Relation of graphical follicle models to the cumulative live birth rate in GnRH-antagonist stimulation treatment cycles
Authors: Yang Jingwei , Liu Xiaojie , Ye Hong , Li Fujie , Zhang Lihong , Huang Guoning , Zhang Xiaodong 
Published: August 2022

Abstract
Background: Previous studies have observed the number and size of follicles are two independent indicators of whether the oocyte is adequate and mature and are used to predict the trigger time in routine clinical practice. However, due to individualized differences, it currently relies mainly on physician experience. It is necesaary to explore an innovative, simple, and graphical model for predicting clinical results in ovary stimulation treatment and facilitating personalized protocol adjustment.Methods: This retrospective study included 8405 patients who started their first in vitro fertilization cycle with a GnRH-ant protocol including fresh and subsequent frozen-thawed cycles during 2016-2020. Using follicle size and number, we classified follicles recorded on the human chorionic gonadotropin (HCG) day by size (small, medium, large). Producing graphical models, and classified into Inverted-trapezoid (large follicles in dominant proportion), Polygon (moderate follicles in dominant proportion), Trapezoid (small follicles in dominant proportion), and Rectangle (equivalent proportions of the three size categories). The Cochran-Mantel-Haenszel (CMH) and Generalized Linear Model(GLM) were used to evaluate the difference among models about maturity, fertilization, and the number of viable embryos, as well as cumulative live birth rate(CLBR).Results: In GLM analysis, after adjusting the confounders, there are differences between models of CLBR. The CLBR of the different models was higher in the Polygon and Inverted-trapezoid model than Trapezoid and Rectangle model (42.75%, 39.56%, vs. 37.38%, 28.57%, respectively; all P<0.05). For oocytes derived from very large follicles (>20 mm), the CLBR was lower than that of patients with ≤20 mm follicles [26.10% vs. 42.10%, OR = 1.74 (95% confidence interval 1.52–2.00), P<0.01] in Inverted-trapezoid model, but there was no difference between models.And the risk of ovarian hyperstimulation syndrome (OHSS) rate of patients with ≤20 mm follicles was lower than that of patients with >20 mm follicles [8.64% vs. 17.89%, OR = 0.57 (95%CI: 0.49-0.65), P<0.01] in Inverted-trapezoid model. Patients who received an adjusted Gn dose(whether Decreased or Increased-dose protocol) showed no difference in CLBR among models (Polygon vs Inverted-trapezoid vs Trapezoid vs Rectangle model: 47.07% vs. 49.21% vs. 47.69% vs. 42.42%, P>0.05); but when patients continued with the same starting dose in Fixed-dose protocol, the CLBR of the Polygon model was higher than that of other models (40.43% vs. 34.32, 31.13% vs. 26.46%, respectively; all P value <0.05).Conclusion：Our results suggested the follicle models can demonstrate characteristics and the ovarian response of patients. In addition to the patients in very good condition who develop a Polygon model, it is better for other patients to reach the Inverted-trapezoid model with follicles >18 mm and <20 mm. Adjusting the protocol is critical to the outcome. But determining how to improve follicle models by regulating stimulation remains to be further studied.