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

Huiming Yang; Haozhe Miao; Mengfei Yin; Yixuan Wang; Dingying Zhao; Min Yang; Jialin Zou; Wenwen Zhang; Lingling Zhang; Chendan Liu; Yue Wang; Ze Wang; Yunhai Yu; Daimin Wei

doi:10.1016/j.xagr.2024.100334

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

AJOG Glob Rep. 2024 Mar 13;4(2):100334. doi: 10.1016/j.xagr.2024.100334. eCollection 2024 May.

Authors

Huiming Yang^{1

2

3

4}, Haozhe Miao^{1

2

3

4}, Mengfei Yin^{1

2

3

4}, Yixuan Wang^{1

2

3

4}, Dingying Zhao^{1

2

3

4}, Min Yang^{1

2

3

4}, Jialin Zou^{1

2

3

4}, Wenwen Zhang^{1

2

3

4}, Lingling Zhang^{1

2

3

4}, Chendan Liu^{1

2

3

4}, Yue Wang^{1

2

3

4}, Ze Wang^{1

2

3}, Yunhai Yu⁵, Daimin Wei^{1

2

3

4}

Affiliations

¹ Center for Reproductive Medicine, Shandong University, Jinan, China (Drs H Yang, Miao, Yin, Yi Wang, Zhao, M Yang, Zou, W Zhang, L Zhang, Liu, Yu Wang, Z Wang, and Wei).
² Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China (Drs H Yang, Miao, Yin, Yi Wang, Zhao, M Yang, Zou, W Zhang, L Zhang, Liu, Yu Wang, Z Wang, and Wei).
³ Shandong Key Laboratory of Reproductive Medicine, Jinan, China (Drs H Yang, Miao, Yin, Yi Wang, Zhao, M Yang, Zou, W Zhang, L Zhang, Liu, Yu Wang, Z Wang, and Wei).
⁴ Medical Integration and Practice Center, Shandong University, Jinan, China (Drs H Yang, Miao, Yin, Yi Wang, Zhao, M Yang, Zou, W Zhang, L Zhang, Liu, Yu Wang, and Wei).
⁵ Department of Obstetrics and Gynecology, Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China (Dr Yu).

Abstract

Background: Frozen embryo transfer resulted in a higher birthweight and an increased risk of macrosomia than fresh embryo transfer. However, the mechanism was still unclear. When the impact of frozen embryo transfer on fetal growth began was unknown. Crown-rump length at 11-13 weeks had been regarded as a good indicator of fetal growth in the first trimester and had been used for gestational age calculation in women with uncertain last menstrual periods.

Objective: To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, then fresh embryo transfer. The secondary objective was to investigate the potential correlation between crown-rump length and birthweight.

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 between 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 birthweight and the risk of large for gestational age, small for gestational age, macrosomia, low birthweight, and premature delivery. Multivariable linear regression models were used to adjust for potential confounders of crown-rump length.

Results: A total of 6742 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±0.53 cm vs 5.57±0.48 cm, P<.001) and an increased risk of larger-than-expected crown-rump length (13.5% vs11.2%, P=.013) than 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 (regression coefficient, 3.809 [95% confidence intervals, 3.621-3.997], P<.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 and female fetuses. In addition, the crown-rump length was 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<.001) and preterm delivery (9.6% vs 6.7%, P=.004) than normal crown-rump length.

Conclusion: Frozen embryo transfer was associated with a larger crown-rump length than fresh embryo transfer, suggesting that the effect of frozen embryo transfer on fetal growth may begin in the early trimester. Suboptimal fetal growth in the first trimester may be associated with low birthweight and premature delivery.

Keywords: crown-rump length; freeze-only strategy; fresh embryo transfer; frozen-thawed embryo transfer; perinatal outcomes.