P-213 Assisted Hatching as new indication to improve diminished implantation potential after spontaneous collapsed blastocyst
Authors: Mifsud-Giner A , Tejera A , Valera M.A , Delgado A , Meseguer M 
Published: June 2022

Abstract

Study question
To demonstrate whether assisted hatching (AH) could improve reproductive outcome of collapsed blastocysts (CB). Pregnancy rate (PR) and the implantation rate (IR) were studied.

Summary answer
Our results demonstrate an indication of AH for collapsed blastocyst. The AH could reverse or minimize the negative impact of the collapse on implantation.

What is known already
With the introduction of the time-lapse thecnology, different aspects of the embryonic development are analyzed in detail. According to Marcos et al., 2015, the incidence of spontaneous blastocyst collapse is 19% and decreases the implantation potential from 48.5% to 35.1%. Recently, Sciorio et al., 2020 described significantly higher IR of 61.2% and OPR of 53.7% when blastocysts which had not collapsed were replaced compared to cycles in which collapsed blastocysts were transferred (IR rate 22.6% and OPR 17.7%). This study suggests that human collapsed blastocysts are less likely to implant and generate a pregnancy compared with embryos that do not.

Study design, size, duration
Retrospective study performing AH routinely in warmed embryos for 5 years in 4 groups: study groups CB (No-AH /CB- AH) and control groups NCB (No-AH / NCB-AH). To find out if the differences between the study groups were due solely to the effect of AH, we introduced two additional contemporary control groups NCB with and without HA. SET (single embryo transfer) was performed. IR and PR were analyzed and compared using the Chi-square test.

Participants/materials, setting, methods
A total of 754 blastocysts distributed in 4 groups were analyzed: 188 CB without AH (No-AH), 161 CB with AH, 199 NCB No-AH and 206 NCB with AH. All blastocysts were warmed embryos and the collapse was identified retrospectively in a time-lapse system before warming. The AH was performed by laser (removing 1/4 part of the ZP) after warming the embryos.

Main results and the role of chance
Comparing the clinical PR between embryos with or without collapse a significant adverse effect was confirmed by the collapse (CB 47.6% 166/349 vs NCB 60.5% 245/405) p &lt; 0.001. The same trend was observed in the ongoing PR (OPR),(CB 30.7% 107/349 vs NCB 40.2% 163/405, p = 0.006). Regarding the AH effect, and considering all warmed embryos (regardless if they were affected by collapse or not) we did not find any improvement in the PR and IR when we performed AH on the blastocysts. For PR: No-AH: 53.2% 206/387 vs AH: 55.9% 205/367, p = 0.469 and for IR: No-AH: 42.6% 165/387 vs AH: 47.7% 175/367, p = 0.164. Focussing solely on warmed blastocyst which collapsed, and performing AH, we encountered significant differences regarding OPR (No-AH 25.5% 48/188 vs AH 36.6% 59/161, p = 0.025). When selecting only day 5 embryos the same effect was observed (No-AH 25.8% 40/155 vs 37.9% 47/124, p = 0.03).

Limitations, reasons for caution
The collapse was described as ≥ 50% of the surface of the trophectoderm being separated from the ZP regardless how far the trophectoderm cells are apart from the ZP. Some blastocysts suffer a strong collapse reducing considerably the size of the embryo, but in others the collapse is quite subtle.

Wider implications of the findings
Our results demonstrate a real indication for AH in CB. It would be interesting to incorporate continuous embryo monitoring in laboratories to identify collapse to ensure AH and improving results. Maybe these events of collapse would imply an additional metabolic stress which may affect viability or displacing the implantation window.

Trial registration number
not applicable