- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01803893
Prognostic Value of PIF Detection in Embryo Culture Media Correlation With Pregnancy Outcome (PIF-SET1)
Preimplantation Factor (PIF): Prognostic Value of a Non-invasive Embryo Viability Biomarker Detection in Culture Media Followed by Single Embryo Transfer - Correlation With Live Birth.
Study Overview
Detailed Description
The aim of the proposed project is to investigate a non invasive biomarker, PIF (PreImplantation Factor), a 15amino acid peptide (MVRIKPGSANKPSDD) secreted only by viable embryos and placenta (Stamakin et al. RBE 2011).
PIF positive embryos will be able to grow to blastocyst stage and PIF levels could be a marker of progressive pregnancy. We will measure PIF levels in IVF culture media before embryo transfer to correlate IVF pregnancy with PIF levels. Our objective will be to define PIF as a biomarker for viable embryos in order to increase IVF success rates following SET. PIF levels will be retrospectively evaluated after 500 SET.
Our four reproductive centres perform about 200 SET per year and more than 500 in vitro fertilizations.
For women selected for a SET, PIF levels will be evaluated in all embryo culture media, and later at one and two weeks after each transfer of fresh or thawed frozen embryos in maternal serum. Embryo transfers will be done blinded to PIF results. SET or MET will be based on clinical evaluation and conventional embryo criteria. For these women, PIF will be also evaluated and compared with βhCG level on maternal serum.
PIF assessment will be performed using specific antibody marked with a fluorescent dye, in Luminex reader.
Specific Aim One will allow us to evaluate:
- PIF predictive value on implantation rate
- PIF predictive value on pregnancy Methodology All women will be fully informed and a written consent to participate in the study will be duly obtained.
In vitro procedure Oocytes were retrieved after natural cycle or after ovarian hyperstimulation which will be performed using the modified long protocol. Collected oocytes will be fertilized by classic IVF or ICSI. Fertilization will be confirmed by the observation of 2 pronuclei and two polar bodies, after 16-18 hours. Fertilized oocytes will be cultured in 60μl of culture media under oil. Embryo transfer will be performed 72 hours after IVF or ICSI procedure (at day D3) without PIF result. Before transfer, embryo quality will be scored according to number of cells, kinetic of cleavage and fragmentation rate. For women who will have a SET, according to clinical criteria (Age, FSH level, etc…) remaining good quality embryos will be frozen and thawed after uterine preparation in further attempts. All remaining culture supernatants (50-60μl) will be collected, transferred to 8-strip 0.2ml tubes and stored to -80C until they will test for PIF (M) Maternal serum retrieval
Maternal serum will be collected:
- before oocytes retrieval in course of a serum control of ovarian hyperstimulation (S0)
- one week after transfer (S1)
- two week after transfer during serial human β-chorionic gonadotrophin measurements (S2) PIF level evaluation PIF levels in culture supernatants and in maternal serum will be measured retrospectively, using a bead-based competitive assay for use in the Luminex 200 IS system. Results presented as median fluorescence intensity (MFI). PIF levels were derived from standard curve using a 5-parameter logistics curve. The threshold of detection was established by measuring the background from culture media or maternal serum alone, using mean+2SD as a cut off (18.7ng/ml).
Analysis Correlate PIF detection in embryo serum with embryo viability. Results of PIF detection in embryo supernatants will be correlated with pregnancy outcome.
Comparison with embryo selection by PIF+ vs PIF- embryos, using morphology alone, and by morphology combined with PIF presence.
Comparisons between groups will be performed using chi-square analysis and p<0.05 will be considered as statistically significant.
Inclusion/exclusion criteria
Inclusion criteria:
All women included in our centers for classical IVF or ICSI, who will sign the written consent to participate in the study. PIF level evaluation in culture media (M) and pregnancy prognosis (S1 and S2) will be done only for women with SET.
Exclusion criteria Women who will refuse to participate in the program. Planned assessments (time and events table) The overall project is planned to be carried out through five steps work plan in which we will investigate the use of PIF as a biomarker for better embryo selection (only women with SET will be included) and as a early pregnancy marker in maternal serum.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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Paris, France, 93150
- Lab Clement - Seine St. Denis Hospital, Le Blanc Mesnil
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Poissy, France, 2493
- Versailles St. Quentin University
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Cedex
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Poissy, Cedex, France, 78303
- Poissy St Germain Hospital
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Athens, Greece, 11521
- Helena Venizelou Hospital
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Connecticut
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New Haven, Connecticut, United States, 06511
- Yale Women and Children's Center for Blood Disorders & Yale Fertility Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion criteria:
All women included in our centers for classical IVF or ICSI, who will sign the written consent to participate in the study. PIF level evaluation in culture media (M) and pregnancy prognosis (S1 and S2) will be done only for women with SET.
Exclusion criteria Women who will refuse to participate in the program.
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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Embryo culture media
measurement using immunoassay
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maternal serum
measurement by immunoassay
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Detection of PIF in early pregnancy maternal serum
Time Frame: end of pregnancy
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Following PIF positive single embryo transfer, patients' pregnancy will be monitored by standard methods.
This includes: blood tests and ultrasound until pregnancy viability has been established.
The number of patients that fail to implant or end up in implantation failure (ie chemical pregnancy), miscarriage, gestational sac will be recorded.
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end of pregnancy
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Correlation between PIF positive and negative embryos and early pregnancy events
Time Frame: end of pregnancy
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SET embryo transfers will be performed blinded, unrelated to PIF results.
Subsequent to SET, the embryo culture media will be tested for presence/absence of PIF and documented.
Following transfer, patients' pregnancy will be monitored by standard methods.
This includes: blood tests and ultrasound to determine embryo viability.
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end of pregnancy
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Correlation between PIF positive and negative embryos and late pregnancy events
Time Frame: end of pregnancy
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SET embryo transfers will be performed blinded, unrelated to PIF results.
Subsequent to SET, the embryo culture media will be tested for presence/absence of PIF and documented.
Following transfer, patients' pregnancy will be monitored by standard methods.
Once viability is established by standard methods, patients will be followed throughout pregnancy until eventual delivery.
Premature delivery, high risk pregnancy events will be recorded.
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end of pregnancy
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Eytan R Barnea, MD, FACOG, BioIncept LLC
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- BioIncept LLC-1
- GFI Merck Serono 2012 (Other Grant/Funding Number: GFI-1)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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