Contact information
Type
Scientific
Primary contact
Prof Josiane van der Elst
ORCID ID
Contact details
Laboratory Director
Centre for Reproductive Medicine
Universitair Ziekenhuis Brussel
Laarbeeklaan 101
Brussels
B-1090
Belgium
+32 24 77 66 90
Josiane.Vanderelst@uzbrussel.be
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Protocol number: HZ2-05-07
Study information
Scientific title
Acronym
Study hypothesis
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
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).
Study design
Randomised, active controlled, parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
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 names
Cumulase®, sigma hyaluronidase
Primary outcome measures
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)
Secondary outcome measures
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)
Overall trial start date
01/05/2006
Overall trial end date
28/02/2007
Reason abandoned
Eligibility
Participant 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.
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
135
Participant 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
Recruitment start date
01/05/2006
Recruitment end date
28/02/2007
Locations
Countries of recruitment
Netherlands
Trial participating centre
Laboratory Director
Brussels
B-1090
Belgium
Sponsor information
Organisation
University Hospital Brussels (Universitair Ziekenhuis Brussel [UZ Brussel]) (Belgium)
Sponsor details
Centrum Medische Genetica en Centrum Reproductieve Geneeskunde
Brussels
B-1090
Belgium
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
Funder name
Halozyme Therapeutics Inc. (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
University Hospital Brussels (Universitair Ziekenhuis Brussel [UZ Brussel]) (Belgium)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary