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

Abstract

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.

Recurrent Pregnancy Loss: immunological risk factors and immunomodulatory treatments

“…There is considerable debate in the literature about whether the uterine compartment is the only meaningful compartment to examine and whether immune biomarkers in the two tissues correlate [252,[444][445][446][447]. Some authors argue that this debate makes no sense since one cannot with any certainty compare the number of different cell types in different tissue compartments analyzed by different laboratory methods [253]. Moreover, regardless of such a correlation between peripheral blood and the uterine compartment, assessing leukocytes in peripheral blood may still be useful since the immunomodulatory treatment is systemic and may affect immune cells in both tissues in a similar direction.…”

“…RPL patients represent a relatively large subgroup of patients undergoing ART and are often exposed to several diagnostic interventions and adjuvant treatments that have not proven effective. This clinical practice may be a response to emotional patients who request further examinations and interventions even without scientific evidence after numerous failed embryo transfers and/or pregnancy losses [253,450,451]. The current practice of unselective use of these tests and treatments could potentially be harmful and costly and reduce the patient's chances of a live birth, as we can only expect an effect of treatment if it acts on the pathology causing the disease.…”

“…Several other observational studies have suggested a beneficial effect of glucocorticoids in RPL patients with elevated NK cell parameters [252,253]. Therefore, NK cell parameters are widely used as biomarkers to indicate whether glucocorticoid treatment should be prescribed.…”