Accuracy and efficacy of ERA test in yet another debate

Some very important issues are raised in this recently published debate on the ERA test (DOI:10.1093/hropen/hoab010) (DOI:10.1093/hropen/hoab011).

While proponents present their evidence of transcriptomic characterisation of the endometrium, along with optimization and validation of their methodology, it is not hard to see the opponents standpoint. 

First, various lists of genes dysregulated in WOI have been proposed by different groups, mainly due to different methods and complex mathematical models employed, resulting in a variety of genetic signatures around the WOI.

Then, as Next Generation Sequencing Technology (NGS) is replacing array technology fast, all previous ERA test research, including the latest RCT, may require re-evaluation of findings with the more accurate technology of NGS.

Also, as the cellular contribution to the endometrial biopsy reveals cell-specific expression signatures (separating epithelial from stromal cells), the method and depth of biopsy (ratio of cells obtained) maybe important.

Next, timing of biopsy, as proposed by identification of LH surge, or P initiation, may suffer from accurately dating the sample, as proposed by the group of Kliman and Frankfurter (DOI: 10.1016/j.fertnstert.2019.02.011)

Finally, it remains a question whether an endometrial defect, as suggested by a displaced WOI, can account for recurrent implantation failures, given that the nature of such a condition is still under scrutiny

The window of implantation lasts 30-36 hours and depending on the individual may occur between LH+6 to LH+9 in natural cycles or from P+4 to P+7 in HRT cycles. The suggestion that a 12-24 hour shift in the timing of the embryotransfer can bring about a significant modulation on the WOI and thus facilitate implantation needs to be further supported by embryo implantation basic research.`

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