Slow Development of Day 5 Embryo Leads to Compromised Live Birth But Not Birthweight Outcomes

Background: There is currently no consensus regarding developmental cutoff for fresh transfer of slow developing day 5 embryos on. Literature is sparse regarding true prognosis of such embryos. Aim: To investigate live birth and birthweight outcomes of slow developing day 5 transferred embryos. Method: This retrospective multi-center study included 1213 consecutive autologous-oocyte single fresh day 5 transfers performed at 4 Monash IVF clinics during 2016-2019. Repeat cycles by same patients were excluded to avoid clustering effects. Live birth and birthweight were followed up in all pregnancies. Multiple regression was performed to investigate associations between slow day 5 development (defined as ≤ early blastocyst) and (a) live birth, (b) birthweight, and (c) gestation-adjusted birthweight (Z score) to account for gestational age and gender. Results were expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). Results: No implantation was achieved when day 5 embryo failed to reach early blastocyst stage (i.e. ≤morula, n=76). Live birth rate was significantly lower following transfer of early blastocysts (n=237, 16%), in comparison to expanding (n=329, 27%, P=0.001), expanded (n=392, 41%, P=0.000), and ≥hatching blastocysts (n=169, 44%, P=0.000). After adjusting for maternal age, hours post insemination at day 5 assessment, number of oocytes collected, number of 2PNs, and number of embryos frozen; multiple logistic regression showed a significantly reduced likelihood of live birth resulting from early blastocysts in reference to expanding (aOR=0.584, 0.371-0.917, P=0.020), expanded (aOR=0.322, 0.208-0.501, P=0.000), or ≥hatching stages (aOR=0.255, 0.147-0.443, P=0.000). However, early blastocysts resulting in live birth (n=39) did not alter birthweight or Z score in reference to expanding (n=90, P>0.05 respectively), expanded (n=160, P>0.05 respectively), or ≥hatching (n=75, P>0.05 respectively). Conclusion: There is no clinical value of fresh transferring day 5 embryos at ≤morula stage. Fresh early blastocysts lead to a reduced live birth rate but not birthweight outcomes.