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Trial registered on ANZCTR


Registration number
ACTRN12611001226998
Ethics application status
Approved
Date submitted
28/11/2011
Date registered
29/11/2011
Date last updated
12/01/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
MIHO Study - Milk drink to Improve the Health of Oocytes
Scientific title
A two week randomised, placebo-controlled, double blinded study of the efficacy of a novel milk drink for increasing follicular fluid insulin-like growth factor 1 concentration in women who respond poorly to ovarian stimulation during in vitro fertilisation
Secondary ID [1] 273407 0
Nil
Universal Trial Number (UTN)
Trial acronym
MIHO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
in vitro fertilisation 279190 0
Condition category
Condition code
Reproductive Health and Childbirth 279390 279390 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will undergo their usual IVF treatment, but from the 3rd day of the IVF cycle they will be asked to consume 250ml of a milk-based drink in the morning and evening that will contain active components that might increase ovarian blood flow and follicular fluid insulin-like growth factor 1 concentrations, or a placebo. They will continue to consume the 250ml drink daily until the end of their IVF stimulation cycle. At the start and end of their cycle a blood sample will be collected to measure circulating IGF-1 concentrations and the concentrations of reproductive hormones. During their routine day 9/10 follicle tracking scan, blood flow to the ovaries will also be measured using ultrasound. When their eggs are retrieved at the end of their IVF cycle the follicular fluid surrounding the eggs will be collected and analysed for IGF-1 and reproductive hormone concentrations.
Intervention code [1] 283742 0
Treatment: Other
Comparator / control treatment
standard IVF treatment with a flavoured milk drink with no active components
Control group
Placebo

Outcomes
Primary outcome [1] 285978 0
insulin-like growth factor 1 concentrations will be measured in follicular fluid using commercially available kits
Timepoint [1] 285978 0
egg retrieval operation
Secondary outcome [1] 294885 0
ovarian blood flow by Doppler ultrasound
Timepoint [1] 294885 0
Day 9/10 follicle tracking scan
Secondary outcome [2] 294886 0
reproductive hormone (Estradiol, progesterone, testosterone, FSH, hCG, AMH), lactacte and glucose concentrations will be measured in follicular fluid using commercially available kits
Timepoint [2] 294886 0
egg retrieval operation
Secondary outcome [3] 294887 0
insulin-like growth factor 1 concentrations will be measured in blood serum samples using commercially available kits
Timepoint [3] 294887 0
baseline (before IVF cycle) and egg retrieval operation
Secondary outcome [4] 294888 0
IVF outcomes will be assessed by granulosa cell function by measuring follicle estrogen, progesterone and testosterone concentration using commercially available kits
and oocyte competence by measuring fertilisation rate, ability to form a good quality blastocyst embryo.
Timepoint [4] 294888 0
at time of oocyte retrieval (follicular fluid analysis) or first 5 days of embryology development (fertilization, embryo quality)
Secondary outcome [5] 294889 0
pregnancy rates will be calculated using the number of viable fetal hearts seen on ultrasound per 100 embryos transferred
Timepoint [5] 294889 0
8 week gestation pregnancy scan

Eligibility
Key inclusion criteria
Undergoing a gonadotrophin-releasing hormone antagonist cycle of IVF treatment and a poor responder to ovarian hyperstimulation. This includes meeting two of the following three criteria: 1. 40 years or older 2. previously only produced 3 or less mature eggs in response to maximal dose ovarian stimulation during IVF treatment 3. serum anti-mullerian hormone concentration < 7.8 pmol/l or a total antral follicle count <7 (both being accurate markers suggesting a reduced number of eggs left within your ovaries relative to your age).
Minimum age
25 Years
Maximum age
45 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
intolerant/allergic to cow's milk protein, lactose, soy, wheat, egg, gluten, nuts or seeds, concurrent use of human growth hormone, Elonva, long down regulation IVF cycle, oral corticosteroids (Prednisolone) therapy have used dehydroepiandrosterone therapy in last month

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)
Women who appear to be eligible for the study will be informed about the study by the principle investigator or their own treating doctor when attending
Repromed for their IVF treatment. Experimental therapy will be randomly allocated and allocation will be concealed from the participant and study staff. The randomization sequence will be computer generated by a third party not involved in the study. Treatment packs will be sequentially numbered and prepared with either active medication or placebo by a third party contractor. Both active and placebo powder used to produce the study milk drink will be identical in appearance and taste.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Women will be randomised to one for three treatment beverages using a minimisation randomisation schedule to ensure equal numbers of patients in the two main types of diminished ovarian reserve in each group (women <40yrs with low ovarian reserve and women >40 yrs with age appropriate poor ovarian reserve).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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)

Funding & Sponsors
Funding source category [1] 284259 0
Commercial sector/Industry
Name [1] 284259 0
Itek
Address [1] 284259 0
PO Box 546
Salisbury South SA 5106
Country [1] 284259 0
Australia
Primary sponsor type
University
Name
University of South Australia
Address
GPO Box 2471
Adelaide SA
5001
Country
Australia
Secondary sponsor category [1] 269181 0
None
Name [1] 269181 0
Address [1] 269181 0
Country [1] 269181 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286188 0
University of South Australia Human Research Ethics Committee
Ethics committee address [1] 286188 0
GPO Box 2471
Adelaide SA 5001
Ethics committee country [1] 286188 0
Australia
Date submitted for ethics approval [1] 286188 0
15/11/2011
Approval date [1] 286188 0
10/02/2012
Ethics approval number [1] 286188 0
26785

Summary
Brief summary
The purpose of this study is to determine if nutrients that have been shown to improve blood flow and increase circulating insulin-like growth factor 1 concentrations in the blood can improve both blood flow in the ovary and elevate the concentration of insulin-like growth factor 1 in the follicular fluid surrounding the eggs. The ability to increase the concentration of IGF-1 in follicular fluid surrounding the eggs in the ovary in this way may provide an inexpensive and simple alternative to growth hormone treatment for improving egg quality in patients undergoing IVF treatment.
Trial website
Trial related presentations / publications
none
Public notes

Contacts
Principal investigator
Name 33406 0
A/Prof Kelton Tremellen
Address 33406 0
Repromed Adelaide
180 Fullarton Road
Dulwich SA 5056
Country 33406 0
Australia
Phone 33406 0
+61 8 8333 8113
Fax 33406 0
Email 33406 0
KTremellen@repromed.com.au
Contact person for public queries
Name 16653 0
Dr Rebecca Thomson
Address 16653 0
Nutritional Physiology Research Centre
University of South Australia
GPO Box 2471
Adelaide SA
5001
Country 16653 0
Australia
Phone 16653 0
+61 8 8302 1822
Fax 16653 0
Email 16653 0
rebecca.thomson@unisa.edu.au
Contact person for scientific queries
Name 7581 0
A/Prof Kelton Tremellen
Address 7581 0
Repromed Adelaide
180 Fullarton Road,
Dulwich, SA 5065
Country 7581 0
Australia
Phone 7581 0
+61 8 8333 8113
Fax 7581 0
+61 8 8333 8188
Email 7581 0
KTremellen@repromed.com.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary