InfertilityNCT04648566
Endometrium Immunomodulation by in Utero Administration of Peripheral Blood Mononuclear Cells
A study testing Intrauterine administration of hCG-activated peripheral blood mononuclear cells and Intrauterine administration of sperm washing medium in people with Infertility, run by Fertilys at 1 site in Canada.
Trial summary
One of the most limiting factors in the field of assisted reproduction is implantation failure. A new approach to increase the chances of success involves the use of cells from the patient's blood, peripheral blood mononuclear cells (PBMC), which once isolated can be cultured for a few days and then inseminated back… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Infertility
- What is being tested?
- Intrauterine administration of hCG-activated peripheral blood mononuclear cells and Intrauterine administration of sperm washing medium
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 423 participants
- Where
- 1 siteCanada
- Study dates
- 22 Mar 2017to 1 Feb 2020
- Phase
- Interventional
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All infertile patients undergoing in vitro fertilization (IVF) or intrauterine insemination (IUI) with partner's sperm at Fertilys, agreeing to participate in the study and having signed the study participation consent form.
- Study participants must be over 18 years old.
- For the recurrent implantation failure (RIF) group only: Patients described as having RIF, i.e. having had ≥ 3 good quality embryo transfers.
Who cannot join
- For the randomized IUI and IVF groups only: Patients described as having RIF, i.e. having had ≥ 3 embryo transfers or having had a transfer of more than 3 embryos of good quality.
- Patients requiring a donation of gametes (eggs or spermatozoa).
- Couples in which one or the other has a chromosomal abnormality.
- Patients who are starting an IUI cycle under ovulation testing.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Endometrium Immunomodulation Using in Utero Administration of Peripheral Blood Mononuclear Cells
One of the most limiting factors in the field of assisted reproduction is implantation failure. A new approach to increase the chances of success involves the use of cells from the patient's blood, peripheral blood mononuclear cells (PBMC), which once isolated can be cultured for a few days and then inseminated back into the uterine cavity prior to embryo implantation. It has been shown that the immune system plays a major role in the process of embryo implantation. To date, at least three international clinical trials appear to confirm the usefulness of intrauterine administration of PBMC in the setting of repeated implantation failure (RIF) in in vitro fertilization (IVF) (RIF: absence of active pregnancy after ≥ 3 embryo transfers). The clinical pregnancy rate would be doubled or even tripled. This treatment has never been studied in a randomized double-blind clinical trial, in the context of fertilization without RIF or in a classic treatment such as intrauterine insemination (IUI) with the partner sperm.
Our hypothesis is that the creation of an endometrial inflammatory reaction by the administration of PBMC in the uterine cavity allows a better receptivity and consequently a better implantation following an embryo transfer as part of an IVF treatment.
Read more
The objective is to evaluate whether intrauterine administration of PBMC improves embryo implantation following assisted reproduction treatment.
The investigators plan to recruit 148 women undergoing IVF and 220 patients undergoing UII with partner sperm to test our hypothesis. The investigators also plan to recruit all RIF patients accepting to participate in the clinical trial. The study will be prospective, randomized and double-blind. The treated group will receive an intrauterine administration of PBMC while the control group will be administered with sperm washing medium only. PBMC will be obtained from a blood sample (maximum 10 ml) a few days before embryo transfer in IVF cases or on the day of sperm insemination in IUI cases. PBMC will then be isolated in the laboratory on a Ficoll gradient in order to eliminate platelets, polynuclear cells and red blood cells. PBMCs will then be stimulated with phytohemagglutinin (PHA) and human chorionic gonadotropin hormone (hCG) for 48 hours. Lymphocyte phenotyping will be assessed before and after cell activation. In addition, the cytokine profile will be established from the supernatant of the stimulated cells. These data will make it possible to establish a link between the pro-versus anti-inflammatory cytokine profile and implantation success versus failure for each patient. Two days after cell seeding, PBMC will be administered into the uterine cavity of the patient. Embryo transfer will be performed in the same way as the standard treatment on day 3 or 5 according to the criteria established by the IVF laboratory and in agreement with the doctor.
- Conditions
- Infertility
- Being tested
- Intrauterine administration of hCG-activated peripheral blood mononuclear cells, Intrauterine administration of sperm washing medium
- Medical subject headings
- Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intrauterine administration of hCG-activated peripheral blood mononuclear cellsProcedure or surgery
Administration of hCG-activated peripheral blood mononuclear cells in the uterine cavity of the patient
Intrauterine administration of sperm washing mediumProcedure or surgery
Administration of sperm washing medium instead of PBMC in the uterine cavity of the patient
| Study group | Role | What they receive |
|---|---|---|
| IIU control group | Placebo comparator | Not described Receives: Procedure: Intrauterine administration of sperm washing medium |
| IIU PBMC group | Active comparator | Not described Receives: Procedure: Intrauterine administration of hCG-activated peripheral blood mononuclear cells |
| FIV control group | Placebo comparator | Not described Receives: Procedure: Intrauterine administration of sperm washing medium |
| FIV PBMC group | Active comparator | Not described Receives: Procedure: Intrauterine administration of hCG-activated peripheral blood mononuclear cells |
| RIF group | Active comparator | Not described Receives: Procedure: Intrauterine administration of hCG-activated peripheral blood mononuclear cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Biochemical pregnancy rate
Measured: Two weeks following embryo transfer or 3 weeks following intrauterine insemination
Clinical pregnancy rate
Measured: Six to 8 weeks of gestation
Secondary outcomes (3)
Peripheral blood mononuclear cells populations distribution at Day 0
Measured: The day of the patient's ovulation
Peripheral blood mononuclear cells populations distribution at Day 2
Measured: After 48 hours of culture
Cytokines expression levels
Measured: After 48 hours of culture
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2020
- Study start22 Mar 2017
- Primary completion1 Feb 2020
- Study completion1 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 423 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fertilys
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Institut National de la Recherche Scientifique - Centre Armand Frappier Santé Biotechnologie
- Responsible party
- Sponsor
- Investigators
- Pierre Miron, MD, PhD, Principal investigator, Fertilys inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04648566
- Sponsor's protocol ID
- Immunomodulation
- Status last verified
- Nov 2020
- First submitted
- 18 Nov 2020
- Last updated
- 1 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endometrium Immunomodulation Using in Utero Administration of Peripheral Blood Mononuclear Cells
- ClinicalTrials.gov ID
- NCT04648566
- Acronym / sponsor ID
- Immunomodulation
- Conditions
- Infertility
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 423 participants (actual)
- Lead sponsor
- FertilysIndustry (pharma, biotech, devices)
- Collaborators
- Institut National de la Recherche Scientifique - Centre Armand Frappier Santé Biotechnologie
- Study start
- 22 Mar 2017 (actual)
- Primary completion
- 1 Feb 2020 (actual)
- Study completion
- 1 Feb 2020 (actual)
- First posted
- 1 Dec 2020 (actual)
- 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.
One of the most limiting factors in the field of assisted reproduction is implantation failure. A new approach to increase the chances of success involves the use of cells from the patient's blood, peripheral blood mononuclear cells (PBMC), which once isolated can be cultured for a few days and then inseminated back into the uterine cavity prior to embryo implantation. It has been shown that the immune system plays a major role in the process of embryo implantation. To date, at least three international clinical trials appear to confirm the usefulness of intrauterine administration of PBMC in the setting of repeated implantation failure (RIF) in in vitro fertilization (IVF) (RIF: absence of active pregnancy after ≥ 3 embryo transfers). The clinical pregnancy rate would be doubled or even tripled. This treatment has never been studied in a randomized double-blind clinical trial, in the context of fertilization without RIF or in a classic treatment such as intrauterine insemination (IUI) with the partner sperm.
Our hypothesis is that the creation of an endometrial inflammatory reaction by the administration of PBMC in the uterine cavity allows a better receptivity and consequently a better implantation following an embryo transfer as part of an IVF treatment.
The objective is to evaluate whether intrauterine administration of PBMC improves embryo implantation following assisted reproduction treatment.
The investigators plan to recruit 148 women undergoing IVF and 220 patients undergoing UII with partner sperm to test our hypothesis. The investigators also plan to recruit all RIF patients accepting to participate in the clinical trial. The study will be prospective, randomized and double-blind. The treated group will receive an intrauterine administration of PBMC while the control group will be administered with sperm washing medium only. PBMC will be obtained from a blood sample (maximum 10 ml) a few days before embryo transfer in IVF cases or on the day of sperm insemination in IUI cases. PBMC will then be isolated in the laboratory on a Ficoll gradient in order to eliminate platelets, polynuclear cells and red blood cells. PBMCs will then be stimulated with phytohemagglutinin (PHA) and human chorionic gonadotropin hormone (hCG) for 48 hours. Lymphocyte phenotyping will be assessed before and after cell activation. In addition, the cytokine profile will be established from the supernatant of the stimulated cells. These data will make it possible to establish a link between the pro-versus anti-inflammatory cytokine profile and implantation success versus failure for each patient. Two days after cell seeding, PBMC will be administered into the uterine cavity of the patient. Embryo transfer will be performed in the same way as the standard treatment on day 3 or 5 according to the criteria established by the IVF laboratory and in agreement with the doctor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| IIU control group | Placebo comparator | Procedure: Intrauterine administration of sperm washing medium |
| IIU PBMC group | Active comparator | Procedure: Intrauterine administration of hCG-activated peripheral blood mononuclear cells |
| FIV control group | Placebo comparator | Procedure: Intrauterine administration of sperm washing medium |
| FIV PBMC group | Active comparator | Procedure: Intrauterine administration of hCG-activated peripheral blood mononuclear cells |
| RIF group | Active comparator | Procedure: Intrauterine administration of hCG-activated peripheral blood mononuclear cells |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- All infertile patients undergoing in vitro fertilization (IVF) or intrauterine insemination (IUI) with partner's sperm at Fertilys, agreeing to participate in the study and having signed the study participation consent form.
- Study participants must be over 18 years old.
- For the recurrent implantation failure (RIF) group only: Patients described as having RIF, i.e. having had ≥ 3 good quality embryo transfers.
Key exclusion criteria (4 listed)
- For the randomized IUI and IVF groups only: Patients described as having RIF, i.e. having had ≥ 3 embryo transfers or having had a transfer of more than 3 embryos of good quality.
- Patients requiring a donation of gametes (eggs or spermatozoa).
- Couples in which one or the other has a chromosomal abnormality.
- Patients who are starting an IUI cycle under ovulation testing.
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 |
|---|---|---|
| Intrauterine administration of hCG-activated peripheral blood mononuclear cellsAdministration of hCG-activated peripheral blood mononuclear cells in the uterine cavity of the patient | Procedure or surgery | FIV PBMC group, IIU PBMC group, RIF group |
| Intrauterine administration of sperm washing mediumAdministration of sperm washing medium instead of PBMC in the uterine cavity of the patient | Procedure or surgery | FIV control group, IIU control group |
Primary outcome
Biochemical pregnancy rate
Time frame: Two weeks following embryo transfer or 3 weeks following intrauterine insemination
Clinical pregnancy rate
Time frame: Six to 8 weeks of gestation
3 secondary outcomes
Peripheral blood mononuclear cells populations distribution at Day 0
Time frame: The day of the patient's ovulation
Peripheral blood mononuclear cells populations distribution at Day 2
Time frame: After 48 hours of culture
Cytokines expression levels
Time frame: After 48 hours of culture
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 1 Dec 2020.
- Individual participant dataSharing planned: No
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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.
Pierre Miron, MD, PhD principal investigator
Fertilys inc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intrauterine administration of hCG-activated peripheral blood mononuclear cells and Intrauterine administration of sperm washing medium in people with Infertility, run by Fertilys at 1 site in Canada.
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 3 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 1 Dec 2020. 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 Canada. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Biochemical pregnancy rate (time frame: Two weeks following embryo transfer or 3 weeks following intrauterine insemination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Dec 2020.