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Background  Assisted reproductive technology (ART) has been associated with low birth weight of fresh embryo transfer (FRESH) derived and increased birth weight of frozen embryo transfer (FET)-derived newborns. Owing to that, we focused on imprinted insulin-like growth factor 2 ( IGF2 )/ H19  locus known to be important for normal growth. This locus is regulated by  H19  imprinting control region (ICR) with seven binding sites for the methylation-sensitive zinc finger regulatory protein (CTCF). A polymorphism rs10732516 G/A in the sixth binding site for CTCF, associates with a genotype-specific trend to the DNA methylation. Due to this association, 62 couples with singleton pregnancies derived from FRESH (44 IVF/18 ICSI), 24 couples from FET (15 IVF/9 ICSI), and 157 couples with spontaneously conceived pregnancies as controls were recruited in Finland and Estonia for genotype-specific examination. DNA methylation levels at the  H19  ICR,  H19  DMR, and long interspersed nuclear elements in placental tissue were explored by MassARRAY EpiTYPER ( n  = 122). Allele-specific changes in the methylation level of  H19  ICR in placental tissue ( n  = 26) and white blood cells (WBC,  n  = 8) were examined by bisulfite sequencing. Newborns’ ( n  = 243) anthropometrics was analyzed by using international growth standards.    Results  A consistent trend of genotype-specific decreased methylation level was observed in paternal allele of rs10732516 paternal A/maternal G genotype, but not in paternal G/maternal A genotype, at  H19  ICR in ART placentas. This hypomethylation was not detected in WBCs. Also genotype-specific differences in FRESH-derived newborns’ birth weight and head circumference were observed ( P  = 0.04,  P  = 0.004, respectively): FRESH-derived newborns with G/G genotype were heavier ( P  = 0.04) and had larger head circumference ( P  = 0.002) compared to newborns with A/A genotype. Also, the placental weight and birth weight of controls, FRESH- and FET-derived newborns differed significantly in rs10732516 A/A genotype ( P  = 0.024,  P  = 0.006, respectively): the placentas and newborns of FET-derived pregnancies were heavier compared to FRESH-derived pregnancies ( P  = 0.02,  P  = 0.004, respectively).    Conclusions  The observed DNA methylation changes together with the phenotypic findings suggest that rs10732516 polymorphism associates with the effects of ART in a parent-of-origin manner. Therefore, this polymorphism should be considered when the effects of environmental factors on embryonic development are studied.    Electronic supplementary material  The online version of this article (10.1186/s13148-018-0511-2) contains supplementary material, which is available to authorized users.

clinical epigenetics

rs10732516 polymorphism at the IGF2/H19 locus associates with genotype-specific effects on placental DNA methylation and birth weight of newborns conceived by assisted reproductive technology