AzTrials
AzTrials

InfertilityPhase 3NCT01332643

Preimplantation Genetic Diagnosis (PGD) by Array Comparative Genome Hybridization (CGH) and Blastocyst Biopsy

A Phase 3 study testing Preimplantation Genetic Diagnosis in people with Infertility and Miscarriage, run by Reprogenetics at 1 site in Peru.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This study evaluates the effect of single embryo transfer (SET) with and without array CGH for the evaluation of the complete chromosome complement of the blastocyst. Patients will be allocated at random into two groups. Read more about this study

Who is it for?
Ages 30 to 42 years, women only
Conditions the study is for
Infertility, Miscarriage
What is being tested?
Preimplantation Genetic Diagnosis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 sitePeru
Study dates
Apr 2011to Sep 2012
Phase
Phase 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 30 to 42 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Couples with women 30-42 years of age
  • Follicle Stimulating Hormone (FSH) level <11IU/L on day 3 of cycle.

Who cannot join

  • TESA and TESE patients
  • Couples' carriers of chromosomal or genetic diseases
  • Couples that produce less than eight antral follicles on day 2-4 of cycle
  • Patients will be excluded if they produce no blastocysts by day 5

Trial locations and contacts

1 site in 1 country.

Peru1 site

  • Pranor

    Lima, Lima Province

Other trials in Peru

About this study

Official title: Comparison of Single Embryo Transfer With and Without Previous Analysis of All Chromosome Abnormalities Using Microarrays

This study evaluates the effect of single embryo transfer (SET) with and without array CGH for the evaluation of the complete chromosome complement of the blastocyst. Patients will be allocated at random into two groups. The control group will consist of patients in which one embryo will be replaced on day 5 based on morphological and developmental characteristics, and the other embryos reaching blastocyst stage will be vitrified. The test group will consist of patients undergoing embryo biopsy at the blastocyst stage (day 5 of development, embryo freezing, and analysis of the biopsied cells with a comprehensive chromosome analysis technique (array Comparative Genome hybridization or aCGH). Only a chromosomally normal blastocyst will be replaced in a thawed cycle. Inclusion and exclusion criteria are described in the study population section.

Read the detailed description

Rational for the study:

The goal of this study is to determine if the strategy employed for the Test group can solve two major problems in ART, one the still low implantation rate in women of advanced maternal age, and two the frequent occurrence of multiple pregnancies resulting from solving the first problem by replacing too many embryos.

Preimplantation Genetic Diagnosis (PGD) has been proposed as a potential means to achieve these goals, but so far, the results with day 3 biopsy and FISH analysis of 5-12 chromosomes has produced contradictory results, the difference between studies being explained by technical differences (Munne et al. 2010). Three technical developments have recently occurred that can change dramatically the efficacy of PGD. One, blastocyst laser assisted biopsy, which seems less detrimental than cleavage stage biopsy; Two, vitrification of embryos which allows those blastocysts to be frozen with little or no loss of viability, and three, chromosome comprehensive screening techniques, such as array CGH (Gutierrez-Mateo et al. 2011) which allow for the detection of all chromosome abnormalities.

Preliminary data from our center indicates that the technique to be used, an improvement on our prior technique CGH, will result in a very significant improvement in implantation rates and a reduction in miscarriage rates, thus justifying the use of single embryo transfer in this set up.

Supportive Preliminary Research:

In a recent study, the investigators observed a 1.6 fold increase (p < 0.001) in implantation rate when aCGH was applied to blastocyst embryos (Schoolcraft et al. 2010). The test group used CGH, an older and less sensitive iteration of the technique to be used in the proposed study - array CGH. Array CGH has a 6 megabase resolution and screens for 30% of all DNA bases (compared to 0.1% of SNP arrays). With array CGH the false positive and false negative rate is 0% when biopsying blastocysts, and 3% when biopsying day 3 embryos (Gutierrez Mateo et al, 2011). Based on our preliminary data, patients with 5 or more day 3 embryos and less than 43 years of age are the most likely to benefit from PGD, since they produce enough embryos and enough normal embryos so a selection technique, like PGD could chose them and improve their reproductive odds.

Also our PGD preliminary data shows a < 10% of embryo demise after implantation for a population 38 of age (expected would be about 28%).

Study Hypothesis The investigators foresee a significant increase in implantation rates in the Test group compared to the Control group. The investigators calculated that 60 patients in each arm would be needed to achieve a significant increase in implantation rates (p < 0.05) with a power of 80%, based on a comparative study in which the investigators observed a 1.6 fold increase in implantation rate (Schoolcraft et al. 2010).

Study population, interventions:

see below.

Being tested
Preimplantation Genetic Diagnosis
Keywords
Preimplantation Genetic Diagnosis, recurrent pregnancy loss, infertility, genetic screening, trisomy 21, Down syndrome
Medical subject headings
Infertility, Abortion, Spontaneous, Down Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Preimplantation Genetic DiagnosisGenetic

    Also called array CGH from Bluegnome, UK

    All embryos in the test group reaching blastocyst stage will undergo embryo biopsy of 3-10 trophectoderm cells. The cells will be analyzed by array CGH to detect the presence or not of chromosome abnormalities. The embryos will be vitrified and those classified by array CGH as normal, thawed for replacement.

Study groups in NCT01332643
Study groupRoleWhat they receive
TestActive comparatorThe test group will consist of patients undergoing blastocyst biopsy followed by vitrification (embryo freezing), and in which the biopsied cells will be analyzed with a comprehensive chromosome analysis technique (array Comparative Genome hybridization or aCGH) and only one chromosomally normal embryo will be replaced in a thawed cycle.
Receives: Genetic: Preimplantation Genetic Diagnosis
controlNo interventionThe control group will consist of patients in which one embryo will be replaced on day 5 based on morphological and developmental characteristics, and the other embryos reaching blastocyst stage will be vitrified. If patient does not become pregnant, successive embryo transfers of frozen embryos will be performed, but not as part of the study.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Implantation rate

    number of embryos implanted divided by number of embryos replaced. An embryo implanted is measured as a fetal sac by ultrasound observation.

    Measured: three weeks after embryo replacement

Secondary outcomes (4)

  1. miscarriage rate

    lost pregnancies, defined as pregnancies with an observed fetal sac that did not progressed to third trimester.

    Measured: up to the end of second trimester

  2. Pregnancy rate per transfer

    pregnancy defined as the presence of a fetal sac. Pregancy rate per transfer defined as pregnancies divided by patients with a replacement of embryos.

    Measured: three weeks after implantation

  3. Pregnancy rate per retrieval

    pregnancy defined as the presence of a fetal sac. Pregancy rate per retrieval defined as pregnancies divided by patients with an egg retrieval.

    Measured: three weeks after transfer

  4. live birth rate

    pregnancies that arrive to term divided by procedures with an egg retreival.

    Measured: 1 year after embryo transfer

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Apr 2011 (estimated)
  2. Study startApr 2011
  3. Primary completionAug 2012 (estimated)
  4. Study completionSep 2012 (estimated)

Why it stopped: Not enough patients enrolling

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01332643
Sponsor's protocol ID
Reprogenetics-02
Status last verified
May 2012
First submitted
7 Apr 2011
Last updated
30 May 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Gutierrez-Mateo C, Colls P, Sanchez-Garcia J, Escudero T, Prates R, Ketterson K, Wells D, Munne S. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011 Mar 1;95(3):953-8. doi: 10.1016/j.fertnstert.2010.09.010. Epub 2010 Oct 25.

    PubMed 20971462

  • Schoolcraft WB, Fragouli E, Stevens J, Munne S, Katz-Jaffe MG, Wells D. Clinical application of comprehensive chromosomal screening at the blastocyst stage. Fertil Steril. 2010 Oct;94(5):1700-6. doi: 10.1016/j.fertnstert.2009.10.015. Epub 2009 Nov 25.

    PubMed 19939370

  • Munne S, Wells D, Cohen J. Technology requirements for preimplantation genetic diagnosis to improve assisted reproduction outcomes. Fertil Steril. 2010 Jul;94(2):408-30. doi: 10.1016/j.fertnstert.2009.02.091. Epub 2009 May 5.

    PubMed 19409550

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Preimplantation Genetic Diagnosis in people with Infertility and Miscarriage, run by Reprogenetics at 1 site in Peru.

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: stopped early, as of the sponsor's last update on 30 May 2012. 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 Peru. 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 phase mean?

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 was stopped early (reason given: Not enough patients enrolling). Results are not available in the source record.

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?

Implantation rate (time frame: three weeks after embryo replacement). 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 NCT01332643, which also lists 3 linked publications.

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 30 May 2012.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
Clinical Trial NCT01332643 | AzTrials