Journal of Assisted Reproduction and Genetics

, Volume 35, Issue 3, pp 367–391 | Cite as

Revisiting embryo assisted hatching approaches: a systematic review of the current protocols

  • Alessandra Alteri
  • Paola Viganò
  • Ahmad Abu Maizar
  • Luca Jovine
  • Elisa Giacomini
  • Patrizia Rubino


Zona pellucida (ZP) manipulation, termed “assisted hatching” (AH), has been introduced in order to favor embryo hatching and ultimately improve assisted reproductive technology success but with poor proofs of safety and biological plausibility. We herein provide a systematic review of clinical outcomes following the application of different methods of ZP manipulation on fresh or frozen/thawed embryos at different developmental stages in different groups of patients. Out of the 69 papers that compared the clinical outcomes deriving from hatched versus non-hatched embryos, only 11 considered blastocysts while the rest referred to cleavage stage embryos. The ZP thinning of fresh embryos either by chemical or laser approach was shown to provide very limited benefit in terms of clinical outcomes. Better results were observed with procedures implying a higher degree of zona manipulation, including zona removal. Studies comparing the mechanical or chemical procedures to those laser-mediated consistently reported a superiority of the latter ones over the former. Literature is consistent for a benefit of ZP breaching in thawed blastocysts. This review provides the current knowledge on the AH procedure in order to improve its efficacy in the appropriate context. Embryologists might benefit from the approaches presented herein in order to improve Assisted Reproduction Technologies (ART) outcomes.


Zona pellucida Zona hardening Embryo culture Hatching Assisted hatching Implantation failure 


Author’s roles

A.A., P.V., and P.R. provided a substantial contribution to the review conception. All the authors participated in the draft of the article. All authors approved the final version of the article.


This work has not been supported by a grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Alessandra Alteri
    • 1
  • Paola Viganò
    • 2
  • Ahmad Abu Maizar
    • 3
  • Luca Jovine
    • 4
  • Elisa Giacomini
    • 2
  • Patrizia Rubino
    • 5
  1. 1.Obstetrics and Gynaecology DepartmentIRCCS San Raffaele Scientific InstituteMilanItaly
  2. 2.Reproductive Sciences Laboratory, Division of Genetics and Cell BiologyIRCCS San Raffaele Scientific InstituteMilanItaly
  3. 3.California Fertility PartnersLos AngelesUSA
  4. 4.Department of Biosciences and Nutrition & Center for Innovative MedicineKarolinska InstitutetHuddingeSweden
  5. 5.HRC FertilityPasadenaUSA

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