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. 2019 Jun;36(6):1049-1061.
doi: 10.1007/s10815-019-01475-0. Epub 2019 May 20.

Should the flexibility enabled by performing a day-4 embryo transfer remain as a valid option in the IVF laboratory? A systematic review and network meta-analysis

M Simopoulou  1   2 , K Sfakianoudis  3 , P Tsioulou  4 , A Rapani  4 , E Maziotis  4 , P Giannelou  4 , S Grigoriadis  4 , A Pantou  3 , K Nikolettos  5 , N Vlahos  6 , K Pantos  3 , M Koutsilieris  4
Affiliations

Should the flexibility enabled by performing a day-4 embryo transfer remain as a valid option in the IVF laboratory? A systematic review and network meta-analysis

M Simopoulou et al. J Assist Reprod Genet. 2019 Jun.

Abstract

Purpose: The present systematic review and network meta-analysis aims to uniquely bring to literature data supporting the true place of the alternative practice of day-4 embryo transfer (D4 ET) in an IVF laboratory, beyond the one-dimensional option of facilitating a highly demanding program.

Methods: A systematic search was conducted in the databases of PubMed/Medline, Embase, and Cochrane Central Library, resulting to six prospective along with nine retrospective cohort studies meeting eligibility criteria for inclusion. A comparison of D4 ET with day-2 (D2), day-3 (D3), and day-5 (D5) ET, respectively, was performed employing R statistics.

Results: The sourced results indicate no statistically significant difference regarding clinical pregnancy rates, and ongoing pregnancy/live birth rates stemming from the comparison of D4 with D2, D4 with D3, and D4 with D5 ET, respectively. Additionally, no statistically significant difference could be established in respect to cancelation, and miscarriage rates, following the comparison of D4 with D3 and D4 with D5 ET. Interestingly, we report statistically significant lower preterm birth rates associated with D4 ET, in contrast with D5 ET (RR, 0.19; 95% CI, 0.05-0.67; p value = 0.01).

Conclusions: The aforementioned results may serve as advocates buttressing the option of D4 ET as a valid candidate in the ET decision-making process. Possible limitations of the current study are the publication bias stemming from the retrospective nature of certain included studies, along with various deviations among studies' design, referring to number and quality of transferred embryos, or different culture conditions referring to studies of previous decades.

Keywords: Blastocyst; Cleavage embryo; Clinical pregnancy; Day of embryo transfer; Embryo transfer; Morula.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
PRISMA flowchart regarding the search results
Fig. 2
Fig. 2
Assessment of risk of bias of studies included in the meta-analysis
Fig. 3
Fig. 3
Summary of risk of bias assessment regarding each item for each study included in the meta-analysis
Fig. 4
Fig. 4
Forest plot of clinical pregnancy rates per ET cycle resulting from the comparison of D4 ET with D2, D3, and D5 ET respectively
Fig. 5
Fig. 5
Forest plot of ongoing pregnancy/live birth rates resulting from the comparison of D4 ET with D2, D3, and D5 ET respectively
Fig. 6
Fig. 6
Forest plot of clinical pregnancy rates per patient resulting from the comparison of D4 ET with D3 and D5 ET, respectively
Fig. 7
Fig. 7
Forest plot of cancelation rates resulting from the comparison of D4 ET with D3 and D5 ET, respectively
Fig. 8
Fig. 8
Forest plot of miscarriage rate per clinical pregnancy resulting from the comparison of D4 ET with D2, D3, and D5 ET respectively
Fig. 9
Fig. 9
Forest plot of preterm birth rates resulting from the comparison of D4 with D5 ET
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