|- candidate number||12215|
|- NTR Number||NTR3387|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||6-apr-2012|
|- Secondary IDs||NL36590.000.12 CCMO|
|- Public Title||A multicentre randomized controlled trial on the efficacy of laser assisted hatching in poor prognosis patients undergoing IVF or ICSI.|
|- Scientific Title||A multicentre randomized controlled trial on the efficacy of laser assisted hatching in poor prognosis patients undergoing IVF or ICSI.|
|- ACRONYM||The AHA trial|
|- hypothesis||Laser assisted hatching increases the live birth rate in poor prognosis patients.|
|- Healt Condition(s) or Problem(s) studied||IVF, ICSI, Assisted reproductive technologies|
|- Inclusion criteria||Repeated implantation failure.|
|- Exclusion criteria||1. Couples with no indication for IVF/ICSI treatment or with contraindications for IVF/ICSI treatment such as cardiovascular-pulmonary disease, severe diabetes, bleeding disorders, immunodeficiency and morbid obesity (i.e. a BMI of over 35);|
2. Not able or willing to provide informed consent;
3. Unable to speak or read the Dutch language;
4. Medical contraindication for pregnancy or childbirth;
5. Positive serology for Hepatitis B (in the case of ICSI) or HIV (in the case of IVF and ICSI). (conform: Standpunt inzake screening op infectieziekten bij kunstmatig geassisteerde voortplanting, www.embryologen.nl).
|- mec approval received||yes|
|- multicenter trial||yes|
|- control||Not applicable|
|- Type||2 or more arms, randomized|
|- planned startdate ||28-nov-2012|
|- planned closingdate||28-nov-2015|
|- Target number of participants||588|
|- Interventions||In the intervention group, the embryos to be transferred will undergo laser assisted hatching. One eighth of the ZP will be completely breached using the laser. Laser pulse duration should not exceed 400 Ás per pulse at a maximum power of 100%, corresponding to 285mW output peak power in clinical mode. If the isotherm rings are used, the rings corresponding to 60oC and higher should not contact the adjacent blastomeres. Preferably, a part of the ZP is selected with underneath a large area of perivitelline space or in the vicinity of an area with extensive fragmentation.
In the control group, the embryos to be transferred will not undergo laser.
|- Primary outcome||The live birth rate per couple included following one IVF/ICSI treatment, including pregnancies from cryopreserved and thawed embryos transferred before the end of the inclusion period.|
|- Secondary outcome||1. The pregnancy rate (as defined by a positive pregnancy test 14 days following embryo transfer) per treatment cycle started, per oocyte retrieval and per embryo transfer, including pregnancies from cryopreserved and thawed embryos transferred before the end of the inclusion period;|
2. The ongoing pregnancy rate (a vital pregnancy 10 weeks after embryo transfer) per treatment cycle started, per oocyte retrieval and per embryo transfer, including pregnancies from cryopreserved and thawed embryos transferred before the end of the inclusion period;
3. The implantation rate per embryo transferred;
4. The multiple pregnancy rate;
5. The monozygotic twinning rate;
6. The percentage of major and minor malformations in the children born as assessed at birth.
|- Timepoints||1. The live birth rate: Assessed at birth;|
2. The pregnancy rate: 14 days following embryo transfer;
3. The ongoing pregnancy rate: 10 weeks after embryo transfer;
4. The implantation rate: 10 weeks after embryo transfer;
5. The multiple pregnancy rate: 10 weeks after embryo transfer;
6. The monozygotic twinning rate: 10 weeks after embryo transfer;
7. The percentage of major and minor malformations in the children born: assessed at birth.
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES|| M.H.J.M. Curfs|
|- CONTACT for SCIENTIFIC QUERIES|| M.H.J.M. Curfs|
|- Sponsor/Initiator ||Isala Clinics Zwolle|
(Source(s) of Monetary or Material Support)
|- Brief summary||Rationale: |
Hatching is the process in which the embryo is extruded from the zona pellucida which surrounds the oocyte and the embryo just before implantation in the endometrium. Artificial reproductive technologies such as IVF and ICSI have been brought in relation to alterations in the zona pellucida, thereby hampering hatching and diminishing pregnancy rates. Assisted hatching is a laboratory technique which might overcome this negative influence by breaching, dissolving of weakening the zona pellucida. Assisted hatching is applied in many centres worldwide, albeit not in The Netherlands. There is scientific evidence that assisted hatching might especially be effective in poor prognosis patients, however the evidence regarding the efficacy of assisted hatching expressed as live birth rate is only weak. The goal of this study is to provide evidence whether assisted hatching positively influences the live birth rate in poor prognosis patients undergoing IVF or ICSI.
The main objective is to determine if assisted hatching improves the live birth rate in poor prognosis patients. The secondary objective is to gather information on the safety of assisted hatching as determined by the number of congenital abnormalities diagnosed perinatally in comparison with the control group.
Multicentre randomized controlled intervention study.
Poor prognosis patients undergoing IVF or ICSI. Poor prognosis is defined by: Couples with at least two previous IVF or ICSI attempts not resulting in pregnancy (repeated implantation failure).
Patients will be randomized between no intervention and the intervention laser assisted hatching on the embryos transferred.
Main study parameters/endpoints:
The main study parameter is the difference in live birth rate between the control and the assisted hatching group. Besides this, other study parameters include the (ongoing) pregnancy rate, the implantation rate, monozygotic twinning rate and the number of congenital abnormalities diagnosed perinatally.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The burden in the patients allocated to assisted hatching is comparable to that of control patients, i.e. both groups receive a standard IVF or ICSI treatment. In addition, all patients with an ongoing pregnancy will receive a questionnaire on the perinatal outcome of the pregnancy. Embryos in the intervention group will undergo laser assisted hatching before transfer, possibly leading to improved implantation rates. The benefit for the patients in the intervention group is possibly an increased live birth rate. The major risk for the embryos and patients is an increased monozygotic twinning rate after assisted hatching.
|- Main changes (audit trail)|
|- RECORD||6-apr-2012 - 3-dec-2012|