Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000230358
Ethics application status
Approved
Date submitted
25/01/2017
Date registered
13/02/2017
Date last updated
25/11/2019
Date data sharing statement initially provided
20/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The impact of pH on fertilisation in human oocytes
Scientific title
The impact of pH on fertilisation in human oocytes retrieved from women receiving ovarian hyperstimulation as part of IVF (in vitro fertilisation) or ICSI (intra-cytoplasmic sperm injection) treatment.
Secondary ID [1] 291009 0
Nil known
Universal Trial Number (UTN)
U1111-1182-9015
Trial acronym
n/a
Linked study record
n/a

Health condition
Health condition(s) or problem(s) studied:
IVF 301781 0
Infertility 301782 0
Condition category
Condition code
Reproductive Health and Childbirth 301471 301471 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a prospective randomized controlled study. The population to be included as part of this study will be patients already undergoing (having had cycles previously) or about to commence fertility treatment for the first time at Westmead Fertility Centre.
This study will focus on the oocytes collected from these women following ovarian hyperstimulation, which is part of a normal treatment cycle. We will only analyse oocytes from women who have greater than or equal to 8 eggs collected (so that eggs can be randomly assigned to the two different culture pH treatment groups).
Patients undergoing either IVF (in vitro fertilisation) or ICSI (intra-cytoplasmic sperm injection) treatment cycles will be considered for this study. The treatment route (IVF vs. ICSI) is predefined in accordance with the Westmead Fertility Centre protocol, and based on a series of tests (semen analyses etc.) before entering into the study.
The duration of participation is relatively brief as it will be within their treatment cycle, from the point of egg collection that the study commences, and runs until the fertilisation check (approximately 16-19 hours later).
For participants undergoing an IVF cycle, their eggs (in the form of cumulus-oocyte-complexes) will be washed and split evenly between two separate dishes containing different pH G-IVF labelled with A and B. pH of solution A is 7.3 and pH of solution B is 7.45
The eggs will be maintained in the incubator at 37 degrees centigrade and 5 percent CO2 (as standard) until insemination with her partners’ sperm 3-4 hours after egg collection.
Insemination will be using 100,000 sperm (as standard) overnight in the incubator. Fertilisation check will be carried out early morning the next day. Results will be recorded in the WFC database initially, then transferred to the results table for this study.
For participants undergoing an ICSI cycle, the process differs slightly. After egg collection oocytes will be denuded of their surrounding cumulus cells (as standard), split evenly into two separate dishes containing different pH G-IVF labelled A and B (pH of solution A is 7.3 and pH of solution B is 7.45) and left in the incubator at 37 degrees centigrade and 5 percent CO2 for 1 hour to rest (as standard).
After 1 hour, oocytes from dish A will be transferred into ICSI dish A (containing GMOPS media of the same pH, solution A is 7.3 and pH of solution B is 7.45), the spindle will first be visualised and its retardance measured using the Oosight polarised light microscope, before being injected with the partner sperm. The eggs will then be transferred back to a new dish A containing GIVF of the same pH. The same process will be repeated for dish B oocytes. The same embryologist will carry out the ICSI for type A and B eggs.
The eggs will then be placed in the incubator overnight to allow for fertilisation. Fertilisation check will be carried out early morning the next day. Results will be recorded in the WFC database initially, then transferred to the results table for this study.
Intervention code [1] 296973 0
Treatment: Other
Comparator / control treatment
The control group will be the eggs from the patient which are placed in solution A, as this is at pH 7.3, and the standard pH of media used in our clinic. The eggs which are placed in solution B will act as the treatment group, with the results being compared to those from solution A.
Control group
Active

Outcomes
Primary outcome [1] 300865 0
Number of eggs fertilised in solution A (control group) will be compared with the number of eggs fertilised in solution B (treatment group). Fertilisation will be compared by positively identifying the presence of two pronuclei inside the egg the day after it has been exposed to sperm (either via in vitro fertilisation or intra-cytoplasmic sperm injection).
Timepoint [1] 300865 0
16-19hrs post exposure to partner sperm
Secondary outcome [1] 331072 0
The fertilised eggs will be kept in the lab for upto 5 days for pre-implantation development before they are transferred back to the patients uterus.
The eggs which were fertilised in solution A (control) will be kept separately from the eggs fertilised in solution B (treatment group) throughout the pre-implantation development period. Embryo grading will be performed on all embryos on the day of transfer (as standard) this could be day 2, 3 or 5 of embryo development. Grades will be recorded per embryo to allow for retrospective analysis to understand if pH at the time of fertilisation has an impact on embryo quality.
Timepoint [1] 331072 0
Embryo grades are awarded on the day of embryo transfer - this may be either 2, 3 or 5 days after fertilisation has taken place (routine practice). The grade will be recorded in the patient notes and then transferred to our secure database.
Embryo grading is carried out using the Gardner Scoring System, which is used universally to score embryos.

Eligibility
Key inclusion criteria
Patients will be asked if they would like to participate if they present for fertility treatment at WFC and fulfil the following:
1) Good understanding/ability of English language to enable them to give an informed consent
2) Less than 42 years old at the time of her treatment cycle
3) Equal to or greater than 8 oocytes collected
4) No more than one prior failed fresh cycle at WFC
5) Heterosexual and same sex couples will be offered to take part
Minimum age
18 Years
Maximum age
41 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients will be excluded from this study if;
1) There is severe male factor infertility requiring sperm extraction via microdissection/open biopsy (PESA/TESA patients can be included)
2) A prior history of poor fertilisation (less than 50 percent oocytes fertilising normally)
3) Oncology patients
4) Unable to speak English without assistance of an interpreter

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
For IVF cases, allocation is not concealed as the eggs will be split evenly between solution A (control) and solution B (treatment). In cases where there is an odd number of eggs the embryologist will randomly decide whether the extra egg goes in solution A or B.
For ICSI cases, allocation concealment will be applied when the embryologist has to divide the eggs into either solution A (control) or solution B (treatment pH). Eggs will be washed first and all placed together in a single dish, eggs will then be denuded using hyaluronic acid (as per standard treatment).
After denudation eggs will be randomly split into dish A or dish B based on the number of MII (mature).
MI eggs (not yet mature) will be assigned a number from a random generator (www.random.org) and if an even number is generated then they will be assigned to dish A, if odd then dish B. From this point eggs will remain either A or B and left for one hour in the incubator prior to injection with partner sperm.
ICSI will be carried out in either an A or B dish, with eggs being transferred to either an A or B GIVF dish for incubation overnight to allow for fertilisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
www.random.org will be used to assign eggs to A or B (even numbers Group A and odd numbers Group B).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The primary outcome of fertilisation rate in both treatment groups will be analysed using Fisher’s non-parametric permutation test for paired observations.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
6/03/2017
Actual
10/04/2017
Date of last participant enrolment
Anticipated
28/08/2020
Actual
Date of last data collection
Anticipated
28/08/2020
Actual
Sample size
Target
300
Accrual to date
240
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7389 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 15182 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 295435 0
Commercial sector/Industry
Name [1] 295435 0
Westmead Fertility Centre
Country [1] 295435 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Westmead Fertility Centre
Address
G Block, Level 2
Westmead Hospital
Westmead
NSW 2145
Country
Australia
Secondary sponsor category [1] 294256 0
None
Name [1] 294256 0
Address [1] 294256 0
Country [1] 294256 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296768 0
Bellberry Limited
Ethics committee address [1] 296768 0
Ethics committee country [1] 296768 0
Australia
Date submitted for ethics approval [1] 296768 0
01/06/2016
Approval date [1] 296768 0
12/07/2016
Ethics approval number [1] 296768 0
2016-01-055

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1399 1399 0 0
/AnzctrAttachments/371354-ApprovalLetter-HREC2016-01-055.pdf (Ethics approval)

Contacts
Principal investigator
Name 68474 0
Dr Cecilia Sjoblom
Address 68474 0
Westmead Fertility Centre
Westmead Hospital
G Block, Level 2
Westmead NSW 2145
Country 68474 0
Australia
Phone 68474 0
+61 2 9845 7484
Fax 68474 0
Email 68474 0
[email protected]
Contact person for public queries
Name 68475 0
Harriet Swearman
Address 68475 0
Westmead Fertility Centre
Westmead Hospital
G Block, Level 2
Westmead NSW 2145
Country 68475 0
Australia
Phone 68475 0
+61412874668
Fax 68475 0
Email 68475 0
[email protected]
Contact person for scientific queries
Name 68476 0
Harriet Swearman
Address 68476 0
Westmead Fertility Centre
Westmead Hospital
G Block, Level 2
Westmead NSW 2145
Country 68476 0
Australia
Phone 68476 0
+61412874668
Fax 68476 0
Email 68476 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data is anonymised


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.