P-184 The effect of oocyte vitrification accounting for both open and closed systems on embryo developmental arrest rate. A systematic review and network meta-analysis
Authors: Pantou A , Maziotis E , Sfakianoudis K , Grigoriadis S , Kokkini G , Trypidi A , Kokkali G , Asimakopoulos B , Pantos K , Simopoulou M 
Published: June 2022

Abstract

Study question
To investigate the effect of oocyte vitrification on embryo developmental arrest rate accounting for both open and closed systems.

Summary answer
Open and closed vitrification systems are equally associated with a statistically significant higher embryo developmental arrest rate per MII oocyte vitrified compared to fresh oocytes.

What is known already
Oocyte cryopreservation has increased in popularity as it enhances women’s reproductive autonomy. Numerous studies have been published evaluating its effectiveness. However, the majority of published evidence commonly include comparisons with the now considered as “outdated” method of slow freezing. Additionally, data principally report on fertilization rates and clinical outcomes. It may be timely and essential to focus strictly on the effect of oocyte vitrification on the developmental potential of the embryo. Further to this, data are lacking on whether employing an open or closed vitrification system may affect the outcome of vitrification.

Study design, size, duration
A systematic search of the literature was performed in the databases Pubmed/Medline, Embase, and Cochrane Central Library limited to articles published in English up to October 2021. Only studies employing vitrification were included in this meta-analysis. A total of 17 published prospective studies were eligible. The population consists of oocytes that were either vitrified or fresh and subjected to ICSI. A network meta-analysis was performed comparing the type of vitrification system employed and fresh oocytes.

Participants/materials, setting, methods
The primary outcome measure was developmental arrest rate per MII oocyte vitrified prior to reaching cleavage or blastocyst stage. The secondary outcome measures were fertilization rate per MII oocyte vitrified and developmental arrest rate per 2PN zygote. Further to this, a subgroup analysis was performed according to the stage of developmental arrest. To rank the efficiency between the fresh oocytes and the oocytes vitrified employing the open and closed system, the P-Score was employed.

Main results and the role of chance
The seventeen studies reporting on the effect of oocyte vitrification on embryo developmental arrest per MII oocyte vitrified, presented with high heterogeneity I2=81%. Vitrified oocytes employing either the open or closed vitrification system presented with a statistically higher embryo developmental arrest rate when compared to fresh oocytes (open-systems:RR:1.16; 95%CI:1.07-1.26; closed-systems:RR:1.19 95%CI:1.06-1.34). No statistically significant difference was observed between the two vitrification systems (open vs closed:RR:0.99;95%CI:0.89-1.10). Subgroup analysis was performed according to the developmental stage of embryo arrest. Similarly to the pooled results, when subgrouping for embryos arresting prior to the cleavage stage, a statistically significant difference on developmental arrest was identified when vitrifying (open-systems:RR:1.44; 95%CI:1.18-1.77; closed-systems:RR:1.51 95%CI:1.12-2.04; 8 studies). However, when subgrouping for embryos arresting prior to the blastocyst stage, no statistically significant difference on developmental arrest was observed when vitrifying (open-systems:RR:1.06; 95%CI:0.98-1.15; closed systems:RR:1.10 95%CI:0.98-1.24; 9 studies). Fertilization rate was significantly lower for vitrified oocytes compared to fresh (open-systems:RR:0.86; 95%CI:0.79-0.93; closed-systems:RR:0.81 95%CI:0.72-0.92), while no statistically significant difference was observed between the two vitrification systems (open vs closed:RR:1.04; 95%CI:0.93-1.16). When comparing developmental arrest rate per 2PN zygote no statistically significant difference was detected between vitrification versus fresh (open-systems:RR:1.01; 95%CI:0.87-1.17; closed-systems:RR:0.98 95%CI:0.78-1.22), or between the two vitrification systems (open vs closed:RR:1.03;95%CI:0.82-1.30).

Limitations, reasons for caution
The limited number of studies included along with the heterogeneity identified present as limitations of this study. Further studies and especially Randomized Controlled Trials should be conducted in order to evaluate possible effects of oocyte vitrification on embryo development.

Wider implications of the findings
Oocyte vitrification results to higher developmental arrest rates per oocyte vitrified but not per 2PN zygote. Both vitrification systems perform equally in affecting developmental arrest. The differential expression of miRNAs and cytokinesis-related genes are identified by this systematic review as potential pathways influencing developmental potential following oocyte vitrification.

Trial registration number
Not applicable