Comparing Two Types of Endometrial Activation Prior to Embryo Transfer

Not Applicable

Completed

• Conditions: Infertility; Endometrial Disorder
• Interventions: Procedure: Endometrial scratch with Pipelle curette; Procedure: Endometrial scratch with Shepard catheter

• Registration Number: NCT04363879
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

To determine if two types of endometrial activation (Pipelle curette or Shepard catheter) prior to embryo transfer result in similar live birth rates. Also to determine if patients experience similar pain from both types of endometrial activation.

Detailed Description

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.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2014-06-16
• Primary Completion: 2017-07-01
• Study Completion: 2017-07-01
• Study First Submitted: 2020-04-22
• Study First Submitted QC: 2020-04-24
• Study First Posted: 2020-04-27
• Results First Submitted: 2020-04-30
• Results First Submitted QC: 2020-05-14
• Results First Posted: 2020-05-27
• Status Verified: 2022-09
• Last Update Submitted: 2022-10-12
• Last Update Posted: 2022-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 195

Inclusion Criteria

• All patients undergoing embryo transfer who are in the cycle prior to their embryo transfer

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Exclusion Criteria

• Patients not undergoing embryo transfer
• Known pregnancy
• Active pelvic infection
• Known endometrial hyperplasia or cancer
• Inability to tolerate endometrial catheter placement
• Severe cervical stenosis
• Patients who will receive operative hysteroscopy in the cycle prior to embryo transfer

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Endometrial scratch with Pipelle curette	Endometrial scratch with Pipelle curette	For patients in the Pipelle curette group, physicians inserted the Pipelle curette into the uterus and removed an adequate endometrial sample using vigorous motion.
Endometrial scratch with Shepard catheter	Endometrial scratch with Shepard catheter	For patients in the Shepard catheter group, physicians performed a four-quadrant scratch technique by inserting the Shepard insemination catheter into the uterus at 12:00. The catheter was then turned one-quarter turn and withdrawn. This was repeated two more times so that four endometrial quadrants were touched by the catheter at 12:00, 3:00, 6:00, and 9:00.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Live Births Per Transfers Performed	Collected up to 1 year after the last embryo transfer	Number (count) of births per number of subjects undergoing embryo transfer

Secondary Outcome Measures

Name	Time	Method
Pain Quantifcation After Endometrial Scratch	Immediately following endometrial scratch	Pain assessed by Visual analog scale (Numeric rating scale, units from 1-10 with 1 being no pain and 10 being maximum pain)
Number (Count) of Positive Pregnancy Tests Per Number of Subjects Undergoing Embryo Transfer	Collected up to 1 year after the last embryo transfer
Number (Count) of Pregnancies Per Number of Patients Undergoing Embryo Transfer	Collected up to 1 year after the last embryo transfer