NCT03660735

Brief Summary

Many IVF clinics offer testing for immune cells in the blood and endometrium as it has been suggested that abnormal levels of these cells can affect fertility or the chance of an IVF cycle working. However, routinely offering these tests remains highly controversial as the scientific evidence behind the tests is not of a high quality. The PIP Study aims to find out how a woman's blood and endometrial immune cells affect the likelihood of an IVF cycle working and whether or not they are different in women with subfertility and implantation failure. This feasibility study aims to find out if it is possible to enrol enough women into the research study. If this is successful, the investigators will then go on to recruit a larger group of women into the main PIP study to enable them to investigate the impact of immune profiling on IVF success in more detail.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
250

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Sep 2018

Typical duration for all trials

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 9, 2018

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 7, 2018

Completed
19 days until next milestone

Study Start

First participant enrolled

September 26, 2018

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2021

Completed
Last Updated

October 29, 2018

Status Verified

October 1, 2018

Enrollment Period

2.8 years

First QC Date

July 9, 2018

Last Update Submit

October 26, 2018

Conditions

Sub-fertilityRecurrent Implantation Failure

Keywords

Immune ProfilingPre-IVF

Outcome Measures

Primary Outcomes (1)

  • Recruitment of 250 participants to subgroups relevant to a future larger study

    Recruitment rate of participants screened eligible for the study * of recruits who are undoing a first or second IVF cycle with ICSI for male factor subfertility * of recruits with a history of recurrent implantation failure

    At study completion, this is anticipated to be 3 years.

Secondary Outcomes (4)

  • To describe the normal variation in blood and endometrial immune cell populations in the mid-luteal phase of the menstrual cycle of women in undergoing IVF for a severe male factor subfertility who go on to have a live birth

    Blood and endometrial biopsies will be analysed throughout the study (a period of 36 months) but comparison between groups will take place after 3 years, at study completion

  • To identify if there are significant differences in endometrial or blood immune cell populations in: Women with a history of Recurrent Implantation Failure Women with a history of subfertility

    Blood and endometrial biopsies will be analysed throughout the study (a period of 36 months) but comparison between groups will take place after 3 years, at study completion

  • To identify if there are differences in immune cell parameters between successful and failed cycles

    Blood and endometrial biopsies will be analysed throughout the study (a period of 36 months) but comparison between groups will take place after 3 years, at study completion

  • To identify if there is a relationship between endometrial and peripheral blood immune cell parameters

    Blood and endometrial biopsies will be analysed throughout the study (a period of 36 months) but comparison between groups will take place after 3 years, at study completion

Other Outcomes (1)

  • Identify novel differences in the endometrial cellular landscape and cell function in women with recurrent implantation failure and subfertility

    Blood and endometrial biopsies will be analysed throughout the study (a period of 36 months) but comparison between groups will take place after 3 years, at study completion

Study Arms (3)

Male Factor Subfertility

Participant is undergoing first or second cycle of IVF and ICSI for male factor subfertility

Recurrent Implantation Failure

Participant is undergoing an IVF cycle to treat subfertility with a history of Recurrent Implantation Failure (RIF).

Female Subfertility

Participant is undergoing an IVF cycle to treat at least 1 year of subfertility

Eligibility Criteria

Age18 Years - 39 Years
Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsFemale participants only
Healthy VolunteersNo
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
Study Population

Participants will be women attending an IVI Midlands, IVI Oxford clinic or the Wolfson Fertility Centre age \<40 years who are undertaking an IVF cycle.

You may qualify if:

  • Participant is willing and able to give informed consent for participation in the study.
  • Female, aged 18 years to 39 years at the time of egg collection.
  • Participant has an ovulatory cycle of 25-35 days.
  • Participant is undergoing:
  • A first or second cycle of IVF and ICSI for male factor subfertility, or
  • An IVF cycle to treat subfertility with a history of RIF, or
  • An IVF cycle to treat at least 1 year of subfertility
  • We do not plan to target specific numbers in each group. Rather, the numbers that recruit in each group will be assessed at the end of the study and may well influence the design of the main study.

You may not qualify if:

  • The participant may not enter the study if ANY of the following apply:
  • Donor egg cycle.
  • Age 40 or above at the time of egg collection.
  • Ovulatory cycle of \<25 or \>35 days or evidence of anovulation
  • Involved in a interventional research study of any medication that may have an effect on the immune system
  • Patient taking oral steroids or other immunomodulatory medication

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Wolfson Fertility Centre

London, United Kingdom

RECRUITING

IVI Oxford

Oxford, United Kingdom

NOT YET RECRUITING

Related Publications (9)

  • Rai R, Sacks G, Trew G. Natural killer cells and reproductive failure--theory, practice and prejudice. Hum Reprod. 2005 May;20(5):1123-6. doi: 10.1093/humrep/deh804. Epub 2005 Mar 10.

    PMID: 15760961BACKGROUND

  • Beer AE, Kwak JY, Ruiz JE. Immunophenotypic profiles of peripheral blood lymphocytes in women with recurrent pregnancy losses and in infertile women with multiple failed in vitro fertilization cycles. Am J Reprod Immunol. 1996 Apr;35(4):376-82. doi: 10.1111/j.1600-0897.1996.tb00497.x.

    PMID: 8739457BACKGROUND

  • Kwak-Kim JY, Chung-Bang HS, Ng SC, Ntrivalas EI, Mangubat CP, Beaman KD, Beer AE, Gilman-Sachs A. Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Hum Reprod. 2003 Apr;18(4):767-73. doi: 10.1093/humrep/deg156.

    PMID: 12660269BACKGROUND

  • Ng SC, Gilman-Sachs A, Thaker P, Beaman KD, Beer AE, Kwak-Kim J. Expression of intracellular Th1 and Th2 cytokines in women with recurrent spontaneous abortion, implantation failures after IVF/ET or normal pregnancy. Am J Reprod Immunol. 2002 Aug;48(2):77-86. doi: 10.1034/j.1600-0897.2002.01105.x.

    PMID: 12389596BACKGROUND

  • McGrath E, Ryan EJ, Lynch L, Golden-Mason L, Mooney E, Eogan M, O'Herlihy C, O'Farrelly C. Changes in endometrial natural killer cell expression of CD94, CD158a and CD158b are associated with infertility. Am J Reprod Immunol. 2009 Apr;61(4):265-76. doi: 10.1111/j.1600-0897.2009.00688.x.

    PMID: 19260857BACKGROUND

  • Seshadri S, Sunkara SK. Natural killer cells in female infertility and recurrent miscarriage: a systematic review and meta-analysis. Hum Reprod Update. 2014 May-Jun;20(3):429-38. doi: 10.1093/humupd/dmt056. Epub 2013 Nov 27.

    PMID: 24285824BACKGROUND

  • Moffett A, Regan L, Braude P. Natural killer cells, miscarriage, and infertility. BMJ. 2004 Nov 27;329(7477):1283-5. doi: 10.1136/bmj.329.7477.1283.

    PMID: 15564263BACKGROUND

  • Polanski LT, Baumgarten MN, Quenby S, Brosens J, Campbell BK, Raine-Fenning NJ. What exactly do we mean by 'recurrent implantation failure'? A systematic review and opinion. Reprod Biomed Online. 2014 Apr;28(4):409-23. doi: 10.1016/j.rbmo.2013.12.006. Epub 2014 Jan 17.

    PMID: 24581986BACKGROUND

  • Nastri CO, Lensen SF, Gibreel A, Raine-Fenning N, Ferriani RA, Bhattacharya S, Martins WP. Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst Rev. 2015 Mar 22;(3):CD009517. doi: 10.1002/14651858.CD009517.pub3.

    PMID: 25803542BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Per participant the study will require a maximum of 30ml of blood this will be taken via 3xLiHep 4.5ml vacutainers and 1 x EDTA 4.5ml vacutainer. Endometrial biopsy samples will be obtained using an Endocell Disposable endometrial cell sampler. The biopsy tissue will be transferred into 10ml falcon tube containing sterile PBS.

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital Diseases

Study Officials

  • Ingrid Granne, DPhil MA MBBS MRCOG

    University of Oxford

    STUDY DIRECTOR

Central Study Contacts

Ingrid Granne, DPhil MA MBBS MRCOG

CONTACT

01865 740887ingrid.granne@wrh.ox.ac.uk

Lydia Brook, MNurSci, BSc

CONTACT

07971720340lydia.brook@wrh.ox.ac.uk

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 9, 2018

First Posted

September 7, 2018

Study Start

September 26, 2018

Primary Completion

August 1, 2021

Study Completion

August 1, 2021

Last Updated

October 29, 2018

Record last verified: 2018-10

Locations

GB(2)