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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12614000657628
Ethics application status
Approved
Date submitted
10/06/2014
Date registered
24/06/2014
Date last updated
26/11/2018
Date data sharing statement initially provided
26/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pipelle for pregnancy in couples with subfertility related to polycystic ovarian syndrome
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 subfertility related to polycystic ovarian syndrome
Secondary ID [1] 284679 0
nil
Universal Trial Number (UTN)
U111111556458
Trial acronym
PIP-PCOS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polycystic ovarian syndrome 292019 0
Condition category
Condition code
Reproductive Health and Childbirth 292365 292365 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 stimulated cycle (clomiphene, letrozole or metformin).
Intervention code [1] 289464 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 stimulated cycle (clomiphene, letrozole or metformin).
Control group
Placebo

Outcomes
Primary outcome [1] 292220 0
Live birth - delivery of a live infant at least 20 weeks gestation
Timepoint [1] 292220 0
Approximately 9 months following the end of the study period
Secondary outcome [1] 308449 0
Clinical pregnancy - on ultrasound, the presence of at least one gestational sac
Timepoint [1] 308449 0
6 weeks following each ovulation induction cycle (3 consecutive ovulation induction cycles, unless pregnancy occurs)
Secondary outcome [2] 308450 0
Ongoing pregnancy - on ultrasound, the presence of at least one gestational sac and heartbeat
Timepoint [2] 308450 0
12 weeks following each ovulation induction cycle (3 consecutive ovulation induction cycles, unless pregnancy occurs)
Secondary outcome [3] 308451 0
Multiple pregnancy - on ultrasound, the presence of more than one heartbeat
Timepoint [3] 308451 0
6 weeks following each ovulation induction cycle (3 consecutive ovulation induction cycles, unless pregnancy occurs)
Secondary outcome [4] 308452 0
Adverse events - including miscarriage, ectopic pregnancy, pain or bleeding following the procedure, infection etc.
Timepoint [4] 308452 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 meet the criteria for PCOS, at least two of the following: 1) oligoovulation or anovulation (progesterone test) 2) excess androgen activity (elevated serum testosterone or clinical signs such as excess hair), 3) polycystic ovaries (as evidenced on ultrasound) – as per the Rotterdam criteria
4. Have either a) two ovaries and two probably patent fallopian tube (confirmed by hysteroscopy or HSG - one tube may spasm/not free spill). b) been ovulating on ovulation induction mediction for 6 months or less (as HSG may not be recommended until failure to achieve pregnancy following three or more cycles of successful ovulation), or c) 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) less than or equal to 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). For PCOS women, this includes three months of consecutive ovulation induction (unless pregnancy occurs)
8. Be willing to remain on ovulation induction medication for the study period (unless pregnancy occurs), either: clomiphene, letrozole or metformin (or a combination). Doses may vary.
9. Women who’s male partner has normal semen analysis (volume at least 1.5ml, progressive motility at least 32%, concentration at least 15million/ml) or a total motile count of equal to or more than 10 million
Minimum age
18 Years
Maximum age
42 Years
Gender
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 planned ovulation induction cycle, or planning to undergo a procedure involving disruptive instrumentation at any stage during the study.
2. The presence of any other cause of infertility, where spontaneous conception is unlikely (e.g. large fibroids)
3. Recurrent miscarriage
4. Entered previously into this study or participation in another trial in the last 30 days
5. 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


Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
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 outside Australia
Country [1] 6101 0
Brazil
State/province [1] 6101 0
Country [2] 7359 0
Egypt
State/province [2] 7359 0
Cairo
Country [3] 21070 0
New Zealand
State/province [3] 21070 0
Country [4] 21071 0
United Kingdom
State/province [4] 21071 0

Funding & Sponsors
Funding source category [1] 289365 0
Hospital
Name [1] 289365 0
Auckland District Health Board
Address [1] 289365 0
Bldg 14, Greenlane Clinical Centre Level 7/214 Green Ln W, Greenlane 1051
Country [1] 289365 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] 288050 0
None
Name [1] 288050 0
Address [1] 288050 0
Country [1] 288050 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291131 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 291131 0
Ministry of Health
C/- MEDSAFE, Level 6, Deloitte House
10 Brandon Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 291131 0
New Zealand
Date submitted for ethics approval [1] 291131 0
29/04/2014
Approval date [1] 291131 0
06/06/2014
Ethics approval number [1] 291131 0
14/NTA/62

Summary
Brief summary
The favourable effect of local endometrial biopsy (LEB) in women undergoing embryo transfer or natural conception indicates that the LEB 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 polycystic ovarian syndrome (PCOS), LEB may also be beneficial for these couples.
Unfortunately, research concerning the utility of LEB in couples with subfertility related to PCOS is sparse.
We plan to address the current limitations by conducting a pragmatic, double-blind, randomised controlled trial of LEB in couples with subfertility related to PCOS.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48750 0
Prof Cynthia Farquhar
Address 48750 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 48750 0
New Zealand
Phone 48750 0
+64 9 3737599 EXT 89493
Fax 48750 0
Email 48750 0
c.farquhar@auckland.ac.nz
Contact person for public queries
Name 48751 0
Miss Sarah Lensen
Address 48751 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 48751 0
New Zealand
Phone 48751 0
+64 9 3737599 EXT 89487
Fax 48751 0
Email 48751 0
s.lensen@auckland.ac.nz
Contact person for scientific queries
Name 48752 0
Prof Cynthia Farquhar
Address 48752 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 48752 0
New Zealand
Phone 48752 0
+64 9 3737599 EXT 89493
Fax 48752 0
Email 48752 0
c.farquhar@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
It is highly likely the IPD will be available for sharing on request, however we need to confirm arrangements with the Sponsor/University
What supporting documents are/will be available?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
Summary results
No Results