The difference in early trimester fetal growth between singletons after frozen embryo transfer and fresh embryo transfer

Background Frozen embryo transfer resulted in a higher birth weight and an increased risk of macrosomia compared with fresh embryo transfer. However, the mechanism was still unclear. When did the impact of frozen embryo transfer on fetal growth begin was unknown. Crown-rump length at 11-13 weeks had been regarded as a good indicator of fetal growth at the first trimester and had been used for gestational age calculation in women with uncertain last menstrual period. Objective To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, compared with fresh embryo transfer. The secondary objective was to investigate the potential correlation between the crown-rump length and birth weight. Study Design This was a retrospective cohort study conducted at the Reproductive Medical Center of Shandong University. A total of 4949 patients who obtained singleton pregnancy after frozen embryo transfer and 1793 patients who got singleton pregnancy after fresh embryo transfer during January 1, 2017 and December 31, 2022 were included. The primary outcome was the crown-rump length measured via ultrasound at 11-13 weeks gestation. The secondary outcomes were perinatal outcomes including birth weight and the risk of large for gestational age, small for gestational age, macrosomia, low birth weight and premature delivery. Multivariable linear regression models were used to adjust for potential confounders of crown-rump length. Results A total of 6,742 live singleton births after frozen embryo transfer or fresh embryo transfer were included in this study. In the univariable analysis, the frozen embryo transfer group had a larger crown-rump length (5.75±0.53cm vs. 5.57±0.48cm, P<0.001), and an increased risk of larger-than-expected crown-rump length (13.5% vs.11.2%, P=0.013) compared with the fresh embryo transfer group. After adjusting for confounders in multivariable linear regression models, frozen embryo transfer was still associated with a larger crown-rump length (adjusted odds ratio: 0.020, 95% confidence intervals: 0.133-0.212, P<0.001). When subgrouped by fetal gender, the crown-rump length of the frozen embryo transfer group was larger than the fresh embryo transfer group in both male fetus and female fetus. The crown-rump length was also consistently larger in the frozen embryo transfer group than the fresh embryo transfer group in subgroups of the peak estradiol levels. The comparisons among different crown-rump length groups showed that smaller-than-expected crown-rump length was associated with increased risks of small for gestational age (6.3% vs.3.0%, P<0.001) and preterm delivery (9.6% vs.6.7%, P=0.004) than normal crown-rump length. Conclusions Frozen embryo transfer was associated with a larger crown-rump length compared with fresh embryo transfer, suggesting that the effect of frozen embryo transfer on fetal growth may begin at early trimester. Suboptimal fetal growth in the first trimester may be associated with low birth weight and premature delivery.