Plain English Summary
Background and study aims
In vitro fertilisation (IVF) is a technique to help people with fertility problems to have a baby. During IVF, an egg is removed from the woman's ovaries and fertilised with sperm in a laboratory (intra-cytoplasmic sperm injection [ICSI]). The fertilised egg (embryo) is then returned to the woman's womb to grow and develop. Preimplantation genetic screening (PGS) involves checking the embryos for common chromosome abnormalities. PGS has mainly involved checking a limited number of chromosomes (5-9 chromosomes). Embryos with the correct number of chromosomes are selected for transfer to the woman's womb. However, this test has produced contradictory results that can be explained by technical differences and the limited number of chromosomes assessed. The 24 chromosomes array-comparative genomic hybridization (array-CGH) PGS test involves assessing all 24 chromosomes, which may overcome the technical difficulties that beset earlier PGS studies. Therefore, the aim of this study is to find out whether PGS for all 24 chromosomes by array-CGH increases pregnancy and live birth rates.
Who can participate?
Women aged 36 or younger with a history of more than two failed IVF/ICSI cycles without pregnancy
What does the study involve?
Participants are randomly allocated to undergo ICSI either with or without PGS for all 24 chromosomes by array-CGH. The morphology (shape) of the embryos obtained and the pregnancy and live birth rates in both groups are compared.
What are the possible benefits and risks of participating?
PGS is provided free of charge and may improve the participants’ odds of conceiving. The information obtained from this study may also help to advance the science involved with PGS in IVF. Egg retrieval is a common procedure, but complications can still sometimes occur. There are risks involved with any treatment involving fertility drugs and egg retrieval.
Where is the study run from?
GENOMA Molecular Genetics Laboratory (Italy)
When is the study starting and how long is it expected to run for?
December 2011 to December 2012
Who is funding the study?
1. BlueGnome (UK)
2. GENOMA Molecular Genetics Laboratory (Italy)
3. Genera (Italy)
Who is the main contact?
Dr Francesco Fiorentino
fiorentino@laboratoriogenoma.it
Trial website
Contact information
Type
Scientific
Primary contact
Dr Francesco Fiorentino
ORCID ID
Contact details
Via di Castel Giubileo
11
Rome
00138
Italy
+39 (0)68 811 270
fiorentino@laboratoriogenoma.it
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
18112011
Study information
Scientific title
Preimplantation genetic screening (PGS) by array-comparative genomic hybridization (CGH) on day 5 embryos with day 6 fresh transfer in repeated implantation failure (RIF) patients: a randomised double-blinded study
Acronym
Study hypothesis
Patients with repeated implantation failure (RIF) have a higher ongoing pregnancy rate and live birth rate after embryo transfer of embryos with a normal chromosomal pattern analysed by 24 chromosome aneuploidy screeninig (PGS) compared with patients who had an embryo transfer on day 6 without PGS.
Ethics approval
The Local Ethics Committee (Genoma, Rome, Italy), 18/10/2011
Study design
Prospective randomised double-blinded study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Infertility
Intervention
Control group: ICSI procedure, day 5 Laser Assisted drilling without Preimplantaion Genetic Screening, day 6 embryo transfer
Study group: ICSI and Preimplantation Genetic Screening with array-CGH, embryo biopsy on day 5, day 6 embryo transfer
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measure
Live birth rate [Time Frame: 1 year after embryo transfer]; pregnancies that arrive to term divided by procedures with an egg retrieval
Secondary outcome measures
1. Ongoing pregnancy rate per embryo transfer [Time Frame: 20 weeks after embryo transfer]. Ongoing pregnancy defined as the presence of a fetal sac. Pregnancy rate per transfer defined as pregnancies divided by patients with a replacement of embryos.
2. Pregnancy rate per retrieval [Time Frame: 20 weeks after embryo transfer]. pregnancy defined as the presence of a fetal sac. Pregnancy rate per retrieval defined as pregnancies divided by patients with an egg retrieval.
3. Ongoing pregnancy rate per started cycle [ Time Frame: 20 weeks after embryo transfer ]
4. Ongoing implantation rate [Time Frame: 12 weeks after embryo transfer ]
5. Number of embryos implanted divided by number of embryos replaced. An embryo implanted is measured as a fetal sac by ultrasound observation.
6. Embryo transfer rate per started cycle
Overall trial start date
01/12/2011
Overall trial end date
31/12/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Female patients aged 36 years old or younger undergoing an Intra-cytoplasmic sperm injection (ICSI) attempt at GENERA Clinic in Rome
2. History of more than two failed In vitro fertilisation (IVF)/ICSI cycles; without clinical pregnancy with transfer of at least one good quality embryos per transfer
3 .≥6 metaphase II (MII) oocytes retrieved
4. Signed consent form
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
200
Participant exclusion criteria
1. Azoospermic male partner
2. Severe male factor infertility defined as ejaculate sperm of < 1million sperm/ml
3. Hydrosalpinx
4. Polycystic ovary syndrome (PCOS)
5. Pre-implantation genetic diagnosis (PGD) cycles [Single Gene Disorders (SGD) or Translocations or other chromosomal abmormalities]
6. Female patients with pathological uterine cavity
7. Number of retrieved MII oocytes < 6
8. Known American Society for Reproductive Medicine (ASRM) Grade III or IV endometriosis
9. Maternal disease that is not clinically stable and known to impact the ability to become pregnant or carry a pregnancy to term (lupus, chronic liver or kidney disease, body mass index (BMI) >35, uncontrolled hypertension, anti-phospholipid antibody, thrombophilia, insulin dependent diabetes)
Recruitment start date
01/12/2011
Recruitment end date
31/12/2012
Locations
Countries of recruitment
Italy
Trial participating centre
Via di Castel Giubileo, 11
Rome
00138
Italy
Sponsor information
Organisation
BlueGnome Ltd (UK)
Sponsor details
Breaks House
Mill Court
Great Shelford
Cambridge
CB22 5LD
United Kingdom
+44 (0)122 384 4441
info@cambridgebluegnome.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Genoma Molecular Genetics Laboratory (Italy)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Genera (Italy)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
BlueGnome (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list