Therapeutic endometrial scratching and implantation after in vitro fertilization: a multicenter randomized controlled trial

Endometrial scratching in the luteal phase preceding ovarian stimulation significantly enhances the clinical pregnancy rate in women with three or more prior implantation failures.

Like Comment

Volume 112, Issue 6, Pages 1015–1021

Authors:

Mia Steengaard Olesen, M.D., Ph.D., Benedicte Hauge, M.D.a, Lisbeth Ohrt, B.SN., Tine Nørregaard Olesen, M.D., Janne Roskær, B.SN., Vibeke Bæk, B.Sc., Helle Olesen Elbæk, M.D., Bugge Nøhr, M.D., Ph.D., Mette Nyegaard, MSc, Ph.D., Michael Toft Overgaard, Ph.D., Peter Humaidan, D.M.Sc., Axel Forman, D.M.Sc., Inge Agerholm, M.Sc., Ph.D.

Abstract:

Objective

To study whether endometrial scratching in the luteal phase before ovarian stimulation increases clinical pregnancy rates in women with one or more previous implantation failures.

Design

A nonblinded multicenter randomized clinical trial.

Setting

Fertility clinics.

Patient(s)

Three hundred four eligible patients scheduled for IVF/intracytoplasmic sperm injection were randomized. The intervention group (n = 151) underwent endometrial scratching in the luteal phase before controlled ovarian stimulation, while no intervention was performed in the control group (n = 153).

Intervention(s)

Endometrial scratching with a Pipelle de Cornier catheter in the luteal phase before ovarian stimulation.

Main Outcome Measure(s)

Clinical pregnancy rate and prenatal and birth data.

Result(s)

There was no overall significant improvement in clinical pregnancy rates between the control and intervention groups (38.5% vs. 44.4%; relative risk = 1.15; confidence interval [0.86–1.55]). However, subgroup analyses revealed that women with three or more previous implantation failures had a significant increase in clinical pregnancy rate (31.1% vs. 53.6%; relative risk = 1.72; confidence interval [1.05–2.83]) after scratching. No difference was seen as regards prenatal and birth data between the two groups.

Conclusion(s)

Endometrial scratching in the luteal phase before ovarian stimulation significantly enhances the clinical pregnancy rate in women with three or more prior implantation failures. This result seems to corroborate previous reports, which found that particularly women with repeated implantation failure seem to gain a positive effect from endometrial scratching. Importantly, there were no significant differences in prenatal data and birth data between the groups.

Clinical Trial Registration Number

NCT01963819.


Read the full text here.

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

2 Comments

Go to the profile of Samuel Santos-Ribeiro
Samuel Santos-Ribeiro 11 months ago

This is great new information adding more insight on the endometrial scratching dilemma! The investigators challenge us to consider scratching with patients who have suffered 3 or more previous failed implantation attempts based on a subgroup analysis. In the control arm, CPRs seemed relatively stable around 30% regardless of the number or previous transfers. Meanwhile, in the intervention arm, while the overall CPR was around 36%, the CPRs in the subgroup analysis had a stark variation according to whether 1, 2 or 3 previous failed implantation attempts had occurred (38%, 18% and 45%, respectively). How much of this effect is due to the intervention (especially between 1 and 2 previous failures) and how much of it is due to chance?

Go to the profile of Micah J Hill
Micah J Hill 11 months ago

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.