A Randomized Comparison of Microfluidic Chip vs Density Gradient Centrifugation on the Euploidy Rate of Pre-implantation Genetic Testing
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 318
- Locations
- 1
- Primary Endpoint
- Euploid rate of blastocysts
Study Overview
Brief Summary
Infertile women attending for PGT at the Centre of Assisted Reproduction and Embryology, Queen Mary Hospital and Kwong Wah Hospital will be recruited during ovarian stimulation for IVF. Subsequently, they will be randomly assigned on the day of oocyte retrieval by a laboratory staff into one of the following two groups in a 1:1 ratio : (1) the microfluidic chip group and (2) the density gradient centrifugation group for sperm preparation and subsequent use in fertilization. Other IVF procedures will be the same as the standard practice of the Centre. Both women and clinicians will be blinded from the group allocation i.e. a double blind study.
Detailed Description
The study aims to investigate the treatment of couples undergoing in vitro fertilization (IVF). Eligible couples will be recruited for the study after providing informed written consent following counseling. The IVF protocol involves various steps. Women will undergo preimplantation genetic testing (PGT) as clinically indicated. Ovarian stimulation will be carried out using gonadotropin injections, and regular ultrasound monitoring will be conducted to track the growth of follicles. To prevent a premature LH surge, progestin primed ovarian stimulation or a GnRH antagonist will be administered. Once at least three follicles reach a size of over 17 mm, a trigger injection of either human chorionic gonadotrophin or a GnRH agonist will be given to induce final maturation. Oocyte retrieval will be performed 36 hours after the trigger under transvaginal ultrasound guidance.
The recruited women will be randomly assigned to one of two groups: the microfluidic chip group or the density gradient centrifugation group. Randomization and blinding will be ensured to maintain the integrity of the study. Only the laboratory staff involved in sperm preparation will be aware of the group assignment, while the women and clinicians will be blinded to the treatment groups.
Semen specimens will be collected by masturbation on the day of oocyte retrieval, following a period of 2-7 days of sexual abstinence. The semen samples will undergo evaluation according to WHO guidelines, including semen volume, sperm concentration, and percent motile spermatozoa. Sperm DNA damage will be assessed using an alkaline single-cell gel electrophoresis (Comet) assay. The extent of DNA damage in spermatozoa will be examined using specific parameters.
Sperm preparation will be performed based on the randomization list. In the microfluidic chip group, the Sperm Separation Device will be used, and the prepared sample will be collected in a test tube. In the density gradient centrifugation group, sperm preparation will be completed using a discontinuous density gradient centrifugation method, and the resulting sperm pellet will be washed and resuspended.
Oocytes will be fertilized through intracytoplasmic sperm injection, and normal fertilization will be confirmed by the presence of two pronuclei. A few cells will be taken from the blastocysts for comprehensive chromosome analysis. Cryopreservation of all blastocysts will be done, and only euploid blastocysts without aneuploidies will be replaced in subsequent frozen embryo transfer cycles.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
On the day of oocyte retrieval, recruited women will be randomly assigned into one of the following two groups according to a computer-generated randomization list with a 1:1 ratio and a block size of 10. The randomization list will be prepared by a designated research nurse who is not involved in care of the women and opened by a laboratory staff.
- The microfluidic chip group and
- The density gradient centrifugation group
The women and clinicians will be blinded to the treatment groups they are assigned. Only the laboratory staff in the IVF laboratory performing sperm preparation will be aware of the group assignment.
Eligibility Criteria
- Ages
- — to 43 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Women aged <43 years at the time of ovarian stimulation for IVF
- •Women undergoing PGT for monogenic diseases, structural rearrangement of chromosomes or aneuploidy
- •Sperm concentration of the raw semen with at least 0.15 million motile sperm per ml or 100 motile sperm per 50 low power field (200x) of observation
Exclusion Criteria
- •Use of frozen semen for insemination
- •Use of donor oocytes and spermatozoa
- •Submucosal fibroid or hydrosalpinx shown on pelvic scanning and not surgically treated;
- •Women who had been recruited into this study before and
- •Women joining other randomized trials
Outcomes
Primary Outcomes
Euploid rate of blastocysts
Time Frame: 3 months
Euploid rate of blastocysts biopsied
Secondary Outcomes
- Ongoing pregnancy rate(3 years)
- DNA fragmentation(3 years)
- Live birth rate of the first embryo transfer(3 years)
- Miscarriage rate pregnancy(3 years)
- Clinical pregnancy rate of the first embryo transfer(3 years)
- Positive urine pregnancy test rate per the first embryo transfer(3 years)
- Multiple pregnancy rate(3 years)
- Ectopic pregnancy rate(3 years)
Investigators
Professor Ernest Hung-Yu Ng
Clinical Professor
The University of Hong Kong