Effect of assisted hatching on pregnancy outcomes following 1,678,872 single embryo transfers based on the Japan Assisted Reproductive Technology Registry

Assisted hatching (AH) is a reproductive technique that artificially thins or breaches the zona pellucida to facilitate hatching. Despite its widespread use, there is insufficient evidence to conclude that AH improves pregnancy outcomes, particularly when performed selectively. Here we conducted a retrospective study using the Japan Assisted Reproductive Technology Registry from January 2010 to December 2019. AH was performed in 55.0% of 1,678,872 single embryo transfers (SETs), with higher frequency in advanced age women, frozen-thawed ET cycles, blastocyst transfer cycles, and hormonal replacement cycles. After adjusting for these covariates, the propensity-weighted clinical pregnancy rate (29.6% vs. 31.3%) and live birth rate (21.2% vs. 22.4%) were marginally but significantly lower in the AH group compared to the without-AH group. Moreover, AH increased risks of miscarriage (0.82% increase), multiple pregnancy (0.23% increase), and placenta accreta spectrum (0.12% increase). Subgroup analysis indicated that AH was effective for frozen-thawed blastocyst ET cycles in women under 35 years but worsened pregnancy outcomes in many groups, especially those with fresh or cleavage-stage embryos and women older than 40 years. These findings suggest that the impact of AH on pregnancy outcomes varies based on the characteristics of patients and ET cycles, prompting further discussion of its indications.