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

May 25, 2012 updated by: Reprogenetics

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Peru
      • Lima, Peru
        • Pranor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 42 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Test
The 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.
Genetic: Preimplantation Genetic Diagnosis
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.
Other Names:
  • array CGH from Bluegnome, UK
No Intervention: control
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. If patient does not become pregnant, successive embryo transfers of frozen embryos will be performed, but not as part of the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Implantation rate
Time Frame: three weeks after embryo replacement
number of embryos implanted divided by number of embryos replaced. An embryo implanted is measured as a fetal sac by ultrasound observation.
three weeks after embryo replacement

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
miscarriage rate
Time Frame: up to the end of second trimester
lost pregnancies, defined as pregnancies with an observed fetal sac that did not progressed to third trimester.
up to the end of second trimester
Pregnancy rate per transfer
Time Frame: three weeks after implantation
pregnancy defined as the presence of a fetal sac. Pregancy rate per transfer defined as pregnancies divided by patients with a replacement of embryos.
three weeks after implantation
Pregnancy rate per retrieval
Time Frame: three weeks after transfer
pregnancy defined as the presence of a fetal sac. Pregancy rate per retrieval defined as pregnancies divided by patients with an egg retrieval.
three weeks after transfer
live birth rate
Time Frame: 1 year after embryo transfer
pregnancies that arrive to term divided by procedures with an egg retreival.
1 year after embryo transfer

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Reprogenetics

Collaborators

McGill University
Yale University
Reprogenetics Lationoamerica S.A.C, Lima, Peru
Pranor S.R.L., Lima, Peru

Investigators

  • Principal Investigator: Santiago Munne, PhD, Reprogenetics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2011

Primary Completion (Anticipated)

August 1, 2012

Study Completion (Anticipated)

September 1, 2012

Study Registration Dates

First Submitted

April 7, 2011

First Submitted That Met QC Criteria

April 8, 2011

First Posted (Estimate)

April 11, 2011

Study Record Updates

Last Update Posted (Estimate)

May 30, 2012

Last Update Submitted That Met QC Criteria

May 25, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Reprogenetics-02

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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