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Comparing Two Types of Endometrial Activation Prior to Embryo Transfer

Comparing Two Types of Endometrial Activation Prior to Embryo Transfer: A Pilot Study

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04363879
Enrollment
195
Registered
2020-04-27
Start date
2014-06-16
Completion date
2017-07-01
Last updated
2022-10-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Endometrial Disorder, Infertility

Keywords

Endometrial scratch

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.

Interventions

PROCEDUREEndometrial 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.

PROCEDUREEndometrial 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.

Sponsors

Wake Forest University Health Sciences
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Intervention model description

Parallel treatment arms for two types of endometrial scratch

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
Yes

Inclusion criteria

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

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

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants With Live Births Per Transfers PerformedCollected up to 1 year after the last embryo transferNumber (count) of births per number of subjects undergoing embryo transfer

Secondary

MeasureTime frameDescription
Pain Quantifcation After Endometrial ScratchImmediately following endometrial scratchPain 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 TransferCollected up to 1 year after the last embryo transfer
Number (Count) of Pregnancies Per Number of Patients Undergoing Embryo TransferCollected up to 1 year after the last embryo transfer

Participant flow

Participants by arm

ArmCount
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 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.
78
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. 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.
92
Total170

Baseline characteristics

CharacteristicEndometrial Scratch With Pipelle CuretteEndometrial Scratch With Shepard CatheterTotal
Age, Continuous33.8 Years
STANDARD_DEVIATION 4.6
34.2 Years
STANDARD_DEVIATION 3.9
34.0 Years
STANDARD_DEVIATION 4.2
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
16 Participants75 Participants91 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
62 Participants17 Participants79 Participants
Race and Ethnicity Not Collected0 Participants
Region of Enrollment
United States
78 participants92 participants170 participants
Sex: Female, Male
Female
78 Participants92 Participants170 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 780 / 92
other
Total, other adverse events
0 / 780 / 92
serious
Total, serious adverse events
0 / 780 / 92

Outcome results

Primary

Number of Participants With Live Births Per Transfers Performed

Number (count) of births per number of subjects undergoing embryo transfer

Time frame: Collected up to 1 year after the last embryo transfer

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Endometrial Scratch With Pipelle CuretteNumber of Participants With Live Births Per Transfers Performed37 Participants
Endometrial Scratch With Shepard CatheterNumber of Participants With Live Births Per Transfers Performed43 Participants
Secondary

Number (Count) of Positive Pregnancy Tests Per Number of Subjects Undergoing Embryo Transfer

Time frame: Collected up to 1 year after the last embryo transfer

ArmMeasureValue (NUMBER)
Endometrial Scratch With Pipelle CuretteNumber (Count) of Positive Pregnancy Tests Per Number of Subjects Undergoing Embryo Transfer56 positive pregnancy tests
Endometrial Scratch With Shepard CatheterNumber (Count) of Positive Pregnancy Tests Per Number of Subjects Undergoing Embryo Transfer62 positive pregnancy tests
Secondary

Number (Count) of Pregnancies Per Number of Patients Undergoing Embryo Transfer

Time frame: Collected up to 1 year after the last embryo transfer

ArmMeasureValue (NUMBER)
Endometrial Scratch With Pipelle CuretteNumber (Count) of Pregnancies Per Number of Patients Undergoing Embryo Transfer44 number of pregnancies
Endometrial Scratch With Shepard CatheterNumber (Count) of Pregnancies Per Number of Patients Undergoing Embryo Transfer55 number of pregnancies
Secondary

Pain Quantifcation After 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)

Time frame: Immediately following endometrial scratch

ArmMeasureValue (MEAN)Dispersion
Endometrial Scratch With Pipelle CurettePain Quantifcation After Endometrial Scratch3.9 score on a scaleStandard Deviation 2.2
Endometrial Scratch With Shepard CatheterPain Quantifcation After Endometrial Scratch3.0 score on a scaleStandard Deviation 2.4

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026