Abstract

Abstract Study question Does freezing embryos have any effects on neonatal and postnatal health? Does extended embryo culture have any impact on these health outcomes? Summary answer frozen embryo transfer (FET) infants were more likely be large gestational age, but with lower odds of recurrent upper respiratory infection and dermatitis. What is known already Infants born from frozen embryo transfers tend to have higher birth weights and are less likely to be small for gestational age. There are no notable variations in congenital malformations or child development. However, there’s a lack of long-term follow-up data. Study design, size, duration In this retrospective cohort study conducted in Taiwan, data from the national assisted reproductive technology (ART) database spanning from January 1st, 2013, to December 31st, 2017, was utilized. The study categorizes cases into fresh and frozen embryo transfer groups, with additional subdivisions based on cleavage and blastocyst stage transfers. Singletons born in each group were then linked to the National Health Insurance Database for follow-up on health conditions until December 13th, 2018. Participants/materials, setting, methods We collected data on singleton births resulting from assisted reproductive technology procedures performed in Taiwan from January 1st, 2013, to December 31st, 2017. Our analysis included 10,669 eligible infants. We investigated factors such as gestational age, birth weight, and various systemic diseases, encompassing neurological disorders, facial and eye abnormalities, cardiovascular diseases, respiratory disease, gastrointestinal disorders, renal system disorders, musculoskeletal disorders, skin and submucous disorders, chromosomal abnormalities, infections, and birth injuries. Main results and the role of chance Compared to infants conceived from fresh embryos, those born to mothers who underwent frozen embryo transfer (FET) were more likely to be large for gestational age (OR 1.63, 95% CI 1.30-2.04 for blastocyst and OR 1.69, 95% CI 1.36-2.10 for cleavage stage), and to have a neonatal birth weight of ≥ 4000g (OR 1.88, 95% CI 1.15-3.07 for blastocyst and OR 2.64, 95% CI 1.63-4.28 for cleavage stage). However, they were less likely to be small for gestational age (OR 0.68, 95% CI 0.56-0.82 for blastocyst and OR 0.68, 95% CI 0.56-0.82 for cleavage stage). Infants born from frozen embryo transfers also experienced lower odds of recurrent upper respiratory infection (OR 0.72, 95% CI 0.60-0.86 for blastocyst and OR 0.60, 95% CI 0.52-0.69 for cleavage stage), as well as eczema and dermatitis (OR 0.75, 95% CI 0.62-0.91 for blastocyst and OR 0.75, 95% CI 0.62-0.91 for cleavage stage). There was no observed effect on infant health between blastocyst and cleavage stage embryo transfers. Limitations, reasons for caution Our retrospective study design may not possess the same level of rigor as a randomized controlled trial (RCT). The follow-up period in our study ranged from 1 to 5 years, and some diseases may not manifest within this short-term timeframe, necessitating longer-term tracking for more comprehensive observation. Wider implications of the findings The result highlights the potential benefits of FET in reducing the risk of low birth weight. The observed decrease respiratory infections and skin disorders among FET infants suggests a possible advantage in immune system development or environmental adaptability. Further research with longer-term tracking is warranted. Trial registration number KMUHIRB-E(I)-20210222

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