title: Advanced sperm selection techniques for assisted reproduction.
abstract: BACKGROUND
  Assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) bring together gametes outside of the body to enhance the probability of fertilisation and pregnancy. Advanced sperm selection techniques are increasingly being employed in ART, most commonly in cycles utilising ICSI. Advanced sperm selection techniques are thought to improve the chance that structurally intact and mature sperm with high DNA integrity are selected for fertilisation. Advanced sperm selection strategies include selection according to surface charge; sperm apoptosis; sperm birefringence; ability to bind to hyaluronic acid; and sperm morphology under ultra-high magnification. These techniques theoretically improve ART outcomes.
  
  
  OBJECTIVE
  To evaluate the impact of advanced sperm selection techniques on ART outcomes.
  
  
  METHODS
  Systematic search of electronic databases (Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American and Caribbean Health Science Information Database (LILACS)), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (Web of Knowledge) and grey literature (OpenGrey) for relevant randomised controlled trials. We handsearched the reference lists of included studies and similar reviews. The search was conducted in May 2014.
  
  
  METHODS
  We included randomised controlled trials (RCTs) comparing an advanced sperm selection technique versus standard IVF or ICSI or versus another advanced sperm selection technique. We excluded studies of sperm selection using ultra-high magnification (intracytoplasmic morphologically selected sperm injection, or IMSI), as they are the subject of a separate Cochrane review. Quasi-randomised and pseudo-randomised trials were excluded. Our primary outcome measure was live birth rate per woman randomly assigned. Secondary outcome measures included clinical pregnancy per woman randomly assigned, miscarriage per clinical pregnancy and fetal abnormality per clinical pregnancy.
  
  
  METHODS
  Two review authors independently assessed eligibility of studies and risk of bias, and performed data extraction. Disagreements were resolved by consultation with a third review author. Study investigators were consulted to resolve other queries that arose. Risk ratios (RRs) were calculated with 95% confidence intervals (CIs). We planned to combine studies using a fixed-effect model, if sufficient data were available. The quality of the evidence was evaluated using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods.
  
  
  RESULTS
  Two RCTs were included in the review. Both evaluated sperm selection by hyaluronanic acid binding for ICSI, but only one reported live births. No studies were identified that were related to surface charge selection, sperm apoptosis or sperm birefringence.One RCT compared hyaluronanic acid binding versus conventional ICSI. Live birth was not reported. Evidence was insufficient to show whether there was a difference between groups in clinical pregnancy rates (RR 1.01, 95% CI 0.84 to 1.22, one RCT, 482 women). This evidence was deemed to be of low quality, mainly as the result of poor reporting of methods and findings. Miscarriage data were unclear, and fetal abnormality rates were not reported.The other RCT compared two different hyaluronanic acid binding techniques, SpermSlow and physiological intracytoplasmic sperm injection (PISCI). Evidence was insufficient to indicate whether there was a difference between groups in rates of live birth (RR 1.16, 95% CI 0.65 to 2.05, one RCT, 99 women), clinical pregnancy (RR 1.07, 95% CI 0.67 to 1.71, one RCT, 99 women) or miscarriage (RR 0.76, 95% CI 0.24 to 2.44, one RCT, 41 women). The evidence for these comparisons was deemed to be of low quality, as it was limited by imprecision and poor reporting of study methods. Fetal abnormality rates were not reported.
  
  
  CONCLUSIONS
  Evidence was insufficient to allow review authors to determine whether sperm selected by hyaluronanic acid binding improve live birth or pregnancy outcomes in ART, and no clear data on adverse effects were available. Evidence was also insufficient to show whether there is a difference in efficacy between the hyaluronic acid binding methods SpermSlow and PICSI. No randomised evidence evaluating sperm selection by sperm apoptosis, sperm birefringence or surface charge was found.Further studies of suitable quality are required to evaluate whether any of these advanced sperm selection techniques can be recommended for use in clinical practice.
authors.affiliation: Queensland Fertility Group Research Foundation, 55 Little Edward St, Level 2 Boundary Court, Spring Hill, Brisbane, Queensland, Australia, 4000.
authors.forename: Simon
authors.initials: S
authors.lastname: McDowell
authors.forename: Ben
authors.initials: B
authors.lastname: Kroon
authors.forename: Emily
authors.initials: E
authors.lastname: Ford
authors.forename: Ysanne
authors.initials: Y
authors.lastname: Hook
authors.forename: Demián
authors.initials: D
authors.lastname: Glujovsky
authors.forename: Anusch
authors.initials: A
authors.lastname: Yazdani
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001718:Birefringence; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D008297:Male; D016032:Randomized Controlled Trials as Topic; D020554:Sperm Injections, Intracytoplasmic / Q000379:methods*; D053625:Sperm Retrieval; D013094:Spermatozoa / Q000502:physiology*
chemical_list: D006820:Hyaluronic Acid