BMI in children aged 1-18 years conceived after ART with fresh and frozen embryo transfer: a systematic review and meta-analyses.

BACKGROUND Children conceived by ART exhibit varying birthweights based on the specific ART method employed. Those born after frozen embryo transfer (FET) are more prone to being born with a high birthweight and more children are born large-for-gestational age, while those born after fresh embryo transfer (fresh-ET) tend to have lower birthweights and are more often categorized as small-for-gestational age. Extensive research has established a link between both low and high birthweight and an increased risk of childhood obesity. One of the prevailing hypotheses suggests that ART may induce epigenetic modifications during fertilization, implantation, and early embryonic stages, influencing not only size at birth but also BMI and overall health of the offspring later in life. OBJECTIVE AND RATIONALE This systematic review was undertaken to determine if available evidence in the literature supports the hypothesis that BMI is affected in children born after ART compared with naturally conceived children. SEARCH METHODS A literature search was performed until 20 March 2025, in PubMed (MEDLINE), EMBASE, and the Cochrane databases for original papers using medical subject headings, Emtree-terms, and free text words. The inclusion criteria were growth and anthropometrics (including BMI) in children born after ART aged 1-18 years. The review was done according to the PRISMA guidelines and data were extracted from the included studies whenever possible. The Robins-I tool was used to assess bias and GRADE was used to evaluate the certainty of the evidence in the included studies. OUTCOMES A total of 22 026 studies were found after removal of duplicates. Of these, 80 articles were selected for a full-length read-through. Additionally, 52 studies from the reference lists were identified and included for full-length read-through. Of these 132 studies, 32 met the inclusion criteria and were included in the qualitative analysis. Three meta-analyses were conducted. The first (A) compared BMI as SD scores (SDS) in children born after ART (n = 8902) with children born after natural conception (NC) (n = 61 818), and resulted in no difference in BMI (mean-difference 0.02, 95% CI: (-0.03; 0.06), I2 = 9%, moderate certainty). The second (B) investigated the difference in BMI (kg/m2) in children born after ART (n = 4297) and children born after NC (n = 37 233), and showed a slight decline in BMI of -0.16 kg/m2 (95% CI: (-0.26; -0.07), I2=87%, moderate certainty) in ART-conceived children versus NC children. The third meta-analysis (C) examined BMI (SDS) in children born after FET (n = 5146) compared with those born after fresh-ET (n = 15 709), and resulted in no difference in BMI (SDS) (mean-difference 0.08, 95% CI: (-0.02; 0.18), I2=84%) between FET and fresh-ET. Of the 32 studies included, 24 were classified as having low-quality evidence, while 8 were rated as very low quality, when combining the tools of Robins-I and GRADE. WIDER IMPLICATIONS This systematic review provides a comprehensive summary of the existing literature investigating the BMI of children born after ART compared with children conceived naturally. It adds novel and reliable information to the field by using age and sex-standardized values. The results of this systematic review and meta-analyses are reassuring. To further understand the health of the ART population, there is a need for longitudinal research on body composition among children and adults conceived through various ART methods including cryopreservation. REGISTRATION NUMBER PROSPERO CRD42021257788.