Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001139662
Ethics application status
Approved
Date submitted
10/10/2014
Date registered
28/10/2014
Date last updated
17/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of in vitro embryo culture conditions on metabolism of optimal human embryos in infertile couples
Scientific title
Which cultivation conditions could yield more optimal human embryos of infertile couples using different levels of oxygen ( 5% versus 20% O2) by using morphokinetics and a method of profiling amino acids
Secondary ID [1] 285475 0
none
Universal Trial Number (UTN)
U1111-1162-7559
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
infertility 293252 0
Condition category
Condition code
Reproductive Health and Childbirth 293523 293523 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomized cultivation of human embryos with different levels of oxygen (5% versus 20%) from the day of fertilization (day 0) till the day of embryo transfer (day 5). On the day 3, the best embryos (based on morphokinetics) will be cultivated separately till the day 5. On the day 5, blastocyst media of the transffered embryo will be analyzed by LC-MS/MS ( liquid chromatography-mass spectrometry) to identify specific metabolic amino acid profile of the transffered embryos.
Intervention code [1] 290412 0
Treatment: Other
Comparator / control treatment
Comparator treatment is cultivation of embryos with 20% O2 as it was standard treatment for many years.
Control group
Active

Outcomes
Primary outcome [1] 293340 0
Clinical Pregnancy Rate (CPR) - assessed by serum hCG assay and fetal ultrasound
Timepoint [1] 293340 0
4 weeks after embryo transfer
Primary outcome [2] 293341 0
Fertilization Rate (FR) - assessed by checking pronuclear stage of oocytes on day 1 by microscope evaluation
Timepoint [2] 293341 0
24 hours after oocite pick-up
Primary outcome [3] 293342 0
Amino acid profiles of transffered embryos - assessed by LC-MS/MS (liquid chromatography-mass spectrometry)
Timepoint [3] 293342 0
On the day 5 of cultivation
Secondary outcome [1] 310821 0
Live birth rate (LBR) - assessed by live birth of a child
Timepoint [1] 310821 0
About 9 months after embryo transfer

Eligibility
Key inclusion criteria
Infertile patients in stimulated cycles
Minimum age
22 Years
Maximum age
42 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Severe male infertility (azoospermia, cryptozoospermia)

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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
Number of participants is defined by power analysis of chi quadrat test and with respect to number of patients in our clinic.Number of participants is 100. Female participants are divided in 3 age categories: 22-34, 35-39 and 40-42. Number of patients of each group should be over 30.
Data will be analyzed by Kolmogorov-Smirnov Test and due to the given results parametric or non-parametric test will be used: chi quadrat test, t-test, Mann-Whitney U test, Kruskal-Wallis test.

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
92 samples were collected and the study stopped before collection of 100 samples because our hospital changed culture media supplier and different cultivation conditions would cause bias.
Date of first participant enrolment
Anticipated
3/11/2014
Actual
1/03/2015
Date of last participant enrolment
Anticipated
22/12/2016
Actual
18/10/2016
Date of last data collection
Anticipated
18/07/2017
Actual
18/07/2017
Sample size
Target
100
Accrual to date
Final
92
Recruitment outside Australia
Country [1] 6403 0
Croatia
State/province [1] 6403 0
Zagreb

Funding & Sponsors
Funding source category [1] 290077 0
Hospital
Name [1] 290077 0
Clinical Hospital Centre Zagreb
Country [1] 290077 0
Croatia
Primary sponsor type
Individual
Name
NINA GELO
Address
Clinical Hospital Centre Zagreb, Petrova 13, 10 000 Zagreb
Country
Croatia
Secondary sponsor category [1] 288772 0
None
Name [1] 288772 0
Address [1] 288772 0
Country [1] 288772 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291792 0
University of Zagreb, School of Medicine
Ethics committee address [1] 291792 0
Salata 3, 10 000 Zagreb
Ethics committee country [1] 291792 0
Croatia
Date submitted for ethics approval [1] 291792 0
13/05/2014
Approval date [1] 291792 0
17/06/2014
Ethics approval number [1] 291792 0
Ethics committee name [2] 291793 0
University Hospital Centre Zagreb
Ethics committee address [2] 291793 0
Kispaticeva 12, 10 000 Zagreb
Ethics committee country [2] 291793 0
Croatia
Date submitted for ethics approval [2] 291793 0
15/05/2014
Approval date [2] 291793 0
17/06/2014
Ethics approval number [2] 291793 0

Summary
Brief summary
Cultivation of embryos in the new incubator using 5% O2, unlike the previous 20% O2, opens the
question whether this increases biological potential of embryos for implantation or not and which
methods for determination of this potential are more accurate and reliable. Given that the existing data
on the benefits of cultivation with 5% O2 are contradictory considering the age of the patient, it is
necessary to carry out research on a larger number of samples of all ages. Current methodology for
determining the biological potential of embryos -morphology assessment should be supplemented by
an objective method that is not subject to the subjective judgment of biologists –embryologist. Such a
potential method is determination of the metabolic profile of amino acids of embryos by analyzing the
spent media in which they are cultivated. It is necessary to determine the sensitivity and applicability of
such methods. Given the fact that we work with human material it is necessary that a method is
absolutely non-invasive.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 52014 0
Ms NINA GELO
Address 52014 0
Clinical Hospital Centre Zagreb
Petrova 13, 10 000 Zagreb
Country 52014 0
Croatia
Phone 52014 0
+385 1 460 4765 or +385 91 252 1235
Fax 52014 0
+385 1 2376 267
Email 52014 0
[email protected]
Contact person for public queries
Name 52015 0
Ms NINA GELO
Address 52015 0
Clinical Hospital Centre Zagreb

Petrova 13, 10 000 Zagreb
Country 52015 0
Croatia
Phone 52015 0
+385 1 460 4765
Fax 52015 0
+385 1 2376 267
Email 52015 0
[email protected]
Contact person for scientific queries
Name 52016 0
Ms NINA GELO
Address 52016 0
Clinical Hospital Centre Zagreb
Petrova 13, 10 000 Zagreb
Country 52016 0
Croatia
Phone 52016 0
+385 1 460 4765
Fax 52016 0
+385 1 2376 267
Email 52016 0
[email protected]

No information has been provided regarding IPD availability


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
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