Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000656639
Ethics application status
Approved
Date submitted
10/06/2014
Date registered
24/06/2014
Date last updated
16/05/2022
Date data sharing statement initially provided
10/07/2019
Date results information initially provided
16/05/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Pipelle for pregnancy in couples with unexplained infertility
Scientific title
A single-blind, randomised controlled trial assessing the effect of endometrial pipelle biopsy vs. sham biopsy on live birth rate in couples with unexplained infertility
Secondary ID [1] 284678 0
nil
Universal Trial Number (UTN)
U111111556458
Trial acronym
PIP-UE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Unexplained infertility 292018 0
Condition category
Condition code
Reproductive Health and Childbirth 292364 292364 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Women will undergo a single endometrial pipelle biopsy performed between days 1 and 12 of a 28 day menstrual cycle. For women with shorter or longer cycles, this time frame can be adjusted accordingly.
Intervention code [1] 289463 0
Treatment: Other
Comparator / control treatment
Women will undergo a single endometrial sham biopsy (the biopsy cannula will be placed at the anterior fornix and not inserted into the uterus). This procedure will be performed between days 1 and 12 of a 28 day menstrual cycle. For women with shorter or longer cycles, this time frame can be adjusted accordingly.
Control group
Placebo

Outcomes
Primary outcome [1] 292219 0
Live birth - delivery of a live infant at least 20 weeks gestation
Timepoint [1] 292219 0
Approximately 9 months following the end of the study
Secondary outcome [1] 308445 0
Clinical pregnancy - on ultrasound, the presence of at least one gestational sac
Timepoint [1] 308445 0
6 weeks following each menstrual cycle (3 consecutive menstrual cycles)
Secondary outcome [2] 308446 0
Ongoing pregnancy -on ultrasound, the presence of at least one gestational sac and heartbeat
Timepoint [2] 308446 0
12 weeks following each menstrual cycle (3 consecutive menstrual cycles)
Secondary outcome [3] 308447 0
Multiple pregnancy - on ultrasound, the presence of more than one heartbeat
Timepoint [3] 308447 0
6 weeks after each menstrual cycle (3 consecutive menstrual cycles)
Secondary outcome [4] 308448 0
Adverse events - including miscarriage, ectopic pregnancy, pain or bleeding following the procedure, infection etc.
Timepoint [4] 308448 0
Bleeding and pain: on the day of the procedure or the following day
Infection: for 1 month following the procedure
Ectopic pregnancy and miscarriage: up to 20 weeks following the cycle in which pregnancy occurs

Eligibility
Key inclusion criteria
1. Couples having regular unprotected sexual intercourse in a relationship where pregnancy is desired
2. Women is between 18-42 years of age at the time of randomisation
3. Women who are diagnosed with unexplained infertility: normal ovulation (21-35 day menstrual cycles with variation <8 days and luteal phase progesterone test), normal semen analysis (progressive motility atleast 32%, volume at least 1.5ml, conc. at least 15million/ml) or total motile count equal to or more than 10 million
4. Have either a) at two ovaries and two probably patent fallopian tubes (confirmed by hysteroscopy or HSG) or b) a previous intrauterine pregnancy, and no subsequent surgery or ectopic pregnancy that may reduce tubal patency or ovarian function
5. A body mass index (BMI) of equal to or less than 35
6. Have a negative cervical PAP smear within the last 3 years
7. Be willing to have regular sexual intercourse following the procedure in the month of the procedure, and for two months following the procedure (or until pregnancy occurs)
Minimum age
18 Years
Maximum age
42 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have had any disruptive instrumentation within the uterine cavity (e.g. hysteroscopy, hysterosalpingogram, laparoscopy, surgically managed miscarriage or endometrial biopsy) within three months prior to day one of the first study menstrual cycle, or planning to undergo a procedure involving disruptive instrumentation at any stage during the study.
2. Entered previously into this study or participation in another trial in the last 30 days
3. Any contraindication to endometrial biopsy or being pregnant and/or carrying a pregnancy to term

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)
To ensure allocation concealment, randomisation of eligible individuals will be performed by an online randomisation system built into the data collection software.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A computer generated block randomisation schedule, stratified for each fertility centre, will be created and protected by the database manager.
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
Completed
Date of first participant enrolment
Anticipated
1/07/2014
Actual
25/06/2014
Date of last participant enrolment
Anticipated
Actual
31/12/2019
Date of last data collection
Anticipated
Actual
31/12/2020
Sample size
Target
350
Accrual to date
Final
117
Recruitment outside Australia
Country [1] 6100 0
Brazil
State/province [1] 6100 0
Country [2] 7372 0
Egypt
State/province [2] 7372 0
Cairo
Country [3] 10712 0
New Zealand
State/province [3] 10712 0
Country [4] 10713 0
United Kingdom
State/province [4] 10713 0

Funding & Sponsors
Funding source category [1] 289364 0
Hospital
Name [1] 289364 0
Auckland District Health Board
Country [1] 289364 0
New Zealand
Primary sponsor type
Hospital
Name
Auckland District Health Board
Address
Bldg 14, Greenlane Clinical Centre Level 7/214 Green Ln W, Greenlane 1051
Country
New Zealand
Secondary sponsor category [1] 288049 0
None
Name [1] 288049 0
Address [1] 288049 0
Country [1] 288049 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291130 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 291130 0
Ministry of Health
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 291130 0
New Zealand
Date submitted for ethics approval [1] 291130 0
29/04/2014
Approval date [1] 291130 0
06/06/2014
Ethics approval number [1] 291130 0
14/NTA/62

Summary
Brief summary
The favourable effect of endometrial biopsy in women undergoing embryo transfer or natural conception indicates that the biopsy somehow enhances the endometrial receptivity in a group of women whose endometrium is otherwise not adequately receptive to an implanting embryo. As it is likely that poor endometrial receptivity is at least partly contributing to the experienced infertility in cases of unexplained infertility, endometrial biopsy may also be beneficial for these couples.

Unfortunately, research concerning the utility of endometrial biopsy in couples with unexplained infertility who are trying to conceive spontaneously is sparse.
We plan to address the current limitations by conducting a pragmatic, double-blind, randomised controlled trial, of endometrial biopsy in couples with unexplained infertility.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48746 0
Prof Cynthia Farquhar
Address 48746 0
Department of Obstetrics and Gynaecology and National Women's Health, University of Auckland, Level 12, ACH Support Building, Auckland City Hospital, Park Road, Grafton Private Bag 92019 Auckland 1020
Country 48746 0
New Zealand
Phone 48746 0
+64 9 3737599 EXT 89493
Fax 48746 0
Email 48746 0
[email protected]
Contact person for public queries
Name 48747 0
Miss Sarah Lensen
Address 48747 0
Department of Obstetrics and Gynaecology and National Women's Health, University of Auckland, Level 12, ACH Support Building, Auckland City Hospital, Park Road, Grafton Private Bag 92019 Auckland 1020
Country 48747 0
New Zealand
Phone 48747 0
+64 9 3737599 EXT 89487
Fax 48747 0
Email 48747 0
[email protected]
Contact person for scientific queries
Name 48748 0
Prof Cynthia Farquhar
Address 48748 0
Department of Obstetrics and Gynaecology and National Women's Health, University of Auckland, Level 12, ACH Support Building, Auckland City Hospital, Park Road, Grafton Private Bag 92019 Auckland 1020
Country 48748 0
New Zealand
Phone 48748 0
+64 9 3737599 EXT 89493
Fax 48748 0
Email 48748 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 IPD
When will data be available (start and end dates)?
Data will be available once primary analyses are completed and published, approx mid 2021. There is no end-date on the availability of this data.
Available to whom?
Researchers with bonafide research projects
Available for what types of analyses?
Variable
How or where can data be obtained?
By email request to [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16086Study protocolDOI 10.1186/s13063-016-1301-9https://trialsjournal.biomedcentral.com/track/pdf/10.1186/s13063-016-1301-9[email protected] NA 366422-(Uploaded-27-07-2020-09-16-27)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Wong TY, Lensen S, Wilkinson J, Glanville EJ, Acha... [More Details]
Basic resultsNo 366422-(Uploaded-09-05-2022-12-06-15)-Basic results summary.docx
Plain language summaryNo 1. Research question To investigate whether endom... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEndometrial injury for pregnancy following sexual intercourse or intrauterine insemination.2022https://dx.doi.org/10.1002/14651858.CD011424.pub4
EmbaseEffect of endometrial scratching on unassisted conception for unexplained infertility: a randomized controlled trial.2022https://dx.doi.org/10.1016/j.fertnstert.2021.12.009
EmbaseEndometrial injury for pregnancy following sexual intercourse or intrauterine insemination.2021https://dx.doi.org/10.1002/14651858.CD011424.pub3
EmbaseEndometrial injury for pregnancy following sexual intercourse or intrauterine insemination.2016https://dx.doi.org/10.1002/14651858.CD011424.pub2
N.B. These documents automatically identified may not have been verified by the study sponsor.