P-760 The effect of assisted hatching on pregnancy outcomes in 1,833,485 single embryo transfer based on Japan Assisted Reproductive Technology Registry System
Authors: Kusamoto A , Harada M , Kawahara T , Urata Y , Hirota Y , Osuga Y 
Published: July 2024

Abstract

Study question
Does assisted hatching (AH) affect pregnancy outcomes especially when it was performed selectively on specified group?

Summary answer
No clinically significant effect of AH on pregnancy outcomes was demonstrated for the entire single embryo transfer (SET) cycle after adjusting for covariates.

What is known already
AH is a technique used in assisted reproduction by artificially thinning or making a small hole in the zona pellucida in order to facilitate the hatching process. It is suggested that AH may improve the chance of embryo implantation and success of pregnancy. However, there is insufficient evidence to conclude that AH improves pregnancy outcomes, despite its widespread and longtime use. In 2014, the Practice Committee of ASRM recommended that AH should not be conducted routinely for all patients. On the other hands, it has been suggested that AH could be effective for patients with poor prognosis.

Study design, size, duration
A retrospective observational study based on the national ART registry maintained by the Japan Society of Obstetrics and Gynecology (JSOG) was performed. The study included 1,833,485 single embryo transfer (SET) for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) from January 2010 to December 2019. This study was approved by the Registration and Research Subcommittee of the JSOG and Tokyo University Ethics Committee.

Participants/materials, setting, methods
To determine the effect of AH, the rate of clinical pregnancy and live birth were compared in SET with and without AH as primary outcome measures. In addition, the prevalence of miscarriage, multiple pregnancy, ectopic pregnancy, placental malposition, and placenta accreta were analyzed as secondary outcomes. We performed inverse probability of treatment weighting and outcome regression analyses.

Main results and the role of chance
Out of 1,833,485 SET cycles, AH was conducted in 983,242 cycles (53.6%). In all SET cycles, clinical pregnancy rate (CRP) and live birth rate (LBR) were 31.0% vs. 26.2%, and 21.6% vs. 18.7% in AH vs. without AH group, respectively. AH was more frequently performed in patients with advanced maternal age, frozen-thawed ET cycles (88% vs. 47%, AH vs. without AH), blastocyst transfer cycles (70% vs. 42%), patients with tubal factor (17% vs 14.3%), and hormonal replacement cycles (66% vs. 43%). After adjusting for these covariates, the propensity-weighted CPR (28.4% vs. 29.1%, AH vs. without AH) and LBR (20.1% vs. 20.6%) were slightly yet significantly lower in AH group. As secondary outcomes, AH may lead to increased risk of multiple pregnancy (0.21% increase), ectopic pregnancy (0.02%), and placenta accreta (0.03%), and 0.24% decreased risk of miscarriage. On the other hands, subgroup analysis suggested that AH could be effective in the following cycles: frozen-thawed cycles with either blast or cleavage with maternal age under 35 years, and fresh blastocyst transfer cycles with maternal age over 40 years.

Limitations, reasons for caution
The limitation of this study is that the information regarding the history of repeated implantation failure and methods of AH were not included in this registry system. Another limitation is that duplicate data from same patients who underwent multiple embryo transfers exists in this retrospective study for 10 years.

Wider implications of the findings
Despite of frequent use of AH in Japan, AH in SET cycles for all patients is not recommended because of increased risk of adverse events without improvement of pregnancy outcomes. On the other hands, AH may improve pregnancy outcomes for some groups associated with maternal age and duration of culture.

Trial registration number
not applicable’