Freeze-all

Background of the study: Ovarian hyperstimulation does not only lead to the maturation of multiple oocytes but also causes changes in the endometrium that hamper endometrium receptivity thereby creating suboptimal implantation chances for the transferred embryo. Disengagement of the ovarian hyperstimulation from the embryo transfer by freezing all embryos followed by a transfer in a subsequent unstimulated cycle, overcomes this problem. It is not known which women benefit most from disengagement.
Objective of the study: To test the hypothesis that in women undergoing IVF/ICSI a freeze-all strategy results in higher ongoing pregnancy rates and is more cost-effective compared to a fresh embryo transfer.

Study design: multicentre marker-RCT with a cost-effectiveness analysis.

Study population: Subfertile women between 18 and 43 years undergoing IVF/ICSI.

Intervention (if applicable):Cryopreservation of all embryos at day 3-4 and postponed first transfer of the embryo in an unstimulated cycle. Cryopreservation of all supernumerary embryos and tranfser in unstimulated cycles. In both study arms a blood sample on the day of ovulation trigger is mandatory to measure serum progesterone as a marker for endometrium receptivity.

Primary study parameters/outcome of the study: Ongoing pregnancy rate per woman and progesterone serum level at day of ovulation trigger.

Secundary study parameters/outcome of the study (if applicable):

1. multiple ongoing pregnancy rates

2. live birth rates

3. cumulative ongoing pregnancy rates

4. time to pregnancy

5. costs

6. health-related quality of life (HRQL)

7. embryologic parameters: morphology, implantation rate

8. freeze-thaw survival per centre

9. endometrial parameters: thickness, appearance

Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if applicable): No incapacitated subjects nor minors are involved in this study. No risks additional to standard treatment are associated with the study. Benefits of participating in the study are potential higher pregnancy chances in the freeze-all arm.

4-apr-2016: Trial not started, investigators are no longer in equipoise.

In women undergoing IVF/ICSI a freeze-all strategy results in higher ongoing pregnancy rates and is more cost-effective compared to a fresh embryo transfer.

48 months

Cryopreservation of all embryos at day 3-4 and postponed first transfer of the embryo in an unstimulated cycle. Cryopreservation of all supernumerary embryos and tranfser in unstimulated cycles. In both study arms a blood sample on the day of ovulation trigger is mandatory to measure serum progesterone as a marker for endometrium receptivity.