The Influence Of Serum Progesterone Level In Late Follicular Stage On The Outcome Of Fresh Cycle Assisted Pregnancy With Antagonist Regimen And Threshold Effect Analysis

ObjectiveAnalyze the impact of progesterone（P）levels in late follicular phase on the outcomes of assisted reproduction treatments after fresh embryo transfer in patients with normal ovarian response during controlled ovarian stimulation（COS）using gonadotropin releasing hormone antagonist（Gn RH-ant）,and to explore the related factors that may lead to progesterone elevation in late follicular phase during COS using antagonist in patients with normal ovarian response.MethodsRetrospectively analysis of clinical data of ovarian normal response patients who received the first in vitro fertilization/intracytoplasmic sperm injection embryo transfer（IVF/ICSI-ET）treatment in the antagonist protocol for ovulation promotion at our reproductive center from January 2016 to December2021,a total of 2467 cycles were enrolled.Divide human chorionic gonadotropin（h CG）daily P into six subgroups:<0.5 ng/m L（Group A）,0.5～<0.75 ng/m L（Group B）,0.75～<1.0 ng/m L（Group C）,1.0～<1.25ng/m L（Group D）,1.25～<1.5 ng/m L（Group E）,and≥1.5 ng/m L（Group F）,and compare clinical parameters and assisted outcomes among each subgroup,exploring the impact of late follicular phase progesterone levels on assisted reproduction treatments outcomes after fresh embryo transfer cycle in patients with normal ovarian response through univariate analysis,categorical multivariate Logistic regression analysis,curve fitting,and threshold effect analysis,find the threshold value for increased progesterone levels.Finally,a categorical multivariate Logistic regression analysis was used to investigate the relevant influencing factors of late follicular phase progesterone elevation during the COS process with antagonist in patients with normal ovarian response.ResultsA total of 2467 cycles were enrolled,of which 1290 cycles were clinically pregnant,with a clinical pregnancy rate of 52.29%and a live birth rate of 42.8%.Comparing the clinical parameters and pregnancy outcomes of different P levels on the day of h CG,the results showed significant differences in body mass index（BMI）and basal follicle stimulating hormone（FSH）among the baseline data of the six groups of patients（P<0.05）.As the daily P of h CG increased,the clinical pregnancy rate and live birth rate gradually decreased.The clinical pregnancy rates of Group A（54.87%）and Group B（53.53%）were significantly higher than those of Group E（41.67%）and Group F（36.84%）,while the clinical pregnancy rates of Group C（50.51%）were significantly higher than those of Group F（36.84%）,with statistical significance（P<0.05）;The live birth rates of Group A（45.22%）and Group B（43.99%）were significantly higher than those of Group E（31.67%）and Group F（28.94%）,while the live birth rates of Group C（41.28%）were significantly higher than those of Group F（28.94%）,with a statistically significant difference（P<0.05）.After adjusting for confounding factors,multivariate Logistic regression analysis showed that h CG daily P was an independent factor significantly affecting the clinical pregnancy rate（OR=0.61,95%CI0.48～0.77,P<0.001）and live birth rate（OR=0.63,95%CI 0.50～0.81,P<0.001）in fresh embryo transfer cycles.Threshold value effect analysis showed that when h CG daily P≥1.26 ng/m L,the clinical pregnancy rate and live birth rate significantly decreased with the increase of h CG daily P for every 0.1 ng/m L increase in h CG daily P level in the fresh embryo transfer cycle,the clinical pregnancy rate decreased by8.8%（OR=0.12,95%CI 0.03～0.54,P=0.006）,and the live birth rate decreased by 9.1%（OR=0.09,95%CI0.02～0.50,P=0.006）.After adjusting for confounding factors,multivariate Logistic regression analysis showed that Gn initiation dose,total number of Gn days,total Gn amount,E₂ on h CG day,and number of≥14mm follicles on h CG day were all positively correlated with elevated progesterone levels（P<0.05）.Conclusions1.The elevation of late follicular phase progesterone in the antagonist protocol for patients with normal ovarian response is an independent risk factor that affects the clinical pregnancy rate and live birth rate in the fresh embryo transfer cycle.When the late follicular progesterone in the fresh embryo transfer cycle is≥1.26ng/m L,the clinical pregnancy rate and live birth rate are significantly reduced,fresh embryo transfer should be cautious,and when it is≥1.5ng/m L,it is recommended to freeze all.2.Gn initiation dose,total Gn days,total Gn dose,E₂ level on h CG day,and number of follicles≥14mm on h CG day are related influencing factors for the elevation of progesterone levels in late follicular phase of patients with normal ovarian response in the antagonist protocol.