Prospective randomised sibling-oocyte study using recombinant human hyaluronidase Cumulase® versus Sigma hyaluronidase in intracytoplasmic sperm injection patients

ISRCTN	ISRCTN89831716
DOI	https://doi.org/10.1186/ISRCTN89831716
Protocol serial number	Protocol number: HZ2-05-07, NL953 (NTR979)
Sponsor	University Hospital Brussels (Universitair Ziekenhuis Brussel [UZ Brussel]) (Belgium)
Funders	Halozyme Therapeutics Inc. (USA), University Hospital Brussels (Universitair Ziekenhuis Brussel [UZ Brussel]) (Belgium)

Submission date: 27/06/2007
Registration date: 27/06/2007
Last edited: 25/10/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Pregnancy and Childbirth

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Josiane van der Elst
Scientific

Laboratory Director
Centre for Reproductive Medicine
Universitair Ziekenhuis Brussel
Laarbeeklaan 101
Brussels
B-1090
Belgium

Phone	+32 24 77 66 90
Email	Josiane.Vanderelst@uzbrussel.be

Study information

Primary study design	Interventional
Study design	Randomised, active controlled, parallel group trial
Secondary study design	Randomised controlled trial
Scientific title	Prospective randomised sibling-oocyte study using recombinant human hyaluronidase Cumulase® versus Sigma hyaluronidase in intracytoplasmic sperm injection patients
Study objectives	Non-inferiority trial in order to evaluate the effectiveness of the new compound (recombinant human hyaluronidase or Cumulase®), effectiveness being defined by intactness after Intracytoplasmic Sperm Injection (ICSI) and fertilisation rate.
Ethics approval(s)	Approval received from the local medical ethics committee (Academisch Ziekenhuis - Vrije Universiteit Brussel) on the 2nd March 2006 (ref: Protocol HZ2-05-07, version 1.0 dd. 27/12/2005).
Health condition(s) or problem(s) studied	Intracytoplasmic Sperm Injection (ICSI), Hyaluronidase
Intervention	Oocyte collection and denudation: At the moment of oocyte retrieval (day 0), sibling Cumulus Oocyte Complexes(COC's) were allocated to two separate oocyte collection dishes in an alternating way. A computer generated random list (balanced blocks of six) was used for allocation of the first dish to either Cumulase® or bovine hyaluronidase denudation. Collection and denudation of the oocytes was done in Hepes buffered Human Tubal Fluid (HTF) medium (Cambrex Bioscience, Verviers, Belgium) supplemented with Synthetic Serum Supplement (SSS) (Irvine Scientific, Wicklow, Ireland). Cumulase® denudation (Halozyme Therapeutics Inc., San Diego, USA) involved incubation in 80 U/ml, including Pasteur pipetting of all sibling COCs together (time of incubation to be determined during the study). When most of the cumulus was removed, oocytes were rinced twice in HTF medium prior to further mechanical decoronisation in the absence of the enzyme. The level of additional mechanical stripping was quantified by counting the number of times that individual oocytes had to be pipetted in and out of a small hand-made pipette (inner diameter 135 µm) using a Swemed pipette holder (Vitrolife, Kungsbacka, Sweden). Denudation in bovine hyaluronidase (Type VIII, Sigma Chemical Company, St Louis, USA) was done similarly except for using a 40 U/ml concentration of the enzyme, because of long-term laboratory experience with this concentration. Incubation time and level of mechanical stripping were evaluated similarly. Incubation time of the cumulus oocyte complexes was 62 and 63 seconds for Cumulase® and bovine hyaluronidase respectively. Duration of follow up was until positive human Chorionic Gonadotropin (hCG) (i.e. 14 to 17 days post oocyte retrieval). Baseline outcome measures: Enzyme incubation time, mechanical denudation and number of mature oocytes available for ICSI are measured at the moment of oocyte denudation, which takes place immediately or ± 2 hours after oocyte retrieval (day 0). ICSI is performed on mature oocytes immediately after denudation.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Cumulase®, sigma hyaluronidase
Primary outcome measure(s)	1. Oocyte intactness after ICSI, measured ± 18 - 20 hours after ICSI (day 1 of culture) 2. Fertilisation rate, measured ± 18 - 20 hours after ICSI (day 1 of culture)
Key secondary outcome measure(s)	1. Embryo development: 1.1. Day 3 embryo development is assessed on day 3 of embryo culture 1.2. Day 5 embryo development is assessed on day 5 of embryo culture 2. Positive human Chorionic Gonadotropin (hCG) after embryo transfer, measured in two blood samples given day 14 and day 17 after oocyte retrieval (day 0)
Completion date	28/02/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target sample size at registration	135
Key inclusion criteria	Women undergoing ICSI treatment with fresh ejaculate sperm cells, no older than 38 years of age and presenting between 8 and 16 Cumulus Oocyte Complexes (COC's) at ovum pick up.
Key exclusion criteria	1. Surgically extracted sperm preparations 2. Embryo biopsy cycles 3. Women older than 38 years 4. Women with less than 8 or more than 16 COC's
Date of first enrolment	01/05/2006
Date of final enrolment	28/02/2007

Locations

Countries of recruitment

Belgium
Netherlands

Study participating centre

Laboratory Director

Brussels
B-1090
Belgium

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Abstract results		01/06/2007	25/10/2021	No	No

Editorial Notes

25/10/2021: Publication reference added.