A Study to Assess if Scratching the Lining of the Womb Prior to IVF Treatment Increases the Chances of Pregnancy
Condition: Infertility
MeSH terms: Infertility
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This study aims to see if taking a small sample from the lining of the womb (the 'scratch')
      before starting in vitro fertilization (IVF) treatment can influence the chance of getting
      pregnant and having a healthy, term baby.

      This study also aims to explore why an embryo is not accepted or indeed rejected by the
      lining of the womb. This will be analysed by carefully looking at the sample taken from the
      lining of the womb under the microscope and analysing the levels of natural killer (NK)
      cells. These cells are thought to regulate the implantation process and to be altered in some
      women with infertility and miscarriage.
    

Detailed description: 
      Following consent, participants will be randomised to one of the two trial interventions
      (endometrial biopsy, or ultrasound scan only = no intervention) by a member of the research
      team. The procedures will be scheduled for luteinising hormone (LH) day +7 to +9 of the
      menstrual cycle directly preceding commencement of down-regulation medications. A urine
      pregnancy test will be performed before the studied procedure. Just prior to the biopsy and
      directly following it, a transvaginal ultrasound scan will be performed to assess the length
      of the uterine cavity and endometrial parameters, including blood flow characteristics using
      power Doppler imaging. Endometrial sample will be obtained using standard sampling procedure
      by appropriately trained clinician.

      Participants randomised to treatment arm will undergo an endometrial biopsy procedure using
      Pipelle endometrial sampler (Pipelle de Cornier, Laboratoire CCD, Paris, France) or Wallace/
      Wallach endometrial sampler as an alternative device on cycle day LH+7 to LH+9 of the cycle
      directly preceding commencement of down-regulation prior to IVF or ICSI treatment. The
      endometrial sampling will be repeated a maximum of four times (all during the same
      appointment on day LH+7 to LH+9 of menstrual cycle) to assure a sufficient sample is
      obtained. If following the first two attempts, the endometrial sample is sufficient,
      procedure will be deemed complete. The Pipelle sampler will be introduced up to the uterine
      fundus (based on clinical touch technique and ultrasound measurements), and attempts will be
      made to obtain samples from all four walls of the endometrial cavity.

      Participants randomised to control group will also be supplied with home LH testing kits
      after informing the unit of the will to participate. Once the ovulation test is positive, the
      participant will contact the unit to arrange the ultrasound appointment on day LH+7 to LH+9
      of the cycle directly preceding commencement of IVF/ICSI treatment. 48 to 72 hours later and
      additional appointment will be scheduled for ultrasound scan and blood tests.

      Subjects will then be randomised to one of the two treatment arms based on a computer
      generated pseudo-random code using random permuted blocks of randomly varying size, created
      by the University of Nottingham Clinical Trials Unit (CTU). As a pilot feasibility study, the
      randomisation will not be stratified by any factors. Allocation to treatments will be in the
      ratio 1:1. The corresponding treatment allocation will be transmitted to the unblinded
      clinician, who will arrange the appropriate appointments for study procedures.

      Due to the nature of the study, no blinding of participant or researchers is possible.
    

Intervention name(s): Endometrial biopsy; Transvaginal ultrasound
Intervention type(s): Procedure; Device
Intervention description(s): Endometrial biopsy will be performed in the study group and timed according to a positive urinary LH (ovulation) kit at LH+7 to +9 days.; A detailed assessment of the endometrium will be performed including two- and three- dimensional ultrasound, as well as power Doppler acquisitions.
Other intervention name(s): Pipelle de Cornier (CCD, Paris).; GE Voluson E8 (Austria)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Infertility; Endometrium; Live birth