Immune Therapy
Bondi & Colorado Protocols
The drivers to implement new innovations into clinical practice are strong and numerous in IVF, and much of the progress made since the very early days of assisted conception has derived from the willingness of patients to try something new, and doctors to look for more information.
Specifically in relation to recurrent implantation failure, to effectively address the treatment challenges requires us to reassess the data currently available which discusses proposed treatment approaches such as Immune Therapy.
One type of immune treatment, often known in NSW as the “Bondi Protocol” and for the past 40 years around the world, as the “Colorado Protocol” (devised by Dr Bill Schoolcraft) is a regimen of medications, usually including the anticoagulant Clexane and the corticosteroid, prednisolone, taken from the start of an IVF cycle and through the first trimester of pregnancy (12 weeks gestation).
What does the research say?
In studies comparing live-birth and pregnancy rates between intervention and control groups, no significant differences were found overall. However, for couples undergoing IVF, there was a slight increase in pregnancy rates among women receiving glucocorticoid (inflammation and general h health) treatment. Further analysis showed no significant impact on miscarriage rates or on preventing ovarian hyperstimulation syndrome.
A more recent study on a combined therapy with prednisolone and low molecular weight heparin (LMWH) found higher pregnancy success rates, but the study’s design raised concerns about bias. Glucocorticoids have also been suggested as a treatment for women with autoantibodies, which are linked to implantation failure and repeated pregnancy loss.
Some studies reported increased pregnancy rates in women with these antibodies after glucocorticoid treatment. However, it’s important to note that few studies met an acceptable scientific approach as they were double-blinded or placebo-controlled, raising concerns about the reliability of the results.
Despite promising findings, the evidence supporting the use of glucocorticoids in these cases remains uncertain due to potential biases and the lack of rigorous study designs.
Overall, there is no clear evidence to support empirical use of corticosteroids during the luteal phase (the two weeks between ovulation, & egg collection, and period) in women undergoing IVF/ICSI. This does not imply that they are wholly without value, however. The challenge remains to differentiate those women who may benefit from those who will see no effect or indeed a detrimental impact of treatment.
Current research has shown no definitive link between Immune Therapy and higher pregnancy rates for women, but there have been numerous indications of some positive outcomes. According to a publication in the American Journal of Reproductive Immunology from 2022, the immune therapy protocol “may improve IVF success rates in women with evidence of immune dysfunction.”
So why undergo the treatment?
The treatment is relatively non-expensive and easily administered and monitored by an experienced fertility specialist. The protocol has been in circulation for over 40 years as developed by Dr Bill Schoolcraft, and is still classified as ‘experimental’ with no definitive research to suggest it improves success rates.
At Demeter Fertility our specialists believe there are other more effective treatment regiments that can and should be tried however are always happy to explore this medication regimen for patients who would prefer it.
The regimen is very straight forward and consists of daily injections of Clexane and prednisolone in tablet form, along with the recommended fertility medications as part of your individualised treatment plan.
If you are interested in undergoing Immune therapy you can discuss this with one of our fertility specialists during your initial consult.
Sacks G, Zhang J. Prednisolone and enoxaparin (clexane) therapy (‘the Bondi protocol’) for repeated IVF failure. Am J Reprod Immunol. 2022 Nov;88(5):e13616. doi: 10.1111/aji.13616. Epub 2022 Sep 11. PMID: 36067527; PMCID: PMC9788304
Hviid MM, Macklon N. immune modulation treatment – where is the evidence? Fertile Steril 2017:107;1284-93