title: The ICSI procedure from past to future: a systematic review of the more controversial aspects.
abstract: BACKGROUND
  ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly due to the high level of standardization reached by the procedure. There are, however, some aspects that deserve attention and can still be ameliorated. The aim of this systematic review was to evaluate the results of available publications dealing with the management of specific situations during ICSI in order to support embryologists in trying to offer the best laboratory individualized treatment.
  
  
  METHODS
  This systematic review is based on material obtained by searching PUBMED between January 1996 and March 2015. We included peer-reviewed, English-language journal articles that have evaluated ICSI outcomes in the case of (i) immature oocytes, (ii) oocyte degeneration, (iii) timing of the various phases, (iv) polar body position during injection, (v) zona-free oocytes, (vi) fertilization deficiency, (vii) round-headed sperm, (viii) immotile sperm and (ix) semen samples with high DNA fragmentation.
  
  
  RESULTS
  More than 1770 articles were obtained, from which only 90 were specifically related to the issues developed for female gametes and 55 for the issues developed for male gametes. The studies selected for this review were organized in order to provide a guide to overcome roadblocks. According to these studies, the injection of rescue metaphase I oocytes should be discouraged due to poor clinical outcomes and a high aneuploidy rates; laser-assisted ICSI represents an efficient method to solve the high oocyte degeneration rate; the optimal ICSI timing and the best polar body position during the injection have not been clarified; injected zona-free oocytes, if handled carefully, can develop up to blastocyst stage and implant; efficient options can be offered to patients who suffered fertilization failure in previous conventional ICSI cycles. Most controversial and inconclusive are data on the best method to select a viable spermatozoa when only immotile spermatozoa are available for ICSI and, to date, there is no reliable approach to completely filter out spermatozoa with fragmented DNA from an ejaculate. However, most of the studies do not report essential clinical outcomes, such as live birth, miscarriage and fetal abnormality rate, which are essential to establish the safety of a procedure.
  
  
  CONCLUSIONS
  This review provides the current knowledge on some controversial technical aspects of the ICSI procedures in order to improve its efficacy in specific contexts. Notwithstanding that embryologists might benefit from the approaches presented herein in order to improve ICSI outcomes, this area of expertise still demands a greater number of well-designed studies, especially in order to solve open issues about the safety of these procedures.
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rubino
authors.affiliation: Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Viganò
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, viale Bracci 14, 53100 Siena, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Luddi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Policlinico Le Scotte, viale Bracci 14, 53100 Siena, Italy piomboni@unisi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Piomboni
mesh_terms: D053627:Asthenozoospermia / Q000473:pathology / Q000628:therapy; D053938:DNA Fragmentation; D005260:Female; D005306:Fertilization / Q000502:physiology; D006801:Humans; D008297:Male; D008677:Metaphase / Q000502:physiology; D008845:Microinjections / Q000009:adverse effects / Q000379:methods / Q000639:trends; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects / Q000379:methods / Q000639:trends*; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology
keywords: ICSI; fertilization failure; globozoospermia; metaphase I oocyte; oocyte activation; sperm; zona-free oocyte