Abstract
IntroductionFertility treatment with frozen thawed embryo transfer (FET) is widely used. Women treated in artificial cycles (AC-FET) receive high doses of estrogen in contrast to natural cycles (NC-FET), where no estrogen is administered. Estrogen substitution may be associated with increased risk of thromboembolism. Our aim is therefore to characterize changes in blood coagulation parameters defined as surrogate thrombotic risk markers in women undergoing estrogen substitution during AC-FET. MaterialsIn our prospective cohort study, we enrolled 34 women in either: AC-FET (n = 19) or NC-FET (n = 15). Women were recruited at the Department of Obstetrics and Gynaecology, Horsens Fertility Clinic, Denmark, from August 2019 – November 2020. Blood samples were obtained at four timepoints. Thrombin generation, platelet aggregation and fibrinolysis were evaluated as thrombotic risk markers. ResultsWithin the AC-FET group, we found a significantly shorter lagtime (p < 0.05) and time to peak (TTP) (p < 0.001) after hormone substitution compared to baseline. Furthermore, a significantly higher mean peak (p < 0.0001) and larger endogenous thrombin potential (ETP) (p < 0.0001) was observed. When compared to the NC-FET group, women receiving AC-FET had a significantly shorter mean TTP (p < 0.005), higher mean peak (p < 0.0001) and larger ETP (p < 0.05). Additionally, we demonstrated a significantly prolonged lysis time within the AC-FET group (p < 0.001). ConclusionOur results indicate that women receiving AC-FET have a significantly increased thrombin generation which may increase the thromboembolic risk in women being estrogen substituted.
Highlights
Fertility treatment with frozen thawed embryo transfer (FET) is widely used
We observed that women who did not get pregnant in the artificial frozen embryo transfer cycle (AC-FET) group at sample 2, had a prolonged lagtime (3.585 ± 1.3 min versus 3.100 ± 1.4 min) (p = 0.02), larger endogenous thrombin potential (ETP) (1564 ± 382.5 nM min vs 1948 ± 478 nM min) (p < 0.01), higher peak (245 ± 46.8 nM vs 342 ± 36 nM) (p < 0.001) and shorter time to peak (TTP) (6.7 ± 1.9 min versus 5.6 ± 1.5 min) (p < 0.01)
Mean of difference in these women were calculated within the AC-FET group with lagtime − 0.375 [95% CI − 0.66 to − 0.1], ETP 340 [95% CI 247 to 433], peak 93 [95% CI 69 to 116] and ttPeak − 1.12 [95% CI − 1.64 to − 0.62]
Summary
Fertility treatment with frozen thawed embryo transfer (FET) is widely used. Women treated in artificial cycles (AC-FET) receive high doses of estrogen in contrast to natural cycles (NC-FET), where no estrogen is administered. Our aim is to characterize changes in blood coagulation parameters defined as surrogate thrombotic risk markers in women undergoing estrogen substitution during AC-FET. Results: Within the AC-FET group, we found a significantly shorter lagtime (p < 0.05) and time to peak (TTP) (p < 0.001) after hormone substitution compared to baseline. When compared to the NCFET group, women receiving AC-FET had a significantly shorter mean TTP (p < 0.005), higher mean peak (p < 0.0001) and larger ETP (p < 0.05). Conclusion: Our results indicate that women receiving AC-FET have a significantly increased thrombin generation which may increase the thromboembolic risk in women being estrogen substituted. More than 7300 women (around 50% of all IVF treatments) in Denmark undergo frozen embryo transfer (FET) each year (2019) [9]
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