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

PurposeThe 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.MethodsA 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.ResultsThe 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).ConclusionsThe 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.