Impact of blood hypercoagulability on in vitro fertilization outcomes: a prospective longitudinal observational study

Abstract

Background: Blood coagulation plays a crucial role in the blastocyst implantation process and its alteration may be related to in vitro fertilization (IVF) failure. We conducted a prospective observational longitudinal study in women eligible for IVF to explore the association between alterations of coagulation with the IVF outcome and to identify the biomarkers of hypercoagulability which are related with this outcome. Methods: Thirty-eight women eligible for IVF (IVF-group) and 30 healthy, age-matched women (control group) were included. In the IVF-group, blood was collected at baseline, 5-8 days after administration of gonadotropin-releasing hormone agonist (GnRH), before and two weeks after administration of human follicular stimulating hormone (FSH). Pregnancy was monitored by measurement of βHCG performed 15 days after embryo transfer. Thrombin generation (TG), minimal tissue factor-triggered whole blood thromboelastometry (ROTEM®), procoagulant phospholipid clotting time (Procoag-PPL®), thrombomodulin (TMa), tissue factor activity (TFa), factor VIII (FVIII), factor von Willebrand (FvW), D-Dimers and fibrinogen were assessed at each time point. Results: Positive IVF occurred in 15 women (40%). At baseline, the IVF-group showed significantly increased TG, TFa and TMa and significantly shorter Procoag-PPL versus the control group. After initiation of hormone treatment TG was significantly higher in the IVF-positive as compared to the IVF-negative group. At all studied points, the Procoag-PPL was significantly shorter and the levels of TFa were significantly higher in the IVF-negative group compared to the IVF-positive one. The D-Dimers were higher in the IVF negative as compared to IVF positive group. Multivariate analysis retained the Procoag-PPL and TG as predictors for the IVF outcome. Conclusions: Diagnosis of women with hypercoagulability and their stratification to risk of IVF failure using a model based on the Procoag-PPL and TG is a feasible strategy for the optimization of IVF efficiency that needs to be validated in prospective trials.

An enhanced clot growth rate before in vitro fertilization decreases the probability of pregnancy

“…Our data are consistent with a previous study by Gerotziafas et al, who showed that the procoagulant phospholipid-dependent clotting time (Procoag-PPL) and tissue factor activity (TFa) in plasma before IVF treatment indicated a hypercoagulant shift in the samples of women with unsuccessful outcomes compared with the women who became pregnant [42]. However, in their study, the results of the thrombin generation assay and TEG before the start of IVF were not associated with IVF outcomes [42].…”

“…Our data are consistent with a previous study by Gerotziafas et al, who showed that the procoagulant phospholipid-dependent clotting time (Procoag-PPL) and tissue factor activity (TFa) in plasma before IVF treatment indicated a hypercoagulant shift in the samples of women with unsuccessful outcomes compared with the women who became pregnant [42]. However, in their study, the results of the thrombin generation assay and TEG before the start of IVF were not associated with IVF outcomes [42]. In another paper by El Masry and colleagues [4], it was shown that women who had a negative outcome have a more pronounced decrease in protein C activity than women who became pregnant, which also points to the connection between the initially present procoagulant disorder and a negative IVF outcome.…”

“…The shift towards hypercoagulation following hormonal therapy has remained consistent with that shown in previous studies [12,42,46,47]. However, the timing of maximum hypercoagulation differs among the assays (the clot growth velocity is maximal on the day of oocyte retrieval; prothrombin and fibrinogen levels are maximal on the day of ET, and D-dimer levels are maximal one week after ET).…”

“…Other tests (APTT, prothrombin, and fibrinogen) before the start of therapy stayed within the normal range and did not correlate with IVF outcome. The same results for D-dimers and fibrinogen were achieved in a previous study [42]. The difference in platelet count before the start of IVF treatment between the pregnant and nonpregnant groups is an interesting phenomenon.…”

Recurrent Implantation Failure and Low Molecular Weight Heparin

“…However, the sample size was small and does not allow generalizability of results [64]. The results of this study need to be validated in larger powered studies, to optimize IVF efficiency.…”