Administration of prednisolone and low molecular weight heparin in patients with repeated implantation failures: a cohort study

Abstract

Conflicting results exist for low molecular weight heparin (LMWH) and prednisolone when tested as separate adjuncts for the improvement of the clinical outcomes in patients with repeated implantation failures (RIF) undergoing IVF/ICSI treatment. Through a cohort study, we evaluated the combined effect of both drugs on pregnancy parameters in 115 women with RIF. Clinical pregnancy rate was the primary end point while the sample size was calculated through the results of a pilot study. Clinical and IVF cycle characteristics were also compared between the groups. Baseline and cycle characteristics were comparable between groups. Biochemical and clinical pregnancy rates were similar in both groups [23/57 (40.4%) vs. 14/58 (24.1%), and 17/57 (29.8%) vs. 11/58 (19%), p = .063, and .175, respectively]. Similarly, miscarriage rates were comparable between the groups (35.7% vs. 34.8%), as well as live birth rates [15/57 (26.3%) vs. 9/58 (15.5%), p = .154]. In conclusion, the administration of LMWH with prednizolone in subfertile women with RIF seems not to improve clinical pregnancy rates, but a full-scaled RCT would definitely be more accurate.

<p>In vitro Fertilization Procedures with Embryo Transfer and Their Association with Thrombophilia, Thrombosis and Early Antithrombotic Treatments</p>

“…44 On the other hand, as previously underlined, heparin has also been considered as an adjunct drug in assisted reproduction, in particular during peri-implantation, in order to increase the rate of successful pregnancies. [45][46][47] LMWHs as tinzaparin and enoxaparin may also modulate the expression of heparin binding epidermal growth factor (HB-EGF) in addition an effect on decidual and endometrial stromal cells has been reported. 48 Furthermore, heparin, similarly to heparin sulfate proteoglycans or HB-EGF, should be involved in blastocyst adhesion, invasion and proliferation.…”

Prednisolone Alters Endometrial Decidual Cells and Affects Decidual-Trophoblast Interactions

“…Overall, this study demonstrates that prednisolone alters decidualized hESF and altered decidual-trophoblast interactions. The clinical consequences of these changes are unknown, however, as all available data suggests that corticosteroid administration has no beneficial effect for IVF (Kaye et al, 2017;Mohammadi Yeganeh et al, 2018), RPL (Tang et al, 2013;Cooper et al, 2019;Woon et al, 2020), or repeated implantation failure (Siristatidis et al, 2018) and the emerging evidence that corticosteroid use during pregnancy may be associated with poor obstetrical outcomes (Boyd et al, 2015;Bandoli et al, 2017), offlabel use of corticosteroids, in particular prednisolone, during the period of decidualization (secretory phase of the menstrual cycle and the 1st trimester), should be carefully considered.…”

Prednisone for patients with recurrent implantation failure: study protocol for a double-blind, multicenter, randomized, placebo-controlled trial

“…A prospective pilot study confirmed that prednisolone was useful in patients with at least two previous IVF failures and serum antiovarian antibody [ 23 ]. However, a recent retrospective cohort study demonstrated that the administration of prednisolone with LMWH in women with RIF (two or more failed fresh IVF or ICSI cycles followed by embryo transfer) does not improve pregnancy outcomes [ 17 ].…”

“…According to the meta-analysis published in 2013, the live birth rate was estimated to be 16.1% in women with 3 or more failed embryo transfer cycles [ 16 ]. In women with 2 or more failed embryo transfer cycles, the live birth rate varied from 15.5 to 29% [ 17 – 19 ]. It is reported that the combined administration of prednisone and low molecular weight heparin or aspirin can improve live birth rate by 10.8–14% [ 17 , 20 , 21 ].…”

“…In women with 2 or more failed embryo transfer cycles, the live birth rate varied from 15.5 to 29% [ 17 – 19 ]. It is reported that the combined administration of prednisone and low molecular weight heparin or aspirin can improve live birth rate by 10.8–14% [ 17 , 20 , 21 ]. In the present study, we plan to test the primary hypothesis of a difference of 10% in the live birth rate between the two randomization arms.…”