Definition of RIF and failure of add-ons

Definition of RIF and failure of add-ons

Zion Ben Rafael MD

Founder and Co-chairmen COGI Congress

In the last 30 years an “iatrogenic invention” namely “repeated implantation failure” (RIF) was coined in patients failing 1-3 cycles or 4-10 embryos in under <40 years old patients. This definition is baseless, it is not related to the etiology of the failure, can have a different reason in every cycle, and does not include crucial information on women's age. (Ben Rafael 2020). We now know that most failures are due to the embryo’s aneuploidy which is age-dependent and cannot be mended by any measure of add-ons. So it is not surprising that after so many years and thousands of publications, none of the many add-ons were proven (ESHRE “traffic lights”). Current RIF definitions are responsible for many misleading publications and unwarranted procedures as solutions namely, add-ons. Google search for “RIF/scholar” turned over 2M results in 2020, and 3.7 M today (seriously!), mainly suggesting running tests that were probably done prior to IVF, or starting a plethora of unrelated add-ons, or unproven stimulation protocols. Obviously, publications originating from such studies are false.  ESHRE workshop quoted that in general “Much of the published medical research is apparently flawed cannot be replicated or has limited or no utility (altman1994). RIF and add-ons contribute to too many bad publications leading also to a drop in the quality of treatment and results worldwide (Gleicher)

When did add-ons originate? Most add-ons were developed in the 1990th, When LBR was frustratingly low ~6%.  So, every new idea was quickly embraced without the required proof and despite having no relationship to the etiology of failure, with the hope of increasing the success rate. But today overall LBR of all European Countries and all ages is 22.2% (ESHRE, HFEA), and the original reason for applying unproven add-on procedures vanished. Nevertheless, 74% of patients in the UK and 84% in Australia are still offered add-ons probably for financial reasons.

It was found that LBR after transfer of a single euploid embryo, in women under <35 years is about 60% per cycle and 92.6% after 3 cycles (Pirtea et al) fantastic results, which clearly indicate that no current add-ons are needed or can work since “it is all in the embryo”  and add-ons like “ERA test” (pET), “Endometrial Scratching”, “Assisted Hatching”, “freeze all” and all other adjuvant therapies, each manipulating unrelated parts of the IVF equation cannot mend an aneuploid embryo. Since we know that the rate of euploid embryos sharply drops from 55% at 35 years to 8.5% at 42 years, and accordingly, LBR drops with age from 22% at 38 years to 6% at 42, it is impossible to discuss RIF, without factoring the chances of success (which drops” with age.  

In summary, Aneuploidy is the main reason for repeated IVF failures, and no add-ons can mend it or be used except for research purposes. Add-ons are chiefly used to increase the cash stream and give the patients false hopes to prevent them from quitting after failure. True RIF is very rare, and publications based on standard RIF definitions should be reviewed with skepticism, (and rejected)