Large for gestational age and macrosomia in singletons born after frozen/thawed embryo transfer (FET) in assisted reproductive technology (ART)

Abstract

Increase in success rates with frozen embryo transfer (FET) and reduced risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies has lead to a steady rise in FET. Further, FET is associated with lower risk of prematurity and low birth weight in singletons, when compared with fresh transfer. However, there is a growing concern of increased risk of large for gestational (LGA) and/or macrosomic children after FET. Macrosomic/LGA births have a higher risk of cesarean section, fetal hypoxia and stillbirth. Improvements in cryopreservation techniques indicate that FET is a trend expected to continue and a freeze-all policy has lately been introduced. With this review, we wished to evaluate the association between FET and LGA and/or macrosomia. We searched electronic databases on January 12, 2018. Ten studies on LGA and six studies on macrosomia were eligible for meta-analysis. We found that the risk of LGA in FET was increased 1.5-fold (AOR = 1.50 95% CI 1.44-1.57 p < 0.001) compared to fresh cycles and 1.3-fold (AOR = 1.31 95% CI 1.20-1.43 p < 0.001) compared to natural conception (NC). Similarly we found a 1.7-fold increased risk of macrosomia in FET compared to fresh transfer (AOR = 1.71 95% CI 1.59-1.83 p < 0.001) and a 1.4-fold increased risk compared to NC (AOR = 1.42 95% CI 1.17-1.71 p < 0.001). Whether the increased risk of LGA and macrosomia is associated with higher long-term health risks remains unknown. Future studies should explore epigenetics modifications in children born after FET and predictors of long-term diseases need to be examined further with longitudinal studies.

Is Embryo Cryopreservation Causing Macrosomia—and What Else?

“…Luke et al (27) found that in siblings sharing the same mother, children born after FET had a higher risk of LGA than their siblings born after fresh ET (27). Berntsen and Pinborg (28) evaluated the association between FET and LGA and/or macrosomia. Their meta-analysis, consisting of 10 studies on LGA and 6 on macrosomia has revealed that the risk of LGA in FET was increased 1.5-fold and 1.3-fold compared to fresh cycles and NC, respectively.…”

Air‐liquid interface cell culture: From airway epithelium to the female reproductive tract

“…Even if assisted reproductive technologies (ARTs) are successful in many species, in vitro embryos differ from their in vivo derived counterparts in terms of their cryotolerance, lipid content and developmental competence (reviewed in Rizos et al, 2008). Furthermore, epidemiological human studies have shown altered birthweight profiles in ART compared with spontaneously conceived singletons (Berntsen & Pinborg, 2018;Hunter, 2017). While conception with cryopreserved embryos resulted in a higher risk of large-for-gestational-age babies, conception with fresh embryos had a higher risk for small-for-gestational-age babies (Berntsen & Pinborg, 2018;Hunter, 2017).…”

“…Furthermore, epidemiological human studies have shown altered birthweight profiles in ART compared with spontaneously conceived singletons (Berntsen & Pinborg, 2018;Hunter, 2017). While conception with cryopreserved embryos resulted in a higher risk of large-for-gestational-age babies, conception with fresh embryos had a higher risk for small-for-gestational-age babies (Berntsen & Pinborg, 2018;Hunter, 2017). Further animal studies in offspring conceived via ART found altered gene expression profiles related to glucose metabolism.…”

Reproductive and perinatal outcomes of a frozen embryo transfer in the programs of assisted reproductive technologies(literature review)

“…Результаты метаанализа показали существенную разницу в частоте LGA после FET и переноса свежих эмбрионов (ОШ 1,50; 95% ДИ 1,44-1,57; p<0,001), а также после FET и NC (ОШ 1,31; 95% ДИ 1,20-1,43; р<0,001). Установлены и различия в частоте развития макросомии плода после FET и переноса свежих эмбрионов (ОШ 1,71; 95% ДИ 1,59-1,83; p<0,001), а также после FET и NC (ОШ 1,42; 95% ДИ 1,17-1,71; p<0,001) соответственно [36].…”