Mechanical endometrial stimulation (injury) improves clinical pregnancy rate in IVF-ET cycles

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The success of in vitro fertilization and embryo transfer (IVF-ET) is contributed by a number of factors, which include the couples’ profile, uterine pathology, drug protocols, laboratory conditions, embryo quality and embryo transfer technique. 
Implantation of the embryo still remains the key factor for IVF success. For implantation to occur, a genetically normal blastocyst (day 5 embryo) should attach and invade a well-synchronized endometrium, under the influence of estrogen and progesterone hormones. 

Implantation may fail due to poor embryo quality or abnormal embryo genetics but can often fail due to poor ‘endometrial receptivity’.

Even today, repeated implantation failure despite of transfer of good-quality embryos continues to be a dilemma. The implementation of effective and simple treatment protocol for a satisfactory pregnancy rate in assisted reproduction is very important especially in the case of previous unsuccessful attempts.

Recently, a number of locally acting molecules including growth factors, cytokines, matrix metalloproteinases (MMPs), adhesion molecules, extracellular matrix components, and homeobox element containing genes, which mediate the action of the steroids hormones on the endometrium, have been discovered. (1,2)
Based on these basic physiologic findings, different investigators demonstrated a significant increase in the implantation, clinical pregnancy, and live birth rates in patients who underwent endometrial scraping in the cycle immediately preceding the IVF cycle (3-5). They proposed that the injury made on the endometrium could lead to a increased secretion of growth factors and cytokines during the process of wound healing, which could help in implantation.

In 2012, El-Toukhy (6) have also demonstrated by reviewing in an meta analysis that clinical pregnancy rate was significantly improved in IVF after local endometrial injury. 
The scientific explanation of the effect of this endometrial injury is not yet fully clear. This phenomenon could be due to the injury-induced endometrial decidualization secondary to up-regulation of genes encoding for locally acting mediators. Injury- induced decidu­alization is the most effective under progesterone (after ovulation period) influ­ence. However, whether endome­trial injury in the second phase leads to a better clinical outcome than in the first phase is unclear. 
Second mechanism might be the wound healing effect. Endometrial injury might provoke the wound healing, involving a massive secretion of different cytokines and growth factors. The other mechanisms may be endo­metrial gene modulation. Kalma et al (7). reported that the expression of 183 genes increased 2- to 10-fold and the expression of 39 genes was down regulated at least two fold in biopsy-treated patients. 
Pipelle endometrial sampling is an easy and safe outpatient procedure and can be used for this purpose. It seems a cost effective, easily applicable and efficient procedure with almost no complication risk (pain/discomfort and a minimal risk for infection) . 

With the hope of increasing the pregnancy rate, the endometrial injury technique is applied in our clinic to patients with repeated IVF failure despite good or excellent embryo quality, in whom uterine receptivity appears to be the major underlying problem. 

We charge no additional cost for this simple intervention.

References:

1. Dey SK, Lim H, Das SK, Reese J, Paria BC, Daikoku T, et al. Molecular cues to implantation. Endocr Rev 2004;25:341-73.
2. Minas V, Loutradis D, Makrigiannakis A. Factors controlling blastocyst implantation. Reprod Biomed Online 2005;10:205-16.
3. Barash A, Dekel N, Fieldust S, Segal I, Schechtman E, Granot I. Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil Steril 2003;79:1317-22.
4. Narvekar SA, Gupta N, Shetty N, Kottur A, Srinivas M, Rao KA. Does local endometrial injury in the nontransfer cycle improve the IVF-ET outcome in the subsequent cycle in patients with previous unsuccessful IVF? A randomized controlled pilot study.
J Hum Reprod Sci. 2010 Jan;3(1):15-9. 
5. Raziel A, Schachter M, Strassburger D, Berno O, Ron-El R, Friedler S. Favorable influence of local injury to the endometrium in intracytoplasmic intracytoplasmicsperm injection patients with high-order implantation failure. Fertil Steril 2007;87:198-201.
6. El-Toukhy T, Sunkara S, Khalaf Y. Local endometrial injury and IVF outcome: a systematic review and meta-analysis. Reprod Biomed Online. 2012 Oct;25(4):345-54. 
7. Kalma Y, Granot I, Gnainsky Y, Or Y, Czernobilsky B, Dekel N, et al. Endometrial biopsy-induced gene modulation: First evidence for the expression of bladder transmembranal uroplakin Ib in human endometrium. Fertil Steril 2009;91:1042-9,1049.e1-9