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

ISRCTN	ISRCTN41698043
DOI	https://doi.org/10.1186/ISRCTN41698043
Secondary identifying numbers	18112011

Submission date: 18/11/2011
Registration date: 09/12/2011
Last edited: 12/06/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Urological and Genital Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

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

Contact information

Dr Francesco Fiorentino
Scientific

Via di Castel Giubileo, 11
Rome
00138
Italy

Phone	+39 (0)68 811 270
Email	fiorentino@laboratoriogenoma.it

Study information

Study design	Prospective randomised double-blinded study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
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
Study objectives	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(s)	The Local Ethics Committee (Genoma, Rome, Italy), 18/10/2011
Health condition(s) or problem(s) studied	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
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 study start date	01/12/2011
Completion date	31/12/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target number of participants	200
Key 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
Key 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)
Date of first enrolment	01/12/2011
Date of final enrolment	31/12/2012

Locations

Countries of recruitment

Italy

Study participating centre

Via di Castel Giubileo, 11

Rome
00138
Italy

Sponsor information

BlueGnome Ltd (UK)
Industry

Breaks House
Mill Court
Great Shelford
Cambridge
CB22 5LD
United Kingdom

Phone	+44 (0)122 384 4441
Email	info@cambridgebluegnome.com
Website	http://www.cambridgebluegnome.com/
"ROR"	https://ror.org/027c2yv63

Funders

Funder type

Industry

Genoma Molecular Genetics Laboratory (Italy)

No information available

Genera (Italy)

No information available

BlueGnome (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

12/06/2017: Plain English summary added.