InfertilityPhase 2/3NCT01882842
A Study to Assess if Scratching the Lining of the Womb Prior to IVF Treatment Increases the Chances of Pregnancy
A Phase 2/3 study testing Endometrial biopsy and Transvaginal ultrasound in people with Infertility, run by Nottingham University Hospitals NHS Trust at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 49 years, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Endometrial biopsy and Transvaginal ultrasound
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2013to Jun 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Women with history of primary or secondary infertility undergoing fresh IVF/ ICSI treatment or frozen embryo replacement cycle
- Age <49
Who cannot join
- Non- ovulatory cycles
- Absent uterus
- Uterine instrumentation within previous 3 menstrual cycles
- Women in the oocyte donation program
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Nurture Fertility
Nottingham, Nottinghamshire, NG7 2UH
About this study
Official title: 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.
Read the 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.
- Conditions
- Infertility
- Being tested
- Endometrial biopsy, Transvaginal ultrasound
- Keywords
- Infertility, Endometrium, Live birth
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endometrial biopsyProcedure or surgery
Also called Pipelle de Cornier (CCD, Paris).
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.
Transvaginal ultrasoundDevice
Also called GE Voluson E8 (Austria)
A detailed assessment of the endometrium will be performed including two- and three- dimensional ultrasound, as well as power Doppler acquisitions.
| Study group | Role | What they receive |
|---|---|---|
| Endometrial biopsy arm | Experimental | 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. Receives: Procedure: Endometrial biopsy; Device: Transvaginal ultrasound |
| Control group | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately 9 months after completion of the last procedure of the last study participant.
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Approximately 9 months after completion of the last procedure of the last study participant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2013 (estimated)
- Study startFeb 2013
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nottingham University Hospitals NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Nottingham, University Hospitals Coventry and Warwickshire NHS Trust
- Responsible party
- Sponsor
- Investigators
- Nick Raine-Fenning, PhD, Study chair, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01882842
- Sponsor's protocol ID
- 12GY005
- Status last verified
- Nov 2016
- First submitted
- 3 Jun 2013
- Last updated
- 22 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
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(6):CD009517. doi: 10.1002/14651858.CD009517.pub4.
PubMed 34110001
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of Endometrial Biopsy on the Outcome of In Vitro Fertilization (IVF) /Intra-Cytoplasmic Sperm Injection (ICSI) Treatment (Endoscratch): A Feasibility Pilot Study
- ClinicalTrials.gov ID
- NCT01882842
- Acronym / sponsor ID
- 12GY005
- Conditions
- Infertility
- Keywords
- Infertility, Endometrium, Live birth
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- Nottingham University Hospitals NHS TrustUniversity, hospital or other
- Collaborators
- University of Nottingham, University Hospitals Coventry and Warwickshire NHS Trust
- Study start
- Feb 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 20 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Endometrial biopsy arm | Experimental | Procedure: Endometrial biopsy, Device: Transvaginal ultrasoundParticipants 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. |
| Control group | No intervention | –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. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Women with history of primary or secondary infertility undergoing fresh IVF/ ICSI treatment or frozen embryo replacement cycle
- Age <49
Key exclusion criteria (4 listed)
- Non- ovulatory cycles
- Absent uterus
- Uterine instrumentation within previous 3 menstrual cycles
- Women in the oocyte donation program
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Endometrial biopsyAlso: Pipelle de Cornier (CCD, Paris).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. | Procedure or surgery | Endometrial biopsy arm |
| Transvaginal ultrasoundAlso: GE Voluson E8 (Austria)A detailed assessment of the endometrium will be performed including two- and three- dimensional ultrasound, as well as power Doppler acquisitions. | Device | Endometrial biopsy arm |
Primary outcome
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.
Time frame: Approximately 9 months after completion of the last procedure of the last study participant.
7 secondary outcomes
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Approximately 9 months after completion of the last procedure of the last study participant.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2016.
- Derived from this study: PubMed 34110001Lensen 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(6):CD009517. doi: 10.1002/14651858.CD009517.pub4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nick Raine-Fenning, PhD study chair
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Endometrial biopsy and Transvaginal ultrasound in people with Infertility, run by Nottingham University Hospitals NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Approximately 9 months after completion of the last procedure of the last study participant.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01882842, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2016.