Progesterone levels on hCG trigger day and neonatal outcomes in fresh embryo transfers: a retrospective threshold analysis of GnRH antagonist versus agonist long protocols.
- 1Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Abstract
Background
Elevated progesterone levels on the day of human chorionic gonadotropin (hCG) trigger are known to adversely affect pregnancy outcomes in fresh embryo transfer (fET) cycles, but their impact on neonatal outcomes remains poorly understood. This study aimed to investigate the association between progesterone levels on hCG trigger day and neonatal outcomes, and to explore the progesterone threshold, so as to provide reference for clinical decision-making.Methods
This retrospective cohort study included 2, 201 patients who achieved singleton live births following fET between April 1, 2021 and December 31, 2024. All patients were ≤ 42 years of age and underwent either a GnRH antagonist protocol or an agonist long protocol. A multivariable regression analysis was performed to detect the relationship between progesterone level and neonatal outcomes. Smooth curve fitting and threshold effect analysis were used to evaluate the cutoff value of progesterone level.Results
In the overall population, higher progesterone levels were significantly associated with increased risks of preterm delivery (PTD) (adjusted OR: 1.89, 95% CI: 1.03 to 3.47, P = 0.0399) and low birthweight (LBW) (adjusted OR: 2.67, 95% CI: 1.14 to 6.24, P = 0.0231). These associations were observed only in the GnRH antagonist protocol, particularly with progesterone ≥ 1.0 ng/mL significantly elevating the risks of PTD (adjusted OR: 4.54, 95% CI: 2.16 to 9.56, P = 0.0021) and LBW (adjusted OR: 4.16, 95% CI: 1.15 to 15.07, P = 0.0378). Threshold analysis further identified progesterone > 0.90 ng/mL as the inflection point for PTD (adjusted OR: 6.60, 95% CI: 2.52 to 14.56, P = 0.0131) and progesterone > 0.98 ng/mL for LBW (adjusted OR: 7.50, 95% CI: 3.71 to 15.87, P = 0.0038) in antagonist cycles. No such associations were found in the GnRH agonist long protocol.Conclusions
Our findings suggest that in GnRH antagonist cycles, a serum progesterone level exceeding 0.90 ng/mL on hCG trigger day may serve as an independent predictor of an increased risk of PTD in singletons born after fET. These results highlight the need for enhanced perinatal surveillance in this population, and call for further validation in larger prospective multicenter studies.
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BibTeX
@article{wu2026progesterone,
title = {{Progesterone levels on hCG trigger day and neonatal outcomes in fresh embryo transfers: a retrospective threshold analysis of GnRH antagonist versus agonist long protocols.}},
author = {Jing Wu and Hengde Zhang and Jianlei Huang and Li Hai and Xinxin Liang and Dan Liu and Jing Zhou and Xuan Li and Yuping He and Xiaohong Wang},
journal = {Frontiers in endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1982427},
url = {https://europepmc.org/article/MED/42908548},
note = {CC BY},
}
RIS
TY - JOUR
TI - Progesterone levels on hCG trigger day and neonatal outcomes in fresh embryo transfers: a retrospective threshold analysis of GnRH antagonist versus agonist long protocols.
AU - Jing Wu
AU - Hengde Zhang
AU - Jianlei Huang
AU - Li Hai
AU - Xinxin Liang
AU - Dan Liu
AU - Jing Zhou
AU - Xuan Li
AU - Yuping He
AU - Xiaohong Wang
PY - 2026
DA - 2026/10/07
JO - Frontiers in endocrinology
DO - 10.3389/fendo.2026.1982427
UR - https://europepmc.org/article/MED/42908548
AB - Background Elevated progesterone levels on the day of human chorionic gonadotropin (hCG) trigger are known to adversely affect pregnancy outcomes in fresh embryo transfer (fET) cycles, but their impact on neonatal outcomes remains poorly understood. This study aimed to investigate the association between progesterone levels on hCG trigger day and neonatal outcomes, and to explore the progesterone threshold, so as to provide reference for clinical decision-making.Methods This retrospective cohort study included 2, 201 patients who achieved singleton live births following fET between April 1, 2021 and December 31, 2024. All patients were ≤ 42 years of age and underwent either a GnRH antagonist protocol or an agonist long protocol. A multivariable regression analysis was performed to detect the relationship between progesterone level and neonatal outcomes. Smooth curve fitting and threshold effect analysis were used to evaluate the cutoff value of progesterone level.Results In the overall population, higher progesterone levels were significantly associated with increased risks of preterm delivery (PTD) (adjusted OR: 1.89, 95% CI: 1.03 to 3.47, P = 0.0399) and low birthweight (LBW) (adjusted OR: 2.67, 95% CI: 1.14 to 6.24, P = 0.0231). These associations were observed only in the GnRH antagonist protocol, particularly with progesterone ≥ 1.0 ng/mL significantly elevating the risks of PTD (adjusted OR: 4.54, 95% CI: 2.16 to 9.56, P = 0.0021) and LBW (adjusted OR: 4.16, 95% CI: 1.15 to 15.07, P = 0.0378). Threshold analysis further identified progesterone > 0.90 ng/mL as the inflection point for PTD (adjusted OR: 6.60, 95% CI: 2.52 to 14.56, P = 0.0131) and progesterone > 0.98 ng/mL for LBW (adjusted OR: 7.50, 95% CI: 3.71 to 15.87, P = 0.0038) in antagonist cycles. No such associations were found in the GnRH agonist long protocol.Conclusions Our findings suggest that in GnRH antagonist cycles, a serum progesterone level exceeding 0.90 ng/mL on hCG trigger day may serve as an independent predictor of an increased risk of PTD in singletons born after fET. These results highlight the need for enhanced perinatal surveillance in this population, and call for further validation in larger prospective multicenter studies.
SN - 1664-2392
ER -