Background: Experimental studies have demonstrated that thrombin and plasmin interact with a wide range of proteins that can alter the physiological processes of implantation and trophoblast development.

Aims: To determine the value of excessive thrombin generation and hypofibrinolysis in the occurrence of IVF failures and the possibility of their therapeutic correction.

Methods: A prospective randomized controlled trial was conducted in 765 patients. 25 laboratory parameters were analyzed including evaluation of thrombin generation (endogenous thrombin potential – ETP and thrombin peak) and determination of the index of fibrinolysis-activating endothelial ability (FAEA=t-PA/PAI-1)*100%. To correct the findings, nadroparin calcium and Intermittent Pneumatic Compression (IPC) were used.

Results: It was found that excessive thrombin generation in blood plasma and/or low fibrinolytic activity in the IVF cycle were observed in 78.8% of cases. The critical thresholds of these shifts associated with the risk of unsuccessful attempts of IVF cycles were calculated: ETP>1900nmol/min (OR=27.8, p=0.0001), Peak trombini>360nmol/l
(OR=22.8; p=0.0001) and the FAEA>11% (OR=11.5; p=0.003).
The algorithm of correcting the findings in the hemostatic system in women in the IVF cycle is shown in figure 1. In the groups of patients with critical thresholds of the found shifts during the treatment according to the specified algorithm at the end of the IVF program, a decrease in the ability to generate thrombin in terms of ETR and thrombin peak by 13.9% (p=0.0041) and 11.6% (p=0.0038), respectively, and an increase in fibrinolytic activity according to the FAEA index by 2.1 times (p=0.0001) were observed. Regardless of the method of therapeutic effect, the onset of pregnancy in the group of patients receiving treatment increased by 24.0% overall (Figure 2).

Conclusions: In the IVF cycle, 78.8% of cases show excessive plasma thrombin generation in blood plasma and/or low fibrinolytic activity, therapeutic correction of which increases the chance of pregnancy by 24.0% [p=0.0001; NTT:4.35, 95%CI(3.18-6.90)].

[Figure 1. The algorithm of detecting and correcting the findings in the hemostatic system in women in the IVF cycle]

[Figure 2. The proportion of successful pregnancies in IVF programs for therapeutic correction.]

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/efficiency-of-inhibition-of-thrombin-generation-and-stimulation-of-fibrinolysis-in-vitro-fertilization-programs/