A multicentre randomized controlled trial on the efficacy of laser assisted hatching in poor prognosis patients undergoing IVF or ICSI.

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.



Objective:

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.



Study design:

Multicentre randomized controlled intervention study.



Study population:

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).



Intervention:

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.

Laser assisted hatching increases the live birth rate in poor prognosis patients.

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.

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 µs 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.