Condition category
Pregnancy and Childbirth
Date applied
27/06/2007
Date assigned
27/06/2007
Last edited
28/06/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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 COC’s 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

http://www.uzbrussel.be

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

Publication citations

Additional files

Editorial Notes