Impact of frozen thawed embryo transfer in hormone substituted cycles on thrombotic risk markers

Abstract

Introduction: 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. 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. Materials: In 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. 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. 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). 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.

Analysis of Relevant Factors Affecting the Pregnancy Rate of Frozen-Thawed Embryo Transfer Cycle

“…The artificial cycle is a process of simulating the action of the natural ovulation cycle hormone changes on the endometrium, thereby affecting the receptivity of the endometrium. Numerous studies have favored the use of natural cycles for endometrial preparation, concerning the safety of drugs for endometrial preparation and pregnancy rates [ 5 , 6 ]. However, it is worth noting that the artificial cycle can choose the best time for embryo transfer, with a low cancellation rate.…”

Clinical pregnancy rate for frozen embryo transfer with HRT: a randomized controlled pilot study comparing 1 week versus 2 weeks of oestradiol priming

“…The wider implications of such a study are the TTP reduction which could reduce the costs but also increased patient comfort and acceptance when choosing FET over fresh ET (Stormlund et al, 2019), and the safety. In fact, even in terms of safety, a shorter duration of E2 supplementation could provide an advantage relating to the possible reduced risk of thrombotic and hypertensive disorders associated with the FET-HRT protocol (Dalsgaard et al, 2022).…”

“…A relationship between the duration of oestrogen priming of the endometrium and the increased occurrence of hypertensive disorders was suggested by Roque et al 2019 (Roque et al, 2019), while Shi et al 2018 (Shi et al, 2018) found no differences in the occurrence of hypertensive disorders between eFET and fresh ET when eFET was performed in a natural cycle. On the other hand, oestrogen stimulation in FET-HRT activates thrombotic risk markers and a restriction in the use of unnecessary hormone exposure is important, as described recently by Dalsgaard et al, (2022). Moreover, still cycle cancellation due to spontaneous ovulation is an uncontrollable phenomenon that can always occur, especially when the oestrogen preparation takes long time, therefore the rationale for a shorter time to oestrogen exposure could potentially lead to less spontaneous ovulations and easier programming of the FET cycle.…”