The Impact of Endometrial Manipulation on IVF Success

Peter Kovacs, MD, PhD


September 13, 2017

The Effect of Endometrial Scratch on Natural-Cycle Cryopreserved Embryo Transfer Outcomes: A Randomized Controlled Study

Mak JS, Chung CH, Chung JP, et al
Reprod Biomed Online. 2017;35:28-36


Two recent studies evaluated the evidence behind multiple add-on therapies offered during in vitro fertilization (IVF).[1,2] Both concluded that most of these interventions lack proper scientific support. IVF success rates are relatively low despite improvements in stimulation protocols and laboratory technology over the past two decades.[3]

Successful implantation requires complex cross-talk between the euploid blastocyst and the receptive endometrium.[4] Testing endometrial receptivity has been the topic of recent research.[5]

In 2003, Barash and colleagues[6] showed that multiple endometrial biopsies performed in the cycle preceding the IVF treatment improved pregnancy and live birth rates among women with recurrent implantation failure (RIF). Since then, several groups have reported similar positive results. Others, however, failed to observe a benefit with endometrial manipulation.[7,8]

The inclusion of heterogeneous patient populations, use of various techniques to induce endometrial injury, timing of the intervention, and number of interventions done could all be responsible for the conflicting results. In addition, most studies have evaluated the effect of endometrial injury in fresh cycles.

Mak and colleagues performed a double-blind, prospective, randomized, controlled trial to evaluate the impact of endometrial scratch on success rates of natural-cycle frozen embryo transfer (FET).

Study Summary

Researchers recruited 229 couples. Of these, 186 completed their assignments. Ninety-three women in the intervention group had luteal-phase endometrial biopsy using a pipette catheter, and 93 women in the control group had intracervical manipulation using a cotton swab.

Baseline characteristics and response to stimulation in the fresh cycle were similar. Most patients had had at least one previous fresh embryo transfer. The number of embryos transferred and the stage of embryo development (cleavage versus blastocyst stage) at transfer were similar.

There were no significant differences between the intervention group and the control group in terms of pregnancy rate (positive human chorionic gonadotropin level) (48.4% vs 43%; relative risk [RR], 1.125; 95% confidence interval [CI], 0.82-1.54), implantation rate (36.5% vs 32.0%; RR, 1.143; 95% CI, 0.80-1.63), or ongoing pregnancy/live birth rate (34.4% vs 31.2%; RR, 1.16; 95% CI, 0.63-2.14).

The authors concluded that endometrial biopsy performed in the cycle preceding natural-cycle FET in an unselected group of patients does not improve clinical outcome.


Intentional endometrial injury in the cycle preceding IVF treatment has been proposed to increase implantation rates among women with RIF. Several mechanisms may explain the effect. Zhou and colleagues[9] showed that local injury to the endometrium resulted in differential expression of over 200 genes in the endometrium. Gnainsky and colleagues[10] showed that the endometrial injury initiates a cascade of proinflammatory events that increase the chance of implantation.

Most studies of endometrial injury have evaluated the effect in fresh cycles, but a few studies have also been done in FET cycles. Aflatoonian and colleagues[11] found a negative effect, Dunne and Taylor[12] reported no effect, and Kanazawa and colleagues[13] found improved outcome with luteal endometrial biopsy on pregnancy rates in FET cycles.

Although not all studies confirmed the positive effect of endometrial injury on subsequent pregnancy rates, most studies and two meta-analyses did find a beneficial effect in patients with RIF. RIF is a clinically challenging problem. Because endometrial biopsy is a relatively noninvasive procedure, with minimal discomfort and no serious risks associated with it, its use should be discussed with the patient before a new IVF attempt as a measure to improve outcome. Further studies will clarify what the best time is to do the procedure, what technique should be used, how many biopsies should be done, and which patient group is most likely to benefit.



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