title: Hyaluronic Acid Binding Sperm Selection for assisted reproduction treatment (HABSelect): study protocol for a multicentre randomised controlled trial.
abstract: The selection of a sperm with good genomic integrity is an important consideration for improving intracytoplasmic sperm injection (ICSI) outcome. Current convention selects sperm by vigour and morphology, but preliminary evidence suggests selection based on hyaluronic acid binding may be beneficial. The aim of the Hyaluronic Acid Binding Sperm Selection (HABSelect) trial is to determine the efficacy of hyaluronic acid (HA)-selection of sperm versus conventionally selected sperm prior to ICSI on live birth rate (LBR). The mechanistic aim is to assess whether and how the chromatin state of HA-selected sperm corresponds with clinical outcomes-clinical pregnancy rate (CPR), LBR and pregnancy loss (PL).
  
  
  
  Couples attending UK Centres will be approached, eligibility screening performed and informed consent sought. Randomisation will occur within 24 hours prior to ICSI treatment. Participants will be randomly allocated 1:1 to the intervention arm (physiological intracytoplasmic sperm injection, PICSI) versus the control arm using conventional methods (ICSI). The primary clinical outcome is LBR ≥37 weeks' gestation with the mechanistic study determining LBR's relationship with sperm DNA integrity. Secondary outcomes will determine this for CPR and PL. Only embryologists performing the procedure will be aware of the treatment allocation. Steps will be taken to militate against biases arising from embryologists being non-blinded. Randomisation will use a minimisation algorithm to balance for key prognostic variables. The trial is powered to detect a 5% difference (24-29%: p=0.05) in LBR ≥37 weeks' gestation. Selected residual sperm samples will be tested by one or more assays of DNA integrity.
  
  
  
  HABSelect is a UK NIHR-EME funded study (reg no 11/14/34; IRAS REF. 13/YH/0162). The trial was designed in partnership with patient and public involvement to help maximise patient benefits. Trial findings will be reported as per CONSORT guidelines and will be made available in lay language via the trial web site (http://www.habselect.org.uk/).
  
  
  
  ISRCTN99214271; Pre-results.
authors.affiliation: Department: Centre for Primary Care & Public Health, Queen Mary University of London, London, UK.
authors.forename: K D
authors.initials: KD
authors.lastname: Witt
authors.affiliation: Department: Centre for Primary Care & Public Health, Queen Mary University of London, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Beresford
authors.affiliation: School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Charity Registration No. 1099960 (InfertilityNetworkUK), London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Brian
authors.affiliation: Centre for Human Reproductive Science, University of Birmingham, Birmingham Women's Fertility Centre, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: A
authors.initials: A
authors.lastname: Coomarasamy
authors.affiliation: Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Cutting
authors.affiliation: Department: Centre for Primary Care & Public Health, Queen Mary University of London, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Hooper
authors.affiliation: Centre for Human Reproductive Science, University of Birmingham, Birmingham Women's Fertility Centre, Birmingham Women's NHS Foundation Trust, Birmingham, UK.
authors.forename: J
authors.initials: J
authors.lastname: Kirkman-Brown
authors.affiliation: Assisted Conception Unit, Guy's and St Thomas's Hospital, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Khalaf
authors.affiliation: Queen's University Belfast, Institute of Pathology, Belfast, UK.
authors.forename: S E
authors.initials: SE
authors.lastname: Lewis
authors.affiliation: Department of Human Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: A
authors.initials: A
authors.lastname: Pacey
authors.affiliation: Dental Translational and Clinical Research Unit, School of Dentistry, University of Leeds, Leeds, UK.
authors.forename: S
authors.initials: S
authors.lastname: Pavitt
authors.affiliation: Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.
authors.forename: R
authors.initials: R
authors.lastname: West
authors.affiliation: Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM), University of Leeds, Leeds, UK.
authors.forename: D
authors.identifier: 0000-0002-1709-108X
authors.initials: D
authors.lastname: Miller
authors.forename: Rachel
authors.lastname: Cutting
mesh_terms: D000022:Abortion, Spontaneous; D000293:Adolescent; D000328:Adult; D001723:Birth Rate; D002843:Chromatin; D002985:Clinical Protocols; D004247:DNA; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate; D012107:Research Design; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods*; D013094:Spermatozoa; D055815:Young Adult
chemical_list: D002843:Chromatin; D006820:Hyaluronic Acid; D004247:DNA
keywords: REPRODUCTIVE MEDICINE