Impact of Local Endometrial Injury on Implantation Rates in Fresh Embryo Transfer Cycles

The application of in-vitro fertilization (IVF) has provided remarkable opportunities for infertile couple to conceive in the last four decades. Historically IVF was performed for patients with bilateral tubal obstruction, but its use is presently widespread. Although the efficacy of assisted reproductive technology continues to improve, endometrial implantation remains the limiting step towards a successful pregnancy. Reduced endometrial receptivity and embryonic defects are the probable primary causes of implantation failure during IVF(1). Patients with repeated implantation failure despite transferring good-quality embryos continue to be a major dilemma for clinicians and are a topic of great research interest. Barash et al. unintentionally discovered and initially reported that an endometrial biopsy prior to IVF in women who have had one or more implantation failures was associated with an increased clinical pregnancy (66.7% vs 30.3%, p<0.01) and live birth rates 48.9% vs 22.5%, p=0.02) compared to a control group(2). The mechanism by which a local endometrial injury (LEI) may increase the pregnancy rate is still not fully clear. Possible etiologies include its role in promoting a beneficial local inflammatory response, inducing endometrial decidualization, or improving endometrial maturation synchrony (3-6).

Following Barash et al's publication, several randomized controlled studies confirmed their findings (7-11). However, there has been extensive heterogeneity among studies, including the number of biopsies, how the biopsy is performed and the selected patient population. On the other hand all the studies have in common that the endometrial biopsy was performed prior to the start of the IVF cycle.

The optimal timing of an endometrial biopsy with respect to an IVF cycle is unknown. There is reason to suspect that an endometrial biopsy during the follicular phase of an IVF stimulation cycle may improve pregnancy outcomes, although this has not been directly examined. We therefore propose a randomized controlled study to evaluate the impact of an endometrial biopsy on the implantation and pregnancy rate in both the luteal phase prior to the IVF cycle as well as the follicular phase of the concurrent IVF cycles.