Dr. Scoccia, thank you for your commentary on our recent meta-analysis as well as the review of one we published several years ago. Your summary of the literature was spot on and I think you precisely highlight the areas where the is insufficient literature to make conclusions on follicle flushing: namely natural cycle and minimal stimulation IVF. Thank you for an excellent commentary!
Authors, we had a question from a reader yesterday, that somehow dropped off the site. They were wondering if you could post the full 18 questions here that you gave to patients?
I appreciate the rapid guidance from ASRM last week and the much more in depth followup this week. Our clinic, by policy, follows these guidances as policy. Having such thoughtful and informed guidance, from the experts and leaders in our field, is invaluable.
Thank you for this thoughtful reflection of the history and relevance of the progestin challenge test. Twenty years from now, many of the tests we employ today will also become historic relics. It is great to see an article both acknowledging the important of a test and its modern clinical irrelevance. This is progress. Understanding the endocrine principals that underpin a test is still important to our fellows, even if the test itself no longer has clinical utility.
Kudos to Dr. Speroff for shaping our specialty and to those who take the torch for the next generation.
Very interesting discussion on the ethics and regulation of add-ons in IVF. Since the birth of the new field of assisted reproduction, the rapid progress and evolution would not have been possible if every innovation had been subjected to a rigorous approval process - nobody could provide a guarantee that interventions that revolutionized the field (IVF / ICSI / donor egg-based treatments etc etc etc) would be completely "safe" and without harm before doing them.
So it appears that progress in our field occurs via a combination of adopting promising new interventions while being prudent and following the "do no harm" principle as much as possible. Regarding add-ons, this means being open to adjunct treatments that may actually improve outcomes, while ensuring that no harm to the patient or the unborn baby is done, and while not making false promises.
Therefore the most important paragraph of this article appears to be "Informed consent when effectiveness is questionable". Prescribing androgens or growth hormone to a "poor responder" seems reasonable to me based on the available evidence - see review article on adjuncts in the same issue- as long as the patient is informed that these treatments are "off-label", still under investigation, and not proven to be beneficial beyond a shadow of a doubt (but showing promise in some studies).
I agree with your point Alex. From my perspective, the problem is that as a field we tend to be very fast adopters. "Add ons" tend to become standards in our clinic, before the evidence supports their wide usage. And some clinics use add ons as marketing and patient recruiting strategies. As clinicians, its a challenge to appropriately counsel the individual patient in front of us, when they request these interventions or ask for "anything else that can be done". As a specialty however, I think we are guilty of broadly adding interventions before the evidence supports their use.
I want to echo Samuel's comment. How much of this may be due to chance?
The primary outcome showed no difference. There was no benefit to scratching in the RCT.
The authors then looked at subgroups according to 1, 2, or 3 prior implantation failures. They looked at outcomes of CPR, OPR, LBR, SAB, and implantation. This was done in both ITT and PP analyses. This resulted in 27 subgroup comparisons. There was no control for multiple comparisons. These comparisons were post hoc, and not in the trial registry.
The results of these analyses showed an increase in CPR in patients with 3 or more prior failures (P=0.046). However this same subgroup did not show an improvement in LBR (P=0.069).
It is interesting how we might chose to interpret these findings. In this case, the authors chose to make this positive CPR increase in patients with 3 or more failures the only finding in the abstract conclusion. The primary tested finding was not even mentioned in the conclusions.
My interpretation would be much more cautious. The primary hypothesis that was tested demonstrated no benefit to scratching. This should be the main conclusion of the abstract.
The secondary findings have to be interpreted with caution due to several points:
1. post hoc, not registered finding.
2. findings of 1 of 27 subgroup analyses, which is emphasized over the other null findings and the primary finding
3. no adjustment for multiple subgroup comparisons
4. while there was statistical improvements in CPR, there was no statistical improvement in LBR, the more important outcome. So why is CPR emphasized?
We all interpret results through different lenses. My own interpretation of this data is that it offers no support to the practice of endometrial scratch, even in women with 3 or more failures.
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Micah J Hill
Interactive Associate in Chief, Fertility and Sterility
David, thank you for the thoughtful insight on two distinct but linked developments. The behind the scenes knowledge of the intertwined timing is so interesting. This entire edition is so fascinating to read!