Fresh versus Frozen Embryo Transfer in In Vitro Fertilization/Intracytoplasmic Sperm Injection Cycles: A Systematic Review and Meta-Analysis of Neonatal Outcomes

Background and Objectives: Although considerable research has been devoted to examining the distinctions between fresh and frozen embryo transfer regarding obstetric outcomes and rates of pregnancy success, there is still a scarcity of thorough analyses that specifically examine neonatal outcomes. The objective of our study was to provide an in-depth analysis of neonatal outcomes that occur after the transfer of fresh and frozen embryos (ET vs. FET) in IVF/ICSI cycles. Materials and Methods: Multiple databases (PubMed/MEDLINE, Cochrane Library, Web of Science, Wiley, Scopus, Ovid and Science Direct) were searched from January 1980 to February 2024. Two reviewers conducted the article identification and data extraction, meeting inclusion and exclusion criteria. The methodological quality was evaluated using the Newcastle-Ottawa Scale (NOS) or the revised Cochrane Risk of Bias Tool. The meta-analysis was performed using RevMan 5.4. Results: Twenty studies, including 171,481 participants in total, were subjected to qualitative and quantitative analyses. A significant increase in preterm birth rates was noted with fresh embryo transfer compared to FET in the overall IVF/ICSI population (OR 1.26, 95% CI 1.18-1.35, p < 0.00001), as well as greater odds of a low birth weight (OR 1.37, 95% CI 1.27-1.48, p < 0.00001) and small-for-gestational-age infants in this group (OR 1.81, 95% CI 1.63-2.00, p < 0.00001). In contrast, frozen embryo transfer can result in macrosomic (OR 0.59, 95% CI 0.54-0.65, p < 0.00001) or large-for-gestational-age infants (OR 0.64, 95% CI 0.60-0.69, p < 0.00001). No significant difference was observed regarding congenital malformations or neonatal death rates. Conclusions: This systematic review confirmed that singleton babies conceived by frozen embryo transfer are at lower risk of preterm delivery, low birthweight and being small for gestational age than their counterparts conceived by fresh embryo transfer. The data support embryo cryopreservation but suggest that elective freezing should be limited to cases with a proven indication or within the framework of a clinical study.