Prothrombotic biomarkers during controlled ovarian stimulation for assisted reproductive technology

Objective: To assess the impact of 3 different ovarian stimulation protocols on surrogate biomarkers of coagulation. Design: Observational multicenter cohort study. Setting: The study was conducted in assisted reproductive technology (ART) units. Patients: Infertile women undergoing ART in 2017-2019 were included. Interventions: None. Main Outcome Measure(s): Our primary outcome was the endogenous thrombin potential (ETP) assessed by the calibrated automated thrombogram. The ETP was measured at baseline (T1), on the day of ovulation triggering (T2), and 7 days after triggering (T3). Three protocols were prescribed according to the standards used and without hormonal before treatment: agonist protocol with human cho-rionic gonadotropin (hCG) trigger (ag-hCG), antagonist protocol with hCG trigger (atg-hCG), or GnRH agonist trigger. The evolution of ETP was compared among groups using a mixed-effects linear regression model. Result(s): Sixty-four women with a mean age of 37.8 years participated in the study: of which 24, 16, 24 received ag-hCG, atg-hCG, and GnRH agonist triggers, respectively. As expected, the mean serum estradiol levels in GnRH agonist trigger were statistically higher at T2 and lower at T3 than that for both ag-hCG and atg-hCG. Overall, the ETP evolution over time was statistically different between the groups. Values were similar between groups at T1 and increased at T2 in each group. The greatest difference occurred between T2 and T3 in each group. The ETP continued to increase at T3 in ag-hCG (+110 nM/L x min) and atg-hCG (+171 nM/L x min), but it remained stable in GnRH agonist trigger (-2 nM/L x min). Sex hormone-binding globulin showed persistent increase at T3 despite the fall in estradiol levels, particularly in the GnRH agonist trigger group. Conclusion(s): The ag-hCG and atg-hCG groups were associated with a higher hypercoagulable state at T3 than the GnRH agonist trigger group. However, our results show the persistence of a hypercoagulable state after the GnRH agonist triggering despite a sharp drop in estradiol levels. These findings may support the use of GnRH agonist trigger protocol in patients with high thrombotic risk and gives new insight into the fact that coagulation parameters could be disturbed for long time periods. Clinical Trial Registration Number: NCT04188444 (Fertil Steril (R) 2023;119:976-84. (c) 2023 by American Society for Reproductive Medicine.)