Risk of stillbirth in singleton gestations following in vitro methods of conception: a systematic review and meta-analysis.

Abstract

In vitro methods of conception are associated with adverse perinatal outcomes. It is unclear if the risk of stillbirth is increased also. This systematic review and meta-analysis aimed to estimate the risk of stillbirth in singleton gestations following in vitro methods of conception compared to non-in vitro conceptions. A comprehensive search in PubMed, Embase, CINAHL, and Cochrane Library was undertaken from database inception to February 2021, with backward citation tracking. Eligible studies included randomized controlled trials, cohort studies, or case-control studies that assessed stillbirth following in vitro fertilisation and/or intracytoplasmic sperm injection in comparison to non-in vitro methods of conception, including spontaneous conceptions, intrauterine insemination, and ovarian stimulation. The Newcastle-Ottawa Scale was used to assess risk of bias. A summary odds ratio (OR) for stillbirth following in vitro methods of conception compared to non-in vitro methods was calculated using a random-effects model for meta-analysis. Thirty-three cohort studies met inclusion criteria. There was an increased risk of stillbirth with in vitro methods: OR 1.41 (95% CI 1.20-1.65); however, the crude baseline risk of stillbirth was low (4.44/1000 total births). Subgroup analysis did not demonstrate an increased risk when in vitro methods were compared to conception without in vitro methods in the context of subfertility. Compared to non-in vitro conceptions, in vitro conceptions have an increased risk of stillbirth. However, there is insufficient evidence to demonstrate whether this risk is associated with in vitro techniques or underlying subfertility. This meta-analysis found an increased risk of stillbirth in singletons from in vitro methods of conception.