The Inclusion Principles of Human Embryos in the WOW-Based Time-Lapse System: A Retrospective Cohort Study.

Yuqiong Wang,Yang Xu,Xilin Qian,Yanrong Kuai,Sheng Wang

doi:10.3389/fendo.2021.549216

Yuqiong Wang, Yang Xu + Show 3 more

Open Access

https://doi.org/10.3389/fendo.2021.549216

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Abstract

A time-lapse system (TLS) with a well-of-the-well (WOW) dish, which allows individual identification and the possibility of autocrine and paracrine signaling between group-cultured embryos, has been widely used in clinic. However, there is a need to re-think the inclusion principles of human embryos in WOW-based TLS, especially for grade IV (G4) embryos, which are considered to potentially have detrimental effects on surrounding embryos. Here, we carried out a single-center, large-cohort, retrospective study, comprising 303 patients undergoing IVF (148 cases) and ICSI (155 cases), with a total of 3282 embryos, to compare embryonic development until the blastocyst stage in the group culture system with or without G4 embryos. Further, LC-MS/MS was used to analyze the G1-G4 embryo secretome to understand the influence of G4 embryos on the group culture microenvironment. We proved that polypronuclear (PPN) embryos positively contribute to the development of the neighboring embryos through secretion of ILIAP, ITI-H4, and keratin. Existence of more than one G4 embryo had a negative effect on the other embryos (p < 0.05). Moreover, G4 embryos were found to secrete KLKB1 and VTDB, which might harm the neighboring embryos. Thus, our study clarified that when embryos are subjected to group culture in WOW-based TLS, the PPN-derived embryos need not be removed, and it is important to ensure that no more than one G4 embryo is present to avoid negative effects on the neighboring embryos.

Highlights

The time-lapse system (TLS) is an effective method for continuous imaging of embryonic development in vitro; it provides detailed information of the developmental kinetics and cleavage patterns throughout the culture period (1, 2), and maintains a stable and optimal embryo culture environment without having to remove the culture dish from the incubator (1, 3)
The group with PPN embryos showed a higher fertilization rate (p < 0.05), because PPN embryos are usually present in the in-vitro fertilization (IVF) cycle, whose fertilization rate is higher than that of intracytoplasmic sperm injection (ICSI)
In the IVF cycles, the group with PPN embryos showed a higher blastocyst formation rate, transplantable blastocyst formation rate, highquality blastocyst formation rate, and effect sizes; for example, the effect size of 0.15 for blastocyst formation rate indicated that the difference in every unit of PPN embryos presented in the group culture system was associated with a 15% increase in blastocyst formation rate [0.15, 95%CI (0.02, 0.27)]

Summary

Introduction

The time-lapse system (TLS) is an effective method for continuous imaging of embryonic development in vitro; it provides detailed information of the developmental kinetics and cleavage patterns throughout the culture period (1, 2), and maintains a stable and optimal embryo culture environment without having to remove the culture dish from the incubator (1, 3). It is hypothesized that one benefit of group embryo culture is that it allows embryos to modify their microenvironment in an autocrine manner to exert an effect on themselves and/or on neighboring embryos (9), which may provide mutual ‘‘corrective’’ factors that compensate for insufficiency or imbalance in the individual embryo. These factors may act as growth factors or survival factors, protecting the embryos from subsequent cell death (10). Potential embryoderived secretory factors include members of the insulin and insulin-like growth factor and tumor necrosis factor families, epidermal growth factors, fibroblast growth factors, and plateletderived growth factors (11, 12)

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