery, 281 (0.7%) had placenta previa in their index pregnancy, and 571 (1.5%) had IVF pregnancy. The frequency of PAS was 230 (0.6%). IVF pregnancy was independently a risk factor for PAS (adjusted odds ratio [aOR]=8.7, 95% confidence interval [CI] 3.8-20.3), as well as history of prior cesarean delivery (aOR=21.1, 95% CI 11.4-39.2) and presence of placenta previa (aOR=94.6, 95% CI 29.3-305.1). When adjusted for number of prior cesarean deliveries the correlation persisted for IVF aOR=6.7, 95% CI 2.9-15.6 Conclusion Our data demonstrate that IVF is an independent risk factor for PAS, although its relative clinical importance compared to the presence of placenta previa and history of cesarean delivery is small. The pathophysiology behind this relationship remains to be investigated.