Assessing obstetric outcomes: A systematic review and meta-analysis comparing fresh, artificial, and natural thaw embryo transfer cycles

The increasing utilisation of in vitro fertilisation (IVF) has prompted significant interest in determining the optimal endometrial environment to increase pregnancy rates and minimise the obstetric complications associated with various embryo transfer strategies. To determine which cycle is associated with increased obstetric complications: fresh embryo transfer (FreshET), natural thaw (NatThawET) or artificial thaw (ArtThawET). Outcomes of interest included: hypertensive disorders of pregnancy (HDP), gestational diabetes (GD), pre-term birth (PTB), post-partum haemorrhage (PPH) and large for gestational age (LGA). A comprehensive search of MEDLINE, EMBASE, CENTRAL, and PUBMED was conducted from 1947 to May 17, 2022. Two independent reviewers carried out the screening, and data extraction for the following comparisons: ArtThawET vs NatThawET, ArtThawET vs FreshET, and NatThawET vs FreshET. Meta-analysis was conducted using a fixed-effect Mantel-Haenszel model. The quality of the studies was assessed using GRADEpro. A total of 23 studies were included in this review. ArtThawET was associated with a significantly increased odds of HDP (odds ratio (OR) 1.76, confidence interval (CI) 1.66-1.86), PTB (OR 1.18, CI 1.13-1.23), PPH (OR 2.61, CI 2.3-2.97) and LGA (OR 1.11, CI 1.07-1.15), compared to NatThawET. ArtThawET was also associated with increased odds of HDP (OR 2.13, CI 1.89-2.4), PPH (OR 3.52, CI 3.06-4.04) and LGA (OR 2.12, CI 1.77-2.56), compared to FreshET. Furthermore, NatThawET demonstrated increased odds of HDP (OR 1.20, CI 1.11-1.29), PPH (OR 1.25, CI 1.14-1.38) and LGA (OR 1.85, CI 1.66-2.07) compared to FreshET. When clinically feasible, ArtThawET should be avoided as a first-line option for IVF to reduce the risk of obstetric complications. An adequately powered, multicentre randomised controlled trial is necessary to confirm these findings and investigate the underlying pathophysiology.