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

Wong, Karen T; Carson, Kaitlyn R; Crane, Joan M G

BACKGROUND In vitro methods of conception are associated with adverse perinatal outcomes. It is unclear if the risk of stillbirth is increased also. OBJECTIVE 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. SEARCH STRATEGY A comprehensive search in PubMed, Embase, CINAHL, and Cochrane Library was undertaken from database inception to February 2021, with backward citation tracking. SELECTION CRITERIA 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. DATA COLLECTION AND ANALYSIS 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. MAIN RESULTS 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. CONCLUSIONS 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.