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

Lu, Yao; Yan, Junhao; Liu, Jiayin; Tan, Jichun; Hong, Yan; Wei, Daimin; Chen, Zi‐Jiang; Sun, Yun

doi:10.1186/s13063-020-04630-6

Cited by 12 publications

(9 citation statements)

References 23 publications

(26 reference statements)

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“…Several studies indicate that prednisone may be highly beneficial in treating patients with RIF [ 20 ]. A 2020 study found that prednisone can affect pregnancy outcomes in patients with RIF [ 21 ]. The in vitro studies reveal that progesterone may inhibit TNF-α-induced apoptosis [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

In silico evidence for prednisone and progesterone efficacy in recurrent implantation failure treatment

et al. 2022

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Increased expression and activation of tumor necrosis factor-α (TNF-α) could lead to recurrent implantation failure (RIF). Therefore, TNF-α inhibition may be a strategic way to enhance the implantation rate in women with RIF. Nowadays, monoclonal antibodies are considered an effective therapeutic method for TNF-α inhibition. Unfortunately, monoclonal antibody treatments have several disadvantages. Thus, the design of small molecules capable of inhibiting TNF-α has become critical in recent years. In silico drug repurposing of FDA-approved drugs for TNF-α inhibition was used in this study. PyRx tools were employed for virtual screening. Additionally, the free energy of binding, the number of hydrogen bonds, and the number of drug contacts with the protein were calculated using the molecular dynamics (MD) simulation method. Virtual screening results reveal that 17 of 2471 FDA-approved drugs benefited from favorable binding energy with TNF-α (delta G < − 10 kcal/mol). Two of the 17 drugs, progesterone and prednisone, were the most frequently used without adverse effects during pregnancy. As a result, MD simulation was used to investigate these two drugs further. According to the MD simulation results, prednisone appears to have a higher affinity for TNF-α than progesterone, and consequently, the prednisone complex stability is higher. For the first time, this study examined the possible role of prednisone and progesterone in inhibiting TNF-α using in silico methods. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00894-022-05093-z.

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Section: Discussionmentioning

confidence: 99%

In silico evidence for prednisone and progesterone efficacy in recurrent implantation failure treatment

et al. 2022

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“…Other treatment hypotheses might be valid and some RCTs are ongoing in order to test them. In this context, of particular relevance is the study protocol published by Lu et al 179 . Authors aim to determine if prednisone can enhance live birth in women with RIF undergoing IVF.…”

Section: Discussionmentioning

confidence: 99%

“…Authors aim to determine if prednisone can enhance live birth in women with RIF undergoing IVF. Interestingly, studies have shown that prednisone could not only suppress the inflammatory response in pre-implantation endometrium, but also stimulate the secretion of hCG and promote proliferation and invasion of trophoblast 179 . The efficacy of ad hoc treatments in women with known diseases and RIF also deserves to be clarified.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of therapies and interventions for repeated embryo implantation failure: a systematic review and meta-analysis

Busnelli

Somigliana

Cirillo

et al. 2021

Sci Rep

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The aim of the present systematic review and meta-analysis was to assess the effect of the different therapeutic options for repeated embryo implantation failure (RIF) on a subsequent IVF cycle outcome. Twenty-two RCTs and nineteen observational studies were included. Pooling of results showed a beneficial effect of intrauterine PBMC infusion on both CPR (RR 2.18; 95% CI 1.58–3.00; p < 0.00001; OR 2.03; 95% CI 1.22–3.36; p = 0.006) and LBR (RR 2.41; 95% CI 1.40–4.16; p = 0.002; OR 3.73; 95% CI 1.13–12.29; p = 0.03), of subcutaneous G-CSF administration on CPR (RR 2.29; 95% CI 1.58–3.31; p < 0.0001) and of intrauterine PRP infusion on CPR (RR 2.45; 95% CI 1.55–3.86; p = 0.0001). Observational studies also demonstrated a positive effect of IVIG and intrauterine hCG infusion on both CPR and LBR and of atosiban on CPR. Studies investigating intrauterine G-CSF infusion, LMWH, intravenous intralipid, hysteroscopy, blastocyst-stage ET, ZIFT, PGT-A and AH failed to observe an impact on IVF outcome. The quality of the evidence that emerged from RCTs focused on intrauterine PBMC infusion and subcutaneous G-CSF administration was moderate. For all other therapies/interventions it varied from low to very low. In conclusion, intrauterine PBMC infusion and subcutaneous G-CSF administration are the most promising therapeutic options for RIF. However, further well conducted RCTs are necessary before their introduction into clinical practice.

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“…The clinical pregnancy rate in the prednisolone group was significantly higher (48.3% vs. 29.6%), although livebirth rates were not reported. Another randomised trial of prednisolone in women with RIF has been registered and results are awaited 60 …”

Section: Discussionmentioning

confidence: 99%

“…Another randomised trial of prednisolone in women with RIF has been registered and results are awaited. 60 Immune therapy in reproductive medicine has a long history of excessive claims to be 'the answer' and equally excessive counter claims that it is 'useless' . The reality is that it is, at best, just one possible factor out of many that influence the outcome of IVF.…”

Section: Discussionmentioning

confidence: 99%

Prednisolone and enoxaparin (clexane) therapy (‘the Bondi protocol’) for repeated IVF failure

Sacks

Zhang

2022

American J Rep Immunol

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Problem: What is the impact of an empirical immune therapy protocol of prednisolone and enoxaparin (clexane) (the 'Bondi protocol') on women with repeated in vitro fertilization (IVF) failure? Method of study: This was a retrospective review of live birth outcomes conducted on all transfer cycles performed by a single clinician (GS) at IVFAustralia between February 2016 and April 2020. This study consisted of 1786 transfer cycles, including 460 cycles treated with the Bondi protocol and 1326 without. Women with repeated IVF failure were given the Bondi protocol based on blood NK cell activity. Primary outcome was live birth and statistical analysis was performed with GraphPad Prism software with significance for P-values < .05.Results: Overall 'Bondi' and 'normal' protocol cycles had similar rates of IVF/ICSI, fresh/frozen transfers and use of preimplantation genetic testing (PGT). Women given the Bondi protocol were older, had more previous cycles and had higher blood NK cell activity. There was no significant difference in live birth rates (Bondi 26%, normal 28%).Bondi protocol live birth rates per transfer cycle were as high as 40% in patients under 38 years old. The Bondi protocol was more effective as NK activity increased from 'normal' to 'borderline' to 'high' . For high NK cell activity levels, live birth rates were over four times higher for women on the Bondi protocol (28%) than those on normal protocols (6%, P = .0007). Conclusion:This study describes a simple and relatively safe immune therapy protocol that may improve IVF success rates in women with evidence of immune dysfunction.

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

Cited by 12 publications

References 23 publications

In silico evidence for prednisone and progesterone efficacy in recurrent implantation failure treatment

In silico evidence for prednisone and progesterone efficacy in recurrent implantation failure treatment

Efficacy of therapies and interventions for repeated embryo implantation failure: a systematic review and meta-analysis

Prednisolone and enoxaparin (clexane) therapy (‘the Bondi protocol’) for repeated IVF failure

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