Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001206112
Ethics application status
Approved
Date submitted
31/07/2019
Date registered
29/08/2019
Date last updated
1/11/2022
Date data sharing statement initially provided
29/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Ovarian rejuvenation for menopausal or perimenopausal women using autologous platelet rich plasma (A-PRP) injection into the ovaries, for women seeking in vitro fertilisation (IVF) treatment, aiming to improve IVF outcomes.
Scientific title
Ovarian rejuvenation using intra-ovarian injection of autologous platelet-rich plasma (A-PRP) for peri-menopausal and menopausal women.
Secondary ID [1] 298826 0
Nil known
Universal Trial Number (UTN)
U1111-1237-4831
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Premature ovarian failure 313779 0
Poor ovarian response 313780 0
Advanced maternal age 313781 0
Condition category
Condition code
Reproductive Health and Childbirth 312183 312183 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Autologous platelet-rich plasma (A-PRP) will be injected into the ovaries of perimenopausal and menopausal women.

The PRP preparation kit is Alocuro PRO PRP 30mL device approved by the Therapeutics Goods Agency (TGA) listed on the Australian Register of Therapeutic Goods (ARTG) as a class II medical device, manufacturer - GoodmorningBio Co Ltd, Republic of Korea.
The kit contains:*Venepuncture equipment; Butterfly needle / White top syringe / Yellow top syringe x 4 (each containing 1mL of anti-coagulant). *PRP Preparation equipment; 30mL PRO PRP device (centrifuging tube) / S-Monovette-needle.

Trained phlebotomist's will draw 30mLs of blood as per the manufacturer's instructions. A scientist trained in the preparation of A-PRP will prepare the blood sample as per the manufacturer's instructions, 30mLs of blood will harvest around 4-5mLs of A-PRP. A FRANZCOG trained fertility specialist will inject the A-PRP into both ovaries via transvaginal ultrasound guidance or laparoscopy, using an oocyte pick-up (OPU) needle. If one ovary cannot be safely accessed, only one will be injected, around 2-2.5mLs of A-PRP will be injected per ovary. The injection will occur under either local anaesthetic (LA) or general anaesthetic (GA), either within a cycle of mild ovarian stimulation IVF at the time of the transvaginal oocyte aspiration (TVOA), or outside of a cycle of IVF in the follicular phase of menstruation, or for patients with amenorrhoea at any point.

The intraovarian injection (IOI) of A-PRP may be repeated on subsequent IVF cycles. The blood collection and A-PRP preparation will take place in an RTAC / RTC / NATA accredited fertility clinic – Fertility North. The intraovarian injection will take place in a treatment room at Fertility North (if performed under LA) or Joondalup Health Campus hospital theatres (if performed under GA).
Intervention code [1] 315123 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 320864 0
Changes in follicle numbers on subsequent IVF cycles using mild ovarian stimulation.
Timepoint [1] 320864 0
The number of follicles are counted, measured using transvaginal ultrasound prior to the final maturation of the oocytes in the IVF cycle pre and post the intervention. Only the final number of follicles in the pre and post intervention are considered for comparison. The post intervention follicle count will occur 1-2 months after the intervention (it is patient choice when they commence the repeat cycle of IVF).
Primary outcome [2] 320865 0
Changes in oocyte numbers on subsequent IVF cycles using mild ovarian stimulation.
Timepoint [2] 320865 0
The number of oocytes are counted on the day of the oocyte collection pre and post the intervention, measured at a single time point by the embryologist who identifies the oocytes microscopically at the oocyte collection. The post intervention oocyte count will occur 1-2 months after the intervention (it is patient choice when they commence the repeat cycle of IVF).
Primary outcome [3] 320866 0
Changes in embryo numbers on subsequent IVF cycles using mild ovarian stimulation.
Timepoint [3] 320866 0
The number of embryos are counted the day after the oocyte collection when the number of normally fertilised oocytes are assessed microscopically by the embryologist. pre and post the intervention, measured at a single time point. The post intervention embryo count will occur 1-2 months after the intervention (it is patient choice when they commence the repeat cycle of IVF).
Secondary outcome [1] 373118 0
Changes in anti-mullerian hormone (AMH) measured via a blood test.


Timepoint [1] 373118 0
Measured at a single time point, 1-3 months post intervention.
Secondary outcome [2] 373752 0
Changes in follicle stimulating hormone (FSH) measured via a blood test.
Timepoint [2] 373752 0
Measured at a single time point, day 2-3 of menstrual cycle, between 1-3 months post intervention.
Secondary outcome [3] 373753 0
Clinical pregnancy rates in subsequent IVF cycles using mild ovarian stimulation.
Timepoint [3] 373753 0
Following the intrauterine transfer of an embryo created within the IVF cycle either pre or post intervention. Measured using transvaginal ultrasound 7 weeks post oocyte collection day following a positive hGC result, which is measured via a blood test. The Australian and New Zealand Reproduction Database (ANZARD) definition of clinical pregnancy will be used. If clinical pregnancy (fetal heartbeat or gestational sac cannot be confirmed), a repeat transvaginal ultrasound will be performed as decided by the ultrasonographer.
Secondary outcome [4] 373760 0
Resumption of menses for patients with amenorrhoea, reported by the participant.
Timepoint [4] 373760 0
Measured at a single time point, 1-3 months post intervention.

Eligibility
Key inclusion criteria
i. Low AMH (<1.5 pmol/L).
ii. High basal FSH (>14 mIU/mL).
iii. Classified with premature ovarian failure (POF) (Menopausal reproductive hormones <40 years of age).
iv. Classified as having poor ovarian response (POR) (As per Bologna Criteria).
v. A history of poor IVF outcomes, including failed oocyte retrievals, no mature oocytes available for insemination, failed fertilisation of oocytes, no embryos available for transfer.
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
i. Patients with normal hormonal profiles, previous acceptable / good responses to ovarian stimulation and good numbers of embryos available for embryo transfer or cryopreservation (greater than 3).
ii. Patients with POF due to a genetic condition e.g. Turners syndrome.
iii. Patients with Idiopathic thrombocytopenia (autoimmune platelet deficiency).
iv. Patients who are unable to undergo an IVF treatment cycle for any reason.

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
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
There is no expected sample size for the study, results and outcomes will be analysed on a yearly basis irrespective of the numbers of participants. An estimation of the number of participants within the first year is around 80, based on current patient numbers undergoing mild ovarian stimulation IVF cycles at the clinic who are diagnosed with POF / POR.

Descriptive statistics such as number, frequencies, percentages, tables, graphs, means and standard deviations will be used for comparison. Inferential statistics will be obtained using paired t test pre and post intervention (p<0.05).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2019
Actual
1/11/2019
Date of last participant enrolment
Anticipated
31/12/2023
Actual
Date of last data collection
Anticipated
31/07/2024
Actual
Sample size
Target
400
Accrual to date
50
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 14319 0
Joondalup Health Campus - Joondalup
Recruitment postcode(s) [1] 27321 0
6027 - Joondalup

Funding & Sponsors
Funding source category [1] 303377 0
Other
Name [1] 303377 0
Fertility North
Country [1] 303377 0
Australia
Primary sponsor type
Other
Name
Fertility North
Address
Fertility North
Suite 30, Level 2,
Joondalup Private Hospital,
60 Shenton Ave,
Joondalup
WA 6027
Country
Australia
Secondary sponsor category [1] 303410 0
None
Name [1] 303410 0
Address [1] 303410 0
Country [1] 303410 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303909 0
Ramsay Health Care WA/SA Human Research Ethics Committee (RHC WA/SA HREC)
Ethics committee address [1] 303909 0
Ethics committee country [1] 303909 0
Australia
Date submitted for ethics approval [1] 303909 0
23/07/2019
Approval date [1] 303909 0
25/10/2019
Ethics approval number [1] 303909 0
1938

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 95210 0
Dr Vince Chapple
Address 95210 0
Fertility North,
Suite 30, Level 2,
Joondalup Private Hospital,
60 Shenton Ave,
Joondalup,
WA 6127
Country 95210 0
Australia
Phone 95210 0
+61 08 93011075
Fax 95210 0
Email 95210 0
[email protected]
Contact person for public queries
Name 95211 0
Yanhe Liu
Address 95211 0
Fertility North,
Suite 30, Level 2,
Joondalup Private Hospital,
60 Shenton Ave,
Joondalup,
WA 6127
Country 95211 0
Australia
Phone 95211 0
+61 08 93011075
Fax 95211 0
Email 95211 0
[email protected]
Contact person for scientific queries
Name 95212 0
Yanhe Liu
Address 95212 0
Fertility North,
Suite 30, Level 2,
Joondalup Private Hospital,
60 Shenton Ave,
Joondalup,
WA 6127
Country 95212 0
Australia
Phone 95212 0
+61 08 93011075
Fax 95212 0
Email 95212 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All of the individual participant data collected during the trial after de-identification.
When will data be available (start and end dates)?
Immediately following publication, no end date.
Available to whom?
Published results will be available to the general public. Raw data will be available on a case-by-case basis at the discretion of the Primary Sponsor.
Available for what types of analyses?
To achieve the aims in the approved proposal.
How or where can data be obtained?
Access subject to approvals by the Primary Sponsor / Principle Investigator - Vince Chapple, via the Public / Scientific contact person Katie Feenan [email protected]


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.