Independent factors influencing large-for-gestation birth weight in singletons born after in vitro fertilization

Abstract

Purpose Higher risk for birth of singletons being large for gestational age (LGA) has been revealed after in vitro fertilization (IVF) frozen-thawed embryo-transfer (FET). This phenomenon is now being investigated, since there is a speculation that these neonates could suffer from underlying epigenetic disturbances. The aim of the study was to expose independent LGA risk factors and to identify those connected to the IVF techniques. Methods Altogether, 4508 singleton pregnancies and births were included in the cohort case-matched study. Two hundred eleven singleton pregnancies and births after FET and 916 after fresh embryo transfer (ET) were included into two study groups. The IVF procedures were performed at the University Medical Centre Ljubljana between 2004 and 2011. For each IVF pregnancy, three matched consecutive controls after natural conception were included. Using logistic regression models, we observed LGA connection to maternal parameters (smoking, hypertension, parity, BMI, gestational diabetes, IVF conception, FET, double ET, and ICSI procedure).Results Singletons born after FET had a significantly higher risk for being LGA (p=0.032; OR 1.697; 95 % CI 1.047-2.752). BMI 25-30 was a significant independent risk factor for LGA in the IVF groups (FET p=0.041, OR 2.460, 95 % CI 1.030-5.857 and fresh ET p=0.003; OR 2.188, 95 % CI 1.297-3.691). ICSI and double ET had no significant effect on LGA occurrence. Conclusions Besides maternal BMI, FET is a significant independent LGA risk factor in IVF patients. Other observed factors (smoking, hypertension, multiparity, GDM, ICSI procedure, or number of embryos transferred) do not influence LGA risk significantly.

Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles

“…These analyses indicate that frozen embryo state [4][5][6][7][8][9][10][11][12][13] is associated with an increased risk for LGA, and blastocyst embryo stage is associated with a decreased risk for SGA. The magnitude of the increase we found in the 2nd birthweight in the fresh/frozen pairs of siblings of +222 g is in accord with prior studies (+244 g 4 in an Australian population, +250 g 10 and +286 g 6 in Danish populations), and far exceeds the +81 g attributable only to an increase in parity.…”

“…Prior studies have also consistently reported an excess of large-for-gestational age (LGA) birthweights among children born from frozen embryos; [4][5][6][7][8][9][10][11][12] longer embryo culture of fresh embryos has also been implicated as a potential cause of LGA [13].…”

Fresh and Frozen-Thawed Embryo Transfer Compared to Natural Conception: Differences in Perinatal Outcome

“…Others have shown that this syndrome is genetically similar to the Beckwith-Wiedemann's syndrome in humans, which is indeed epigenetic [47]. In recent research, it was shown that BMI is an independent risk factor for being LGA; however, the investigators were unable to show a connection between BMI and transfer of cryopreserved embryos and therefore conclude that FET is also an independent risk factor for being LGA [48]. Other possible explanations could be the ART procedures itself, embryo quality or maternal factors [11,49,50].…”

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

“…The number of FET singletons in the studies varied from 211 (Korosec, Frangez, Steblovnik, Verdenik, & Bokal, 2016) to 55.898 (Litzky et al, 2017). The studies were conducted all over the world.…”