Injuring the Endometrium to Improve IVF Success

Endometrial Injury in Women Undergoing Assisted Reproductive Techniques

Nastri CO, Gibreel A, Raine-Fenning N, Maheshwari A, Ferriani RA, et al
Cochrane Database Syst Rev. 2012;7:CD00951

Endometrial Injury

A healthy young woman has approximately a 25% chance to achieve a successful pregnancy with each menstrual cycle. After about 1 year of trying to become pregnant, 15% of couples will remain unsuccessful. At that point, an evaluation is typically done and some type of fertility treatment is initiated. If fertility treatments fail repeatedly, in vitro fertilization (IVF) is eventually recommended. This treatment offers the best per-attempt chance for pregnancy, which is why patients have the highest level of expectation for treatment success. Therefore, it is not surprising that unsuccessful IVF can lead to significant disappointment. When insurance does not cover the treatment, expenses can also be significant. This results in much pressure on both the patients and the treating team.

Despite these expectations, the overall live birth rate is only 30% with IVF.^[1] In most cases, this is a consequence of problems (mainly aneuploidy) with the embryo. Several other factors (eg, endometriosis, fibroids, adenomyosis, immunologic or hematologic problems, hydrosalpinx) can also reduce success rates. When treatments fail repeatedly, the evaluation can be extended and certain additional therapeutic measures can be offered.

The benefit of endometrial "injury" induced before the start of IVF treatment has been evaluated in recent years. Several mechanisms are believed to play a role in improving the outcome with this intervention. After endometrial injury, cytokines that are released during the repair process induce endometrial changes favorable for implantation. Endometrial injury also induces decidualization, which favors implantation as well. The healing after the injury slows endometrial development, which is otherwise accelerated after stimulation, thereby increasing the likelihood for an in-phase endometrium at the time of transfer.^[2] This review summarizes the available evidence about the effect of intentional endometrial injury on IVF success rates.

Study Summary

Randomized controlled trials that evaluated the effect of endometrial injury performed within 6 months of IVF were considered for the analysis. Five studies involving 294 women in the injury group and 297 women in the control group were included. The Pipelle biopsy equipment was used in 4 studies and the Novak curette in 1. In most trials, a biopsy was performed. In 4 trials, the biopsy was done in the luteal phase of the preceding cycle, whereas in 1 study it was done on the day of retrieval.

The live birth rate reported in 2 studies was higher in the biopsy group (odds ratio [OR], 2.46; 95% confidence interval [CI], 1.28-4.72). The clinical pregnancy rate (reported in all 4 trials in which biopsy was done in the previous cycle) also was higher in the injury group (OR, 2.61; 95% CI, 1.71-3.97). The study in which the biopsy was performed on the day of retrieval found a detrimental effect of endometrial injury on clinical pregnancy rate (OR, 0.28; 95% CI, 0.13-0.61).^[3] Nastri and colleagues concluded that endometrial injury induced in the cycle before IVF treatment improves ongoing pregnancy and live birth rates in patients with previous IVF failure.

Viewpoint

A healthy embryo and a receptive endometrium are both essential for successful implantation. The health of the embryo is determined primarily by a woman's age because the rate of aneuploidy increases with increasing age. When the embryo is unhealthy, it is unlikely to implant or is likely to be lost early.

With advanced age, very little can be done to improve the outcome. However, most patients are unwilling to accept this fact and are more willing to try anything to improve their chances of becoming pregnant. This has led to a series of studies evaluating the benefit of numerous adjuvant therapies as part of IVF. One of these options is intentional endometrial injury.

The effectiveness of this intervention has been evaluated in a few studies, and various explanations of why it might improve pregnancy rates have been offered. This Cochrane review found benefit when endometrial injury was done in the luteal phase of the preceding cycle. The intervention was shown to increase implantation, ongoing pregnancy, and live birth rates without increasing the rate of miscarriage. The results of the 4 studies that evaluated luteal biopsy all point to the same benefit, but a biopsy performed in the treatment cycle on the day of retrieval was associated with a negative effect.

Endometrial injury can cause some discomfort and minimal risks. Because it seems to improve treatment outcomes, this intervention could be offered to increase chances for pregnancy when previous IVF attempts have failed.

Abstract

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.