Comparing Two Types of Endometrial Activation Prior to Embryo Transfer

Assisted reproductive technologies (ART), including in vitro fertilization (IVF), are methods used to treat infertility, which affects approximately 10% reproductive aged women. Physicians at the Women's Institute perform over 300 embryo transfer procedures every year. Despite advances and improvements in ART over the past three decades, clinical pregnancy rate and live birth rate remain 30-40% and 20-30%. Implantation is essential for successful ART and IVF procedures, and many interventions have been studied to possibly improve implantation rates and thus pregnancy and live birth rates.

Endometrial activation is one such intervention, sometimes referred to as endometrial "activation" or "scratch," and it is defined as "intentional endometrial injury, such as endometrial biopsy or curettage, in women undergoing ART".

A previous study found that implantation rates, clinical pregnancy rates, and live birth rates were more than twofold higher in women who underwent endometrial biopsy in the cycle before subsequent IVF treatment. Another study which examines endometrial activation prior to IVF similarly has concluded that endometrial activation prior to the embryo transfer cycle significantly improves clinical pregnancy rates and live birth rates in women undergoing ART. Although the type of endometrial procedure is not specified, the timing activation was found be most effective when performed in the cycle prior to the embryo transfer.

The mechanism of increase endometrial receptivity is still unknown; however three proposed hypothesis exist. The first hypothesis proposes that local activation of the endometrium induces endometrial decidualization which increases the probability of embryo implantation. The second hypothesis is that endometrial healing following endometrial activation increases secreted cytokines, interleukins, growth factors, macrophages, and dendritic cells which are beneficial to embryo implantation. The final hypothesis suggests that endometrial maturation is abnormally advanced during ovarian stimulation, so endometrial activation may lead to better synchronicity between the endometrium and the embryo..

Endometrial activation has been found to have clear benefit in pregnancy and live birth rates in a previous study, however no uniform technique has been determined. The objective of this study is to compare two types of endometrial disruption - a vigorous endometrial biopsy with a Pipelle curette and a four quadrant endometrial "scratch" using a Shepard insemination catheter - to determine if the live birth rates are equivalent for the two methods. The investigators also will compare pain with the two types of endometrial activation. By comparing two distinct types of endometrial activation, the goal is to determine which method is both effective and tolerable to patients.

The Shepherd catheter is a 1.8 mm malleable insemination catheter that can be curved to traverse the cervix. It is also used by some physicians in the Women's Institute to perform saline infusion sonography. When the catheter is inserted under ultrasound guidance, it is often placed in the subendometrial tissue, and causes deflection and disruption of the endometrium but is tolerated well. The Pipelle is a 3.1 mm semi-rigid catheter with an internal stylet plunger. A biopsy is performed by placing the catheter into the uterus, withdrawing the stylet to create suction, and aspirating endometrial tissue into the catheter.

A study done by Leclair et al. found that the mean pain that women had when the Pipelle was used for an endometrial biopsy was 6.2±2.4 on a visual analog scale from 1-10 (5). Pain with the Shepard catheter has not been studied when it is used for endometrial biopsy.