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Trial registered on ANZCTR


Registration number
ACTRN12618000603213
Ethics application status
Approved
Date submitted
20/03/2018
Date registered
18/04/2018
Date last updated
14/01/2019
Date data sharing statement initially provided
14/01/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of PIEZO ICSI to improve fertilisation rates of oocytes
Scientific title
Determining the effect of intracytoplasmic sperm injection using a Piezo ICSI technique on fertilisation rates of oocytes.
Secondary ID [1] 294394 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
PIEZO Trial
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Infertility 307122 0
Condition category
Condition code
Reproductive Health and Childbirth 306236 306236 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This trial is for the use of an alternative method for intracytoplasmic sperm injection (ICSI) using a Piezo ICSI machine. Piezo ICSI will be performed by trained senior embryologists at Repromed for our patients that have consented to partaking in the trial. The most common form of ICSI uses a bevelled spiked pipette to penetrate the zona pellucid where the cytoplasm is aspirated into the micropipette to break the membrane. After the membrane is broken the sperm is injected into the cytoplasm and the micropipette is withdrawn (termed conventional ICSI). In piezo-ICSI a piezoelectric actuator is used to move the capillary in an ultra rapid fashion by producing ultra-fast submicron motion which propels the capillary forward. The way this works is that the actuator is made of material that when a voltage is applied it changes shape and thus extrudes a force which moves the capillary in a forward jack hammer like motion. This technique is a more ‘gentle’ approach to the standard ICSI technique and therefore may improve outcomes as there is no bevel or spike on the pipette and may reduce the level of damage on the egg.

The duration of the sperm injection procedure depends on the number of eggs being injected however, the time spent per egg should not significantly differ from the standard. despite this the time for each egg injected will be recorded and compared to routine ICSI cases to ensure they are comparable. All injections will be undertaken by trial co-investigators.
Intervention code [1] 300687 0
Treatment: Devices
Comparator / control treatment
The control group will be patients that have insemination using the standard ICSI technique currently used. The most common form of ICSI uses a bevelled spiked pipette to penetrate the zona pellucid where the cytoplasm is aspirated into the micropipette to break the membrane. After the membrane is broken the sperm is injected into the cytoplasm and the micropipette is withdrawn (termed conventional ICSI). In addition prior to injection the sperm is immobilised using a striking technique. During this process the sperm flagellum is crushed by sliding the needle on the mid proportion of the flagellum until a kink is seen. The immobilisation technique is necessary to ensure leakage of cytosolic factors through the site of the damaged sperm membrane into the ooplasm which will hopefully facilitate commencement of the fertilisation process.
Control group
Active

Outcomes
Primary outcome [1] 305254 0
normal fertilisation rate. Fertilisation of oocytes will be assessed the morning after insemination. Normal fertilisation of an oocyte is assessed by the presence of 2 polar bodies and 2 pronuclei. This is visualised by a scientist under a microscope, no further tool or tests will be used or are applicable..
Timepoint [1] 305254 0
The day after injection when fertilisation can be assessed
Secondary outcome [1] 344645 0
oocyte degeneration rate. This is determined visually down a microscope by a scientist and is indicated by collapse of cytoplasmic membrane and degeneration of cytoplasm.
Timepoint [1] 344645 0
The day after injection when fertilisation can be assessed is single time-point to assess oocyte degeneration.
Secondary outcome [2] 344793 0
embryo quality. This is determined visually down a microscope by a scientist on day 3, 4, 5 and 6 of embryo culture.
Timepoint [2] 344793 0
A day 3 assessment is performed to track embryo development. A day 4/day 5 assessment is performed to assess suitability for transfer and /or day 5/day 6 assessment for embryos that are of a suitable quality to be frozen
Secondary outcome [3] 344795 0
Pregnancy rate.
Timepoint [3] 344795 0
This is determined by measuring the patients blood 16 days after egg collection for beta HCG level.
Secondary outcome [4] 344796 0
Fetal heart assessment
Timepoint [4] 344796 0
This is measured by ultrasound at between 6 to 8 weeks post egg collection.
Secondary outcome [5] 345646 0
Miscarriage rate
Timepoint [5] 345646 0
This is determined as the % of pregnancies that not determined to be on going after initial fetal heart scan at 6 to 8 weeks post egg collection.

Eligibility
Key inclusion criteria
All participants must be patients of Repromed who have booked on for IVF treatment where their clinician recommends ICSI as insemination method of choice.
Consenting patients must have greater than or equal to 6 mature oocytes for injection post egg retrieval.
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Gamete donor cycles
Surgical sperm collection requirements
Previous cycle with an ICSI fertilisation of <30%

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sixty-nine patient couples will be recruited by informed consent to participate in this trial to investigate the efficacy of the Piezo intracytoplasmic sperm injection (ICSI) technique as an alternative to standard ICSI. This number of participants has been calculated using a power analysis to detect a 10% increase in fertilisation rate. To adequately power the experiment to achieve the primary outcome of an increase in fertilisation rate, with a statistical significance level set at 0.05 and 90% power, a minimum of 418 oocytes will be required. If each patient has 6 oocytes then sixty-nine participants will be required maximum for enrolment to gain adequate data around the primary outcome.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 10424 0
Repromed Day Surgery - Dulwich
Recruitment postcode(s) [1] 22117 0
5065 - Dulwich

Funding & Sponsors
Funding source category [1] 299029 0
Commercial sector/Industry
Name [1] 299029 0
Repromed
Address [1] 299029 0
180 Fullarton Road Dulwich SA 5065
Country [1] 299029 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Repromed
Address
180 Fullarton Road Dulwich SA 5065
Country
Australia
Secondary sponsor category [1] 298254 0
None
Name [1] 298254 0
Address [1] 298254 0
Country [1] 298254 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299964 0
Women's and Children's Health Network (WCHN) Human Research Ethics Committee's (HREC)
Ethics committee address [1] 299964 0
72 King William Road North Adelaide 5006 South Australia
Ethics committee country [1] 299964 0
Australia
Date submitted for ethics approval [1] 299964 0
18/04/2018
Approval date [1] 299964 0
11/09/2018
Ethics approval number [1] 299964 0
HREC/18/WCHN/46

Summary
Brief summary
The purpose of this study is to investigate the efficacy of piezo ICSI as an alternative to the traditional ICSI technique for human oocyte insemination and to assess if fertilisation rates can be improved. We will be able to assess if this alternative technique which uses a Piezo machine will decrease oocyte degeneration rates as well as improving embryo quality and pregnancy rates. A previous study demonstrated that a significantly higher survival rate post injection was seen for oocytes being injected with piezo rather than conventional ICSI (90% vs 95%) and were higher still using the ultra fine piezo pipette (99%). Fertilisation rates were also higher with piezo ICSI and higher still with ultra fine micropipette ICSI (68% vs 89%) and increased quality of D3 embryos was seen in the piezo groups compared to conventional ICSI. It is hypothesised that the lack of cytoplasmic aspiration coupled with a smaller injection site results in less oocyte damage and is the reason behind the improved outcomes seen. Patients will be recruited from Repromed Dulwich ICSI patient group that have booked on for treatment. To determine the efficacy of this technology initially patients recruited will need to meet the following inclusion criteria to ensure adequate oocytes retrieved so fertilisation data and embryos quality can be assessed in a statistically meaningful manner: Couple for whom the treating clinician recommends ICSI as insemination method of choice and those that have 6 or more mature oocytes for injection post egg retrieval. The hypothesis for this trial is that the use of piezo ICSI technology will increase fertilisation rates and decrease oocyte degeneration rates compared to conventional ICSI. Patient’s outcomes will be compared to a matched cohort of patients that are not participating in the Piezo trial undertaking treatment at a similar time in a 1:2 fashion. The proposed research protocol is as follows:
1. Patients interested in partaking in the trial will be provided with information sheet and consent form and will be contacted by the research team and provided the information sheet and consent form via email and opportunity to ask questions. Patients will be approached by recruitment staff from the list of patients booked on for ICSI treatment.
2. Consent to partake will need to be obtained on or before the day of egg retrieval
3. Patients will be flagged on paperwork at egg retrieval that they are participating in the PIEZO trial so lab can activate plan
4. If patient has less than 6 mature oocytes for injection they will be unable to partake in the trial as this is insufficient number of oocytes to draw adequate conclusions and will instead be inseminated via conventional ICSI
5. If patient has greater than or equal to 6 mature oocytes from injection they will be fully enrolled in the trial and oocytes will be piezo injected
6. Normal laboratory practice occurs from this point onwards


Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82106 0
Dr Deirdre Zander-Fox
Address 82106 0
Repromed. 180 Fullarton Road Dulwich. South Australia. 5065
Country 82106 0
Australia
Phone 82106 0
+61 (08) 83338111
Fax 82106 0
+61 (08) 8333 8188
Email 82106 0
dzander@repromed.com.au
Contact person for public queries
Name 82107 0
Dr Deirdre Zander-Fox
Address 82107 0
Repromed. 180 Fullarton Road Dulwich. South Australia. 5065
Country 82107 0
Australia
Phone 82107 0
+61 (08) 83338111
Fax 82107 0
+61 (08) 8333 8188
Email 82107 0
dzander@repromed.com.au
Contact person for scientific queries
Name 82108 0
Dr Deirdre Zander-Fox
Address 82108 0
Repromed. 180 Fullarton Road Dulwich. South Australia. 5065
Country 82108 0
Australia
Phone 82108 0
+61 (08) 83338111
Fax 82108 0
+61 (08) 8333 8188
Email 82108 0
dzander@repromed.com.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
there is no plan to make IPD available
What supporting documents are/will be available?
No other documents available
Summary results
No Results