Yuan Yan,1– 3,* Jingwen Jiang,1– 4,* Jie Mei,1– 3,* Xiaoyue Shen,1– 3 Yue Jiang,1– 3 Jun Xing,1– 3 Chenyang Huang1– 3 

1Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 2Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 3Center for Molecular Reproductive Medicine, Nanjing University, Nanjing, 210008, People’s Republic of China; 4State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, 210008, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jun Xing, Email xing.jun@msn.com Chenyang Huang, Email dianshui19901562@126.com

Background: The relevance of oestrogen (E2) levels on human chorionic gonadotropin (hCG) trigger day and clinical pregnancy outcomes was unclear. This study aimed to investigate whether E2 levels on the hCG trigger day affect pregnancy outcome in long-acting gonadotropin releasing hormone agonist (GnRHa) down-regulated in-vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles.
Methods: This is a retrospective study including 6967 patients undergoing their first long-acting GnRHa down-regulated IVF/ICSI-ET cycles at the Reproductive Medicine Centre of Nanjing Drum Tower Hospital from January 2016 to December 2021. Smooth curve fit analyses were conducted to identify the relationship between serum E2 levels and the clinical pregnancy rate (CPR), along with the live birth rate (LBR). Threshold effect analyses were conducted to figure out potential cut-off values. Further investigation was also carried out for different types of embryos.
Results: Both CPR and LBR declined as the serum E2 levels on the hCG day elevated. CPR reduced significantly when the serum E2 levels exceeded 5000 pg/mL. While considering the influence of different types of transferred embryos, the blastocyst transfer was more vulnerable to the elevation of serum E2 levels than cleavage-stage embryos, and CPR of blastocyst transfer decreased obviously when serum E2 levels were equal to or greater than 5000 pg/mL. Meanwhile, a higher E2 level leads to a higher incidence of moderate or severe ovarian hyperstimulation syndrome (OHSS).
Conclusion: The CPR decreased significantly as E2 levels increased with serum E level higher than 5000 pg/mL on the hCG day, which was more obvious in blastocyst transfer than cleavage-stage embryo transfer. In addition, the incidence of moderate-to-severe OHSS also significantly increased. Therefore, the whole embryo freezing might be a better choice in patients undergoing long-acting GnRHa down-regulated IVF/ICSI cycles with higher serum E2 level on the hCG trigger day instead of embryo transfer.

Keywords: oestrogen level, hCG trigger day, clinical pregnancy rate, long-acting GnRHa, blastocyst transfer, OHSS