DOI: 10.6084/m9.figshare.14528574.v1
title: Recombinant versus bovine hyaluronidase for oocyte denudation before intracytoplasmic sperm injection: a systematic review and meta-analysis

description: The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The objective of this study was to appraise critically the published randomised controlled trials (RCTs) comparing recombinant hyaluronidase with bovine hyaluronidase for oocyte denudation before intracytoplasmic sperm injection (ICSI). We performed a comprehensive literature search of the standard medical databases in order to identify the RCTs comparing oocyte denudation with recombinant hyaluronidase or bovine hyaluronidase before ICSI. Three RCTs involving 2445 oocytes collected from 200 women were analysed. There was substantial heterogeneity among the included RCTs. A meta-analysis from the available moderate to high quality trials found no statistical difference in terms of fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI.IMPACT STATEMENT<b>What is already known on this subject?</b> The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The long-established source of hyaluronidase has been represented by bovine testes, but concern has been raised regarding the possible negative effects over the fragile oocytes by mechanisms involving low enzyme purity, variable concentrations, trauma, prolonged exposure and integration of external DNA in the oocyte. Recombinant human hyaluronidase has been proposed as an alternative in order to counteract the possible negative effects of using animal derived products.<b>What do the results of this study add?</b> A meta-analysis from the available moderate to high quality trials found no statistical difference in fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI.<b>What are the implications of these findings or clinical practice and/or further research?</b> Future trials should be powered adequately in order to be able to identify the possible small differences between the study groups and they should be conducted according to the CONSORT guidelines as the absence of blinding for outcome assessors can induce detection bias. <b>What is already known on this subject?</b> The removal of cumulus cells in a process called oocyte denudation is required in order to visualise, grade and manipulate the oocytes before injection. The long-established source of hyaluronidase has been represented by bovine testes, but concern has been raised regarding the possible negative effects over the fragile oocytes by mechanisms involving low enzyme purity, variable concentrations, trauma, prolonged exposure and integration of external DNA in the oocyte. Recombinant human hyaluronidase has been proposed as an alternative in order to counteract the possible negative effects of using animal derived products. <b>What do the results of this study add?</b> A meta-analysis from the available moderate to high quality trials found no statistical difference in fertilisation rate, embryo quality and live birth rate between the use of recombinant or bovine hyaluronidase for oocyte denudation before ICSI. <b>What are the implications of these findings or clinical practice and/or further research?</b> Future trials should be powered adequately in order to be able to identify the possible small differences between the study groups and they should be conducted according to the CONSORT guidelines as the absence of blinding for outcome assessors can induce detection bias.