Embryonic development arrest in extended culture during in vitro fertilization (IVF) presents a major challenge to achieving successful pregnancy outcomes. While blastocyst transfer has become the preferred method due to improved implantation rates, a significant proportion of embryos fail to develop to the blastocyst stage, resulting in cycle cancellations and reduced chances of pregnancy. Does failure to reach the blastocyst stage in a first IVF cycle signal an inherently poor prognosis for future attempts?

In this monocentric retrospective matched case-control study (2020–2023) analyzing 1,126 IVF/ICSI cycles, we compared outcomes of patients with total blastocyst culture failure (T1 Failure, n=113) against a propensity-score-matched control group (T1 Control, n=113).

T1 Failure cycles were characterized by significantly fewer mature oocytes (6.54±4.78 vs. 8.29±4.5, p < 0.001) and Day 3 embryos (3.36±3.11 vs. 5.31±3.53, p < 0.001). Notably, 72.6% of patients with initial culture failure achieved transferable blastocysts in their second cycle (T2). In T2, repeat failure was specifically associated with higher basal FSH (8.01±2.85 vs. 6.73±1.87, p = 0.008) and lower AMH levels (2.02±1.48 vs. 3.79±5.43, p = 0.036).

While initial failure is linked to lower oocyte yield and early embryo competence, it is not an absolute barrier to success. Most patients recover in subsequent cycles through protocol optimization, though diminished ovarian reserve remains the primary risk factor for recurrent failure. Our findings underscore the multifactorial nature of embryonic arrest and highlight potential clinical indicators for predicting and managing blastocyst development failure to optimize IVF success rates.