Risk of severe maternal morbidity associated with in vitro fertilisation: a population-based study

Objective: To investigate the association between in vitro fertilisation IVF and severe maternal morbidity (SMM) and to explore the role of multiple pregnancy as an intermediate factor.

Design: Population-based cohort-nested case-control study.

Setting: Six French regions in 2012/13.

Population: Cases were 2540 women with SMM according to the EPIMOMS definition; controls were 3651 randomly selected women who gave birth without SMM.

Methods: Analysis of the associations between IVF and SMM with multivariable logistic regression models, differentiating IVF with autologous oocytes (IVF-AO) from IVF with oocyte donation (IVF-OD). The contribution of multiple pregnancy as an intermediate factor was assessed by path analysis.

Main outcome measures: Severe maternal morbidity overall and SMM according to its main underlying causal condition and by severity (near misses).

Results: The risk of SMM was significantly higher in women with IVF (adjusted OR = 2.5, 95% CI 1.8-3.3). The risk of SMM was significantly higher with IVF-AO, for all-cause SMM (aOR = 2.0, 95% CI 1.5-2.7), for near misses (aOR = 1.9, 95% CI 1.3-2.8), and for intra/postpartum haemorrhages (aOR = 2.3, 95% CI 1.6-3.2). The risk of SMM was significantly higher with IVF-OD, for all-cause SMM (aOR = 18.6, 95% CI 4.4-78.5), for near misses (aOR = 18.1, 95% CI 4.0-82.3), for SMM due to hypertensive disorders (aOR = 16.7, 95% CI 3.3-85.4) and due to intra/postpartum haemorrhages (aOR = 18.0, 95% CI 4.2-77.8). Path-analysis estimated that 21.6% (95% CI 10.1-33.0) of the risk associated with IVF-OD was mediated by multiple pregnancy, and 49.6% (95% CI 24.0-75.1) of the SMM risk associated with IVF-AO.

Conclusion: The risk of SMM is higher in IVF pregnancies after adjustment for confounders. Exploratory results suggest higher risks among women with IVF-OD; however, confidence intervals were wide, so this finding needs to be confirmed. A large part of the association between IVF-AO and SMM appears to be mediated by multiple pregnancy.

Tweetable abstract: The risk of severe maternal morbidity is higher in IVF-conceived pregnancies than in pregnancies conceived by other means.