Yunzhu Lan,1,* Shuang Liu,2,* Emmanuel Osei Nkansah,1 Fang Wang,2 Shaowei Chen,2 Jun Zhang,3 Lan Yuan,4 Jian Xu1 

1Department of Obstetrics and Gynecology, Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of China; 2Department of Reproduction, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Medical Cell Biology and Genetics, School of Basic Medical Sciences, Institute of Cardiovascular Research Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jian Xu, department of Obstetrics and Gynecology, Center for Reproductive Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of China, Email xuj@zju.edu.cn

Objective: To propose a prediction model aimed at increasing the live birth rate of patients undergoing two-cell embryo transfer while eliminating multiple pregnancy complications.
Methods: Women who underwent their first In Vitro Fertilization (IVF) cycle with transferred cleavage-stage embryos at the Affiliated Hospital of Southwest Medical University between January 2016 and December 2024 were included. This study recruited women who received the GnRH agonist long protocol (GnRH-a) or antagonist protocol (GnRH-ant) for ovarian stimulation. In addition, the clinical parameters related to the basic protocol and embryo characteristics were recorded.
Result(s): In the multivariate analysis, we found that female age, endometrial thickness on the Human Chorionic Gonadotropin (HCG) days, patients with Body Mass Index (BMI) > 30, high-quality embryos with 4 cells between 1 and 4 pieces, high-quality embryos with 8 cells, available embryos between 5 and 15 pieces and high-quality embryos between 1 and 4 pieces were crucial factors in the twin pregnancies prediction model (p < 0.05). On the basis of these characteristics, we constructed a nomogram for twin pregnancies. Additionally, we compared the difference between premature and normal births and found that endometrial thickness on HCG days positively correlated with the model score. In the premature group, the endometrial thickness on HCG days was lower than that found in patients without premature births.
Conclusion: Endometrial thickness on the HCG day may influence the outcome of twin pregnancies. The high-quality embryos showed a higher positive correlation with the model score. Patients with preterm birth had less endometrial thickness on the HCG day than patients without premature birth. For patients with high-quality embryos, it is advisable to use single embryo transfer to reduce the rate of twin pregnancies. This nomogram will enhance the counseling of patients with infertility challenges.
Plain Language Summary: A. Multiple pregnancy complications, including preterm births and birth defects associated with assisted reproductive technologies, have shown an increasing trend, mainly due to ovarian stimulation. Therefore, research on the formulation of pregnancy outcome prediction models is necessary to serve as a potential personalized protocol for controlled ovarian stimulation.
B. The study outcome suggests that endometrial thickness on the HCG day is a clinical factor that may increase the rate of multiple pregnancy complications; thus, the lower the endometrial thickness on the HCG day, the higher the risk of preterm birth.
C. We sought to propose a prediction model to achieve a high live birth rate in patients undergoing two cleavage-stage embryos transfer, while eliminating twin pregnancies. This study reports, for the first time, a nomogram that can be used to predict pregnancy outcomes with the clinical characteristics of patients whose first IVF cycles were performed with two cleavage-stage embryos.

Keywords: endometrial thickness, twin pregnancies, cleavage embryos, nomogram model, preterm birth