Can Tweaking the Immune System Really Boost IVF Success?

This is, indeed, exactly what a French group of investigators recently suggested in a paper in Frontiers in Immunology, 1 and we wish we could believe it. Their study allegedly started with several logical first steps: They enrolled 493 between 2015 and 2023 (quite a long, drawn-out study!) in whom they obtained luteal-phase endometrial biopsies, which were used to perform what the investigators called “endometrial immune profiling.” Without going into too much detail, such profiling involved certain cytokine biomarkers. If this testing revealed an immunological endometrial “dysregulation,” these patients were randomized to standard IVF (no immune treatment) or so-called “personalized” embryo transfer they also called “precision therapy” and, as they explained, adapted to the immune abnormalities found. The primary endpoint of the study was live birth rate in a first embryo transfer.

And the claim then was that the live birth rate with precision care (41.4%) was significantly better than with standard IVF (29.7%; P =0.035), - by no means an impressive difference and especially troubling because the authors noted that the difference was especially notable in patients with morphologically poor embryos and women with 2 or more failed embryo transfers. Our interpretation of these latter associations would, indeed, be that something else but the endometrium may be the problem in these IVF cycles. How can one keep treatment protocols in IVF steady over so many years? And then on top of it, there were all of these individual so-called “precision” treatments which, of course, greatly varied but really only impressed based on their total lack of sophistication: Endometrial scratching, supplementation with hCG in the luteal phase, and advise to have sexual intercourse post-embryo transfer. What kind of “immunological precision medicine is that?

Moreover, the protocol changed halfway, basically simply giving up on randomization. And then in 2017 inclusion criteria were amended. In short, not surprising at all, given the alleged 10-year study length, this was anything but a prospectively randomized study. In short, yet another completely worthless immunological study making completely unwarranted claims about reproductive immunology. This will not help the recovery of the reproductive immunology field, and, on a sidenote, it will also not help the poor image of the Frontier journals in the scientific community. And we almost forgot, the first two authors allegedly were awarded two patents for the treatment(s) in this paper. What a crazy world we are living in, and – clearly a “WORST PAPER IN THE VOICE AWARD” from CHR.