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Trial registered on ANZCTR


Registration number
ACTRN12625000922471
Ethics application status
Approved
Date submitted
24/06/2025
Date registered
25/08/2025
Date last updated
25/08/2025
Date data sharing statement initially provided
25/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised Controlled Trial Investigating Intrauterine Platelet-Rich Plasma in Women with Repeated Implantation Failure
Scientific title
A Randomised Controlled Trial Investigating Intrauterine Platelet-Rich Plasma in Women with Repeated Implantation Failure
Secondary ID [1] 313784 0
None
Universal Trial Number (UTN)
Trial acronym
RIF PRP RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infertility 336545 0
Condition category
Condition code
Reproductive Health and Childbirth 333060 333060 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Platelet Rich Plasma (PRP) is an autologous blood product enriched with growth factors and cytokines. PRP is created from a small blood sample obtained from the participant and processed through centrifugation to separate and concentrate platelets. It is currently thought of as experimental but due to positive results in some studies it is used in clinical practice by some private clinicians at a cost to the patient in a variety of clinical scenarios including recurrent implantation failure, thin or scarred endometrium or injected into the ovary to help with response to hormonal stimulation in assisted reproductive technology. There is a long history of its use in other specialties for example musculoskeletal medicine and dermatology.
PRP production involves no external devices or medications requiring regulatory approval. PRP can be created through the help of a commercially available kit. There is no evidence suggesting harm associated with PRP use.
The treatment group will receive a single intrauterine infusion of PRP 2-3 days prior to embryo transfer.
participants randomised to the intervention arm will undergo:
• Blood collection of 8.5 mL, mixed with 1.5 mL of anticoagulant (acid citrate), 2–3 days prior to embryo transfer.
• The sample is processed on-site using a two-step centrifugation protocol to isolate approximately 0.75 mL of PRP. Before administration, PRP is activated by mixing with 0.25 mL of non-coagulated whole blood.
• A single intrauterine infusion of PRP will be performed using a soft embryo transfer catheter (e.g., GuardiaTM Access, Cook Medical), inserted through the cervix and up to the internal os. The PRP is infused gently into the endometrial cavity.
• The procedure will be conducted by a fertility specialist or gynaecologist, in accordance with site-specific protocols.
Participants in the placebo arm will undergo an identical procedure including blood draw and catheter insertion, but without PRP infusion.

Adherence to the intervention protocol will be monitored through audit of clinic medical records, review of procedure documentation, and case report forms (CRFs). Each site will be required to document the completion of blood collection, PRP preparation, and the intrauterine infusion procedure, including timing relative to embryo transfer. Study-specific procedure logs and REDCap data entries will be used to confirm protocol compliance across both intervention and placebo arms.
Intervention code [1] 330464 0
Treatment: Other
Comparator / control treatment
The placebo group will undergo all steps identical to the intervention group, including venepuncture and insertion of the intrauterine catheter up to the internal cervical os, but without the infusion of PRP or any other substance. The procedure will be performed using the same type of soft embryo transfer catheter (e.g., GuardiaTM Access, Cook Medical) as the intervention group.
The sham procedure will be conducted 2–3 days prior to embryo transfer, matching the timing of the intervention group to preserve blinding and procedural consistency. Blood collected from placebo participants will be discarded following standard biohazard protocols.
Control group
Placebo

Outcomes
Primary outcome [1] 340597 0
Clinical Pregnancy Rate
Timepoint [1] 340597 0
Primary outcome will be assessed by 20 weeks of gestation
Secondary outcome [1] 444556 0
Biochemical pregnancy
Timepoint [1] 444556 0
10 days post embryo transfer
Secondary outcome [2] 444557 0
Chemical miscarriage rate
Timepoint [2] 444557 0
Assessed cumulatively for each participant and reported at the conclusion of the study (up to 20 weeks gestation or earlier if pregnancy is non-viable).
Secondary outcome [3] 444558 0
Live birth
Timepoint [3] 444558 0
Assessed cumulatively at the end of follow-up for each participant (up to 20 weeks gestation or pregnancy conclusion).
Secondary outcome [4] 450274 0
Early miscarriage rate
Timepoint [4] 450274 0
Assessed cumulatively for each participant and reported at the conclusion of the study.
Secondary outcome [5] 450275 0
Late miscarriage rate
Timepoint [5] 450275 0
Assessed cumulatively for each participant and reported at the conclusion of the study.
Secondary outcome [6] 450276 0
Total miscarriage rate
Timepoint [6] 450276 0
Assessed cumulatively at the end of follow-up for each participant (up to 20 weeks gestation or pregnancy conclusion).

Eligibility
Key inclusion criteria
Women aged 20-42 years.
Body Mass Index (BMI) less than 40 kg/m².
Diagnosed with Recurrent Implantation Failure (RIF) based on an age-personalised cumulative clinical pregnancy rate calculation. For participants using donor gametes, the diagnosis of RIF will be based on the egg donor’s age to ensure consistency in embryo quality assessment.
Embryos graded higher than 3BB, based on the Gardner and Schoolcraft morphology criteria, will be considered good quality for inclusion in the study.
Participants undergoing PGT-A as part of their treatment.
Participants undergoing a single blastocyst transfer (fresh or frozen) during an IVF cycle.
Patients who have undergone an endometrial receptivity test in a previous cycle will not be excluded, provided they meet all other eligibility criteria. However, the timing of embryo transfer for this study will follow the standard protocol and will not be adjusted based on prior receptivity test results.
Minimum age
20 Years
Maximum age
42 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Known chromosomal abnormalities in either the patient or partner, only in cases where embryos have not undergone PGT-A testing. Patients with chromosomal abnormalities may be included if they are transferring tested euploid embryos, as these abnormalities are unlikely to affect implantation outcomes in such cases.
Structural uterine abnormalities.
Haematological disorders.
Autoimmune diseases.
Untreated hydrosalpinx.
Uncontrolled endocrinological disorders.
Platelet count less than 150 x 10^9/L.
Current use of anticoagulant medications or recent use of aspirin within 10 days, or non-steroidal anti-inflammatory drugs (NSAIDs) within 24 hours, prior to PRP collection.
Patients with an endometrial thickness less than 7 mm on the day of transfer determination will not be included, as thin endometrium is associated with poor implantation outcomes. Endometrial thickness will be assessed by ultrasound, and patients with suboptimal thickness will be deferred until the endometrium measures at least 7 mm.

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 (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2025
Actual
Date of last participant enrolment
Anticipated
1/10/2029
Actual
Date of last data collection
Anticipated
1/07/2030
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 27571 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 27572 0
Melbourne IVF - East Melbourne
Recruitment hospital [3] 28288 0
Genea Fertility East Melbourne - East Melbourne
Recruitment hospital [4] 28289 0
Life Fertility - Fitzroy
Recruitment postcode(s) [1] 43684 0
3052 - Parkville
Recruitment postcode(s) [2] 43685 0
3002 - East Melbourne
Recruitment postcode(s) [3] 44502 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 318250 0
Charities/Societies/Foundations
Name [1] 318250 0
Sylvia and Charles Viertel Charitable Foundation Clinical Investigator Award (recipient: A/Prof Wan Tinn Teh)
Country [1] 318250 0
Australia
Funding source category [2] 319778 0
Charities/Societies/Foundations
Name [2] 319778 0
Stafford Fox Medical Research Foundation
Country [2] 319778 0
Australia
Primary sponsor type
Hospital
Name
The Royal Women's Hospital, Melbourne
Address
Country
Australia
Secondary sponsor category [1] 320635 0
None
Name [1] 320635 0
Address [1] 320635 0
Country [1] 320635 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316891 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 316891 0
Ethics committee country [1] 316891 0
Australia
Date submitted for ethics approval [1] 316891 0
29/01/2025
Approval date [1] 316891 0
04/06/2025
Ethics approval number [1] 316891 0
HREC/114669/MH-2025

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

Contacts
Principal investigator
Name 139334 0
A/Prof Wan Tinn Teh
Address 139334 0
Royal Women's Hospital, Locked Bag 300, Public Fertility Care (Level 2), Grattan Street and Flemington Road, Parkville, VIC, 3052
Country 139334 0
Australia
Phone 139334 0
+61 383453220
Fax 139334 0
Email 139334 0
[email protected]
Contact person for public queries
Name 139335 0
Sarah Holdsworth-Carson
Address 139335 0
Royal Women's Hospital, Locked Bag 300, Public Fertility Care (Level 2), Grattan Street and Flemington Road, Parkville, VIC, 3052
Country 139335 0
Australia
Phone 139335 0
+61 383453220
Fax 139335 0
Email 139335 0
[email protected]
Contact person for scientific queries
Name 139336 0
Einat Haikin-Herzberger
Address 139336 0
Royal Women's Hospital, Locked Bag 300, Public Fertility Care (Level 2), Grattan Street and Flemington Road, Parkville, VIC, 3052
Country 139336 0
Australia
Phone 139336 0
+61 383453220
Fax 139336 0
Email 139336 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.