RCT Study to Validate niPGT-A Clinical Benefit. (niPGT-A_RCT)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04000152|
Recruitment Status : Recruiting
First Posted : June 27, 2019
Last Update Posted : December 31, 2020
Chromosomal aneuploidies are linked with spontaneous miscarriages and abnormal offspring in human pregnancies. In addition, some types of aneuploidy are reported to prevent implantation. Thus, there is a need to identify the embryos with highest implantation potential on in vitro fertilization (IVF) programs.
Since embryo morphology and kinetics have a weak association with embryo ploidy, trophectoderm biopsy plus Next-Generation Sequencing (NGS) is becoming a very popular approach to determine the embryo chromosomal status. This technique is called Preimplantation Genetic Testing for Aneuploidy (PGT-A). Although shown to be efficient, it is invasive for the embryo, requires specific technical skills and it remains expensive. Therefore, the development of a non-invasive, rapid and cheaper method for assessing embryo ploidy status would represent a progress in the field of IVF.
The non-invasive approach has been explored by some groups that analyzed the Spent Blastocyst Medium (SBM) where the embryo was incubated up to the time of transfer or freezing. In daily routine, this media is discarded after finishing the culture of the embryo. Importantly, though, this media reportedly contains traces of embryonic cell-free DNA (cfDNA) that can represent the genetic load of the embryo.
On the basis of that, the hypothesis of this study is that embryo prioritization according to the analysis of the embryonic cfDNA in the SBM could improve ongoing pregnancy rate in 10 percentual points compared to standard blastocyst transfer based on morphology.
|Condition or disease||Intervention/treatment||Phase|
|Aneuploidy Chromosome Abnormality Infertility||Diagnostic Test: niPGT-A Other: Morphology criteria||Not Applicable|
Current Preimplantation Genetic Testing for Aneuploidy (PGT-A) techniques analyze the full chromosome content of a single or few cells with high sensitivity and specificity using Next-Generation Sequencing (NGS). Although shown to be efficient, the technique suffers from some limitations. It requires an embryo biopsy, specific technical skills and it still remains expensive. Therefore, non-invasive techniques for assessing embryo ploidy status are sought as an alternative. Such non-invasive approaches would have various advantages over current strategies, including the elimination of a costly micromanipulation biopsy procedure and the avoidance of risks associated with cell removal. Furthermore, it would be more advantageous, especially for those patients who undergo in vitro fertilization (IVF) treatment but do not have PGT-A indication or they are not willing to have their embryos tested with invasive techniques.
One of the recent advances in the field is the identification of embryonic cell-free DNA (cfDNA) during embryo culture in the lab. It is released to the culture drop (SBM) and represents the chromosome content of the embryo. In a recent pilot study, we analyzed the concordance rates between trophectoderm (TE) biopsy and SBM. In SBM collected on day 6/7 of development, the results were concordant with TE biopsies in 84% of samples, with a false-positive rate of 8.6% and a false-negative rate of 2.5%. These findings are encouraging and were the base for the design of the current RCT study.
The main objective of this study is to evaluate the potential clinical benefits of a new non-invasive method for PGT-A, based on the analysis of the embryonic cfDNA released into SBM.
Considering a dropout rate of around 30% (treatment or monitoring failures and no day 6/7 blastocysts to transfer), a total of 872 participants will be randomized before the ovum pick-up. They will be allocated on a balanced way (1:1 ratio) in one of the two arms: 1) Single Embryo Transfer (SET) on day 6/7 with deferred blastocyst transfer based on the chromosomal status according to the analysis of the SBM; 2) SET on day 6/7 with deferred blastocyst transfer based on embryo morphology. Reproductive outcomes (defined following The International Glossary on Infertility and Fertility Care, 2017) will be compared between the two groups.
Data exported from the clinical histories and source documents will be duly codified to protect the clinical and personal information of patients in accordance with the current legislation. This information will be exported to an electronic Case Report Form (eCRF). An interim analysis of this data is planned once 30% of the recruitment has been reached. Besides, the study will be overseen by an independent Data Monitoring Committee after 30% of patients´ recruitment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1108 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized Controlled Clinical Study to Assess the Benefit of Non-invasive PGT-A, by the Analysis of Spent Blastocyst Media, as a Tool for Embryo Prioritization in Infertile Patients Undergoing Assisted Reproduction.|
|Actual Study Start Date :||June 14, 2019|
|Estimated Primary Completion Date :||April 2023|
|Estimated Study Completion Date :||June 2023|
Active Comparator: Control group (group 1)
Deferred single blastocyst transfer with blastocyst selection according to morphology.
Other: Morphology criteria
Embryos for transfer will be selected by the only applicable technique, the assessment of morphology according to Gardner´s criteria, which is the most standardized method.
Experimental: Intervention group (group 2)
Deferred single blastocyst transfer with blastocyst selection according to the analysis of the spent culture media (niPGT-A).
Diagnostic Test: niPGT-A
Two scenarios should be considered according to the results in the SBM analysis:
- Non-invasive analysis of the chromosomal status of the embryo [ Time Frame: 7 days ]Number and structure of the embryo chromosomes
- Ongoing pregnancy rate [ Time Frame: Over 12 weeks ]Number of ongoing pregnancies per single embryo transfer
- NGS results of the SBM [ Time Frame: 7 days at least ]Informativity rates and prioritization category of the SBM analysis results with embryo development, culture conditions and collection time
- Non-Invasive Prenatal Testing (NIPT) [ Time Frame: Up to 12 weeks ]Incidence of chromosomal abnormalities in NIPT within ongoing pregnancy cases
- Clinical miscarriage rate [ Time Frame: Up to 6 months after the ovum pick-up ]Number of clinical miscarriages per total number of ongoing pregnancies
- Analysis of the Products of Conception (POC) [ Time Frame: Up to 20 weeks ]Incidence of chromosomal abnormalities in POC within miscarriage cases
- Cumulative ongoing pregnancy rate [ Time Frame: Over 6 months after the ovum pick-up ]Cumulative ongoing pregnancy rate per patient in the 6 months after the pick-up
- Time to get an ongoing pregnancy [ Time Frame: Up to 6 months after the ovum pick-up ]Time to get an ongoing pregnancy within the 6 months after the pick-up
- Live birth rate [ Time Frame: Over 40 weeks ]Number of babies born per embryo transfer
- Cumulative live birth rate [ Time Frame: Over 6 months after the ovum pick-up ]Cumulative live birth rate per patient in the 6 months after the pick-up
- Obstetrical outcomes comparison [ Time Frame: Over 40 weeks ]To compare birth weight, gestational age, APGAR, type of delivery, pregnancy complications, etc.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04000152
|Contact: Carlos Gómez, BSc MSc||+34 email@example.com|
|Contact: Carmen Rubio, PhD||+34 firstname.lastname@example.org|
|United States, California|
|Fertility Associates of California (FSAC)||Recruiting|
|Thousand Oaks, California, United States, 91361|
|Contact: Mousa Shamonki, MD 805-719-7531 email@example.com|
|Principal Investigator: Mousa Shamonki, MD|
|United States, Florida|
|South Florida Institute for Reproductive Medicine (IVFMD)||Active, not recruiting|
|Florida City, Florida, United States, 33458|
|United States, Massachusetts|
|Boston IVF Fertility Clinic||Active, not recruiting|
|Boston, Massachusetts, United States, 02109|
|Crecer: Centro de Reproducción y Genética Humana||Recruiting|
|Mar Del Plata, Buenos Aires, Argentina|
|Contact: Alicia Pené, BSc firstname.lastname@example.org|
|Contact: Débora Petrona, MD email@example.com|
|Principal Investigator: Alicia Pené, BSc|
|Saresa - Reproducción Humana Asistida||Recruiting|
|Salta, Argentina, 4400|
|Contact: María Florencia Giménez Marcuzzi, BSc +54 387-422-2272 firstname.lastname@example.org|
|Contact: Juan José Aguilera, MD +54 387-422-2272 email@example.com|
|Principal Investigator: María Florencia Giménez Marcuzzi, BSc|
|Nilo Frantz - Centro de Reprodução Humana||Not yet recruiting|
|Boa Vista, Porto Alegre, Brazil, 91330-002|
|Contact: Adriana Bos-Mikich, MD + 55 51 3328 4680 firstname.lastname@example.org|
|Contact: Nilo Frantz, MD +55 51 3328 4680 email@example.com|
|Principal Investigator: Nilo Frantz, MD|
|Vida - Centro de Fertilidade||Not yet recruiting|
|Rio De Janeiro, Brazil, 22793-080|
|Contact: María Cecilia de Almeida Cardoso, MD +55 21 2493 0758 firstname.lastname@example.org|
|Principal Investigator: María Cecilia de Almeida Cardoso, MD|
|Hôpital Foch||Not yet recruiting|
|Suresnes, France, 92150|
|Contact: Marine Poulain, PhD +33 (0)18.104.22.168.21 email@example.com|
|Principal Investigator: Marine Poulain, PhD|
|Principal Investigator: Jean-Marc Ayoubi, MD|
|Società Italiana Studi di Medicina della Riproduzione (S.I.S.M.e.R.)||Not yet recruiting|
|Bologna, Italy, 40138|
|Contact: Luca Gianaroli, MD 051 307307 firstname.lastname@example.org|
|Principal Investigator: Luca Gianaroli, MD|
|Centro Procreazione Assistita DEMETRA||Not yet recruiting|
|Firenze, Italy, 50141|
|Contact: Francesca Benini, MSc PhD (+39) 055 488709 email@example.com|
|Contact: Claudia Livi, MD (+39) 055 488709 firstname.lastname@example.org|
|Principal Investigator: Francesca Benini, MSc PhD|
|Promea S.p.A||Not yet recruiting|
|Torino, Italy, 10126|
|Contact: Antonio Monaco, MD +39 011-664-0800 email@example.com|
|Principal Investigator: Antonio Monaco, MD|
|Hospital Ruber Internacional||Recruiting|
|Madrid, Spain, 28035|
|Contact: Josu Franco Iriarte, PhD (+34) 913875017 firstname.lastname@example.org|
|Contact: Amelia Villa, MD (+34) 91387504 email@example.com|
|Principal Investigator: Elena Carrillo de Albornoz Riaza, MD PhD|
|Bahçeci Health Group||Not yet recruiting|
|Istanbul, Turkey, 34394|
|Contact: Meral Gultomruk, BSc (+90) 2123103100 firstname.lastname@example.org|
|Contact: Mustafa Bahçeci, MD PhD (+90) 2123103166 email@example.com|
|Principal Investigator: Mustafa Bahçeci, MD PhD|
|Principal Investigator:||Carmen Rubio, PhD||Igenomix S.L.|
|Study Chair:||Carlos Simón, MD PhD||Igenomix S.L.|