Search for optimal frozen embryo transfer endometrial preparation protocol continues despite a large randomized trial's findings.

Despite the worldwide increase in frozen embryo transfer (FET), the search for the best protocol to prime the endometrium continues. A high-quality randomized controlled trial (RCT) is the gold standard for intervention studies, offering the most reliable scientific evidence to guide healthcare practices while avoiding or minimizing bias and the risk of spurious causality. Even though peer review is currently considered the gold standard when evaluating new scientific knowledge, it still bears some weaknesses. This Commentary highlights how critical manuscript reading remains essential even when publication is in a high-impact journal. As an example, the authors wish to focus on a recent open-label RCT published in The Lancet. A total of 1428 IVF patients were randomly assigned to three FET protocols: true natural cycle (n = 476), modified natural cycle (n = 476) and artificial cycle (n = 476). One or two day 3 embryos or one blastocyst were transferred in all patients. The authors concluded that both the primary (live birth rate after one FET) and secondary outcome measures, including obstetric and neonatal outcomes, were comparable among the three FET protocols. However, the several shortcomings discussed in this Commentary limit the generalizability of the findings of this RCT to current practice.