A Study to Assess if Scratching the Lining of the Womb Prior to IVF Treatment Increases the Chances of Pregnancy

The Efficacy of Endometrial Biopsy on the Outcome of In Vitro Fertilization (IVF) /Intra-Cytoplasmic Sperm Injection (ICSI) Treatment (Endoscratch): A Feasibility Pilot Study

This study aims to see if taking a small sample from the lining of the womb (the 'scratch') before starting in vitro fertilization (IVF) treatment can influence the chance of getting pregnant and having a healthy, term baby.

This study also aims to explore why an embryo is not accepted or indeed rejected by the lining of the womb. This will be analysed by carefully looking at the sample taken from the lining of the womb under the microscope and analysing the levels of natural killer (NK) cells. These cells are thought to regulate the implantation process and to be altered in some women with infertility and miscarriage.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Procedure: Endometrial biopsy; Device: Transvaginal ultrasound

Detailed Description

Following consent, participants will be randomised to one of the two trial interventions (endometrial biopsy, or ultrasound scan only = no intervention) by a member of the research team. The procedures will be scheduled for luteinising hormone (LH) day +7 to +9 of the menstrual cycle directly preceding commencement of down-regulation medications. A urine pregnancy test will be performed before the studied procedure. Just prior to the biopsy and directly following it, a transvaginal ultrasound scan will be performed to assess the length of the uterine cavity and endometrial parameters, including blood flow characteristics using power Doppler imaging. Endometrial sample will be obtained using standard sampling procedure by appropriately trained clinician.

Participants randomised to treatment arm will undergo an endometrial biopsy procedure using Pipelle endometrial sampler (Pipelle de Cornier, Laboratoire CCD, Paris, France) or Wallace/ Wallach endometrial sampler as an alternative device on cycle day LH+7 to LH+9 of the cycle directly preceding commencement of down-regulation prior to IVF or ICSI treatment. The endometrial sampling will be repeated a maximum of four times (all during the same appointment on day LH+7 to LH+9 of menstrual cycle) to assure a sufficient sample is obtained. If following the first two attempts, the endometrial sample is sufficient, procedure will be deemed complete. The Pipelle sampler will be introduced up to the uterine fundus (based on clinical touch technique and ultrasound measurements), and attempts will be made to obtain samples from all four walls of the endometrial cavity.

Participants randomised to control group will also be supplied with home LH testing kits after informing the unit of the will to participate. Once the ovulation test is positive, the participant will contact the unit to arrange the ultrasound appointment on day LH+7 to LH+9 of the cycle directly preceding commencement of IVF/ICSI treatment. 48 to 72 hours later and additional appointment will be scheduled for ultrasound scan and blood tests.

Subjects will then be randomised to one of the two treatment arms based on a computer generated pseudo-random code using random permuted blocks of randomly varying size, created by the University of Nottingham Clinical Trials Unit (CTU). As a pilot feasibility study, the randomisation will not be stratified by any factors. Allocation to treatments will be in the ratio 1:1. The corresponding treatment allocation will be transmitted to the unblinded clinician, who will arrange the appropriate appointments for study procedures.

Due to the nature of the study, no blinding of participant or researchers is possible.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG7 2UH
      • Nurture Fertility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women with history of primary or secondary infertility undergoing fresh IVF/ ICSI treatment or frozen embryo replacement cycle
• Age <49

Exclusion Criteria:

• Non- ovulatory cycles
• Absent uterus
• Uterine instrumentation within previous 3 menstrual cycles
• Women in the oocyte donation program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endometrial biopsy arm; Participants randomised to this arm arm will undergo an endometrial biopsy procedure using Pipelle endometrial sampler (Pipelle de Cornier, Laboratoire CCD, Paris, France) or Wallace/ Wallach endometrial sampler as an alternative device on cycle day LH+7 to LH+9 of the cycle directly preceding commencement of down-regulation prior to IVF or ICSI treatment. A transvaginal ultrasound scan will be performed prior to the biopsy.	Procedure: Endometrial biopsy; Endometrial biopsy will be performed in the study group and timed according to a positive urinary LH (ovulation) kit at LH+7 to +9 days.; Other Names: Pipelle de Cornier (CCD, Paris).; Device: Transvaginal ultrasound; A detailed assessment of the endometrium will be performed including two- and three- dimensional ultrasound, as well as power Doppler acquisitions.; Other Names: GE Voluson E8 (Austria)
No Intervention: Control group; Participants randomised to control group will undergo a transvaginal ultrasound scan on day LH+7 to LH+9 of the cycle directly preceding commencement of IVF/ICSI treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
A difference in the term (37 completed weeks of gestation), singleton live birth rate in women undergoing IVF/ICSI treatment following endometrial biopsy versus control subjects.	Approximately 9 months after completion of the last procedure of the last study participant.

Secondary Outcome Measures

Outcome Measure	Time Frame
A difference in the live birth rate (birth of a live baby after 24th week of gestation and before 37th completed weeks) in women undergoing IVF/ICSI treatment following endometrial biopsy versus control subjects.	Approximately 9 months after completion of the last procedure of the last study participant.
A difference in the multiple pregnancy rate in women undergoing IVF/ICSI treatment following endometrial biopsy versus control subjects.	Approximately 9 months after completion of the last procedure of the last study participant.
A difference in the implantation rate in women undergoing IVF/ICSI treatment following endometrial biopsy versus control subjects.	Approximately 9 months after completion of the last procedure of the last study participant.
A difference in the biochemical pregnancy rate in women undergoing IVF/ICSI treatment following endometrial biopsy versus control subjects.	Approximately 9 months after completion of the last procedure of the last study participant.
A difference in the clinical pregnancy rate in women undergoing IVF/ICSI treatment following endometrial biopsy versus control subjects.	Approximately 9 months after completion of the last procedure of the last study participant.
A difference in the miscarriage rate (loss of pregnancy before viability) in women undergoing IVF/ICSI treatment following endometrial biopsy versus control subjects.	Approximately 9 months after completion of the last procedure of the last study participant.
A difference in the ectopic pregnancy rate in women undergoing IVF/ICSI treatment following endometrial biopsy versus control subjects.	Approximately 9 months after completion of the last procedure of the last study participant.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sonographic markers of endometrial receptivity	Detailed endometrial assessment will be performed using two-, three- dimensional ultrasound, as well as power and pulse-wave Doppler ultrasound imaging. Results of these measurements will be correlated with subsequent IVF/ICSI treatment outcome.	Approximately 2 years

Collaborators and Investigators

• Sponsor: Nottingham University Hospitals NHS Trust
• Collaborators: University of Nottingham; University Hospitals Coventry and Warwickshire NHS Trust
• Investigators: Study Chair: Nick Raine-Fenning, PhD, University of Nottingham

Publications and helpful links

General Publications

• Lensen SF, Armstrong S, Gibreel A, Nastri CO, Raine-Fenning N, Martins WP. Endometrial injury in women undergoing in vitro fertilisation (IVF). Cochrane Database Syst Rev. 2021 Jun 10;6:CD009517. doi: 10.1002/14651858.CD009517.pub4.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 3, 2013
• First Submitted That Met QC Criteria: June 18, 2013
• First Posted (Estimate): June 20, 2013

Study Record Updates

• Last Update Posted (Estimate): November 22, 2016
• Last Update Submitted That Met QC Criteria: November 21, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Infertility; Endometrium; Live birth
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: 12GY005